Baxter Healthcare Corporation

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Baxter Healthcare Corporation Drugs

Metronidazole

Metronidazole

Treatment of Anaerobic Bacterial Infections

The recommended dosage schedule for adults is:

Loading Dose

15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult).

Maintenance Dose

7.5 mg/kg infused over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose.

Parenteral therapy may be changed to oral metronidazole when conditions warrant, based upon the severity of the disease and the response of the patient to Metronidazole Injection, USP treatment. The usual adult oral dosage is 7.5 mg/kg every six hours (approximately 500 mg for a 7-kg adult).

A maximum of 4 g should not be exceeded during a 24-hour period.

The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract and endocardium may require longer treatment.

Dosage Adjustments

Patients with Severe Hepatic Impairment

For patients with severe hepatic impairment (Child-Pugh C), the metronidazole dose should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Patients Undergoing Hemodialysis

Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation. The clearance of metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of metronidazole cannot be separated from a hemodialysis session, supplementation of metronidazole dosage following a hemodialysis session should be considered, depending on the patient’s clinical situation (see CLINICAL PHARMACOLOGY).

Prophylaxis

For surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is:
a. 15 mg/kg infused over 30 to 60 minutes and completed approximately one hour before surgery; followed by b. 7.5 mg/kg infused over 30 to 60 minutes at 6 and 12 hours after the initial dose.
It is important that (1) administration of the initial preoperative dose be completed approximately one hour before surgery so that adequate drug levels are present in the serum and tissues at the time of initial incision, and (2) Metronidazole Injection, USP be administered, if necessary, at 6-hour intervals to maintain effective drug levels. Prophylactic use of Metronidazole Injection, USP should be limited to the day of surgery only, following the above guidelines.

Caution: Metronidazole Injection, USP is to be administered by slow intravenous drip infusion only, either as a continuous or intermittent infusion. Additives should not be introduced into Metronidazole Injection, USP. If used with a primary intravenous fluid system, the primary solution should be discontinued during metronidazole infusion. DO NOT USE EQUIPMENT CONTAINING ALUMINUM (e.g., NEEDLES, CANNULAE) THAT WOULD COME IN CONTACT WITH THE DRUG SOLUTION.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Butalbital

Butalbital

2.1 Intravenous Dosing

Mesna may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below.

Mesna injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage weight by weight (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of ifosfamide. The total daily dose of mesna is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below in Table 1.
* The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of mesna to ifosfamide should be maintained.
Table 1. Recommended Intravenous Dosing Schedule

0 Hours

4 Hours

8 Hours

Ifosfamide

1.2 g/m2

–

–

Mesna injection*

240 mg/m2

240 mg/m2

240 mg/m2

2.2 Intravenous and Oral Dosing

Mesna may be given on a fractionated dosing schedule of a single bolus injection followed by two oral administrations of MESNEX tablets as outlined below.

Mesna injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration. MESNEX tablets are given orally in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. The total daily dose of mesna is 100% of the ifosfamide dose. The recommended dosing schedule is outlined in Table 2.
* The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of mesna to ifosfamide should be maintained.
Table 2. Recommended Intravenous and Oral Dosing Schedule

0 Hours

2 Hours

6 Hours

Ifosfamide

1.2 g/m2

–

–

Mesna injection*

240 mg/m2

–

–

MESNEX tablets

–

480 mg/m2

480 mg/m2

The efficacy and safety of this ratio of intravenous mesna and oral MESNEX has not been established as being effective for daily doses of ifosfamide higher than 2 g/m2.

Patients who vomit within two hours of taking oral MESNEX should repeat the dose or receive intravenous mesna.

2.3 Monitoring for Hematuria

Maintain adequate hydration and sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. If severe hematuria develops when mesna is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.

2.4 Preparation for Intravenous Administration and Stability

Preparation

Determine the volume of mesna injection for the intended dose.

Dilute the volume of mesna injection for the dose in any of the following fluids to obtain a final concentration of 20 mg/mL:
• 5% Dextrose Injection, USP • 5% Dextrose and 0.2% Sodium Chloride Injection, USP • 5% Dextrose and 0.33% Sodium Chloride Injection, USP • 5% Dextrose and 0.45% Sodium Chloride Injection, USP • 0.9% Sodium Chloride Injection, USP • Lactated Ringer’s Injection, USP
Stability

The mesna injection multidose vials may be stored and used for up to 8 days after initial puncture.

Store diluted solutions at 25°C (77°F). Use diluted solutions within 24 hours.

Do not mix mesna injection with epirubicin, cyclophosphamide, cisplatin, carboplatin, and nitrogen mustard.

The benzyl alcohol contained in mesna injection vials can reduce the stability of ifosfamide. Ifosfamide and mesna may be mixed in the same bag provided the final concentration of ifosfamide does not exceed 50 mg/mL. Higher concentrations of ifosfamide may not be compatible with mesna and may reduce the stability of ifosfamide.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any solutions which are discolored, hazy, or contain visible particulate matter should not be used.
Cyclophosphamide

Cyclophosphamide

During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide should be administered in the morning.

2.1 Dosing for Malignant Diseases

Adults and Pediatric PatientsIntravenous When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

OralOral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.

When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide as well as that of the other drugs.

2.2 Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients

An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males [see Use in Specific Populations (8.4)].

2.3 Preparation, Handling and Administration

Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing Cyclophosphamide for Injection, USP. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide for Injection, USP.

Cyclophosphamide for Injection, USP

Intravenous Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide vials if there are signs of melting. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.

Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.

For Direct Intravenous Injection

Reconstitute Cyclophosphamide with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.
Table 1: Reconstitution for Direct Intravenous Injection
Strength

Volume of 0.9% Sodium Chloride

Cyclophosphamide Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

For Intravenous Infusion

Reconstitution of Cyclophosphamide:Reconstitute Cyclophosphamide using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.
Table 2: Reconstitution in preparation for Intravenous Infusion
Strength

Volume of Diluent

Cyclophosphamide

Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

Dilution of Reconstituted Cyclophosphamide:Further dilute the reconstituted Cyclophosphamide solution to a minimum concentration of 2 mg per mL with any of the following diluents:
• 5% Dextrose Injection, USP • 5% Dextrose and 0.9% Sodium Chloride Injection, USP • 0.45% Sodium Chloride Injection, USP
To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.

Storage of Reconstituted and Diluted Cyclophosphamide Solution:

If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 3.
Table 3: Storage of Cyclophosphamide Solutions * Storage time is the total time cyclophosphamide is in solution including the time it is reconstituted in 0.9% Sterile Sodium Chloride Injection, USP or Sterile Water for Injection, USP.
Diluent

Storage

Room Temperature

Refrigerated

Reconstituted Solution (Without Further Dilution)

0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

Sterile Water for Injection, USP

Do not store; use immediately

Diluted Solutions*

0.45% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

5% Dextrose Injection, USP

up to 24 hrs

up to 36 hrs

5% Dextrose and 0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 36 hrs

Use of Reconstituted Solution for Oral Administration

Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF). Such preparations should be stored under refrigeration in glass containers and used within 14 days.
Obizur

Obizur

For intravenous use after reconstitution only

2.1 Dose
• Dose, dosing frequency, and duration of treatment with OBIZUR depend on the location and severity of bleeding episode, target factor VIII levels, and the patient’s clinical condition. Monitor replacement therapy in cases of major surgery or life-threatening bleeding episodes. • Each vial of OBIZUR has the recombinant porcine factor VIII potency in units stated on the vial. • Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses. Titrate dose and frequency based on factor VIII recovery levels and individual clinical response.
A guide for dosing OBIZUR for the treatment and prevention of bleeding episodes is provided in Table 1. Maintain the factor VIII activity within the target range. Plasma levels of factor VIII should not exceed 200% of normal or 200 units per dL.
Table 1 Dosing for Treatment of Bleeding Episodes
Type of Bleeding

Factor VIII Level Required (Units per dL or % of normal)

Initial Dose (Units per kg)

Subsequent Dose

Frequency and Duration of Subsequent Dosing

Minor and Moderate Superficial muscle/no neurovascular compromise, and joint

50-100

200

Titrate subsequent doses to maintain recommended factor VIII trough levels and individual clinical response

Dose every 4 to 12 hours, frequency may be adjusted based on clinical response and measured factor VIII levels

Major

Moderate to severe intramuscular bleeding, retroperitoneal, gastrointestinal, intracranial

100-200 (To treat an acute bleed)

50-100 (After acute bleed is controlled, if required)

2.2 Reconstitution
• Use aseptic technique during the reconstitution procedure. • If the patient needs more than one vial of OBIZUR per injection, reconstitute each vial according to the following instructions: 1. Bring the OBIZUR vial and the pre-filled diluent syringe to room temperature. 2. Remove the plastic cap from the OBIZUR vial (Figure A). 3. Wipe the rubber stopper with an alcohol swab (not supplied) and allow it to dry prior to use. 4. Peel back the cover of the vial adapter package (Figure B). Do not to touch the luer-lock (tip) in the center of the vial adapter. Do not remove the vial adapter from the plastic package. 5. Place the vial adapter package on a clean surface with the luer-lock pointing up. 6. Snap off the tamper resistant cap of the pre-filled syringe (Figure C). 7. While firmly holding the vial adapter package, connect the pre-filled syringe to the vial adapter by pushing the syringe tip down onto the luer lock in the center of the vial adapter, and turning it clockwise until the syringe is secured. Do not over tighten (Figure D). 8. Remove the plastic package (Figure E). 9. Place the OBIZUR vial on a clean, flat, hard surface. Place the vial adapter over the OBIZUR vial and firmly push the filter spike of the vial adapter through the center of the OBIZUR vial’s rubber circle until the clear plastic cap snaps onto the vial (Figure F). 10. Push the plunger down to slowly inject all of the diluent from the syringe into the OBIZUR vial. 11. Gently swirl (in a circular motion) the OBIZUR vial without removing the syringe until all of the powder is fully dissolved (Figure G). The reconstituted solution should be inspected visually for particulate matter before administration. Do not use if particulate matter or discoloration is observed. 12. With one hand hold the vial and vial adapter, and with the other hand firmly grasp the barrel of the pre-filled syringe and in a counterclockwise motion unscrew the syringe from the vial adapter (Figure H). 13. Use OBIZUR within 3 hours after reconstitution when stored at room temperature.
2.3 Administration

For intravenous injection only
• Inspect the reconstituted OBIZUR solution for particulate matter and discoloration prior to administration. The solution should be clear and colorless in appearance. Do not administer if particulate matter or discoloration is observed. • Do not administer OBIZUR in the same tubing or container with other medicinal products for infusion. 1. Once all vials have been reconstituted, connect a large syringe to the vial adapter by gently pushing the syringe tip down onto the luer lock in the center of the vial adapter, and turning clockwise until the syringe is secured. 2. Invert the vial; push the air in the syringe into the vial and withdraw the reconstituted OBIZUR into the syringe (Figure I).
Figure I
3. Unscrew the large syringe counterclockwise from the vial adapter, and repeat this process for all reconstituted vials of OBIZUR until the total volume to be administered is reached. 4. Administer the reconstituted OBIZUR intravenously at a rate of 1 to 2 mL per minute.
2.1 Dose
• Dose, dosing frequency, and duration of treatment with OBIZUR depend on the location and severity of bleeding episode, target factor VIII levels, and the patient’s clinical condition. Monitor replacement therapy in cases of major surgery or life-threatening bleeding episodes. • Each vial of OBIZUR has the recombinant porcine factor VIII potency in units stated on the vial. • Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses. Titrate dose and frequency based on factor VIII recovery levels and individual clinical response.
A guide for dosing OBIZUR for the treatment and prevention of bleeding episodes is provided in Table 1. Maintain the factor VIII activity within the target range. Plasma levels of factor VIII should not exceed 200% of normal or 200 units per dL.
Table 1 Dosing for Treatment of Bleeding Episodes
Type of Bleeding

Factor VIII Level Required (Units per dL or % of normal)

Initial Dose (Units per kg)

Subsequent Dose

Frequency and Duration of Subsequent Dosing

Minor and Moderate Superficial muscle/no neurovascular compromise, and joint

50-100

200

Titrate subsequent doses to maintain recommended factor VIII trough levels and individual clinical response

Dose every 4 to 12 hours, frequency may be adjusted based on clinical response and measured factor VIII levels

Major

Moderate to severe intramuscular bleeding, retroperitoneal, gastrointestinal, intracranial

100-200 (To treat an acute bleed)

50-100 (After acute bleed is controlled, if required)

2.2 Reconstitution
• Use aseptic technique during the reconstitution procedure. • If the patient needs more than one vial of OBIZUR per injection, reconstitute each vial according to the following instructions: 1. Bring the OBIZUR vial and the pre-filled diluent syringe to room temperature. 2. Remove the plastic cap from the OBIZUR vial (Figure A). 3. Wipe the rubber stopper with an alcohol swab (not supplied) and allow it to dry prior to use. 4. Peel back the cover of the vial adapter package (Figure B). Do not to touch the luer-lock (tip) in the center of the vial adapter. Do not remove the vial adapter from the plastic package. 5. Place the vial adapter package on a clean surface with the luer-lock pointing up. 6. Snap off the tamper resistant cap of the pre-filled syringe (Figure C). 7. While firmly holding the vial adapter package, connect the pre-filled syringe to the vial adapter by pushing the syringe tip down onto the luer lock in the center of the vial adapter, and turning it clockwise until the syringe is secured. Do not over tighten (Figure D). 8. Remove the plastic package (Figure E). 9. Place the OBIZUR vial on a clean, flat, hard surface. Place the vial adapter over the OBIZUR vial and firmly push the filter spike of the vial adapter through the center of the OBIZUR vial’s rubber circle until the clear plastic cap snaps onto the vial (Figure F). 10. Push the plunger down to slowly inject all of the diluent from the syringe into the OBIZUR vial. 11. Gently swirl (in a circular motion) the OBIZUR vial without removing the syringe until all of the powder is fully dissolved (Figure G). The reconstituted solution should be inspected visually for particulate matter before administration. Do not use if particulate matter or discoloration is observed. 12. With one hand hold the vial and vial adapter, and with the other hand firmly grasp the barrel of the pre-filled syringe and in a counterclockwise motion unscrew the syringe from the vial adapter (Figure H). 13. Use OBIZUR within 3 hours after reconstitution when stored at room temperature.
2.3 Administration

For intravenous injection only
• Inspect the reconstituted OBIZUR solution for particulate matter and discoloration prior to administration. The solution should be clear and colorless in appearance. Do not administer if particulate matter or discoloration is observed. • Do not administer OBIZUR in the same tubing or container with other medicinal products for infusion. 1. Once all vials have been reconstituted, connect a large syringe to the vial adapter by gently pushing the syringe tip down onto the luer lock in the center of the vial adapter, and turning clockwise until the syringe is secured. 2. Invert the vial; push the air in the syringe into the vial and withdraw the reconstituted OBIZUR into the syringe (Figure I).
Figure I
3. Unscrew the large syringe counterclockwise from the vial adapter, and repeat this process for all reconstituted vials of OBIZUR until the total volume to be administered is reached. 4. Administer the reconstituted OBIZUR intravenously at a rate of 1 to 2 mL per minute.
Flexbumin

Flexbumin

FLEXBUMIN 5% must be administered intravenously.
• Do not use if turbid. • Do not begin administration more than 4 hours after the container has been entered. • Monitor hemodynamic parameters in patients receiving FLEXBUMIN 5% and check for the risk of hypervolemia and cardiovascular overload.[see Precautions] Hypervolemia can occur if the dosage and rate of infusion are not adjusted, giving consideration to the solution concentration and the patient’s clinical status. • Do not dilute with Sterile Water for Injection as this can cause hemolysis in recipients [see Contraindications]. • Do not mix with other medicinal products including blood and blood components. FLEXBUMIN 5% can be used concomitantly with other parenterals such as whole blood, plasma, saline, glucose or sodium lactate when deemed medically necessary. The volume of the total dose and the rate of infusion depend on the patient’s condition and response. • Do not mix with protein hydrolysates or solutions containing alcohol since these combinations can cause the proteins to precipitate. • Do not add supplementary medication. • Record the name and batch number of the product to maintain a link between the patient and the product. • Discard unused portion.
Recommended Dosages

Hypovolemia

The dosage of FLEXBUMIN 5% must be individualized. Initial dosage range for older children and adults is 250 to 500 mL and for infants and young children 12 to 20 mL per kilogram body weight. Repeat after 30 minute intervals if the response is not adequate.

Upon administration of additional albumin or if hemorrhage occurs, hemodilution, and a relative anemia can occur. Supplemental administration of compatible red blood cells or compatible whole blood may be required to treat this condition.

Burns

The optimal therapeutic regimen for administration of crystalloid and colloid solutions after extensive burns has not been established. An initial dose of 500 mL is recommended after the first 24 hours following burns.

Hypoalbuminemia

Hypoalbuminemia is usually accompanied by a hidden extravascular albumin deficiency of equal magnitude. Consider total body albumin deficit when determining the amount of albumin necessary to reverse the hypoalbuminemia. Calculate the body albumin compartment to be 80 to 100 mL per kilogram of body weight when using the patient’s serum albumin concentration to estimate the deficit.5,6 Do not exceed a daily dose of 2 g of albumin per kilogram of body weight.

Preparation for Administration
• Check the GALAXY container for minute leaks prior to use by squeezing the bag firmly. If leaks are found, discard solution as sterility can be impaired. • Do not add supplementary medication. • Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. FLEXBUMIN 5% is a transparent or slightly opalescent solution, which may have a greenish tint or may vary from a pale straw to an amber color. Do not use unless solution is clear of particulate matter and seal is intact.
CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.

Administration:
1. Suspend container from eyelet support. 2. Remove plastic protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set. Make certain that the administration set contains an adequate filter (15-micron or smaller).
Esmolol Hydrochloride

Esmolol Hydrochloride

2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

Esmolol hydrochloride is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.
Table 1 Step-Wise Dosing
Step

Action

1

Optional loading dose (500 mcg per kg over 1 minute), then 50 mcg per kg per min for 4 min

2

Optional loading dose if necessary, then 100 mcg per kg per min for 4 min

3

Optional loading dose if necessary, then 150 mcg per kg per min for 4 min

4

If necessary, increase dose to 200 mcg per kg per min

In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.

The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.

Maintenance infusions may be continued for up to 48 hours.

2.2 Intraoperative and Postoperative Tachycardia and Hypertension

In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.

Immediate Control
• Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary. • Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.
Gradual Control
• Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes. • Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.
Maximum Recommended Doses
• For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases. • For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
2.3 Transition from Esmolol Hydrochloride Injection Therapy to Alternative Drugs

After patients achieve adequate control of the heart rate and a stable clinical status, transition to alternative antiarrhythmic drugs may be accomplished.

When transitioning from esmolol hydrochloride to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of esmolol hydrochloride as follows:
1. Thirty minutes following the first dose of the alternative drug, reduce the esmolol hydrochloride infusion rate by one-half (50%). 2. After administration of the second dose of the alternative drug, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue the esmolol hydrochloride infusion.
2.4 Directions for Use

This dosage form is prediluted to provide a ready-to-use, iso-osmotic solution of 10 mg/mL esmolol hydrochloride in sodium chloride recommended for esmolol hydrochloride intravenous administration. The ready-to-use vial may be used to administer a loading dosage by hand-held syringe while the maintenance infusion is being prepared.When using a 10 mg/mL concentration, a loading dose of 0.5 mg/kg infused over 1 minute, for a 70 kg patient is 3.5 mL.

Esmolol hydrochloride injection is not compatible with Sodium Bicarbonate (5%) solution (limited stability) or furosemide (precipitation).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Compatibility with Commonly Used Intravenous Fluids

Esmolol hydrochloride was tested for compatibility with ten commonly used intravenous fluids at a final concentration of 10 mg esmolol hydrochloride per mL. Esmolol hydrochloride was found to be compatible with the following solutions and was stable for at least 24 hours at controlled room temperature or under refrigeration:
• Dextrose (5%) Injection, USP • Dextrose (5%) in Lactated Ringer’s Injection • Dextrose (5%) in Ringer’s Injection • Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP • Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP • Lactated Ringer’s Injection, USP • Potassium Chloride (40 mEq/liter) in Dextrose (5%) Injection, USP • Sodium Chloride (0.45%) Injection, USP • Sodium Chloride (0.9%) Injection, USP
Potassium Chloride In D...

Potassium Chloride In Dextrose And Sodium Chloride

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter anddiscoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear and seal is intact. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

All injections in AVIVA plastic containers are intended for intravenous administration using sterile equipment.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Revex

Revex

Important Information - Dosage Forms

REVEX is supplied in two concentrations that can be identified by their color coded container labels: a concentration suitable for postoperative use (100 µg/mL) in a blue labeled ampul containing ONE (1) mL and a concentration suitable for the management of overdose (1 mg/mL, 10 times as concentrated, 20 times as much drug) in a green labeled ampul containing TWO (2) mL. Proper steps should be taken to prevent use of the incorrect concentration.

General Principles

REVEX should be titrated to reverse the undesired effects of opioids. Once adequate reversal has been established, additional administration is not required and may actually be harmful due to unwanted reversal of analgesia or precipitated withdrawal.

Duration of Action

The duration of action of REVEX is as long as most opioid analgesics. The apparent duration of action of REVEX will vary, however, depending on the half-life and plasma concentration of the narcotic being reversed, the presence or absence of other drugs affecting the brain or muscles of respiration, and the dose of REVEX administered. Partially reversing doses of REVEX (1 µg/kg) lose their effect as the drug is redistributed through the body, and the effects of these low doses may not last more than 30-60 minutes in the presence of persistent opioid effects. Fully reversing doses (1 mg/70 kg) have been shown to last many hours in both experimental and clinical studies, but may complicate the management of patients who are in pain, at high cardiovascular risk, or who are physically dependent on opioids.

The recommended doses represent a compromise between a desirable controlled reversal and the need for prompt response and adequate duration of action. Using higher dosages or shorter intervals between incremental doses is likely to increase the incidence and severity of symptoms related to acute withdrawal such as nausea, vomiting, elevated blood pressure, and anxiety.

Patients Tolerant to or Physically Dependent on Opioids

REVEX may cause acute withdrawal symptoms in individuals who have some degree of tolerance to and dependence on opioids. These patients should be closely observed for symptoms of withdrawal following administration of the initial and subsequent injections of REVEX. Subsequent doses should be administered with intervals of at least 2-5 minutes between doses to allow the full effect of each incremental dose of REVEX to be reached.

Recommended Doses for Reversal of Postoperative Opioid Depression

Use 100µg/mL dosage strength (blue label) and see Table 2 for initial doses.

The goal of treatment with REVEX in the postoperative setting is to achieve reversal of excessive opioid effects without inducing a complete reversal and acute pain. This is best accomplished with an initial dose of 0.25 µg/kg followed by 0.25µg/kg incremental doses at 2-5 minute intervals, stopping as soon as the desired degree of opioid reversal is obtained. A cumulative total dose above 1.0 µg/kg does not provide additional therapeutic effect.
Table 2: Reversal of Postoperative Opioid Depression Body Weight mL of REVEX 100µg/mL Solution 50 kg 0.125 60 kg 0.150 70 kg 0.175 80 kg 0.200 90 kg 0.225 100 kg 0.250
In cases where the patient is known to be at increased cardiovascular risk, it may be desirable to dilute REVEX 1:1 with saline or sterile water and use smaller initial and incremental doses of 0.1 µg/kg.

Management of Known or Suspected Opioid Overdose

Use 1.0 mg/mL dosage strength (green label).

The recommended initial dose of REVEX for non-opioid dependent patients is 0.5 mg/70 kg. If needed, this may be followed by a second dose of 1.0 mg/70 kg, 2-5 minutes later. If a total dose of 1.5 mg /70 kg has been administered without clinical response, additional REVEX (nalmefene hydrochloride injection) is unlikely to have an effect. Patients should not be given more REVEX than is required to restore the respiratory rate to normal, thus minimizing the likelihood of cardiovascular stress and precipitated withdrawal syndrome.

If there is a reasonable suspicion of opioid dependency, a challenge dose of REVEX 0.1 mg/70 kg should be administered initially. If there is no evidence of withdrawal in 2 minutes, the recommended dosing should be followed.

REVEX had no effect in cases where opioids were not responsible for sedation and hypoventilation. Therefore, patients should only be treated with REVEX when the likelihood of an opioid overdose is high, based on a history of opioid overdose or the clinical presentation of respiratory depression with concurrent pupillary constriction.

Repeated Dosing

REVEX is the longest acting of the currently available parenteral opioid antagonists. If recurrence of respiratory depression does occur, the dose should again be titrated to clinical effect using incremental doses to avoid over-reversal.

Hepatic and Renal Disease

Hepatic disease and renal failure substantially reduce the clearance of nalmefene (see Pharmacokinetics). For single episodes of opioid antagonism, adjustment of REVEX dosage is not required. However, in patients with renal failure, the incremental doses should be delivered slowly (over 60 seconds) to minimize the hypertension and dizziness reported following the abrupt administration of nalmefene to such patients.

Loss of Intravenous Access

Should intravenous access be lost or not readily obtainable, a pharmacokinetic study has shown that a single dose of REVEX should be effective within 5-15 minutes after intramuscular or subcutaneous doses of 1.0 mg. (See Pharmacokinetics.)
Fosphenytoin Sodium

Fosphenytoin Sodium

The dose, concentration in dosing solutions, and infusion rate of IV fosphenytoin sodium injection is expressed as phenytoin sodium equivalents (PE) to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin sodium injection should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). Fosphenytoin sodium injection has important differences in administration from those for parenteral phenytoin sodium (see below).

Products with particulate matter or discoloration should not be used. Prior to IV infusion, dilute fosphenytoin sodium injection in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL.

Status Epilepticus
The loading dose of fosphenytoin sodium injection is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min. Because of the risk of hypotension, fosphenytoin should be administered no faster than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of fosphenytoin sodium injection infusions. Because the full antiepileptic effect of phenytoin, whether given as fosphenytoin sodium injection or parenteral phenytoin, is not immediate, other measures, including concomitant administration of an IV benzodiazepine, will usually be necessary for the control of status epilepticus. The loading dose should be followed by maintenance doses of fosphenytoin sodium injection, or phenytoin either orally or parenterally.
If administration of fosphenytoin sodium injection does not terminate seizures, the use of other anticonvulsants and other appropriate measures should be considered.

IM fosphenytoin sodium injection should not be used in the treatment of status epilepticus because therapeutic phenytoin concentrations may not be reached as quickly as with IV administration. If IV access is impossible, loading doses of fosphenytoin sodium injection have been given by the IM route for other indications.

Nonemergent Loading and Maintenance Dosing

The loading dose of fosphenytoin sodium injection is 10 - 20 mg PE/kg given IV or IM. The rate of administration for IV fosphenytoin sodium injection should be no greater than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of fosphenytoin sodium injection infusions.

The initial daily maintenance dose of fosphenytoin sodium injection is 4 - 6 mg PE/kg/day.

IM or IV Substitution For Oral Phenytoin Therapy

Fosphenytoin sodium injection can be substituted for oral phenytoin sodium therapy at the same total daily dose.

Dilantin capsules are approximately 90% bioavailable by the oral route. Phenytoin, supplied as fosphenytoin sodium injection, is 100% bioavailable by both the IM and IV routes. For this reason, plasma phenytoin concentrations may increase modestly when IM or IV fosphenytoin sodium injection is substituted for oral phenytoin sodium therapy.

The rate of administration for IV fosphenytoin sodium injection should be no greater than 150 mg PE/min.

In controlled trials, IM fosphenytoin sodium injection was administered as a single daily dose utilizing either 1 or 2 injection sites. Some patients may require more frequent dosing.

Dosing in Special Populations

Patients with Renal or Hepatic Disease

Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution (seeCLINICAL PHARMACOLOGY, Special Populations). Unbound phenytoin concentrations may be more useful in these patient populations. After IV fosphenytoin sodium injection administration to patients with renal and/or hepatic disease, or in those with hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance. This has the potential to increase the frequency and severity of adverse events (seePRECAUTIONS).

Elderly Patients

Age does not have a significant impact on the pharmacokinetics of fosphenytoin following fosphenytoin sodium injection administration. Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric

The safety of fosphenytoin sodium injection in pediatric patients has not been established.
Robinul

Robinul

NOTE: CONTAINS BENZYL ALCOHOL (seePRECAUTIONS)

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

ROBINUL Injection may be administered intramuscularly, or intravenously, without dilution, in the following indications.

Adults

Preanesthetic Medication

The recommended dose of ROBINUL Injection is 0.004 mg/kg by intramuscular injection, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.

Intraoperative Medication

ROBINUL Injection may be used during surgery to counteract drug-induced or vagal reflexes and their associated arrhythmias (e.g., bradycardia). It should be administered intravenously as single doses of 0.1 mg and repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.

Reversal of Neuromuscular Blockade

The recommended dose of ROBINUL Injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe.

Peptic Ulcer

The usual recommended dose of ROBINUL Injection is 0.1 mg administered at 4-hour intervals, 3 or 4 times daily intravenously or intramuscularly. Where more profound effect is required, 0.2 mg may be given. Some patients may need only a single dose, and frequency of administration should be dictated by patient response up to a maximum of four times daily.

ROBINUL Injection is not recommended for the treatment of peptic ulcer in pediatric patients (seePRECAUTIONS– Pediatric Use).

Pediatric Patients

(seePRECAUTIONS– Pediatric Use)

Preanesthetic Medication

The recommended dose of ROBINUL Injection in pediatric patients is 0.004 mg/kg intramuscularly, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.

Infants

(1 month to 2 years of age) may require up to 0.009 mg/kg.

Intraoperative Medication

Because of the long duration of action of ROBINUL Injection if used as preanesthetic medication, additional ROBINUL Injection for anticholinergic effect intraoperatively is rarely needed; in the event it is required the recommended pediatric dose is 0.004 mg/kg intravenously, not to exceed 0.1 mg in a single dose which may be repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.

Reversal of Neuromuscular Blockade

The recommended pediatric dose of ROBINUL Injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe.

Peptic Ulcer

ROBINUL Injection is not recommended for the treatment of peptic ulcer in pediatric patients (seePRECAUTIONS– Pediatric Use).

Diluent Compatibilities

Dextrose 5% and 10% in water, or saline, dextrose 5% in sodium chloride 0.45%, sodium chloride 0.9%, and Ringer’s Injection.

Diluent Incompatibilities

Lactated Ringer’s solution

Admixture Compatibilities

Physical Compatibility

This list does not constitute an endorsement of the clinical utility or safety of co-administration of ROBINUL with these drugs. ROBINUL Injection is compatible for mixing and injection with the following injectable dosage forms: atropine sulfate, USP; Antilirium® (physostigmine salicylate); Benadryl® (diphenhydramine HCl); codeine phosphate, USP; Emete-Con® (benz-quinamide HCl); hydromorphone HCl, USP; Inapsine® (droperidol); Levo-Dromoran® (levorphanol tartrate); lidocaine, USP; meperidine HCl, USP; Mestinon®/Regonol® (pyridostigmine bromide); morphine sulfate, USP; Nubain® (nalbuphine HCl); Numorphan® (oxymorphone HCl); procaine HCl, USP; promethazine HCl, USP; Prostigmin® (neostigmine methylsulfate, USP); scopolamine HBr, USP; Stadol® (butorphanol tartrate); Sublimaze® (fentanyl citrate); Tigan® (trimethobenzamide HCl); and Vistaril® (hydroxyzine HCl). ROBINUL Injection may be administered via the tubing of a running infusion of normal saline.

Admixture Incompatibilities

Physical Incompatibility

Since the stability of glycopyrrolate is questionable above a pH of 6.0 do not combine ROBINUL Injection in the same syringe with Brevital® (methohexital Na); Chloromycetin® (chloramphenicol Na succinate); Dramamine® (dimenhydrinate); Nembutal® (pentobarbital Na); Pentothal® (thiopental Na); Seconal® (secobarbital Na); sodium bicarbonate (Abbott); Valium® (diazepam); Decadron® (dexamethasone Na phosphate); or Talwin® (pentazocine lactate). These mixtures will result in a pH higher than 6.0 and may result in gas production or precipitation.
Lorazepam

Lorazepam

Lorazepam must never be used without individualization of dosage particularly when used with other medications capable of producing central-nervous-system depression.

EQUIPMENT NECESSARY TO MAINTAIN A PATENT AIRWAY SHOULD BE IMMEDIATELY AVAILABLE PRIOR TO INTRAVENOUS ADMINISTRATION OF LORAZEPAM (see WARNINGS).

Status Epilepticus

General Advice

Status epilepticus is a potentially life-threatening condition associated with a high risk of permanent neurological impairment, if inadequately treated. The treatment of status, however, requires far more than the administration of an anticonvulsant agent. It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required. Ventilatory support must be readily available. The use of benzodiazepines, like Lorazepam Injection, is ordinarily only an initial step of a complex and sustained intervention which may require additional interventions, (e.g., concomitant intravenous administration of phenytoin). Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected. Furthermore, patients who are susceptible to further seizure episodes should receive adequate maintenance antiepileptic therapy.

Any health care professional who intends to treat a patient with status epilepticus should be familiar with this package insert and the pertinent medical literature concerning current concepts for the treatment of status epilepticus. A comprehensive review of the considerations critical to the informed and prudent management of status epilepticus cannot be provided in drug product labeling. The archival medical literature contains many informative references on the management of status epilepticus, among them the report of the working group on status epilepticus of the Epilepsy Foundation of America “Treatment of Convulsive Status Epilepticus” (JAMA 1993; 270:854-859). As noted in the report just cited, it may be useful to consult with a neurologist if a patient fails to respond (e.g., fails to regain consciousness).

Intravenous Injection

For the treatment of status epilepticus, the usual recommended dose of Lorazepam Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. If seizures cease, no additional Lorazepam Injection is required. If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg intravenous dose may be slowly administered. Experience with further doses of lorazepam is very limited. The usual precautions in treating status epilepticus should be employed. An intravenous infusion should be started, vital signs should be monitored, an unobstructed airway should be maintained, and artificial ventilation equipment should be available.

Intramuscular Injection

IM lorazepam is not preferred in the treatment of status epilepticus because therapeutic lorazepam levels may not be reached as quickly as with IV administration. However, when an intravenous port is not available, the IM route may prove useful (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Pediatric

The safety of lorazepam in pediatric patients has not been established.

Preanesthetic

Intramuscular Injection

For the designated indications as a premedicant, the usual recommended dose of lorazepam for intramuscular injection is 0.05 mg/kg up to a maximum of 4 mg. As with all premedicant drugs, the dose should be individualized (see also CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Doses of other central-nervous-system-depressant drugs ordinarily should be reduced (see PRECAUTIONS). For optimum effect, measured as lack of recall, intramuscular lorazepam should be administered at least 2 hours before the anticipated operative procedure. Narcotic analgesics should be administered at their usual preoperative time.

There are insufficient data to support efficacy or make dosage recommendations for intramuscular lorazepam in patients less than 18 years of age; therefore, such use is not recommended.

Intravenous Injection

For the primary purpose of sedation and relief of anxiety, the usual recommended initial dose of lorazepam for intravenous injection is 2 mg total, or 0.02 mg/lb (0.044 mg/kg), whichever is smaller. This dose will suffice for sedating most adult patients and ordinarily should not be exceeded in patients over 50 years of age. In those patients in whom a greater likelihood of lack of recall for perioperative events would be beneficial, larger doses as high as 0.05 mg/kg up to a total of 4 mg may be administered (see also CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Doses of other injectable central-nervous-system-depressant drugs ordinarily should be reduced (see PRECAUTIONS). For optimum effect, measured as lack of recall, intravenous lorazepam should be administered 15 to 20 minutes before the anticipated operative procedure.

There are insufficient data to support efficacy or make dosage recommendations for intravenous lorazepam in patients less than 18 years of age; therefore, such use is not recommended.

Dose Administration in Special Populations

Elderly Patients and Patients With Hepatic Disease

No dosage adjustments are needed in elderly patients and in patients with hepatic disease.

Patients With Renal Disease

For acute dose administration, adjustment is not needed for patients with renal disease. However, in patients with renal disease, caution should be exercised if frequent doses are given over relatively short periods of time (see also CLINICAL PHARMACOLOGY).

Dose Adjustment Due to Drug Interactions

The dose of lorazepam should be reduced by 50% when coadministered with probenecid or valproate (see PRECAUTIONS, Drug Interactions).

It may be necessary to increase the dose of lorazepam in female patients who are concomitantly taking oral contraceptives.

Administration

When given intramuscularly, Lorazepam Injection, undiluted, should be injected deep in the muscle mass.

Injectable lorazepam can be used with atropine sulfate, narcotic analgesics, other parenterally used analgesics, commonly used anesthetics, and muscle relaxants.

Immediately prior to intravenous use, Lorazepam Injection must be diluted with an equal volume of compatible solution. Contents should be mixed thoroughly by gently inverting the container repeatedly until a homogenous solution results. Do not shake vigorously, as this will result in air entrapment. When properly diluted, the drug may be injected directly into a vein or into the tubing of an existing intravenous infusion. The rate of injection should not exceed 2.0 mg per minute.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if solution is discolored or contains a precipitate.

Lorazepam Injection is compatible for dilution purposes with the following solutions: Sterile Water for Injection, USP; Sodium Chloride Injection, USP; 5% Dextrose Injection, USP.
Milrinone Lactate

Milrinone Lactate

Milrinone Lactate Injection should be administered with a loading dose followed by a continuous infusion (maintenance dose) according to the following guidelines:
LOADING DOSE — 50 mcg/kg: Administer slowly over 10 minutes The table below shows the loading dose in milliliters (mL) of milrinone (1 mg/mL) by patient body weight (kg). Loading Dose (mL) Using 1 mg/mL Concentration Patient Body Weight kg) kg 30 40 50 60 70 80 90 100 110 120 mL 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0
The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see Maintenance Dose for diluents) may simplify the visualization of the injection rate.
MAINTENANCE DOSE Infusion Rate Total Daily Dose (24 hours) Minimum 0.375 mcg/kg/min 0.59 mg/kg Administer as a continuous intravenous infusion Standard 0.50 mcg/kg/min 0.77 mg/kg Maximum 0.75 mcg/kg/min 1.13 mg/kg
Milrinone Lactate Injection drawn from vials should be diluted prior to maintenance dose administration. The diluents that may be used are 0.45% Sodium Chloride Injection, USP; 0.9% Sodium Chloride Injection, USP; or 5% Dextrose Injection, USP. The table below shows the volume of diluent in milliliters (mL) that must be used to achieve 200 mcg/mL concentration for infusion, and the resultant total volumes.
Desired Infusion Concentration mcg/mL Milrinone 1 mg/mL (mL) Diluent (mL) Total Volume (mL) 200 10 40 50 200 20 80 100
The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

Note: See "Dosage Adjustment in Renally Impaired Patients." Dosage may be titrated to the maximum hemodynamic effect and should not exceed 1.13 mg/kg/day. Duration of therapy should depend upon patient responsiveness.

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.
Milrinone Infusion Rate(mL/hr) Using 200 mcg/mL Concentration Maintenance Dose (mcg/kg/min) Patient Body Weight (kg) 30 40 50 60 70 80 90 100 110 120 0.375 3.4 4.5 5.6 6.8 7.9 9.0 10.1 11.3 12.4 13.5 0.400 3.6 4.8 6.0 7.2 8.4 9.6 10.8 12.0 13.2 14.4 0.500 4.5 6.0 7.5 9.0 10.5 12.0 13.5 15.0 16.5 18.0 0.600 5.4 7.2 9.0 10.8 12.6 14.4 16.2 18.0 19.8 21.6 0.700 6.3 8.4 10.5 12.6 14.7 16.8 18.9 21.0 23.1 25.2 0.750 6.8 9.0 11.3 13.5 15.8 18.0 20.3 22.5 24.8 27.0
When administering milrinone lactate by continuous infusion, it is advisable to use a calibrated electronic infusion device.

WARNING: Do not use in series connections with flexible plastic containers.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dosage Adjustment in Renally Impaired Patients

Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone. Reductions in infusion rate may be necessary in patients with renal impairment. For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table:
Creatinine Clearance (mL/min/1.73 m2) Infusion Rate (mcg/kg/min) 5 0.20 10 0.23 20 0.28 30 0.33 40 0.38 50 0.43
Propranolol Hydrochlori...

Propranolol Hydrochloride

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The usual dose is 1 to 3 mg administered under careful monitoring, such as electrocardiography and central venous pressure. The rate of administration should not exceed 1 mg (1 mL) per minute to diminish the possibility of lowering blood pressure and causing cardiac standstill. Sufficient time should be allowed for the drug to reach the site of action even when a slow circulation is present. If necessary, a second dose may be given after two minutes. Thereafter, additional drug should not be given in less than four hours. Additional propranolol hydrochloride should not be given when the desired alteration in rate or rhythm is achieved.

Transfer to oral therapy as soon as possible.
Meperidine Hydrochlorid...

Meperidine Hydrochloride

For Relief of Pain

Dosage should be adjusted according to the severity of the pain and the response of the patient. While subcutaneous administration is suitable for occasional use, intramuscular administration is preferred when repeated doses are required. If intravenous administration is required, dosage should be decreased and the injection made very slowly, preferably utilizing a diluted solution. Meperidine is less effective orally than by parenteral administration. The dose of meperidine should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of meperidine.

Adults

The usual dosage is 50 to 150 mg intramuscularly or subcutaneously every 3 to 4 hours as necessary. Elderly patients should usually be given meperidine at the lower end of the dose range and observed closely.

Children

The usual dosage is 0.5 to 0.8 mg/lb intramuscularly or subcutaneously up to the adult dose, every 3 to 4 hours as necessary.

For Preoperative Medication

Adults

The usual dosage is 50 to 150 mg intramuscularly or subcutaneously every 3 to 4 hours as necessary. Elderly patients should usually be given meperidine at the lower end of the dose range and observed closely.

Children

The usual dosage is 0.5 to 1 mg/lb intramuscularly or subcutaneously up to the adult dose, 30 to 90 minutes before the beginning of anesthesia.

For Support of Anesthesia

Repeated slow intravenous injections of fractional doses (e.g., 10 mg/mL) or by a continuous intravenous infusion of a more dilute solution (e.g., 1 mg/mL) should be used. The dose should be titrated to the needs of the patient and will depend on the premedication and type of anesthesia being employed, the characteristics of the particular patient and the nature and duration of the operative procedure. Elderly patients should usually be given meperidine at the lower end of the dose range and observed closely.

For Obstetrical Analgesia

The usual dosage is 50 to 100 mg intramuscularly or subcutaneously when pain becomes regular and may be repeated at 1 to 3 hour intervals.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Famotidine

Famotidine

In some hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, Famotidine Injection may be administered until oral therapy can be instituted.

The recommended dosage for Famotidine Injection in adult patients is 20 mg intravenously q 12 h.

The doses and regimen for parenteral administration in patients with GERD have not been established.

Dosage for Pediatric Patients <1 Year of Age Gastroesophageal Reflux Disease (GERD)

See PRECAUTIONS, Pediatric Patients <1 Year of Age.

The studies described in PRECAUTIONS, Pediatric Patients <1 Year of Age suggest the following starting doses in pediatric patients <1 year of age: Gastroesophageal Reflux Disease (GERD) – 0.5 mg/kg/dose of famotidine oral suspension for the treatment of GERD for up to 8 weeks once daily in patients <3 months of age and 0.5 mg/kg/dose twice daily in patients 3 months to <1 year of age. Patients should also be receiving conservative measures (e.g., thickened feedings). The use of intravenous famotidine in pediatric patients <1 year of age with GERD has not been adequately studied.

Dosage for Pediatric Patients 1-16 Years of Age

See PRECAUTIONS, Pediatric Patients 1-16 Years of Age.

The studies described in PRECAUTIONS, Pediatric Patients 1-16 Years of Age suggest that the starting dose in pediatric patients 1-16 years of age is 0.25 mg/kg intravenously (injected over a period of not less than two minutes or as a 15-minute infusion) q 12 h up to 40 mg/day.

While published uncontrolled clinical studies suggest effectiveness of famotidine in the treatment of peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or gastric pH determination and endoscopy. Published uncontrolled studies in pediatric patients have demonstrated gastric acid suppression with doses up to 0.5 mg/kg intravenously q 12 h.

Dosage Adjustments for Patients with Moderate or Severe Renal Insufficiency

In adult patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the elimination half-life of famotidine is increased. For patients with severe renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients. Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of Famotidine Injection may be reduced to half the dose, or the dosing interval may be prolonged to 36-48 hours as indicated by the patient’s clinical response.

Based on the comparison of pharmacokinetic parameters for famotidine in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.

Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas)

The dosage of famotidine in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult intravenous dose is 20 mg q 12 h. Doses should be adjusted to individual patient needs and should continue as long as clinically indicated. In some patients, a higher starting dose may be required. Oral doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.

To prepare intravenous solutions, aseptically dilute 2 mL of Famotidine Injection (solution containing 10 mg/mL) with Sodium Chloride Injection 0.9% or other compatible intravenous solution (see Stability) to a total volume of either 5 mL or 10 mL and inject over a period of not less than 2 minutes.

To prepare intravenous infusion solutions, aseptically dilute 2 mL of Famotidine Injection with 100 mL of Dextrose 5% or other compatible solution (see Stability), and infuse over a 15-30 minute period.

Concomitant Use of Antacids

Antacids may be given orally concomitantly if needed.

Stability

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

When added to or diluted with most commonly used intravenous solutions, e.g., Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5% and 10% or Lactated Ringer’s Injection, diluted Famotidine Injection is physically and chemically stable (i.e., maintains at least 90% of initial potency) for 7 days at room temperature–see HOW SUPPLIED, Storage.

When added to or diluted with Sodium Bicarbonate Injection 5%, Famotidine Injection at a concentration of 0.2 mg/mL (the recommended concentration of famotidine intravenous infusion solutions) is physically and chemically stable (i.e., maintains at least 90% of initial potency) for 7 days at room temperature–see HOW SUPPLIED, Storage. However, a precipitate may form at higher concentrations of Famotidine Injection (>0.2 mg/mL) in Sodium Bicarbonate Injection 5%.
Plasma-lyte 148

Plasma-lyte 148

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear and seal is intact.

All injections in AVIVA plastic containers are intended for intravenous administration using sterile equipment.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Theophylline In Dextros...

Theophylline In Dextrose

General Considerations:

The steady-state peak serum theophylline concentration is a function of the infusion rate and the rate of theophylline clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a serum theophylline concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance. For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either sub-therapeutic or potentially toxic serum theophylline concentrations in individual patients. The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.

When theophylline is used as an acute bronchodilator, the goal of obtaining a therapeutic serum concentration is best accomplished with an intravenous loading dose. Because of rapid distribution into body fluids, the serum concentration (C) obtained from an initial loading dose (LD) is related primarily to the volume of distribution (V), the apparent space into which the drug diffuses:

C = LD/V

If a mean volume of distribution of about 0.5 L/kg is assumed (actual range is 0.3 to 0.7 L/kg), each mg/kg (ideal body weight) of theophylline administered as a loading dose over 30 minutes results in an average 2 mcg/mL increase in serum theophylline concentration. Therefore, in a patient who has received no theophylline in the previous 24 hours, a loading dose of intravenous theophylline of 4.6 mg/kg, calculated on the basis of ideal body weight and administered over 30 minutes, on average, will produce a maximum post-distribution serum concentration of 10 mcg/mL with a range of 6-16 mcg/mL. When a loading dose becomes necessary in the patient who has already received theophylline, estimation of the serum concentration based upon the history is unreliable, and an immediate serum level determination is indicated. The loading dose can then be determined as follows:

D = (Desired C - Measured C)(V)

where D is the loading dose, C is the serum theophylline concentration, and V is the volume of distribution. The mean volume of distribution can be assumed to be 0.5 L/kg and the desired serum concentration should be conservative (e.g., 10 mcg/mL) to allow for the variability in the volume of distribution. A loading dose should not be given before obtaining a serum theophylline concentration if the patient has received any theophylline in the previous 24 hours.

A serum concentration obtained 30 minutes after an intravenous loading dose, when distribution is complete, can be used to assess the need for and size of subsequent loading doses, if clinically indicated, and for guidance of continuing therapy. Once a serum concentration of 10 to 15 mcg/mL has been achieved with the use of a loading dose(s), a constant intravenous infusion is started. The rate of administration is based upon mean pharmacokinetic parameters for the population and calculated to achieve a target serum concentration of 10 mcg/mL (see Table VI). For example, in nonsmoking adults, initiation of a constant intravenous theophylline infusion of 0.4 mg/kg/hr at the completion of the loading dose, on average, will result in a steady-state concentration of 10 mcg/mL with a range of 7-26 mcg/mL. The mean and range of steady-state serum concentrations are similar when the average child (age 1 to 9 years) is given a loading dose of 4.6 mg/kg theophylline followed by a constant intravenous infusion of 0.8 mg/kg/hr. Since there is large interpatient variability in theophylline clearance, serum concentration will rise or fall when the patient’s clearance is significantly different from the mean population value used to calculate the initial infusion rate. Therefore, a second serum concentration should be obtained one expected half-life after starting the constant infusion (e.g., approximately 4 hours for children age 1 to 9 and 8 hours for nonsmoking adults; See Table II for the expected half-life in additional patient populations) to determine if the concentration is accumulating or declining from the post loading dose level. If the level is declining as a result of a higher than average clearance, an additional loading dose can be administered and/or the infusion rate increased. In contrast, if the second sample demonstrates a higher level, accumulation of the drug can be assumed, and the infusion rate should be decreased before the concentration exceeds 20 mcg/mL. An additional sample is obtained 12 to 24 hours later to determine if further adjustments are required and then at 24-hour intervals to adjust for changes, if they occur. This empiric method, based upon mean pharmacokinetic parameters, will prevent large fluctuations in serum concentration during the most critical period of the patient’s course.

In patients with cor pulmonale, cardiac decompensation, or liver dysfunction, or in those taking drugs that markedly reduce theophylline clearance (e.g., cimetidine), the initial theophylline infusion rate should not exceed 17 mg/hr unless serum concentrations can be monitored at 24-hour intervals. In these patients, 5 days may be required before steady-state is reached.

Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight.

Table VI contains initial theophylline infusion rates following an appropriate loading dose recommended for patients in various age groups and clinical circumstances. Table VII contains recommendations for final theophylline dosage adjustment based upon serum theophylline concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient. In general, these recommendations should serve as the upper limit for dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum theophylline concentration.
* To achieve a target concentration of 10 mcg/mL. Use ideal body weight for obese patients. † Lower initial dosage may be required for patients receiving other drugs that decrease theophylline clearance ( e.g., cimetidine). ‡ To achieve a target concentration of 7.5 mcg/mL for neonatal apnea. § Not to exceed 900 mg/day, unless serum levels indicate the need for a larger dose. ¶ Not to exceed 400 mg/day, unless serum levels indicate the need for a larger dose. Table VI. Initial theophylline infusion rates following an appropriate loading dose. Patient population Age Theophylline infusion rate (mg/kg/hr)*† Neonates Postnatal age up to 24 daysPostnatal age beyond 24 days 1 mg/kg q12h/‡ 1.5 mg/kg q 12h/‡ Infants 6-52 weeks old mg/kg/hr = (0.008) (age in weeks) + 0.21 Young children 1-9 years 0.8 Older children 9-12 years 0.7 Adolescents (cigarette or marijuana smokers) 12-16 years 0.7 Adolescents (nonsmokers) 12-16 years 0.5§ Adults (otherwise healthy nonsmokers) 16-60 years 0.4§ Elderly >60 years 0.3¶ Cardiac decompensation, cor pulmonale, liver dysfunction, sepsis with multi-organ failure, or shock 0.2¶ * Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur ( e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS). Table VII. Final dosage adjustment guided by serum theophylline concentration. Peak Serum Concentration Dosage Adjustment <9.9 mcg/mL If symptoms are not controlled and current dosage is tolerated, increase infusion rate about 25%. Recheck serum concentration after 12 hours in children and 24 hours in adults for further dosage adjustment. 10 to 14.9 mcg/mL If symptoms are controlled and current dosage is tolerated, maintain infusion rate and recheck serum concentration at 24 hour intervals. * If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. 15-19.9 mcg/mL Consider 10% decrease in infusion rate to provide greater margin of safety even if current dosage is tolerated.* 20-24.9 mcg/mL Decrease infusion rate by 25% even if no adverse effects are present. Recheck serum concentration after 12 hours in children and 24 hours in adults to guide further dosage adjustment. 25-30 mcg/mL Stop infusion for 12 hours in children and 24 hours in adults and decrease subsequent infusion rate at least 25% even if no adverse effects are present. Recheck serum concentration after 12 hours in children and 24 hours in adults to guide further dosage adjustment. If symptomatic, stop infusion and consider whether overdose treatment is indicated (see recommendations for chronic overdosage). >30 mcg/mL Stop the infusion and treat overdose as indicated (see recommendations for chronic overdosage). If theophylline is subsequently resumed, decrease infusion rate by at least 50% and recheck serum concentration after 12 hours in children and 24 hours in adults to guide further dosage adjustment.
Many intravenous theophylline products are supplied as aminophylline where ethylenediamine is added to solubilize theophylline. Ethylenediamine is not required for solubility of premixed Theophylline and 5% Dextrose Injection. Each milligram of aminophylline dihydrate contains approximately 0.8 milligrams of theophylline anhydrous. Equivalent doses of premixed Theophylline and 5% Dextrose Injection can be determined by multiplying those doses specified as aminophylline dihydrate by 0.8.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

Because dosages of this drug are titrated to response, no additives should be made to Theophylline and 5% Dextrose Injections.
Oxytocin

Oxytocin

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dosage of oxytocin is determined by the uterine response. The following dosage information is based upon various regimens and indications in general use.

A. Induction or Stimulation of Labor

Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor.

Accurate control of the rate of infusion flow is essential. An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane.
An intravenous infusion of nonoxytocin-containing solution should be started. Physiologic electrolyte solution should be used except under unusual circumstances. To prepare the usual solution for infusion, 1-mL Oxytocin Injection, 10 USP Units/mL is combined aseptically with 1,000 mL of nonhydrating diluent (physiologic electrolyte solution). The combined solution, rotated in the infusion bottle to ensure thorough mixing, containing 10 mU/mL. Add the container with dilute oxytocic solution to the system through use of a constant infusion pump or other such device, to control accurately the rate of infusion. The initial dose should be no more than 1 to 2 mU/min. the dose may be gradually increased in increments of no more than 1 to 2 mU/min. until a contraction pattern has been established which is similar to normal labor. The fetal heart rate, resting uterine tone, and the frequency, duration, and the force of contractions should be monitored. The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress. Oxygen should be administered to the mother. The mother and the fetus must be evaluated by the responsible physician.
B. Control of Postpartum Uterine Bleeding
Intravenous Infusion (Drip Method):
To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent (physiologic electrolyte solution) and run a rate necessary to control uterine atony.
Intramuscular Administration:
1 mL (10 units) of oxytocin can be given after the delivery of the placenta.

C. Treatment of Incomplete or Inevitable Abortion

Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops per minutes.
Ativan

Ativan

ATIVAN must never be used without individualization of dosage particularly when used with other medications capable of producing central-nervous-system depression.

EQUIPMENT NECESSARY TO MAINTAIN A PATENT AIRWAY SHOULD BE IMMEDIATELY AVAILABLE PRIOR TO INTRAVENOUS ADMINISTRATION OF LORAZEPAM (see WARNINGS).

Status Epilepticus

General Advice

Status epilepticus is a potentially life-threatening condition associated with a high risk of permanent neurological impairment, if inadequately treated. The treatment of status, however, requires far more than the administration of an anticonvulsant agent. It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required. Ventilatory support must be readily available. The use of benzodiazepines, like ATIVAN Injection, is ordinarily only an initial step of a complex and sustained intervention which may require additional interventions, (e.g., concomitant intravenous administration of phenytoin). Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected. Furthermore, patients who are susceptible to further seizure episodes should receive adequate maintenance antiepileptic therapy.

Any health care professional who intends to treat a patient with status epilepticus should be familiar with this package insert and the pertinent medical literature concerning current concepts for the treatment of status epilepticus. A comprehensive review of the considerations critical to the informed and prudent management of status epilepticus cannot be provided in drug product labeling. The archival medical literature contains many informative references on the management of status epilepticus, among them the report of the working group on status epilepticus of the Epilepsy Foundation of America “Treatment of Convulsive Status Epilepticus” (JAMA 1993; 270:854-859). As noted in the report just cited, it may be useful to consult with a neurologist if a patient fails to respond (e.g., fails to regain consciousness).

Intravenous Injection

For the treatment of status epilepticus, the usual recommended dose of ATIVAN Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. If seizures cease, no additional ATIVAN Injection is required. If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg intravenous dose may be slowly administered. Experience with further doses of ATIVAN is very limited. The usual precautions in treating status epilepticus should be employed. An intravenous infusion should be started, vital signs should be monitored, an unobstructed airway should be maintained, and artificial ventilation equipment should be available.

Intramuscular Injection

IM ATIVAN is not preferred in the treatment of status epilepticus because therapeutic lorazepam levels may not be reached as quickly as with IV administration. However, when an intravenous port is not available, the IM route may prove useful (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Pediatric

The safety of ATIVAN in pediatric patients has not been established.

Preanesthetic

Intramuscular Injection

For the designated indications as a premedicant, the usual recommended dose of lorazepam for intramuscular injection is 0.05 mg/kg up to a maximum of 4 mg. As with all premedicant drugs, the dose should be individualized (see also CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Doses of other central-nervous-system-depressant drugs ordinarily should be reduced (see PRECAUTIONS). For optimum effect, measured as lack of recall, intramuscular lorazepam should be administered at least 2 hours before the anticipated operative procedure. Narcotic analgesics should be administered at their usual preoperative time.

There are insufficient data to support efficacy or make dosage recommendations for intramuscular lorazepam in patients less than 18 years of age; therefore, such use is not recommended.

Intravenous Injection

For the primary purpose of sedation and relief of anxiety, the usual recommended initial dose of lorazepam for intravenous injection is 2 mg total, or 0.02 mg/lb (0.044 mg/kg), whichever is smaller. This dose will suffice for sedating most adult patients and ordinarily should not be exceeded in patients over 50 years of age. In those patients in whom a greater likelihood of lack of recall for perioperative events would be beneficial, larger doses as high as 0.05 mg/kg up to a total of 4 mg may be administered (see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Doses of other injectable central-nervous-system-depressant drugs ordinarily should be reduced (see PRECAUTIONS). For optimum effect, measured as lack of recall, intravenous lorazepam should be administered 15 to 20 minutes before the anticipated operative procedure.

There are insufficient data to support efficacy or make dosage recommendations for intravenous lorazepam in patients less than 18 years of age; therefore, such use is not recommended.

Dose Administration in Special Populations

Elderly Patients and Patients With Hepatic Disease

No dosage adjustments are needed in elderly patients and in patients with hepatic disease.

Patients With Renal Disease

For acute dose administration, adjustment is not needed for patients with renal disease. However, in patients with renal disease, caution should be exercised if frequent doses are given over relatively short periods of time (see also CLINICAL PHARMACOLOGY).

Dose Adjustment Due to Drug Interactions

The dose of ATIVAN should be reduced by 50% when coadministered with probenecid or valproate (see PRECAUTIONS, Drug Interactions).

It may be necessary to increase the dose of ATIVAN in female patients who are concomitantly taking oral contraceptives.

Administration

When given intramuscularly, ATIVAN Injection, undiluted, should be injected deep in the muscle mass.

Injectable ATIVAN can be used with atropine sulfate, narcotic analgesics, other parenterally used analgesics, commonly used anesthetics, and muscle relaxants.

Immediately prior to intravenous use, ATIVAN Injection must be diluted with an equal volume of compatible solution. Contents should be mixed thoroughly by gently inverting the container repeatedly until a homogenous solution results. Do not shake vigorously, as this will result in air entrapment. When properly diluted, the drug may be injected directly into a vein or into the tubing of an existing intravenous infusion. The rate of injection should not exceed 2.0 mg per minute.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if solution is discolored or contains a precipitate.

ATIVAN Injection is compatible for dilution purposes with the following solutions: Sterile Water for Injection, USP; Sodium Chloride Injection, USP; 5% Dextrose Injection, USP.
Phenergan

Phenergan

Important Notes on Administration

PHENERGAN Injection can cause severe chemical irritation and damage to tissues regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration (see WARNINGS - Severe Tissue Injury, Including Gangrene).
The preferred parenteral route of administration for PHENERGAN Injection is by deep intramuscular injection. Under no circumstances should PHENERGAN Injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGS - Severe Tissue Injury, Including Gangrene). Subcutaneous injection is contraindicated as it may result in tissue necrosis. When administered intravenously, PHENERGAN Injection should be given in a concentration no greater than 25 mg per mL and at a rate not to exceed 25 mg per minute. It is preferable to inject through the tubing of an intravenous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intravenous injection of PHENERGAN Injection, the injection should be stopped immediately to evaluate for possible arterial injection or perivascular extravasation.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use PHENERGAN Injection if solution has developed color or contains precipitate.

To avoid the possibility of physical and/or chemical incompatibility, consult specialized literature before diluting with any injectable solution or combining with any other medication. Do not use if there is a precipitate or any sign of incompatibility.

Allergic Conditions

The average adult dose is 25 mg. This dose may be repeated within two hours if necessary, but continued therapy, if indicated, should be via the oral route as soon as existing circumstances permit. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The average adult dose for amelioration of allergic reactions to blood or plasma is 25 mg.

Sedation

In hospitalized adult patients, nighttime sedation may be achieved by a dose of 25 to 50 mg of PHENERGAN Injection.

Nausea and Vomiting

For control of nausea and vomiting, the usual adult dose is 12.5 to 25 mg, not to be repeated more frequently than every four hours. When used for control of postoperative nausea and vomiting, the dosage of analgesics and barbiturates should be reduced accordingly (see PRECAUTIONS – Drug Interactions).

Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see PRECAUTIONS – Pediatric Use).

Preoperative and Postoperative Use

As an adjunct to preoperative or postoperative medication, 25 to 50 mg of PHENERGAN Injection in adults may be combined with appropriately reduced doses of analgesics and atropine-like drugs as desired. Dosage of concomitant analgesic or hypnotic medication should be reduced accordingly (see PRECAUTIONS – Drug Interactions).

PHENERGAN is contraindicated for use in pediatric patients less than two years of age.

Obstetrics

PHENERGAN Injection in doses of 50 mg will provide sedation and relieve apprehension in the early stages of labor. When labor is definitely established, 25 to 75 mg (average dose, 50 mg) PHENERGAN Injection may be given with an appropriately reduced dose of any desired narcotic (see PRECAUTIONS – Drug Interactions). If necessary, PHENERGAN Injection with a reduced dose of analgesic may be repeated once or twice at four-hour intervals in the course of a normal labor. A maximum total dose of 100 mg of PHENERGAN Injection may be administered during a 24-hour period to patients in labor.

Pediatric Patients

PHENERGAN Injection is contraindicated for use in pediatric patients less than 2 years of age (see WARNINGS – Respiratory Depression). Caution should be exercised when administering promethazine hydrochloride to pediatric patients 2 years of age or older. It is recommended that the lowest effective dose of promethazine hydrochloride be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided (see WARNINGS – Respiratory Depression).

In pediatric patients 2 years of age and older, the dosage should not exceed half that of the suggested adult dose. As an adjunct to premedication, the suggested dose is 1.1 mg per kg of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug (see PRECAUTIONS – Drug Interactions). Antiemetics should not be used in vomiting of unknown etiology in pediatric patients.
Promethazine Hydrochlor...

Promethazine Hydrochloride

Important Notes on Administration

Promethazine hydrochloride injection can cause severe chemical irritation and damage to tissues regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration (see WARNINGS - Severe Tissue Injury, Including Gangrene).
The preferred parenteral route of administration for promethazine hydrochloride injection is by deep intramuscular injection. Under no circumstances should promethazine hydrochloride injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGS - Severe Tissue Injury, Including Gangrene). Subcutaneous injection is contraindicated as it may result in tissue necrosis. When administered intravenously, promethazine hydrochloride injection should be given in a concentration no greater than 25 mg per mL and at a rate not to exceed 25 mg per minute. It is preferable to inject through the tubing of an intravenous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intravenous injection of promethazine hydrochloride injection, the injection should be stopped immediately to evaluate for possible arterial injection or perivascular extravasation.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use promethazine hydrochloride injection if solution has developed color or contains precipitate.

To avoid the possibility of physical and/or chemical incompatibility, consult specialized literature before diluting with any injectable solution or combining with any other medication. Do not use if there is a precipitate or any sign of incompatibility.

Allergic Conditions

The average adult dose is 25 mg. This dose may be repeated within two hours if necessary, but continued therapy, if indicated, should be via the oral route as soon as existing circumstances permit. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The average adult dose for amelioration of allergic reactions to blood or plasma is 25 mg.

Sedation

In hospitalized adult patients, nighttime sedation may be achieved by a dose of 25 to 50 mg of promethazine hydrochloride injection.

Nausea and Vomiting

For control of nausea and vomiting, the usual adult dose is 12.5 to 25 mg, not to be repeated more frequently than every four hours. When used for control of postoperative nausea and vomiting, the dosage of analgesics and barbiturates should be reduced accordingly (see PRECAUTIONS - Drug Interactions).

Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see PRECAUTIONS - Pediatric Use).

Preoperative and Postoperative Use

As an adjunct to preoperative or postoperative medication, 25 to 50 mg of promethazine hydrochloride injection in adults may be combined with appropriately reduced doses of analgesics and atropine-like drugs as desired. Dosage of concomitant analgesic or hypnotic medication should be reduced accordingly (see PRECAUTIONS - Drug Interactions).

Promethazine hydrochloride is contraindicated for use in pediatric patients less than two years of age.

Obstetrics

Promethazine hydrochloride injection in doses of 50 mg will provide sedation and relieve apprehension in the early stages of labor. When labor is definitely established, 25 to 75 mg (average dose, 50 mg) promethazine hydrochloride injection may be given with an appropriately reduced dose of any desired narcotic (see PRECAUTIONS - Drug Interactions). If necessary, promethazine hydrochloride injection with a reduced dose of analgesic may be repeated once or twice at four-hour intervals in the course of a normal labor. A maximum total dose of 100 mg of promethazine hydrochloride injection may be administered during a 24-hour period to patients in labor.

Pediatric Patients

Promethazine hydrochloride injection is contraindicated for use in pediatric patients less than 2 years of age (see WARNINGS - Respiratory Depression). Caution should be exercised when administering promethazine hydrochloride to pediatric patients 2 years of age or older. It is recommended that the lowest effective dose of promethazine hydrochloride be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided (see WARNINGS - Respiratory Depression).

In pediatric patients 2 years of age and older, the dosage should not exceed half that of the suggested adult dose. As an adjunct to premedication, the suggested dose is 1.1 mg per kg of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug (see PRECAUTIONS - Drug Interactions). Antiemetics should not be used in vomiting of unknown etiology in pediatric patients.
Bumetanide

Bumetanide

Dosage should be individualized with careful monitoring of patient response.

Parenteral Administration

Bumetanide Injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Parenteral treatment should be terminated and oral treatment instituted as soon as possible.

The usual initial dose is 0.5 to 1 mg intravenously or intramuscularly. Intravenous administration should be given over a period of 1 to 2 minutes. If the response to an initial dose is deemed insufficient, a second or third dose may be given at intervals of 2 to 3 hours, but should not exceed a daily dosage of 10 mg.

Miscibility and Parenteral Solutions

The compatibility tests of bumetanide injection with 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer’s Injection in both glass and plasticized PVC (Viaflex) containers have shown no significant absorption effect with either containers, nor a measurable loss of potency due to degradation of the drug. However, solutions should be freshly prepared and used within 24 hours.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Lorazepam

Lorazepam

Lorazepam must never be used without individualization of dosage particularly when used with other medications capable of producing central-nervous-system depression.

EQUIPMENT NECESSARY TO MAINTAIN A PATENT AIRWAY SHOULD BE IMMEDIATELY AVAILABLE PRIOR TO INTRAVENOUS ADMINISTRATION OF LORAZEPAM (see WARNINGS).

Status Epilepticus

General Advice

Status epilepticus is a potentially life-threatening condition associated with a high risk of permanent neurological impairment, if inadequately treated. The treatment of status, however, requires far more than the administration of an anticonvulsant agent. It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required. Ventilatory support must be readily available. The use of benzodiazepines, like Lorazepam Injection, is ordinarily only an initial step of a complex and sustained intervention which may require additional interventions, (e.g., concomitant intravenous administration of phenytoin). Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected. Furthermore, patients who are susceptible to further seizure episodes should receive adequate maintenance antiepileptic therapy.

Any health care professional who intends to treat a patient with status epilepticus should be familiar with this package insert and the pertinent medical literature concerning current concepts for the treatment of status epilepticus. A comprehensive review of the considerations critical to the informed and prudent management of status epilepticus cannot be provided in drug product labeling. The archival medical literature contains many informative references on the management of status epilepticus, among them the report of the working group on status epilepticus of the Epilepsy Foundation of America “Treatment of Convulsive Status Epilepticus” (JAMA 1993; 270:854-859). As noted in the report just cited, it may be useful to consult with a neurologist if a patient fails to respond (e.g., fails to regain consciousness).

Intravenous Injection

For the treatment of status epilepticus, the usual recommended dose of Lorazepam Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. If seizures cease, no additional Lorazepam Injection is required. If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg intravenous dose may be slowly administered. Experience with further doses of lorazepam is very limited. The usual precautions in treating status epilepticus should be employed. An intravenous infusion should be started, vital signs should be monitored, an unobstructed airway should be maintained, and artificial ventilation equipment should be available.

Intramuscular Injection

IM lorazepam is not preferred in the treatment of status epilepticus because therapeutic lorazepam levels may not be reached as quickly as with IV administration. However, when an intravenous port is not available, the IM route may prove useful (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Pediatric

The safety of lorazepam in pediatric patients has not been established.

Preanesthetic

Intramuscular Injection

For the designated indications as a premedicant, the usual recommended dose of lorazepam for intramuscular injection is 0.05 mg/kg up to a maximum of 4 mg. As with all premedicant drugs, the dose should be individualized (see also CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Doses of other central-nervous-system-depressant drugs ordinarily should be reduced (see PRECAUTIONS). For optimum effect, measured as lack of recall, intramuscular lorazepam should be administered at least 2 hours before the anticipated operative procedure. Narcotic analgesics should be administered at their usual preoperative time.

There are insufficient data to support efficacy or make dosage recommendations for intramuscular lorazepam in patients less than 18 years of age; therefore, such use is not recommended.

Intravenous Injection

For the primary purpose of sedation and relief of anxiety, the usual recommended initial dose of lorazepam for intravenous injection is 2 mg total, or 0.02 mg/lb (0.044 mg/kg), whichever is smaller. This dose will suffice for sedating most adult patients and ordinarily should not be exceeded in patients over 50 years of age. In those patients in whom a greater likelihood of lack of recall for perioperative events would be beneficial, larger doses as high as 0.05 mg/kg up to a total of 4 mg may be administered (see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Doses of other injectable central-nervous-system-depressant drugs ordinarily should be reduced (see PRECAUTIONS). For optimum effect, measured as lack of recall, intravenous lorazepam should be administered 15 to 20 minutes before the anticipated operative procedure.

There are insufficient data to support efficacy or make dosage recommendations for intravenous lorazepam in patients less than 18 years of age; therefore, such use is not recommended.

Dose Administration in Special Populations

Elderly Patients and Patients With Hepatic Disease

No dosage adjustments are needed in elderly patients and in patients with hepatic disease.

Patients With Renal Disease

For acute dose administration, adjustment is not needed for patients with renal disease. However, in patients with renal disease, caution should be exercised if frequent doses are given over relatively short periods of time (see also CLINICAL PHARMACOLOGY).

Dose Adjustment Due to Drug Interactions

The dose of lorazepam should be reduced by 50% when coadministered with probenecid or valproate (see PRECAUTIONS, Drug Interactions).

It may be necessary to increase the dose of lorazepam in female patients who are concomitantly taking oral contraceptives.

Administration

When given intramuscularly, Lorazepam Injection, undiluted, should be injected deep in the muscle mass.

Injectable lorazepam can be used with atropine sulfate, narcotic analgesics, other parenterally used analgesics, commonly used anesthetics, and muscle relaxants.

Immediately prior to intravenous use, Lorazepam Injection must be diluted with an equal volume of compatible solution. Contents should be mixed thoroughly by gently inverting the container repeatedly until a homogenous solution results. Do not shake vigorously, as this will result in air entrapment. When properly diluted, the drug may be injected directly into a vein or into the tubing of an existing intravenous infusion. The rate of injection should not exceed 2.0 mg per minute.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if solution is discolored or contains a precipitate.

Lorazepam Injection is compatible for dilution purposes with the following solutions: Sterile Water for Injection, USP; Sodium Chloride Injection, USP; 5% Dextrose Injection, USP.
Hylenex Recombinant

Hylenex Recombinant

Always use aseptic precautions. Lightly pinch the skin up into a small mound and insert the needle/catheter into the subcutaneous space. Inject HYLENEX recombinant through the catheter hub or injection port closest to the needle/catheter. Begin administration of the injection solution. Solution should start in readily.

2.1 Subcutaneous Fluid Administration

150 U of HYLENEX recombinant injected prior to start of subcutaneous fluid administration will facilitate absorption of 1,000 mL or more of solution. As with all parenteral fluid therapy, observe effect closely, with the same precautions for restoring fluid and electrolyte balance as in intravenous injections. The dose, the rate of injection, and the type of solution (saline, glucose, Ringer's, etc.) must be adjusted carefully to the individual patient. When solutions devoid of inorganic electrolytes are administered subcutaneously, hypovolemia may occur. This may be prevented by using solutions containing adequate amounts of inorganic electrolytes and/or controlling the volume and speed of administration.

HYLENEX recombinant may be added to small volumes of solution, such as fluid replacement solutions or solutions of drugs for subcutaneous injection. Subcutaneous fluids should be administered as directed by a physician. The dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient as well as laboratory determinations. The rate and volume of subcutaneous fluid administration should not exceed those employed for intravenous infusion. For premature infants or during the neonatal period, the daily dosage should not exceed 25 mL/kg of body weight, and the rate of administration should not be greater than 2 mL per minute.

2.2 Dispersion and Absorption of Injected Drugs

Dispersion and absorption of other injected drugs may be enhanced by adding 50-300 U, most typically 150 U hyaluronidase, to the injection solution.

It is recommended that appropriate references be consulted regarding physical or chemical incompatibilities before adding HYLENEX recombinant to a solution containing another drug.

2.3 Subcutaneous Urography

The subcutaneous route of administration of urographic contrast media is indicated when intravenous administration cannot be successfully accomplished, particularly in infants and small children. With the patient prone, 75 U of HYLENEX recombinant is injected subcutaneously over each scapula, followed by injection of the contrast medium at the same sites.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Ampicillin and sulbactam for injection may be administered by either the IV or the IM routes.

For IV administration, the dose can be given by slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection.)

The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older:

The recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection. (See CLINICAL STUDIES section.)

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:
Ampicillin And Sulbactam For Injection Dosage GuideFor Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ SulbactamHalf-Life (Hours)
Recommended
Ampicillin And Sulbactam For Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males
weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Ampicillin and sulbactam for injection may be administered by either the IV or the IM routes.

For IV administration, the dose can be given by slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection.)

The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older:

The recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection. (See CLINICAL STUDIES section.)

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:
Ampicillin And Sulbactam For Injection Dosage GuideFor Patients With Renal Impairment Creatinine Clearance(mL/min/1.73m2) Ampicillin/ SulbactamHalf-Life (Hours)
Recommended
Ampicillin And SulbactamFor Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males
weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value
Ceftriaxone

Ceftriaxone

Ceftriaxone for injection may be administered intravenously or intramuscularly.

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone for injection. Particulate formation can result. ceftriaxone for injection and calcium-containing solutions, including continuous calcium-containing infusions such as parenteral nutrition, should not be mixed or co-administered to any patient irrespective of age, even via different infusion lines at different sites (see CONTRAINDICATIONS AND WARNINGS ).

NEONATES:

Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone for injection (see CONTRAINDICATIONS).

PEDIATRIC PATIENTS:

For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams.

For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 gram) is recommended (see INDICATIONS AND USAGE ).

For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams.

In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

ADULTS:

The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. The total daily dose should not exceed 4 grams.

If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.

For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.

For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.

Generally, ceftriaxone for injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.

When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

No dosage adjustment is necessary for patients with impairment of renal or hepatic function; however, blood levels should be monitored in patients with severe renal impairment (e.g., dialysis patients) and in patients with both renal and hepatic dysfunctions.

DIRECTIONS FOR USE:

Intramuscular Administration: Reconstitute ceftriaxone for injection powder with the appropriate diluent (see COMPATIBILITY AND STABILITY ).

Inject diluent into vial, shake vial thoroughly to form solution. Withdraw entire contents of vial into syringe to equal total labeled dose.

After reconstitution, each 1 mL of solution contains approximately 250 mg or 350 mg equivalent of ceftriaxone according to the amount of diluent indicated below. If required, more dilute solutions could be utilized. A 350 mg/mL concentration is not recommended for the 250 mg vial since it may not be possible to withdraw the entire contents.

As with all intramuscular preparations, ceftriaxone for injection should be injected well within the body of a relatively large muscle; aspiration helps to avoid unintentional injection into a blood vessel.
Vial Dosage Size Amount of Diluent to be Added 250 mg/mL
350 mg/mL
250 mg 0.9 mL
--
500 mg 1.8 mL
1.0 mL
1 g 3.6 mL 2.1 mL 2 g 7.2 mL 4.2 mL
Intravenous Administration:

Ceftriaxone for injection should be administered intravenously by infusion over a period of 30 minutes. Concentrations between 10 mg/mL and 40 mg/mL are recommended; however, lower concentrations may be used if desired. Reconstitute vials with an appropriate IV diluent (see COMPATIBILITY AND STABILITY ).

Vial Dosage Size Amount of Diluent to be Added 250 mg 2.4 mL 500 mg 4.8 mL 1 g 9.6 mL 2 g 19.2 mL
After reconstitution, each 1 mL of solution contains approximately 100 mg equivalent of ceftriaxone. Withdraw entire contents and dilute to the desired concentration with the appropriate IV diluent.

COMPATIBILITY AND STABILITY:

Ceftriaxone has been shown to be compatible with Flagyl®*IV (metronidazole hydrochloride). The concentration should not exceed 5 to 7.5 mg/mL metronidazole hydrochloride with ceftriaxone 10 mg/mL as an admixture. The admixture is stable for 24 hours at room temperature only in 0.9% sodium chloride injection or 5% dextrose in water (D5W). No compatibility studies have been conducted with the Flagyl®*IV RTU® or using other diluents. Metronidazole at concentrations greater than 8 mg/mL will precipitate. Do not refrigerate the admixture as precipitation will occur.

Vancomycin and fluconazole are physically incompatible with ceftriaxone in admixtures. When either of these drugs is to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations.

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone for injection. Particulate formation can result.

Ceftriaxone solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, due to possible incompatibility (see WARNINGS).

Ceftriaxone for injection sterile powder should be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.

Ceftriaxone for injection intramuscular solutions remain stable (loss of potency less than 10%) for the following time periods:
Diluent
Concentration
mg/mL Storage
Room Temp.
(25°C)
Refrigerated
(4°C)
Sterile Water for Injection

100
250, 350
2 days
24 hours
10 days
3 days
0.9% Sodium Chloride
Solution
100
250, 350
2 days
24 hours
10 days
3 days
5% Dextrose Solution

100
250, 350
2 days
24 hours
10 days
3 days
Bacteriostatic Water
+ 0.9% Benzyl Alcohol
100
250, 350
24 hours
24 hours
10 days
3 days
1% Lidocaine Solution
(without epinephrine)
100
250, 350
24 hours
24 hours
10 days
3 days
Ceftriaxone for injection intravenous solutions, at concentrations of 10, 20 and 40 mg/mL, remain stable (loss of potency less than 10%) for the following time periods stored in glass or PVC containers:
* Data available for 10 to 40 mg/mL concentrations in this diluent in PVC containers only. Diluent Storage Room Temp. (25°C) Refrigerated (4°C) Sterile Water 2 days 10 days 0.9% Sodium Chloride Solution 2 days 10 days 5% Dextrose Solution 2 days 10 days 10% Dextrose Solution 2 days 10 days 5% Dextrose + 0.9% Sodium Chloride Solution* 2 days Incompatible 5% Dextrose + 0.45% Sodium Chloride Solution 2 days Incompatible
The following intravenous ceftriaxone for injection solutions are stable at room temperature (25°C) for 24 hours, at concentrations between 10 mg/mL and 40 mg/mL: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine III (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), Ionosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container).

After the indicated stability time periods, unused portions of solutions should be discarded.

Note: Parenteral drug products should be inspected visually for particulate matter before administration.

Ceftriaxone for injection reconstituted with 5% Dextrose or 0.9% Sodium Chloride solution at concentrations between 10 mg/mL and 40 mg/mL, and then stored in frozen state (-20°C) in PVC or polyolefin containers, remains stable for 26 weeks.

Frozen solutions should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Ampicillin and sulbactam for injection may be administered by either the IV or the IM routes.

For IV administration, the dose can be given by slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection .)

The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older:

The recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection. (See CLINICAL STUDIES section.)

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:
Ampicillin And Sulbactam For Injection Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ Sulbactam Half-Life (Hours)
Recommended
Ampicillin And SulbactamFor Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males
weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value
Midazolam Hydrochloride...

Midazolam Hydrochloride

The 1 mL and 2 mL Midazolam Injection vials include a cautionary label that extends above the main label and highlights the drug name and strength per total volume. The purpose of the extended label is to prevent medication errors due to the different strengths of Midazolam Injection. Read the label and confirm you have selected the correct medication and strength. Then locate the “Tear Here” point on the label, and remove this cautionary label prior to removing the flip-off cap.

Midazolam is a potent sedative agent that requires slow administration and individualization of dosage. Clinical experience has shown midazolam to be 3 to 4 times as potent per mg as diazepam. BECAUSE SERIOUS AND LIFE-THREATENING CARDIORESPIRATORY ADVERSE EVENTS HAVE BEEN REPORTED, PROVISION FOR MONITORING, DETECTION AND CORRECTION OF THESE REACTIONS MUST BE MADE FOR EVERY PATIENT TO WHOM MIDAZOLAM INJECTION IS ADMINISTERED, REGARDLESS OF AGE OR HEALTH STATUS. Excessive single doses or rapid intravenous administration may result in respiratory depression, airway obstruction and/or arrest. The potential for these latter effects is increased in debilitated patients, those receiving concomitant medications capable of depressing the CNS, and patients without an endotracheal tube but undergoing a procedure involving the upper airway such as endoscopy or dental (see BOX WARNING and WARNINGS.)

Reactions such as agitation, involuntary movements, hyperactivity and combativeness have been reported in adult and pediatric patients. Should such reactions occur, caution should be exercised before continuing administration of midazolam (see WARNINGS).

Midazolam Injection should only be administered IM or IV (see WARNINGS).

Care should be taken to avoid intra-arterial injection or extravasation (see WARNINGS).

Midazolam Injection may be mixed in the same syringe with the following frequently used premedications: morphine sulfate, meperidine, atropine sulfate or scopolamine. Midazolam, at a concentration of 0.5 mg/mL, is compatible with 5% dextrose in water and 0.9% sodium chloride for up to 24 hours and with lactated Ringer’s solution for up to 4 hours. Both the 1 mg/mL and 5 mg/mL formulations of midazolam may be diluted with 0.9% sodium chloride or 5% dextrose in water.

Monitoring

Patient response to sedative agents, and resultant respiratory status, is variable. Regardless of the intended level of sedation or route of administration, sedation is a continuum; a patient may move easily from light to deep sedation, with potential loss of protective reflexes. This is especially true in pediatric patients. Sedative doses should be individually titrated, taking into account patient age, clinical status and concomitant use of other CNS depressants. Continuous monitoring of respiratory and cardiac function is required (i.e., pulse oximetry).

Adults and Pediatrics

Sedation guidelines recommend a careful presedation history to determine how a patient’s underlying medical conditions or concomitant medications might affect their response to sedation/analgesia as well as a physical examination including a focused examination of the airway for abnormalities. Further recommendations include appropriate presedation fasting.

Titration to effect with multiple small doses is essential for safe administration. It should be noted that adequate time to achieve peak central nervous system effect (3 to 5 minutes) for midazolam should be allowed between doses to minimize the potential for oversedation. Sufficient time must elapse between doses of concomitant sedative medications to allow the effect of each dose to be assessed before subsequent drug administration. This is an important consideration for all patients who receive intravenous midazolam.

Immediate availability of resuscitative drugs and age- and size-appropriate equipment and personnel trained in their use and skilled in airway management should be assured (see WARNINGS).

Pediatrics

For deeply sedated pediatric patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.

Intravenous access is not thought to be necessary for all pediatric patients sedated for a diagnostic or therapeutic procedure because in some cases the difficulty of gaining IV access would defeat the purpose of sedating the child; rather, emphasis should be placed upon having the intravenous equipment available and a practitioner skilled in establishing vascular access in pediatric patients immediately available.

Usual Adult Dose

Intramuscularly
For preoperative sedation/anxiolysis/amnesia (induction of sleepiness ordrowsiness and relief of apprehensionand to impair memoryof perioperative events). The recommended premedication dose of midazolam for good risk (ASA Physical Status I & II) adult patients below the age of 60 years is 0.07 to 0.08 mg/kg IM (approximately 5 mg IM) administered up to 1 hour before surgery. For intramuscular use, midazolamshould be injected deep in alarge muscle mass. The dose must be individualized and reduced when IM midazolam is administered to patients with chronic obstructive pulmonary disease, other higher risk surgical patients, patients 60 or more years of age, and patients who have received concomitant narcotics or other CNS depressants (see ADVERSE REACTIONS). In a study of patients 60 years or older, who did not receive concomitant administration of narcotics, 2 to 3 mg (0.02 to 0.05 mg/kg) of midazolam produced adequate sedation during the preoperative period. The dose of 1 mg IM midazolam may suffice for some older patients if the anticipated intensity and duration of sedation is less critical. As with any potential respiratory depressant, these patients require observation for signs of cardiorespiratory depression after receiving IM midazolam. Onset is within 15 minutes, peaking at 30 to 60 minutes. It can be administered concomitantly with atropine sulfate or scopolamine hydrochloride and reduced doses of narcotics.
Intravenously
Sedation/anxiolysis/amnesia forprocedures (See INDICATIONS AND USAGE):Narcotic premedication results in lessvariability in patient response and areduction in dosage of midazolam.For peroral procedures, the use of anappropriate topical anesthetic isrecommended. For bronchoscopicprocedures, the use of narcoticpremedication is recommended. Midazolam 1 mg/mL formulationis recommended forsedation/anxiolysis/amnesia forprocedures to facilitate slowerinjection. Both the 1 mg/mL and the5 mg/mL formulations may bediluted with 0.9% sodium chloride or5% dextrose in water. When used for sedation/anxiolysis/amnesia for a procedure, dosage must be individualized and titrated. Midazolam should always be titrated slowly; administer over at least 2 minutes and allow an additional 2 or more minutes to fully evaluate the sedative effect. Individual response will vary with age, physical status and concomitant medications, but may also vary independent of these factors. (See WARNINGS concerning cardiac/respiratory arrest/airway obstruction/hypoventilation.) 1. Healthy Adults Below the Age of 60: Titrate slowly to the desired effect, e.g., the initiation of slurred speech. Some patients may respond to as little as 1 mg. No more than 2.5 mg should be given over a period of at least 2 minutes. Wait an additional 2 or more minutes to fully evaluate the sedative effect. If further titration is necessary, continue to titrate, using small increments, to the appropriate level of sedation. Wait an additional 2 or more minutes after each increment to fully evaluate the sedative effect. A total dose greater than 5 mg is not usually necessary to reach the desired endpoint. If narcotic premedication or other CNS depressants are used, patients will require approximately 30% less midazolam than unpremedicated patients. 2. Patients Age 60 or Older, and Debilitated or Chronically Ill Patients: Because the danger of hypoventilation, airway obstruction, or apnea is greater in elderly patients and those with chronic disease states or decreased pulmonary reserve, and because the peak effect may take longer in these patients, increments should be smaller and the rate of injection slower. Titrate slowly to the desired effect, e.g., the initiation of slurred speech. Some patients may respond to as little as 1 mg. No more than 1.5 mg should be given over a period of no less than 2 minutes. Wait an additional 2 or more minutes to fully evaluate the sedative effect. If additional titration is necessary, it should be given at a rate of no more than 1 mg over a period of 2 minutes, waiting an additional 2 or more minutes each time to fully evaluate the sedative effect. Total doses greater than 3.5 mg are not usually necessary. If concomitant CNS depressant premedications are used in these patients, they will require at least 50% less midazolam than healthy young unpremedicated patients. 3. Maintenance Dose: Additional doses to maintain the desired level of sedation may be given in increments of 25% of the dose used to first reach the sedative endpoint, but again only by slow titration, especially in the elderly and chronically ill or debilitated patient. These additional doses should be given only after a thorough clinical evaluation clearly indicates the need for additional sedation. Induction of Anesthesia: Forinduction of general anesthesia,before administration of otheranesthetic agents. Individual response to the drug is variable, particularly when a narcotic premedication is not used. The dosage should be titrated to the desired effect according to the patient’s age and clinical status. When midazolam is used before other intravenous agents for induction of anesthesia, the initial dose of each agent may be significantly reduced, at times to as low as 25% of the usual initial dose of the individual agents. Unpremedicated Patients In the absence of premedication, an average adult under the age of 55 years will usually require an initial dose of 0.3 to 0.35 mg/kg for induction, administered over 20 to 30 seconds and allowing 2 minutes for effect. If needed to complete induction, increments of approximately 25% of the patient’s initial dose may be used; induction may instead be completed with inhalational anesthetics. In resistant cases, up to 0.6 mg/kg total dose may be used for induction, but such larger doses may prolong recovery. Unpremedicated patients over the age of 55 years usually require less midazolam for induction; an initial dose of 0.3 mg/kg is recommended. Unpremedicated patients with severe systemic disease or other debilitation usually require less midazolam for induction. An initial dose of 0.2 to 0.25 mg/kg will usually suffice; in some cases, as little as 0.15 mg/kg may suffice. Premedicated Patients When the patient has received sedative or narcotic premedication, particularly narcotic premedication, the range of recommended doses is 0.15 to 0.35 mg/kg. In average adults below the age of 55 years, a dose of 0.25 mg/kg, administered over 20 to 30 seconds and allowing 2 minutes for effect, will usually suffice. The initial dose of 0.2 mg/kg is recommended for good risk (ASA I & II) surgical patients over the age of 55 years.In some patients with severe systemic disease or debilitation, as little as 0.15 mg/kg may suffice. Narcotic premedication frequently used during clinical trials included fentanyl (1.5 to 2 mcg/kg IV, administered 5 minutes before induction), morphine (dosage individualized, up to 0.15 mg/kg IM), and meperidine (dosage individualized, up to 1 mg/kg IM). Sedative premedications were hydroxyzine pamoate (100 mg orally) and sodium secobarbital (200 mg orally). Except for intravenous fentanyl, administered 5 minutes before induction, all other premedications should be administered approximately 1 hour prior to the time anticipated for midazolam induction. Injectable midazolam can alsobe used during maintenance ofanesthesia, for surgical procedures, asa component of balanced anesthesia.Effective narcotic premedication isespecially recommended in such cases. Incremental injections of approximately 25% of the induction dose should be given in response to signs of lightening of anesthesia and repeated as necessary.
Continuous Infusion
For continuous infusion, midazolam5 mg/mL formulation isrecommended diluted to aconcentration of 0.5 mg/mL with0.9% sodium chloride or 5%dextrose in water. Usual Adult Dose If a loading dose is necessary to rapidly initiate sedation, 0.01 to 0.05 mg/kg (approximately 0.5 to 4 mg for a typical adult) may be given slowly or infused over several minutes. This dose may be repeated at 10 to 15 minute intervals until adequate sedation is achieved. For maintenance of sedation, the usual initial infusion rate is 0.02 to 0.10 mg/kg/hr (1 to 7 mg/hr). Higher loading or maintenance infusion rates may occasionally be required in some patients. The lowest recommended doses should be used in patients with residual effects from anesthetic drugs, or in those concurrently receiving other sedatives or opioids. Individual response to midazolam is variable. The infusion rate should be titrated to the desired level of sedation, taking into account the patient’s age, clinical status and current medications. In general, midazolam should be infused at the lowest rate that produces the desired level of sedation. Assessment of sedation should be performed at regular intervals and the midazolam infusion rate adjusted up or down by 25% to 50% of the initial infusion rate so as to assure adequate titration of sedation level. Larger adjustments or even a small incremental dose may be necessary if rapid changes in the level of sedation are indicated. In addition, the infusion rate should be decreased by 10% to 25% every few hours to find the minimum effective infusion rate. Finding the minimum effective infusion rate decreases the potential accumulation of midazolam and provides for the most rapid recovery once the infusion is terminated. Patients who exhibit agitation, hypertension or tachycardia in response to noxious stimulation, but who are otherwise adequately sedated, may benefit from concurrent administration of an opioid analgesic. Addition of an opioid will generally reduce the minimum effective midazolam infusion rate.
Pediatric Patients
UNLIKE ADULT PATIENTS, PEDIATRIC PATIENTS GENERALLY RECEIVE INCREMENTS OF MIDAZOLAM ON A MG/KG BASIS. As a group, pediatric patients generally require higher dosages of midazolam (mg/kg) than do adults. Younger (less than six years) pediatric patients may require higher dosages (mg/kg) than older pediatric patients and may require close monitoring (see tables below). In obese PEDIATRIC PATIENTS, the dose should be calculated based on ideal body weight. When midazolam is given in conjunction with opioids or other sedatives, the potential for respiratory depression, airway obstruction or hypoventilation is increased. For appropriate patient monitoring, see BOX WARNING, WARNINGS, Monitoring subsection of DOSAGE AND ADMINISTRATION. The health care practitioner who uses this medication in pediatric patients should be aware of and follow accepted professional guidelines for pediatric sedation appropriate to their situation. OBSERVER’S ASSESSMENT OF ALERTNESS/SEDATION (OAA/S) Assessment Categories Responsiveness Speech FacialExpression Eyes CompositeScore Responds readily to name spoken in normal tone normal normal clear; no ptosis 5 (alert) Lethargic response to name spoken in normal tone mild slowing or thickening mildrelaxation glazed or mildptosis (less thanhalf the eye) 4 Responds only after name is called loudly and/or repeatedly slurring orprominent slowing markedrelaxation (slack jaw) glazed and marked ptosis(half the eyeor more) 3 Responds only after mild prodding or shaking few recognizablewords —— —— 2 Does not respond to mild prodding or shaking —— —— —— 1(deep sleep) FREQUENCY OF OBSERVER’S ASSESSMENT OF ALERTNESS/SEDATION COMPOSITE SCORES IN ONE STUDY OF CHILDREN UNDERGOING PROCEDURES WITH INTRAVENOUS MIDAZOLAM FOR SEDATION OAA/S Score AgeRange(years) n 1 (deep sleep) 2 3 4 5 (alert) 1-2 16 6 (38%) 4 (25%) 3 (19%) 3 (19%) 0 >2-5 22 9 (41%) 5 (23%) 8 (36%) 0 0 >5-12 34 1 (3%) 6 (18%) 22 (65%) 5 (15%) 0 >12- 17 18 0 4 (22%) 14 (78%) 0 0 Total (1-17) 90 16 (18%) 19 (21%) 47 (52%) 8 (9%) 0
Intramuscularly
For sedation/anxiolysis/amnesia priorto anesthesia or for procedures,intramuscular midazolam can be usedto sedate pediatric patients tofacilitate less traumatic insertion of anintravenous catheter for titration ofadditional medication. USUAL PEDIATRIC DOSE (NON-NEONATAL). Sedation after intramuscular midazolam is age and dose dependent; higher doses may result in deeper and more prolonged sedation. Doses of 0.1 to 0.15 mg/kg are usually effective and do not prolong emergence from general anesthesia. For more anxious patients, doses up to 0.5 mg/kg have been used. Although not systematically studied, the total dose usually does not exceed 10 mg. If midazolam is given with an opioid, the initial dose of each must be reduced.
Intravenously by Intermittent Injection
For sedation/anxiolysis/amnesiaprior to and during procedures orprior to anesthesia. USUAL PEDIATRIC DOSE (NON-NEONATAL) It should be recognized that the depth of sedation/anxiolysis needed for pediatric patients depends on the type of procedure to be performed. For example, simple light sedation/anxiolysis in the preoperative period is quite different from the deep sedation and analgesia required for an endoscopic procedure in a child. For this reason, there is a broad range of dosage. For all pediatric patients, regardless of the indications for sedation/anxiolysis, it is vital to titrate midazolam and other concomitant medications slowly to the desired clinical effect. The initial dose of midazolam should be administered over 2 to 3 minutes. Since midazolam HCl is water soluble, it takes approximately three times longer than diazepam to achieve peak EEG effects; therefore, one must wait an additional 2 to 3 minutes to fully evaluate the sedative effect before initiating a procedure or repeating a dose. If further sedation is necessary, continue to titrate with small increments until the appropriate level of sedation is achieved. If other medications capable of depressing the CNS are coadministered, the peak effect of those concomitant medications must be considered and the dose of midazolam adjusted. The importance of drug titration to effect is vital to the safe sedation/anxiolysis of the pediatric patient. The total dose of midazolam will depend on patient response, the type and duration of the procedure, as well as the type and dose of concomitant medications. 1. Pediatric patients less than 6 months of age: Limited information is available in non-intubated pediatric patients less than 6 months of age. It is uncertain when the patient transfers from neonatal physiology to pediatric physiology; therefore, the dosing recommendations are unclear. Pediatric patients less than 6 months of age are particularly vulnerable to airway obstruction and hypoventilation; therefore, titration with small increments to clinical effect and careful monitoring are essential. 2. Pediatric patients 6 months to 5 years of age: Initial dose 0.05 to 0.1 mg/kg. A total dose up to 0.6 mg/kg may be necessary to reach the desired endpoint but usually does not exceed 6 mg. Prolonged sedation and risk of hypoventilation may be associated with the higher doses. 3. Pediatric patients 6 to 12 years of age: Initial dose 0.025 to 0.05 mg/kg; total dose up to 0.4 mg/kg may be needed to reach the desired endpoint but usually does not exceed 10 mg. Prolonged sedation and risk of hypoventilation may be associated with the higher doses. 4. Pediatric patients 12 to 16 years of age: Should be dosed as adults. Prolonged sedation may be associated with higher doses; some patients in this age range will require higher than recommended adult doses but the total dose usually does not exceed 10 mg. The dose of midazolam must be reduced in patients premedicated with opioid or other sedative agents including midazolam. Higher risk or debilitated patients may require lower dosages whether or not concomitant sedating medications have been administered (see WARNINGS).
Continuous Intravenous Infusion
For sedation/anxiolysis/amnesia incritical care settings. USUAL PEDIATRIC DOSE (NON-NEONATAL) To initiate sedation, an intravenous loading dose of 0.05 to 0.2 mg/kg administered over at least 2 to 3 minutes can be used to establish the desired clinical effect IN PATIENTS WHOSE TRACHEA IS INTUBATED. (Midazolam should not be administered as a rapid intravenous dose.) This loading dose may be followed by a continuous intravenous infusion to maintain the effect. An infusion of midazolam has been used in patients whose trachea was intubated but who were allowed to breathe spontaneously. Assisted ventilation is recommended for pediatric patients who are receiving other central nervous system depressant medications such as opioids. Based on pharmacokinetic parameters and reported clinical experience, continuous intravenous infusions of midazolam should be initiated at a rate of 0.06 to 0.12 mg/kg/hr (1 to 2 mcg/kg/min). The rate of infusion can be increased or decreased (generally by 25% of the initial or subsequent infusion rate) as required, or supplemental intravenous doses of midazolam can be administered to increase or maintain the desired effect. Frequent assessment at regular intervals using standard pain/sedation scales is recommended. Drug elimination may be delayed in patients receiving erythromycin and/or other P450-3A4 enzyme inhibitors (see Drug Interactions section) and in patients with liver dysfunction, low cardiac output (especially those requiring inotropic support), and in neonates. Hypotension may be observed in patients who are critically ill, particularly those receiving opioids and/or when midazolam is rapidly administered. When initiating an infusion with midazolam in hemodynamically compromised patients, the usual loading dose of midazolam should be titrated in small increments and the patient monitored for hemodynamic instability, e.g., hypotension. These patients are also vulnerable to the respiratory depressant effects of midazolam and require careful monitoring of respiratory rate and oxygen saturation.
Continuous Intravenous Infusion
For sedation in critical care settings. USUAL NEONATAL DOSE Based on pharmacokinetic parameters and reported clinical experience in preterm and term neonates WHOSE TRACHEA WAS INTUBATED, continuous intravenous infusions of Midazolam Injection should be initiated at a rate of 0.03 mg/kg/hr (0.5 mcg/kg/min) in neonates <32 weeks and 0.06 mg/kg/hr (1 mcg/kg/min) in neonates >32 weeks. Intravenous loading doses should not be used in neonates, rather the infusion may be run more rapidly for the first several hours to establish therapeutic plasma levels. The rate of infusion should be carefully and frequently reassessed, particularly after the first 24 hours so as to administer the lowest possible effective dose and reduce the potential for drug accumulation. This is particularly important because of the potential for adverse effects related to metabolism of the benzyl alcohol (see Usage in Preterm Infants and Neonates). Hypotension may be observed in patients who are critically ill and in preterm and term infants, particularly those receiving fentanyl and/or when midazolam is administered rapidly. Due to an increased risk of apnea, extreme caution is advised when sedating preterm and former preterm patients whose trachea is not intubated.
Parenteral drug products should be inspected visually for particulate matter anddiscoloration prior to administration, whenever solution and container permit.
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

For IV administration, the dose can be given by slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older:

The recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established.

Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection. (See CLINICAL STUDIES section.)

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:
Ampicillin And Sulbactam For Injection Dosage GuideFor Patients With Renal Impairment Creatinine Clearance (mL/min/1.73 m2) Ampicillin/Sulbactam Half-Life (Hours) Recommended Ampicillin And SulbactamFor Injection Dosage ≥30 1 1.5-3.0 g q 6 h-q 8 h 15-29 5 1.5-3.0 g q 12 h 5-14 9 1.5-3.0 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males weight (kg) x (140 – age) 72 x serum creatinine Females 0.85 x above value
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

For IV administration, the dose can be given by slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older:

The recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection. (See CLINICAL STUDIES section.)

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:
Ampicillin And Sulbactam For Injection Dosage GuideFor Patients With Renal Impairment Creatinine Clearance (mL/min/1.73 m2) Ampicillin/SulbactamHalf-Life (Hours)
Recommended
Ampicillin And SulbactamFor Injection Dosage ≥ 30 1 1.5-3.0 g q 6 h-q 8 h 15-29 5 1.5-3.0 g q 12 h 5-14 9 1.5-3.0 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males
weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

For IV administration, the dose can be given by slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

The recommended adult dosage of ampicillin and sulbactam for injection is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older:

The recommended daily dose of ampicillin and sulbactam for injection in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous ampicillin and sulbactam for injection. (See CLINICAL STUDIES section.)

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:
Ampicillin And Sulbactam For Injection Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73 m2) Ampicillin/SulbactamHalf-Life (Hours)
Recommended
Ampicillin And Sulbactam For Injection Dosage ≥ 30 1 1.5-3.0 g q 6 h-q 8 h 15-29 5 1.5-3.0 g q 12 h 5-14 9 1.5-3.0 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males
weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value
Aralast Np

Aralast Np

Dose ranging studies using efficacy endpoints have not been performed.

Chronic Augmentation Therapy

FOR INTRAVENOUS USE ONLY. The recommended dosage of ARALAST NP is 60 mg/kg body weight administered once weekly by intravenous infusion. Each vial of ARALAST NP has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label. Administration of ARALAST NP within three hours after reconstitution is recommended to avoid the potential ill effect of any inadvertent microbial contamination occurring during reconstitution. Discard any unused contents.

Infusion Rate

ARALAST NP should be administered at a rate not exceeding 0.08 mL/kg body weight/minute. If adverse events occur, the rate should be reduced or the infusion interrupted until the symptoms subside. The infusion may then be resumed at a rate tolerated by the subject.
Aralast Np

Aralast Np

Dose ranging studies using efficacy endpoints have not been performed.

Chronic Augmentation Therapy

FOR INTRAVENOUS USE ONLY. The recommended dosage of ARALAST NP is 60 mg/kg body weight administered once weekly by intravenous infusion. Each vial of ARALAST NP has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label. Administration of ARALAST NP within three hours after reconstitution is recommended to avoid the potential ill effect of any inadvertent microbial contamination occurring during reconstitution. Discard any unused contents.

Infusion Rate

ARALAST NP should be administered at a rate not exceeding 0.08 mL/kg body weight/minute. If adverse events occur, the rate should be reduced or the infusion interrupted until the symptoms subside. The infusion may then be resumed at a rate tolerated by the subject.
Flumazenil

Flumazenil

Flumazenil injection is recommended for intravenous use only. It is compatible with 5% dextrose in water, lactated Ringer's and 0.9% sodium chloride solutions. If flumazenil injection is drawn into a syringe or mixed with any of these solutions, it should be discarded after 24 hours. For optimum sterility, flumazenil injection should remain in the vial until just before use. As with all parenteral drug products, flumazenil injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

To minimize the likelihood of pain at the injection site, flumazenil injection should be administered through a freely running intravenous infusion into a large vein.

Reversal of Conscious Sedation

Adult Patients

For the reversal of the sedative effects of benzodiazepines administered for conscious sedation, the recommended initial dose of flumazenil injection is 0.2 mg (2 mL) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, a second dose of 0.2 mg (2 mL) can be injected and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 1 mg (10 mL). The dosage should be individualized based on the patient's response, with most patients responding to doses of 0.6 mg to 1 mg (see INDIVIDUALIZATION OF DOSAGE).

In the event of resedation, repeated doses may be administered at 20-minute intervals as needed. For repeat treatment, no more than 1 mg (given as 0.2 mg/min) should be administered at any one time, and no more than 3 mg should be given in any one hour.

It is recommended that flumazenil injection be administered as the series of small injections described (not as a single bolus injection) to allow the practitioner to control the reversal of sedation to the approximate endpoint desired and to minimize the possibility of adverse effects (see INDIVIDUALIZATION OF DOSAGE).

Pediatric Patients

For the reversal of the sedative effects of benzodiazepines administered for conscious sedation in pediatric patients greater than 1 year of age, the recommended initial dose is 0.01 mg/kg (up to 0.2 mg) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, further injections of 0.01 mg/kg (up to 0.2 mg) can be administered and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 0.05 mg/kg or 1 mg, whichever is lower. The dose should be individualized based on the patient's response. The mean total dose administered in the pediatric clinical trial of flumazenil was 0.65 mg (range: 0.08 mg to 1 mg). Approximately one-half of patients required the maximum of five injections.

Resedation occurred in 7 of 60 pediatric patients who were fully alert 10 minutes after the start of flumazenil injection administration (see PRECAUTIONS: Pediatric Use). The safety and efficacy of repeated flumazenil administration in pediatric patients experiencing resedation have not been established.

It is recommended that flumazenil injection be administered as the series of small injections described (not as a single bolus injection) to allow the practitioner to control the reversal of sedation to the approximate endpoint desired and to minimize the possibility of adverse effects (see INDIVIDUALIZATION OF DOSAGE).

The safety and efficacy of flumazenil injection in the reversal of conscious sedation in pediatric patients below the age of 1 year have not been established.

Reversal of General Anesthesia in Adult Patients

For the reversal of the sedative effects of benzodiazepines administered for general anesthesia, the recommended initial dose of flumazenil injection is 0.2 mg (2 mL) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, a further dose of 0.2 mg (2 mL) can be injected and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 1 mg (10 mL). The dosage should be individualized based on the patient's response, with most patients responding to doses of 0.6 mg to 1 mg (see INDIVIDUALIZATION OF DOSAGE).

In the event of resedation, repeated doses may be administered at 20-minute intervals as needed. For repeat treatment, no more than 1 mg (given as 0.2 mg/min) should be administered at any one time, and no more than 3 mg should be given in any one hour.

It is recommended that flumazenil injection be administered as the series of small injections described (not as a single bolus injection) to allow the practitioner to control the reversal of sedation to the approximate endpoint desired and to minimize the possibility of adverse effects (see INDIVIDUALIZATION OF DOSAGE).

Management of Suspected Benzodiazepine Overdose in Adult Patients

For initial management of a known or suspected benzodiazepine overdose, the recommended initial dose of flumazenil injection is 0.2 mg (2 mL) administered intravenously over 30 seconds. If the desired level of consciousness is not obtained after waiting 30 seconds, a further dose of 0.3 mg (3 mL) can be administered over another 30 seconds. Further doses of 0.5 mg (5 mL) can be administered over 30 seconds at 1-minute intervals up to a cumulative dose of 3 mg.

Do not rush the administration of flumazenil injection. Patients should have a secure airway and intravenous access before administration of the drug and be awakened gradually (see PRECAUTIONS).

Most patients with a benzodiazepine overdose will respond to a cumulative dose of 1 mg to 3 mg of flumazenil injection, and doses beyond 3 mg do not reliably produce additional effects. On rare occasions, patients with a partial response at 3 mg may require additional titration up to a total dose of 5 mg (administered slowly in the same manner).

If a patient has not responded 5 minutes after receiving a cumulative dose of 5 mg of flumazenil injection, the major cause of sedation is likely not to be due to benzodiazepines, and additional flumazenil injection is likely to have no effect.

In the event of resedation, repeated doses may be given at 20-minute intervals if needed. For repeat treatment, no more than 1 mg (given as 0.5 mg/min) should be given at any one time and no more than 3 mg should be given in any one hour.

Safety and Handling

Flumazenil injection is supplied in sealed dosage forms and poses no known risk to the healthcare provider. Routine care should be taken to avoid aerosol generation when preparing syringes for injection, and spilled medication should be rinsed from the skin with cool water.
Recombinate

Recombinate

Each vial of RECOMBINATE is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.

The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al4 and is supported by the data generated by 419 clinical pharmacokinetic studies with RECOMBINATE in 67 patients over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.

Examples (Assuming patient’s baseline Factor VIII level is at <1%):

(1) A dose of 1750 IU RECOMBINATE administered to a 70 kg patient, i.e. 25 IU/kg (1750 IU/70 kg), should be expected to cause a peak post-infusion Factor VIII increase of 25 IU/kg x 2 (IU/dL)/(IU/kg) = 50 IU/dL (50% of normal).

(2) A peak level of 70% is required in a 40 kg child. In this situation, the dose would be 70 IU/dL/[2(IU/dL)/(IU/kg)] x 40 kg = 1400 IU.

Recommended Dosage Schedule

Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.
Hemorrhage Degree of hemorrhage Required peak post infusion Factor VIII activity in the blood (as % of normal or IU/dL plasma) Frequency of Infusion Early hemarthrosis or muscle bleed or oral bleed 20-40 Begin infusion every 12 to 24 hours for one-three days until the bleeding episode is resolved (as indicated by pain), or healing is achieved. More extensive hemarthrosis, muscle bleed, or hematoma 30-60 Repeat infusion every 12 to 24 hours for (usually) three days or more until pain and disability are resolved. Life threatening bleeds such as head injury, throat bleed, severe abdominal pain 60-100 Repeat infusion every 8 to 24 hours until threat is resolved Surgery Type of Operation Minor surgery, including tooth extraction 60-80 A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases. Major surgery 80-100 (pre- and post-operative) Repeat infusion every 8 to 24 hours depending on state of healing.
If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be determined and a sufficient dose of RECOMBINATE should be administered to achieve a satisfactory clinical response.

The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages. In presence of a low titer inhibitor, doses larger than those recommended may be necessary as per standard care.

Although dosage can be estimated by the calculations above, it is strongly recommended that whenever possible, appropriate laboratory tests including serial Factor VIII assays be performed on the patient’s plasma at suitable intervals to assure that adequate Factor VIII levels have been reached and are maintained.

Patients should be evaluated for the development of Factor VIII inhibitors, if the expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose.

Reconstitution: Use Aseptic Technique
Bring RECOMBINATE (dry factor concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature. Remove caps from concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place vials on a flat surface. Open the BAXJECT II device package by peeling away the lid, without touching the inside. Do not remove the device from the package. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper. Grip the BAXJECT II package at its edge and pull the package off the device. Do not remove the blue cap from the BAXJECT II device.Do not touch the exposed white plastic spike. Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the RECOMBINATE vial stopper by pushing straight down. The vacuum will draw the diluent into the RECOMBINATE vial. Swirl gently until RECOMBINATE is completely dissolved. After reconstitution, the solution should be colorless to faint yellow, and substantially free from foreign particles.
NOTE: Do not refrigerate after reconstitution. (See Administration)

Administration: Use Aseptic Technique

RECOMBINATE is administered by intravenous (IV) injection after reconstitution.

Administer at room temperature.

RECOMBINATE should be administered not more than 3 hours after reconstitution.

Intravenous Syringe Injection

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be colorless to faint yellow in appearance. If not, do not use the solution and notify Baxter immediately.

Plastic syringes are recommended for use with this product since proteins such as RECOMBINATE tend to stick to the surface of glass syringes.
Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device. DO NOT INJECT AIR. Turn over the connected vials so that the RECOMBINATE vial is on top. Draw the factor concentrate into the syringe by pulling the plunger back slowly. Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration. If a patient is to receive more than one vial of RECOMBINATE, the contents of multiple vials may be drawn into the same syringe. Please note that the BAXJECT II device is intended for use with a single vial of RECOMBINATE and Sterile Water for Injection only, therefore reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.
Rate of Administration

The rate of administration should be a rate that ensures the comfort of the patient. Preparations of RECOMBINATE can be administered at a rate of up to 10 mL per minute with no significant reactions when reconstituted with 10 mL sWFI.

The pulse rate should be determined before and during administration of RECOMBINATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.
Recombinate

Recombinate

Each vial of RECOMBINATE is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.

The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al4 and is supported by the data generated by 419 clinical pharmacokinetic studies with RECOMBINATE in 67 patients over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.

Examples (Assuming patient’s baseline Factor VIII level is at <1%):

(1) A dose of 1750 IU RECOMBINATE administered to a 70 kg patient, i.e. 25 IU/kg (1750 IU/70 kg), should be expected to cause a peak post-infusion Factor VIII increase of 25 IU/kg x 2 (IU/dL)/(IU/kg) = 50 IU/dL (50% of normal).

(2) A peak level of 70% is required in a 40 kg child. In this situation, the dose would be 70 IU/dL/[2(IU/dL)/(IU/kg)] x 40 kg = 1400 IU.

Recommended Dosage Schedule

Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.
Hemorrhage Degree of hemorrhage Required peak post infusion Factor VIII activity in the blood (as % of normal or IU/dL plasma) Frequency of Infusion Early hemarthrosis or muscle bleed or oral bleed 20-40 Begin infusion every 12 to 24 hours for one-three days until the bleeding episode is resolved (as indicated by pain), or healing is achieved. More extensive hemarthrosis, muscle bleed, or hematoma 30-60 Repeat infusion every 12 to 24 hours for (usually) three days or more until pain and disability are resolved. Life threatening bleeds such as head injury, throat bleed, severe abdominal pain 60-100 Repeat infusion every 8 to 24 hours until threat is resolved Surgery Type of Operation Minor surgery, including tooth extractions 60-80 A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases. Major surgery 80-100 (pre- and post-operative) Repeat infusion every 8 to 24 hours depending on state of healing.
If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be determined and a sufficient dose of RECOMBINATE should be administered to achieve a satisfactory clinical response.

The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages. In presence of a low titer inhibitor, doses larger than those recommended may be necessary as per standard care.

Although dosage can be estimated by the calculations above, it is strongly recommended that whenever possible, appropriate laboratory tests including serial Factor VIII assays be performed on the patient’s plasma at suitable intervals to assure that adequate Factor VIII levels have been reached and are maintained. Patients should be evaluated for the development of Factor VIII inhibitors, if the expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose.

Reconstitution: Use Aseptic Technique
Bring RECOMBINATE, (dry factor concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature. Remove caps from concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place vials on a flat surface Remove protective covering from one end of double-ended needle and insert exposed needle through the center of the stopper. Remove protective covering from other end of double-ended needle. Invert diluent vial over the upright RECOMBINATE vial, then rapidly insert free end of the needle through the RECOMBINATE vial stopper at its center. The vacuum in the vial will draw in the diluent. Disconnect the two vials by removing needle from diluent vial stopper, then remove needle from RECOMBINATE vial. Swirl gently until RECOMBINATE is completely dissolved, otherwise active material will be removed by the filter needle. After reconstitution, the solution should be colorless to faint yellow, and substantially free from foreign particles.
NOTE: Do not refrigerate after reconstitution. (See Administration)

Administration: Use Aseptic Technique

RECOMBINATE is administered by intravenous (IV) injection after reconstitution.

Administer at room temperature.

RECOMBINATE should be administered not more than 3 hours after reconstitution.

Intravenous Syringe Injection

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be colorless to faint yellow in appearance. If not, do not use the solution and notify Baxter immediately.

Plastic syringes are recommended for use with this product since proteins such as RECOMBINATE tend to stick to the surface of glass syringes.
Attach filter needle to a disposable syringe and draw back plunger to admit air into the syringe. Insert the needle into reconstituted RECOMBINATE . Inject air into vial and then withdraw the reconstituted material into the syringe. Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration. If a patient is to receive more than one vial of RECOMBINATE, the contents of multiple vials may be drawn into the same syringe by drawing up each vial through a separate unused filter needle. Filter needles are intended to filter the contents of a single vial of RECOMBINATE only.
Rate of Administration

The rate of administration should be a rate that ensures the comfort of the patient. Preparations of RECOMBINATE can be administered at a rate of up to 10 mL per minute with no significant reactions when reconstituted with 10 mL sWFI.

The pulse rate should be determined before and during administration of RECOMBINATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.
Duramorph

Duramorph

DURAMORPH is intended for intravenous, epidural or intrathecal administration.

Not For Use in Continuous Microinfusion Devices

Intravenous Administration

Dosage

The initial dose of morphine should be 2 mg to 10 mg/70 kg of body weight. No information is available regarding the use of DURAMORPH in patients under the age of 18.

Geriatric Use

Administer with extreme caution. (See PRECAUTIONS.)

Epidural Administration

DURAMORPH SHOULD BE ADMINISTERED EPIDURALLY BY OR UNDER THE DIRECTION OF A PHYSICIAN EXPERIENCED IN THE TECHNIQUE OF EPIDURAL ADMINISTRATION AND WHO IS THOROUGHLY FAMILIAR WITH THE LABELING. IT SHOULD BE ADMINISTERED ONLY IN SETTINGS WHERE ADEQUATE PATIENT MONITORING IS POSSIBLE. RESUSCITATIVE EQUIPMENT AND A SPECIFIC ANTAGONIST (NALOXONE INJECTION) SHOULD BE IMMEDIATELY AVAILABLE FOR THE MANAGEMENT OF RESPIRATORY DEPRESSION AS WELL AS COMPLICATIONS WHICH MIGHT RESULT FROM INADVERTENT INTRATHECAL OR INTRAVASCULAR INJECTION. (NOTE: INTRATHECAL DOSAGE IS USUALLY 1/10 THAT OF EPIDURAL DOSAGE.) PATIENT MONITORING SHOULD BE CONTINUED FOR AT LEAST 24 HOURS AFTER EACH DOSE, SINCE DELAYED RESPIRATORY DEPRESSION MAY OCCUR.

Proper placement of a needle or catheter in the epidural space should be verified before DURAMORPH is injected.

Acceptable techniques for verifying proper placement include: a) aspiration to check for absence of blood or cerebrospinal fluid, or b) administration of 5 mL (3 mL in obstetric patients) of 1.5% PRESERVATIVE-FREE Lidocaine and Epinephrine (1:200,000) Injection and then observe the patient for lack of tachycardia (this indicates that vascular injection has not been made) and lack of sudden onset of segmental anesthesia (this indicates that intrathecal injection has not been made).

Epidural Adult Dosage

Initial injection of 5 mg in the lumbar region may provide satisfactory pain relief for up to 24 hours. If adequate pain relief is not achieved within one hour, careful administration of incremental doses of 1 to 2 mg at intervals sufficient to assess effectiveness may be given. No more than 10 mg/24 hr should be administered.

Thoracic administration has been shown to dramatically increase the incidence of early and late respiratory depression even at doses of 1 to 2 mg.

Geriatric Use

Administer with extreme caution. (See PRECAUTIONS.)

Epidural Pediatric Use

No information on use in pediatric patients is available. (See PRECAUTIONS.)

Intrathecal Administration

NOTE: INTRATHECAL DOSAGE IS USUALLY 1/10 THAT OF EPIDURAL DOSAGE.

DURAMORPH SHOULD BE ADMINISTERED INTRATHECALLY BY OR UNDER THE DIRECTION OF A PHYSICIAN EXPERIENCED IN THE TECHNIQUE OF INTRATHECAL ADMINISTRATION AND WHO IS THOROUGHLY FAMILIAR WITH THE LABELING. IT SHOULD BE ADMINISTERED ONLY IN SETTINGS WHERE ADEQUATE PATIENT MONITORING IS POSSIBLE. RESUSCITATIVE EQUIPMENT AND A SPECIFIC ANTAGONIST (NALOXONE INJECTION) SHOULD BE IMMEDIATELY AVAILABLE FOR THE MANAGEMENT OF RESPIRATORY DEPRESSION AS WELL AS COMPLICATIONS WHICH MIGHT RESULT FROM INADVERTENT INTRAVASCULAR INJECTION. PATIENT MONITORING SHOULD BE CONTINUED FOR AT LEAST 24 HOURS AFTER EACH DOSE, SINCE DELAYED RESPIRATORY DEPRESSION MAY OCCUR. RESPIRATORY DEPRESSION (BOTH EARLY AND LATE ONSET) HAS OCCURRED MORE FREQUENTLY FOLLOWING INTRATHECAL ADMINISTRATION THAN EPIDURAL ADMINISTRATION.

Intrathecal Adult Dosage

A single injection of 0.2 to 1 mg may provide satisfactory pain relief for up to 24 hours. (CAUTION: THIS IS ONLY 0.4 TO 2 ML OF THE 5 MG/10 ML AMPUL OR 0.2 TO 1 ML OF THE 10 MG/10 ML AMPUL OF DURAMORPH). DO NOT INJECT INTRATHECALLY MORE THAN 2 ML OF THE 5 MG/10 ML AMPUL OR 1 ML OF THE 10 MG/10 ML AMPUL. USE IN THE LUMBAR AREA ONLY IS RECOMMENDED. Repeated intrathecal injections of DURAMORPH are not recommended. A constant intravenous infusion of naloxone, 0.6 mg/hr, for 24 hours after intrathecal injection may be used to reduce the incidence of potential side effects.

Geriatric Use

Administer with extreme caution. (See PRECAUTIONS.)

Repeat Dosage

If pain recurs, alternative routes of administration should be considered, since experience with repeated doses of morphine by the intrathecal route is limited.

Intrathecal Pediatric Use

No information on use in pediatric patients is available. (See PRECAUTIONS.)
Ketorolac Tromethamine

Ketorolac Tromethamine

IN ADULTS, THE COMBINED DURATION OF USE OF KETOROLAC TROMETHAMINE INJECTION AND KETOROLAC TROMETHAMINE TABLETS IS NOT TO EXCEED FIVE (5) DAYS. IN ADULTS, THE USE OF KETOROLAC TROMETHAMINE TABLETS IS ONLY INDICATED AS CONTINUATION THERAPY TO KETOROLAC TROMETHAMINE INJECTION.

Ketorolac Tromethamine Injection

Adult Patients

Ketorolac Tromethamine Injection may be used as a single or multiple dose on a regular or “prn” schedule for the management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Hypovolemia should be corrected prior to the administration of ketorolac tromethamine (see WARNINGS, Renal Effects). Patients should be switched to alternative analgesics as soon as possible, but ketorolac tromethamine therapy is not to exceed five (5) days.

When administering Ketorolac Tromethamine Injection, the IV bolus must be given over no less than 15 seconds. The IM administration should be given slowly and deeply into the muscle. The analgesic effect begins in ~30 minutes with maximum effect in 1 to 2 hours after dosing IV or IM. Duration of analgesic effect is usually 4 to 6 hours.

Single-Dose Treatment: The Following Regimen Should Be Limited to Single Administration Use Only

Adult Patients

IM Dosing
Patients < 65 years of age: One dose of 60 mg. Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 30 mg.
IV Dosing
Patients < 65 years of age: One dose of 30 mg. Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 15 mg.
Pediatric Patients (2 to 16 Years of Age)

The pediatric population should receive only a single dose of Ketorolac Tromethamine Injection, as follows:

IM Dosing
One dose of 1 mg/kg up to a maximum of 30 mg.
IV Dosing
One dose of 0.5 mg/kg up to a maximum of 15 mg.
Multiple-Dose Treatment (IV or IM) in Adults

Patients < 65 Years of Age

The recommended dose is 30 mg Ketorolac Tromethamine Injection every 6 hours. The maximum daily dose should not exceed 120 mg.

For Patients ≥ 65 Years of Age, Renally Impaired Patients and Patients Less Than 50 Kg (110 lbs)

(see WARNINGS)

The recommended dose is 15 mg Ketorolac Tromethamine Injection every 6 hours. The maximum daily dose for these populations should not exceed 60 mg.

For breakthrough pain do not increase the dose or the frequency of ketorolac tromethamine. Consideration should be given to supplementing these regimens with low doses of opioids prn unless otherwise contraindicated.

Pharmaceutical Information for Ketorolac Tromethamine Injection

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Ketorolac Tromethamine Injection should not be mixed in a small volume (e.g., in a syringe) with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride; this will result in precipitation of ketorolac from solution.

Shortening the recommended dosing intervals may result in increased frequency and severity of adverse reactions.
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Direct Intravenous Single Injections (Bolus)

The initial dose of diltiazem hydrochloride injection should be 0.25 mg/kg actual body weight as a bolus administered over 2 minutes (20 mg is a reasonable dose for the average patient). If response is inadequate, a second dose may be administered after 15 minutes. The second bolus dose of diltiazem hydrochloride injection should be 0.35 mg/kg actual body weight administered over 2 minutes (25 mg is a reasonable dose for the average patient). Subsequent intravenous bolus doses should be individualized for each patient. Patients with low body weights should be dosed on a mg/kg basis. Some patients may respond to an initial dose of 0.15 mg/kg, although duration of action may be shorter. Experience with this dose is limited.

Continuous Intravenous Infusion

For continued reduction of the heart rate (up to 24 hours) in patients with atrial fibrillation or atrial flutter, an intravenous infusion of diltiazem hydrochloride injection may be administered. Immediately following bolus administration of 20 mg (0.25 mg/kg) or 25 mg (0.35 mg/kg) diltiazem hydrochloride injection and reduction of heart rate, begin an intravenous infusion of diltiazem hydrochloride. The recommended initial infusion rate of diltiazem hydrochloride is 10 mg/h. Some patients may maintain response to an initial rate of 5 mg/h. The infusion rate may be increased in 5 mg/h increments up to 15 mg/h as needed, if further reduction in heart rate is required. The infusion may be maintained for up to 24 hours.

Diltiazem shows dose-dependent, non-linear pharmacokinetics. Duration of infusion longer than 24 hours and infusion rates greater than 15 mg/h have not been studied. Therefore, infusion duration exceeding 24 hours and infusion rates exceeding 15 mg/h are not recommended.

Dilution

To prepare diltiazem hydrochloride injection for continuous intravenous infusion, aseptically transfer the appropriate quantity (see chart) of diltiazem hydrochloride injection to the desired volume of either Normal Saline, D5W, or D5W/0.45% NaCl. Mix thoroughly. Use within 24 hours. Keep refrigerated until use.
Diluent Volume Quantity of DiltiazemHCl Injection to Add FinalConcentration Administration Dose* Infusion Rate * 5 mg/h may be appropriate for some patients 100 mL 125 mg (25 mL)Final Volume 125 mL 1 mg/mL 10 mg/h15 mg/h 10 mL/h15 mL/h 250 mL 250 mg (50 mL)Final Volume 300 mL 0.83 mg/mL 10 mg/h15 mg/h 12 mL/h18 mL/h 500 mL 250 mg (50 mL)Final Volume 550 mL 0.45 mg/mL 10 mg/h15 mg/h 22 mL/h33 mL/h
Compatibility

Diltiazem hydrochloride injection was tested for compatibility with three commonly used intravenous fluids at a maximal concentration of 1 mg diltiazem hydrochloride per milliliter. Diltiazem hydrochloride injection was found to be physically compatible and chemically stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinylchloride (PVC) bags at controlled room temperature 15º-30°C (59°-86°F) or under refrigeration 2°-8°C (36°-46°F).
dextrose (5%) injection sodium chloride (0.9%) injection dextrose (5%) and sodium chloride (0.45%) injection
Physical Incompatibilities

Because of potential physical incompatibilities, it is recommended that diltiazem hydrochloride not be mixed with any other drugs in the same container. If possible, it is recommended that diltiazem hydrochloride not be co-infused in the same intravenous line.

Physical incompatibilities (precipitate formation or cloudiness) were observed when diltiazem hydrochloride injection was infused in the same intravenous line with the following drugs: acetazolamide, acyclovir, aminophylline, ampicillin, ampicillin sodium/sulbactam sodium, cefamandole, cefoperazone, diazepam, furosemide, hydrocortisone sodium succinate, insulin (regular: 100 units/mL), methylprednisolone sodium succinate, mezlocillin, nafcillin, phenytoin, rifampin, and sodium bicarbonate.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Transition to Further Antiarrhythmic Therapy

Transition to other antiarrhythmic agents following administration of diltiazem hydrochloride injection is generally safe. However, reference should be made to the respective agent manufacturer’s package insert for information relative to dosage and administration.

In controlled clinical trials, therapy with antiarrhythmic agents to maintain reduced heart rate in atrial fibrillation or atrial flutter or for prophylaxis of PSVT was generally started within 3 hours after bolus administration of diltiazem hydrochloride. These antiarrhythmic agents were intravenous or oral digoxin, Class 1 antiarrthythmics (e.g., quinidine, procainamide), calcium channel blockers, and oral beta-blockers.

Experience in the use of antiarrhythmic agents following maintenance infusion of diltiazem hydrochloride injection is limited. Patients should be dosed on an individual basis and reference should be made to the respective manufacturer’s package insert for information relative to dosage and administration.
Morphine Sulfate

Morphine Sulfate

Morphine Sulfate Injection should be given via the subcutaneous, intramuscular or slow intravenous routes. NOT FOR EPIDURAL OR INTRATHECAL USE.

In patients with severe, chronic pain, dosage should be adjusted according to the severity of the pain and the response and tolerance of the patient. In patients with exceptionally severe, chronic pain or in those who have become tolerant to the analgesic effect of opiate agonists, it may be necessary to exceed the usual dosage.

Reduced dosage is indicated in poor-risk patients, in very young or very old patients and in patients receiving other CNS depressants.

Morphine Sulfate Injection is usually administered subcutaneously; the drug may also be administered by intramuscular or slow intravenous injection. Intramuscular administration is preferred to subcutaneous injection when repeated parenteral doses are necessary, since repeated subcutaneous administration causes local tissue irritation, pain and induration.

Adults

The usual adult subcutaneous or intramuscular dosage of Morphine Sulfate Injection is 10 mg every 4 hours as necessary; dosage may range from 5-20 mg every 4 hours as necessary depending on patient requirements and response.

For intravenous administration, the usual dosage is 4-10 mg administered very slowly over 4-5 minutes. A strength of 2.5-15 mg of morphine sulfate may be diluted in 4-5 mL of sterile water for injection.

Infants and Children

Do not use in premature infants (see CONTRAINDICATIONS). Safety and effectiveness in newborn infants have not been established. Infants and children may receive a subcutaneous dose of 0.1-0.2 mg/kg as necessary; a single pediatric dose should not exceed 15 mg.

PAIN OF MYOCARDIAL INFARCTION-8-15 mg of Morphine Sulfate Injection may be administered parenterally. For very severe pain, additional smaller doses may be given every 3-4 hours.

ANALGESIA DURING LABOR-10 mg of morphine sulfate is usually administered subcutaneously or intramuscularly.

When morphine sulfate is administered intravenously, an opiate antagonist and facilities for administration of oxygen and control of respiration should be available.

Morphine sulfate has been reported to be physically or chemically incompatible with various drug products. Specialized references should be consulted for specific compatibility information.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Phenylephrine Hydrochlo...

Phenylephrine Hydrochloride

Phenylephrine Hydrochloride Injection is generally injected subcutaneously, intramuscularly, slowly intravenously or in dilute solution as a continuous intravenous infusion. In patients with paroxysmal supraventricular tachycardia and, if indicated, in case of emergency, Phenylephrine Hydrochloride Injection is administered directly intravenously. The dose should be adjusted according to the pressor response.
DOSAGE CALCULATIONS Dose Required Use Phenylephrin Hydrochloride Injection 1% 10 mg 1 mL 5 mg 0.5 mL 1 mg 0.1 mL

For convenience in intermittent intravenous administration, dilute 1 mL Phenylephrine Hydrochloride Injection 1% with 9 mL Sterile Water for Injection, USP, to yield 0.1% Phenylephrine Hydrochloride Injection.
Dose Required Use Diluted Phenylephrine Hydrochloride Injection (0.1%) 0.1 mg 0.1 mL 0.2 mg 0.2 mL 0.5 mg 0.5 mL
Mild or Moderate Hypotension

SUBCUTANEOUSLY OR INTRAMUSCULARLY: Usual dose, from 2 mg to 5 mg. Range, from 1 mg to 10 mg. Initial dose should not exceed 5 mg.

INTRAVENOUSLY: Usual dose, 0.2 mg. Range, from 0.1 mg to 0.5 mg. Initial dose should not exceed 0.5 mg.

Injections should not be repeated more often than every 10 to 15 minutes. A 5 mg intramuscular dose should raise blood pressure for one to two hours. A 0.5 mg intravenous dose should elevate the blood pressure for about 15 minutes.

Severe Hypotension and Shock - Including Drug-Related Hypotension

Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, phenylephrine can be administered before and concurrently with blood volume replacement.

Hypotension and occasionally severe shock may result from overdosage or idiosyncrasy following the administration of certain drugs, especially adrenergic and ganglionic blocking agents, rauwolfia and veratrum alkaloids and phenothiazines tranquilizers. Patients who receive a phenothiazine derivative as preoperative medication are especially susceptible to these reactions. As an adjunct in the management of such episodes, Phenylephrine Hydrochloride Injection is a suitable agent for restoring blood pressure.

Higher initial and maintenance doses of phenylephrine are required in patients with persistent or untreated severe hypotension or shock. Hypotension produced by powerful peripheral adrenergic blocking agents, chlorpromazine or pheochromocytomectomy may also require more intensive therapy.

Continuous Infusion:

Add 10 mg of the drug (1 mL of 1 percent solution) to 500 mL of Dextrose Injection, USP or Sodium Chloride Injection, USP (providing a 1:50,000 solution). To raise the blood pressure rapidly, start the infusion at about 100 mcg to 180 mcg per minute (based on 20 drops per mL this would be 100 to 180 drops per minute). When the blood pressure is stabilized (at a low normal level for the individual), a maintenance rate of 40 mcg to 60 mcg per minute usually suffices (based on 20 drops per mL this would be 40 to 60 drops per minute). If the drop size of the infusion system varies from the 20 drops per mL the dose must be adjusted accordingly.

If a prompt initial pressor response is not obtained, additional increments of phenylephrine (10 mg or more) are added to the infusion bottle. The rate of flow is then adjusted until the desired blood pressure level is obtained. (In some cases, a more potent vasopressor, such as norepinephrine bitartrate, may be required.) Hypertension should be avoided. The blood pressure should be checked frequently. Headache and/or bradycardia may indicate hypertension. Arrhythmias are rare.

Spinal Anesthesia-Hypotension

Routine parenteral use of phenylephrine has been recommended for the prophylaxis and treatment of hypotension during spinal anesthesia. It is best administered subcutaneously or intramuscularly three or four minutes before injection of the spinal anesthetic. The total requirement for high anesthetic levels is usually 3 mg, and for lower levels, 2 mg. For hypotensive emergencies during spinal anesthesia, phenylephrine may be injected intravenously, using an initial dose of 0.2 mg. Any subsequent dose should not exceed the previous dose by more than 0.1 mg to 0.2 mg and no more than 0.5 mg should be administered in a single dose.

To combat hypotension during spinal anesthesia in children, a dose of 0.5 mg to 1 mg per 25 pounds body weight, administered subcutaneously or intramuscularly, is recommended.

Prolongation of Spinal Anesthesia

The addition of 2 mg to 5 mg of phenylephrine hydrochloride to the anesthetic solution increases the duration of motor block by as much as approximately 50 percent without any increase in the incidence of complications such as nausea, vomiting or blood pressure disturbances.

Vasoconstrictor for Regional Analgesia

Concentrations about ten times those employed when epinephrine is used as a vasoconstrictor are recommended. The optimum strength is 1:20,000 (made by adding 1 mg of phenylephrine hydrochloride to every 20 mL of local anesthetic solution). Some pressor responses can be expected when 2 mg or more are injected.

Paroxysmal Supraventricular Tachycardia

Rapid intravenous injection (within 20 to 30 seconds) is recommended. The initial dose should not exceed 0.5 mg, and subsequent doses, which are determined by the initial blood pressure response, should not exceed the preceding dose by more than 0.1 mg to 0.2 mg and should never exceed 1 mg.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Adenosine

Adenosine

For rapid bolus intravenous use only.

Adenosine injection should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.

Adult Patients

The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of adenosine has not been systematically studied.

The recommended intravenous doses for adults are as follows:

Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1 to 2 second period).

Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.

Pediatric Patients

The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.

Pediatric Patients with a Body Weight < 50 kg:

Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.

Repeat administration: If conversion of PSVT does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.

Pediatric Patients with a Body Weight ≥ 50 kg:

Administer the adult dose.

Doses greater than 12 mg are not recommended for adult and pediatric patients.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Adenosine

Adenosine

For rapid bolus intravenous use only.

Adenosine injection should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.

Adult Patients

The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of adenosine has not been systematically studied.

The recommended intravenous doses for adults are as follows:

Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1 to 2 second period).

Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.

Pediatric Patients

The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.

Pediatric Patients with a Body Weight < 50 kg:

Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.

Repeat administration: If conversion of PSVT does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.

Pediatric Patients with a Body Weight ≥ 50 kg:

Administer the adult dose.

Doses greater than 12 mg are not recommended for adult and pediatric patients.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Fentanyl Citrate

Fentanyl Citrate

The 2 mL Fentanyl Citrate Injection vial includes a cautionary label that extends above the main label and highlights the drug name, fentanyl. The purpose of the extended label is to prevent selection error with other drugs, such as Sufentanil. Read the label and confirm you have selected the correct medication. Then locate the “Tear Here” point on the label, and remove this cautionary label prior to removing the flip-off cap.

Single Dose - Destroy unused contents.

50 mcg = 0.05 mg = 1 mL

Dosage should be individualized. Some of the factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used and the surgical procedure involved. Dosage should be reduced in elderly or debilitated patients (see PRECAUTIONS).

Vital signs should be monitored routinely.

I. Premedication

Premedication (to be appropriately modified in the elderly, debilitated and those who have received other depressant drugs)—50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly 30 to 60 minutes prior to surgery.

II. Adjunct to General Anesthesia

See Dosage Range Charts.

III. Adjunct to Regional Anesthesia

50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly or slowly intravenously, over one to two minutes, when additional analgesia is required.

IV. Postoperatively (recovery room)

50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly for the control of pain, tachypnea and emergence delirium. The dose may be repeated in one to two hours as needed.

Usage in Children

For induction and maintenance in children 2 to 12 years of age, a reduced dose as low as 2 to 3 mcg/kg is recommended.

Dosage Range Chart

Total Dosage (expressed as fentanyl base)

Low dose—2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). Fentanyl in small doses is most useful for minor, but painful, surgical procedures. In addition to the analgesia during surgery, fentanyl may also provide some pain relief in the immediate postoperative period.

Moderate dose—2 to 20 mcg/kg (0.002 to 0.02 mg/kg) (0.04 to 0.4 mL/kg). Where surgery becomes more major, a larger dose is required. With this dose, in addition to adequate analgesia, one would expect to see some abolition of the stress response. However, respiratory depression will be such that artificial ventilation during anesthesia is necessary, and careful observation of ventilation postoperatively is essential.

High dose—20 to 50 mcg/kg (0.02 to 0.05 mg/kg) (0.4 to 1 mL/kg). During open heart surgery and certain more complicated neurosurgical and orthopedic procedures where surgery is more prolonged, and in the opinion of the anesthesiologist, the stress response to surgery would be detrimental to the well being of the patient, dosages of 20 to 50 mcg/kg (0.02 to 0.05 mg/kg) (0.4 to 1 mL/kg) of fentanyl with nitrous oxide/oxygen have been shown to attenuate the stress response as defined by increased levels of circulating growth hormone, catecholamine, ADH and prolactin. When dosages in this range have been used during surgery, postoperative ventilation and observation are essential due to extended post-operative respiratory depression. The main objective of this technique would be to produce “stress free” anesthesia.

Dosage Range Chart

Maintenance Dose (expressed as fentanyl base)

Low dose—2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). Additional dosages of fentanyl are infrequently needed in these minor procedures.

Moderate dose—2 to 20 mcg/kg (0.002 to 0.02 mg/kg) (0.04 to 0.4 mL/kg). 25 to 100 mcg (0.025 to 0.1 mg) (0.5 to 2 mL) may be administered intravenously or intramuscularly when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.

High dose—20 to 50 mcg/kg (0.02 to 0.05 mg/kg) (0.4 to 1 mL/kg). Maintenance dosage (ranging from 25 mcg [0.025 mg] [0.5 mL] to one half the initial loading dose) will be dictated by the changes in vital signs which indicate stress and lightening of analgesia. However, the additional dosage selected must be individualized especially if the anticipated remaining operative time is short.

As a General Anesthetic

When attenuation of the responses to surgical stress is especially important, doses of 50 to 100 mcg/kg (0.05 to 0.1 mg/kg) (1 to 2 mL/kg) may be administered with oxygen and a muscle relaxant. This technique has been reported to provide anesthesia without the use of additional anesthetic agents. In certain cases, doses up to 150 mcg/kg (0.15 mg/kg) (3 mL/kg) may be necessary to produce this anesthetic effect. It has been used for open heart surgery and certain other major surgical procedures in patients for whom protection of the myocardium from excess oxygen demand is particularly indicated, and for certain complicated neurological and orthopedic procedures.

As noted above, it is essential that qualified personnel and adequate facilities be available for the management of respiratory depression.

See WARNINGS and PRECAUTIONS for use of fentanyl with other CNS depressants, and in patients with altered response.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Ceprotin

Ceprotin

2.1 General

Treatment with CEPROTIN should be initiated under the supervision of a physician experienced in replacement therapy with coagulation factors/inhibitors where monitoring of protein C activity is feasible.

CEPROTIN is administered by intravenous injection after reconstitution of the powder for solution for injection with Sterile Water for Injection. Allergic type hypersensitivity reactions are possible. See WARNINGS/PRECAUTIONS: Hypersensitivity/Allergic Reactions (5.1).

The dose, administration frequency and duration of treatment with CEPROTIN depends on the severity of the protein C deficiency, the patient’s age, the clinical condition of the patient and the patient’s plasma level of protein C. Therefore, the dose regimen should be adjusted according to the pharmacokinetic profile for each individual patient. See DOSAGE AND ADMINISTRATION: Protein C Activity Monitoring (2.2).

Table 1 provides the CEPROTIN dosing schedule for acute episodes, short-term prophylaxis and long-term prophylaxis.
Table 1: CEPROTIN Dosing Schedule for Acute Episodes, Short-term Prophylaxis and Long-term Prophylaxis* NA = Not applicable; Q = every. * Dosing is based upon a pivotal clinical trial of 15 patients. † The dose regimen should be adjusted according to the pharmacokinetic profile for each individual (2.1, 2.2) ‡ CEPROTIN should be continued until desired anticoagulation is achieved. Initial Dose† Subsequent 3Doses† MaintenanceDose† Acute Episode / Short-term Prophylaxis‡ 100-120 IU/kg 60 - 80 IU/kgQ 6 hours 45 - 60 IU/kgQ 6 or 12 hours Long-term Prophylaxis NA NA 45 - 60 IU/kgQ 12 hours
An initial dose of 100-120 IU/kg for determination of recovery and half-life is recommended for acute episodes and short-term prophylaxis. Subsequently, the dose should be adjusted to maintain a target peak protein C activity of 100 %. After resolution of the acute episode, continue the patient on the same dose to maintain trough protein C activity level above 25% for the duration of treatment.

In patients receiving prophylactic administration of CEPROTIN, higher peak protein C activity levels may be warranted in situations of an increased risk of thrombosis (such as infection, trauma, or surgical intervention). Maintenance of trough protein C activity levels above 25% is recommended.

These dosing guidelines are also recommended for neonatal and pediatric patients. See USE IN SPECIFIC POPULATIONS: Pediatric Use (8.4) and CLINICAL PHARMACOLOGY: Pharmacokinetics (12.3).

2.2 Protein C Activity Monitoring

The measurement of protein C activity using a chromogenic assay is recommended for the determination of the patient’s plasma level of protein C before and during treatment with CEPROTIN. The half-life of CEPROTIN may be shortened in certain clinical conditions such as acute thrombosis, purpura fulminans and skin necrosis. SeeCLINICAL PHARMACOLOGY: Pharmacokinetics (12.3). In the case of an acute thrombotic event, it is recommended that protein C activity measurements be performed immediately before the next injection until the patient is stabilized. After the patient is stabilized, continue monitoring the protein C levels to maintain the trough protein C level above 25%.

Patients treated during the acute phase of their disease may display much lower increases in protein C activity. Coagulation parameters should also be checked; however, in clinical trials data were insufficient to establish correlation between protein C activity levels and coagulation parameters.

2.3 Initiation of Vitamin K Antagonists

In patients starting treatment with oral anticoagulants belonging to the class of vitamin K antagonists, a transient hypercoagulable state may arise before the desired anticoagulant effect becomes apparent. This transient effect may be explained by the fact that protein C, itself a vitamin K-dependent plasma protein, has a shorter half-life than most of the vitamin K-dependent proteins (i.e. Factor II, IX and X).

In the initial phase of treatment, the activity of protein C is more rapidly suppressed than that of the procoagulant factors. For this reason, if the patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is obtained. Although warfarin-induced skin necrosis can occur in any patient during the initiation of treatment with oral anticoagulant therapy, individuals with severe congenital protein C deficiency are particularly at risk.

During the initiation of oral anticoagulant therapy, it is advisable to start with a low dose of the anticoagulant and adjust this incrementally, rather than use a standard loading dose of the anticoagulant.

2.4 Preparation of CEPROTIN [Protein C Concentrate (Human)]

Reconstitution: Use Aseptic Technique
Bring the CEPROTIN (powder) and Sterile Water for Injection, USP (diluent) to room temperature. Remove caps from the CEPROTIN and diluent vials. Cleanse stoppers with germicidal solution, and allow them to dry prior to use. Remove protective covering from one end of the double-ended transfer needle and insert exposed needle through the center of the diluent vial stopper. Remove protective covering from the other end of the double-ended transfer needle. Invert diluent vial over the upright CEPROTIN vial; then rapidly insert the free end of the needle through the CEPROTIN vial stopper at its center. The vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product, and contact Baxter Customer Service at 1-888-CEPROTIN (237-7684). Disconnect the two vials by removing the needle from the diluent vial stopper. Then, remove the transfer needle from the CEPROTIN vial. Gently swirl the vial until all powder is dissolved. Be sure that CEPROTIN is completely dissolved; otherwise, active materials will be removed by the filter needle.
2.5 Administration of CEPROTIN [Protein C Concentrate (Human)]

Administration: Use Aseptic Technique

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

After reconstitution, the solution is colorless to slightly yellowish and clear to slightly opalescent and essentially free from visible particles. Do not use the product if the solution does not meet these criteria. CEPROTIN should be administered at room temperature not more than 3 hours after reconstitution.
Attach the filter needle to a sterile, disposable syringe and draw back the plunger to admit air into the syringe. Insert the filter needle into the vial of reconstituted CEPROTIN. Inject air into the vial and then withdraw the reconstituted CEPROTIN into the syringe. Remove and discard the filter needle in a hard-walled Sharps container for proper disposal. Filter needles are intended to filter the contents of a single vial of CEPROTIN only. Attach a suitable needle or infusion set with winged adapter, and inject intravenously as instructed below under Administration by infusion.
Administration by Infusion

CEPROTIN should be administered at a maximum injection rate of 2 mL per minute except for children with a body weight of < 10 kg, where the injection rate should not exceed a rate of 0.2 mL/kg/minute.
Ceprotin

Ceprotin

2.1 General

For intravenous administration only.

Initiate treatment with CEPROTIN under the supervision of a physician experienced in replacement therapy with coagulation factors/inhibitors where monitoring of protein C activity is feasible.

The dose, administration frequency and duration of treatment with CEPROTIN depends on the severity of the protein C deficiency, the patient’s age, the clinical condition of the patient and the patient’s plasma level of protein C. Therefore, adjust the dose regimen according to the pharmacokinetic profile for each individual patient. [see DOSAGE AND ADMINISTRATION: Protein C Activity Monitoring (2.2)].

Table 1 provides the CEPROTIN dosing schedule for acute episodes, short-term prophylaxis and long-term prophylaxis.
Table 1 CEPROTIN Dosing Schedule for Acute Episodes, Short-term Prophylaxis and Long-term Prophylaxis* * Dosing is based upon a pivotal clinical trial of 15 patients. † The dose regimen should be adjusted according to the pharmacokinetic profile for each individual. (2.1, 2.2) ‡ CEPROTIN should be continued until desired anticoagulation is achieved. § NA = Not applicable; Q = every.
Initial Dose†

Subsequent 3 Doses†

Maintenance Dose†

Acute Episode / Short-term Prophylaxis‡

100-120 IU/kg

60 - 80 IU/kgQ 6 hours

45 - 60 IU/kgQ 6 or 12 hours

Long-term Prophylaxis

NA§

NA§

45 - 60 IU/kgQ 12 hours

An initial dose of 100-120 IU/kg for determination of recovery and half-life is recommended for acute episodes and short-term prophylaxis. Subsequently, adjust the dose to maintain a target peak protein C activity of 100 %. After resolution of the acute episode, continue the patient on the same dose to maintain trough protein C activity level above 25% for the duration of treatment.

In patients receiving prophylactic administration of CEPROTIN, higher peak protein C activity levels may be warranted in situations of an increased risk of thrombosis (such as infection, trauma, or surgical intervention). Maintenance of trough protein C activity levels above 25% is recommended.

These dosing guidelines are also recommended for neonatal and pediatric patients. [see USE IN SPECIFIC POPULATIONS: Pediatric Use (8.4) and CLINICAL PHARMACOLOGY: Pharmacokinetics (12.3)].

2.2 Protein C Activity Monitoring

The measurement of protein C activity using a chromogenic assay is recommended for the determination of the patient’s plasma level of protein C before and during treatment with CEPROTIN. The half-life of CEPROTIN may be shortened in certain clinical conditions such as acute thrombosis, purpura fulminans and skin necrosis. [see CLINICAL PHARMACOLOGY: Pharmacokinetics (12.3)]. In the case of an acute thrombotic event, it is recommended that protein C activity measurements be performed immediately before the next injection until the patient is stabilized. After the patient is stabilized, continue monitoring the protein C levels to maintain the trough protein C level above 25%.

Patients treated during the acute phase of their disease may display much lower increases in protein C activity. Coagulation parameters should also be checked; however, in clinical trials data were insufficient to establish correlation between protein C activity levels and coagulation parameters.

2.3 Initiation of Vitamin K Antagonists

In patients starting treatment with oral anticoagulants belonging to the class of vitamin K antagonists, a transient hypercoagulable state may arise before the desired anticoagulant effect becomes apparent. This transient effect may be explained by the fact that protein C, itself a vitamin K-dependent plasma protein, has a shorter half-life than most of the vitamin K-dependent proteins (i.e. Factor II, IX and X).

In the initial phase of treatment, the activity of protein C is more rapidly suppressed than that of the procoagulant factors. For this reason, if the patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is obtained. Although warfarin-induced skin necrosis can occur in any patient during the initiation of treatment with oral anticoagulant therapy, individuals with severe congenital protein C deficiency are particularly at risk.

During the initiation of oral anticoagulant therapy, it is advisable to start with a low dose of the anticoagulant and adjust this incrementally, rather than use a standard loading dose of the anticoagulant.

2.4 Preparation of CEPROTIN [Protein C Concentrate (Human)]

Reconstitution: Use Aseptic Technique
1. Bring the CEPROTIN (powder) and Sterile Water for Injection, USP (diluent) to room temperature. 2. Remove caps from the CEPROTIN and diluent vials. 3. Cleanse stoppers with germicidal solution, and allow them to dry prior to use. 4. Remove protective covering from one end of the double-ended transfer needle and insert exposed needle through the center of the diluent vial stopper. 5. Remove protective covering from the other end of the double-ended transfer needle. Invert diluent vial over the upright CEPROTIN vial; then rapidly insert the free end of the needle through the CEPROTIN vial stopper at its center. The vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product, and contact Baxter Customer Service at 1-888-CEPROTIN (237-7684). 6. Disconnect the two vials by removing the needle from the diluent vial stopper. Then, remove the transfer needle from the CEPROTIN vial. Gently swirl the vial until all powder is dissolved. Be sure that CEPROTIN is completely dissolved; otherwise, active materials will be removed by the filter needle.
2.5 Administration of CEPROTIN [Protein C Concentrate (Human)]

Administration: Use Aseptic Technique

Visually inspect CEPROTIN for particulate matter and discoloration prior to administration.

After reconstitution, the solution should be colorless to slightly yellowish and clear to slightly opalescent and free of visible particles. Do not use the solution if it does not meet this criteria. Administer CEPROTIN at room temperature not more than 3 hours after reconstitution.
1. Attach the filter needle to a sterile, disposable syringe and draw back the plunger to admit air into the syringe. 2. Insert the filter needle into the vial of reconstituted CEPROTIN. 3. Inject air into the vial and then withdraw the reconstituted CEPROTIN into the syringe. 4. Remove and discard the filter needle in a hard-walled Sharps container for proper disposal. Filter needles are intended to filter the contents of a single vial of CEPROTIN only. 5. Attach a suitable needle or infusion set with winged adapter, and inject intravenously as instructed below under Administration by infusion.
Record the name and batch number of the product every time CEPROTIN is administered to a patient.

Administration by Infusion

Administer CEPROTIN at a maximum injection rate of 2 mL per minute except for children with a body weight of < 10 kg, where the injection rate should not exceed a rate of 0.2 mL/kg/minute.
Aerrane

Aerrane

Caution: Operating rooms should be provided with adequate ventilation to prevent the accumulation of anesthetic vapors. Premedication: A premedication regimen, which may be employed depending upon the patient status, to avert excitement during induction, might include an anticholinergic, a tranquilizer, a muscle relaxant, and a short-acting barbiturate.Inspired Concentration: The delivered concentration of AERRANE (isoflurane, USP) should be known. Isoflurane may be vaporized using a flow-through vaporizer specifically calibrated for isoflurane. Vaporizers delivering a saturated vapor which then is diluted (e.g., Vernitrol® Vaporizer) also may be used. The delivered concentration from such a vaporizer may be calculated using the formula:

Isoflurane contains no stabilizer. Nothing in the drug product alters calibration or operation of these vaporizers.

Induction:

Horses: Inspired concentrations of 3.0 to 5.0% isoflurane alone with oxygen following a barbiturate anesthetic induction are usually employed to induce surgical anesthesiain the horse.

Dogs: Inspired concentrations of 2.0 to 2.5% isoflurane alone with oxygen following a barbiturate anesthetic induction are usually employed to induce surgical anesthesia in the dog.These concentrations can be expected to produce surgical anesthesia in 5 to 10 minutes.

Maintenance: The concentration of vapor necessary to maintain anesthesia is much less than that required to induce it.

Horses: Surgical levels of anesthesia in the horse may be sustained with a 1.5 to 1.8% concentration of isoflurane in oxygen.
Dogs: Surgical levels of anesthesia in the dog may be sustained with a 1.5 to 1.8% concentration of isoflurane in oxygen. The level of blood pressure during maintenance is an inverse function of isoflurane concentration in the absence of other complicating problems. Excessive decreases, unless related to hypovolemia, may be due to depth of anesthesia and in such instances may be corrected by lightening the level of anesthesia. Recovery from isoflurane anesthesia is typically uneventful. 2
Aralast Np

Aralast Np

Dose ranging studies using efficacy endpoints have not been performed.

Chronic Augmentation Therapy

FOR INTRAVENOUS USE ONLY. The recommended dosage of ARALAST NP is 60 mg/kg body weight administered once weekly by intravenous infusion. Each vial of ARALAST NP has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label. Administration of ARALAST NP within three hours after reconstitution is recommended to avoid the potential ill effect of any inadvertent microbial contamination occurring during reconstitution. Discard any unused contents.

Infusion Rate

ARALAST NP should be administered at a rate not exceeding 0.08 mL/kg body weight/minute. If adverse events occur, the rate should be reduced or the infusion interrupted until the symptoms subside. The infusion may then be resumed at a rate tolerated by the subject.
Ondansetron

Ondansetron

Prevention of Chemotherapy-Induced Nausea and Vomiting

Adult Dosing

The recommended IV dosage of ondansetron for adults is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. The recommended infusion rate should not be exceeded (see OVERDOSAGE). With the three-dose (0.15 mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron.

Ondansetron Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.

Vial

DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Pediatric Dosing

On the basis of the available information (see CLINICAL TRIALS, Pediatric Studies and CLINICAL PHARMACOLOGY, Pharmacokinetics), the dosage in pediatric cancer patients 6 months to 18 years of age should be three 0.15 mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy, subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron. The drug should be infused intravenously over 15 minutes. Little information is available about dosage in pediatric cancer patients younger than 6 months of age.

Vial

DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Geriatric Dosing

The dosage recommendation is the same as for the general population.

Prevention of Postoperative Nausea and Vomiting

Adult Dosing

The recommended IV dosage of ondansetron for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.

Vial

REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Pediatric Dosing

The recommended IV dosage of ondansetron for pediatric surgical patients (1 month to 12 years of age) is a single 0.1 mg/kg dose for patients weighing 40 kg or less, or a single 4 mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ondansetron.

Vial

REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Geriatric Dosing

The dosage recommendation is the same as for the general population.

Dosage Adjustment for Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first‑day administration of ondansetron.

Dosage Adjustment for Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child‑Pugh2 score of 10 or greater), a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron.

Stability

Ondansetron Injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following IV fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.

Although Ondansetron Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative. After dilution, do not use beyond 24 hours.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Precaution

Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.
Ondansetron

Ondansetron

Prevention of Chemotherapy-Induced Nausea and Vomiting

Adult Dosing

The recommended IV dosage of ondansetron for adults is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. The recommended infusion rate should not be exceeded (see OVERDOSAGE). With the three-dose (0.15 mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron.

Ondansetron Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.

Vial

DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Pediatric Dosing

On the basis of the available information (see CLINICAL TRIALS, Pediatric Studies and CLINICAL PHARMACOLOGY, Pharmacokinetics), the dosage in pediatric cancer patients 6 months to 18 years of age should be three 0.15 mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy, subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron. The drug should be infused intravenously over 15 minutes. Little information is available about dosage in pediatric cancer patients younger than 6 months of age.

Vial

DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Geriatric Dosing

The dosage recommendation is the same as for the general population.

Prevention of Postoperative Nausea and Vomiting

Adult Dosing

The recommended IV dosage of ondansetron for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.

Vial

REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Pediatric Dosing

The recommended IV dosage of ondansetron for pediatric surgical patients (1 month to 12 years of age) is a single 0.1 mg/kg dose for patients weighing 40 kg or less, or a single 4 mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ondansetron.

Vial

REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Geriatric Dosing

The dosage recommendation is the same as for the general population.

Dosage Adjustment for Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

Dosage Adjustment for Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh2 score of 10 or greater), a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron.

Stability

Ondansetron Injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following IV fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.

Although Ondansetron Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative. After dilution, do not use beyond 24 hours.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Precaution

Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.
Dopram

Dopram

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS)

In Postanesthetic Use
Table I. * Dose not to exceed 3 grams/24 hours. Dosage for postanesthetic use—I.V. and infusion. I.V. Administration Recommended Dosagemg/kg Maximum dose per single injectionmg/kg Maximum total dose* mg/kg Single Injection 0.5-1 1.5 1.5 Repeat Injections (5 min. intervals) 0.5-1 1.5 2 Infusion 0.5-1 – 4
By I.V. Injection

(See Table I. Dosage for postanesthetic use—I.V.)

The recommended dose for I.V. administration is 0.5 – 1 mg/kg for a single injection and at 5-minute intervals. Careful observation of the patient during administration and for some time subsequently are advisable. The maximum total dosage by I.V. injection is 2 mg/kg.

By Infusion

The solution is prepared by adding 250 mg of doxapram (12.5 mL) to 250 mL of dextrose 5% or 10% in water or normal saline solution. The infusion is initiated at a rate of approximately 5 mg/minute until a satisfactory respiratory response is observed, and maintained at a rate of 1 to 3 mg/minute. The rate of infusion should be adjusted to sustain the desired level of respiratory stimulation with a minimum of side effects. The maximum total dosage by infusion is 4 mg/kg, or approximately 300 mg for the average adult.

In the Management of Drug-Induced CNS Depression

(See Table II. Dosage for drug-induced CNS depression.)
Table II. * Mild Depression Class 0: Asleep, but can be aroused and can answer questions. Class 1: Comatose, will withdraw from painful stimuli, reflexes intact. † Moderate Depression Class 2: Comatose, will not withdraw from painful stimuli, reflexes intact. Class 3: Comatose, reflexes absent, no depression of circulation or respiration. Dosage for drug-induced CNS depression. METHOD ONE Priming dose single/repeat I.V. Injection METHOD TWO Rate of Intermittent I.V. Infusion Level of Depression mg/kg mg/kg/hr Mild* 1 1-2 Moderate† 2 2-3
Method One

Using Single and/or Repeat Single I.V. Injections
Give priming dose of 2 mg/kg body weight and repeat in 5 minutes. The priming dose for moderate depression is 2 mg/kg and the priming dose for mild depression is 1 mg/kg. Repeat same dose q 1 to 2h until patient wakens. Watch for relapse into unconsciousness or development of respiratory depression, since DOPRAM does not affect the metabolism of CNS-depressant drugs. If relapse occurs, resume injections q 1 to 2h until arousal is sustained, or total maximum daily dose (3 grams) is given. After maximum dose has been given (3 grams), allow patient to sleep until 24 hours have elapsed from first injection of DOPRAM, using assisted or automatic respiration if necessary. Repeat procedure the following day until patient breathes spontaneously and sustains desired level of consciousness, or until maximum dosage (3 grams) is given. Repetitive doses should be administered only to patients who have shown response to the initial dose. Failure to respond appropriately indicates the need for neurologic evaluation for a possible central nervous system source of sustained coma.
Method Two

By Intermittent I.V. Infusion
Give priming dose as in Method One. If patient wakens, watch for relapse; if no response, continue general supportive treatment for 1 to 2 hours and repeat priming dose of DOPRAM. If some respiratory stimulation occurs, prepare I.V. infusion by adding 250 mg of DOPRAM (12.5 mL) to 250 mL of saline or dextrose solution. Deliver at rate of 1 to 3 mg/min (60 to 180 mL/hr) according to size of patient and depth of coma. Discontinue DOPRAM if patient begins to waken or at end of 2 hours. Continue supportive treatment for ½ to 2 hours and repeat Step b. Do not exceed 3 grams/day.
Chronic Obstructive Pulmonary Disease Associated with Acute Hypercapnia
One vial of doxapram (400 mg) should be mixed with 180 mL of dextrose 5% or 10% or normal saline solution (concentration of 2 mg/mL). The infusion should be started at 1 to 2 mg/minute (½ to 1 mL/minute); if indicated, increase to a maximum of 3 mg/minute. Arterial blood gases should be determined prior to the onset of doxapram’s administration and at least every half hour during the two hours of infusion to insure against the insidious development of CO2-RETENTION AND ACIDOSIS. Alteration of oxygen concentration or flow rate may necessitate adjustment in the rate of doxapram infusion. Predictable blood gas patterns are more readily established with a continuous infusion of doxapram. If the blood gases show evidence of deterioration, the infusion of doxapram should be discontinued. ADDITIONAL INFUSIONS BEYOND THE SINGLE MAXIMUM TWO HOUR ADMINISTRATION PERIOD ARE NOT RECOMMENDED.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Diluent Compatibility

Doxapram hydrochloride is compatible with 5% and 10% dextrose in water or normal saline.

Incompatibility

ADMIXTURE OF DOXAPRAM WITH ALKALINE SOLUTIONS SUCH AS 2.5% THIOPENTAL SODIUM, SODIUM BICARBONATE, FUROSEMIDE, OR AMINOPHYLLINE WILL RESULT IN PRECIPITATION OR GAS FORMATION.

Doxapram is also not compatible with ascorbic acid, cefoperazone sodium, cefotaxime sodium, cefotetan sodium, cefuroxime sodium, folic acid, dexamethasone disodium phosphate, diazepam, hydrocortisone sodium phosphate, methylprednisolone sodium, or hydrocortisone sodium succinate.

Admixture of doxapram and ticarcillin disodium results in an 18% loss of doxapram in 3 hours. When doxapram is mixed with minocycline hydrochloride, there is a loss of 8% of doxapram in 3 hours and a 13% loss of doxapram in 6 hours.
Reglan

Reglan

For the Relief of Symptoms Associated with Diabetic Gastroparesis (Diabetic Gastric Stasis)

If only the earliest manifestations of diabetic gastric stasis are present, oral administration of metoclopramide may be initiated. However, if severe symptoms are present, therapy should begin with REGLAN Injection (IM or IV). Doses of 10 mg may be administered slowly by the intravenous route over a 1- to 2-minute period.

Administration of REGLAN Injection (metoclopramide injection, USP) up to 10 days may be required before symptoms subside, at which time oral administration of metoclopramide may be instituted. The physician should make a thorough assessment of the risks and benefits prior to prescribing further metoclopramide treatment.

For the Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy

Intravenous infusions should be made slowly over a period of not less than 15 minutes, 30 minutes before beginning cancer chemotherapy and repeated every 2 hours for two doses, then every 3 hours for three doses.

The initial two doses should be 2 mg/kg if highly emetogenic drugs such as cisplatin or dacarbazine are used alone or in combination. For less emetogenic regimens, 1 mg/kg per dose may be adequate.

For doses in excess of 10 mg, REGLAN Injection should be diluted in 50 mL of a parenteral solution.

The preferred parenteral solution is Sodium Chloride Injection (normal saline), which when combined with REGLAN Injection, can be stored frozen for up to 4 weeks. REGLAN Injection is degraded when admixed and frozen with Dextrose-5% in Water. REGLAN Injection diluted in Sodium Chloride Injection, Dextrose-5% in Water, Dextrose-5% in 0.45% Sodium Chloride, Ringer’s Injection, or Lactated Ringer’s Injection may be stored up to 48 hours (without freezing) after preparation if protected from light. All dilutions may be stored unprotected from light under normal light conditions up to 24 hours after preparation.

If acute dystonic reactions should occur, inject 50 mg Benadryl® (diphenhydramine hydrochloride) intramuscularly, and the symptoms usually will subside.

For the Prevention of Postoperative Nausea and Vomiting

REGLAN Injection should be given intramuscularly near the end of surgery. The usual adult dose is 10 mg; however, doses of 20 mg may be used.

To Facilitate Small Bowel Intubation

If the tube has not passed the pylorus with conventional maneuvers in 10 minutes, a single dose (undiluted) may be administered slowly by the intravenous route over a 1- to 2-minute period.

The recommended single dose is: Pediatric patients above 14 years of age and adults — 10 mg metoclopramide base. Pediatric patients (6-14 years of age) — 2.5 to 5 mg metoclopramide base; (under 6 years of age) — 0.1 mg/kg metoclopramide base.

To Aid in Radiological Examinations

In patients where delayed gastric emptying interferes with radiological examination of the stomach and/or small intestine, a single dose may be administered slowly by the intravenous route over a 1- to 2-minute period.

For dosage, see intubation above.

Use in Patients With Renal or Hepatic Impairment

Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40 mL/min, therapy should be initiated at approximately one-half the recommended dosage. Depending upon clinical efficacy and safety considerations, the dosage may be increased or decreased as appropriate.

See OVERDOSAGE section for information regarding dialysis.

Metoclopramide undergoes minimal hepatic metabolism, except for simple conjugation. Its safe use has been described in patients with advanced liver disease whose renal function was normal.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Heparin Sodium In Dextr...

Heparin Sodium In Dextrose

Heparin Sodium in 5% Dextrose Injection is for intravenous administration only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

The dosage of heparin sodium should be adjusted according to the patient’s coagulation test results. When heparin is given by continuous intravenous infusion, the coagulation time should be determined approximately every 4 hours in the early stages of treatment. When the drug is administered intermittently by intravenous injection, coagulation tests should be performed before each injection, during the early stages of treatment, and at appropriate intervals thereafter. Dosage is considered adequate when the activated partial thromboplastin time (APTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. Physicians should refer to medical literature.

Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy, regardless of the route of administration.

Converting to Oral Anticoagulant

When an oral anticoagulant of the coumarin or similar type is to be begun in patients already receiving heparin sodium, baseline and subsequent tests of prothrombin activity must be determined at a time when heparin activity is too low to affect the prothrombin time. This is about 5 hours after the last I.V. bolus and 24 hours after the last subcutaneous dose. If continuous I.V. heparin infusion is used, prothrombin time can usually be measured at any time.

In converting from heparin to oral anticoagulant, the dose of the oral anticoagulant should be the usual initial amount and thereafter prothrombin time should be determined at the usual intervals. To ensure continuous anticoagulation, it is advisable to continue full heparin therapy for several days after the prothrombin time has reached the therapeutic range. Heparin therapy may then be discontinued without tapering.

Therapeutic Anticoagulant Effect with Full-Dose Heparin

Although dosage must be adjusted for the individual patient according to the results of suitable laboratory tests, the following dosage may be used as a guideline for continuous intravenous infusion (based on 150 lb [68 kg] patient):
Initial Dose: 5,000 units by I.V. Injection Continuous Dose: 20,000 - 40,000 units/24 hours
Pediatric Use

Follow recommendations of appropriate pediatric reference texts. In general, the following dosage schedule may be used as a guideline:
Initial Dose: 50 units/kg (I.V., drip) Maintenance Dose: 100 units/kg (I.V., drip) every four hours, or 20,000 units/M2/24 hours continuously
Geriatric Use

Patients over 60 years of age may require lower doses of heparin.

Surgery of the Heart and Blood Vessels

Patients undergoing total body perfusion for open-heart surgery should receive an initial dose of not less than 150 units of heparin sodium per kilogram of body weight. Frequently, a dose of 300 units per kilogram is used for procedures estimated to last less than 60 minutes or 400 units per kilogram for those estimated to last longer than 60 minutes.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

Because dosages of this drug are titrated to response, no additives should be made to Heparin Sodium in 5% Dextrose Injection.
Artiss Frozen

Artiss Frozen

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of ARTISS depends on the size of the surface to be covered. The approximate surface areas covered by each package size of ARTISS are:
Table 1. Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL
It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of ARTISS Kit (Freeze-Dried)

During preparation of ARTISS Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials:
-Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution
Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:
Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit. Excessive stirring (20 minutes or more) may compromise product quality. If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.
Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen)

During preparation of ARTISS (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT MICROWAVEDO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING

Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Approximate thawing times when using this method are:
Pack Size Room Temperature(In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes
Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes
Quick Thawing

Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Sterile Water Bath(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Non-Sterile Water Bath(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant. The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application. The wound bed will glisten in the area to which fibrin sealant has been applied. Any areas not covered by fibrin sealant will be clearly visible. The skin graft should be attached to the wound bed immediately after ARTISS has been sprayed. The surgeon has approximately 60 seconds to manipulate and position the graft prior to polymerization. To prevent adherence, wet gloves with normal saline before product contact.

After the graft has been applied, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.2)). Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions.
Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System. Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece.
If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A

Vials and pre-filled syringes are for single use only. Discard unused contents.
Glycopyrrolate

Glycopyrrolate

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS)

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Glycopyrrolate Injection may be administered intramuscularly, or intravenously, without dilution, in the following indications.

Adults

Preanesthetic Medication

The recommended dose of Glycopyrrolate Injection is 0.004 mg/kg by intramuscular injection, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.

Intraoperative Medication

Glycopyrrolate Injection may be used during surgery to counteract drug-induced or vagal reflexes and their associated arrhythmias (e.g., bradycardia). It should be administered intravenously as single doses of 0.1 mg and repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.

Reversal of Neuromuscular Blockade

The recommended dose of Glycopyrrolate Injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe.

Peptic Ulcer

The usual recommended dose of Glycopyrrolate Injection is 0.1 mg administered at 4-hour intervals, 3 or 4 times daily intravenously or intramuscularly. Where more profound effect is required, 0.2 mg may be given. Some patients may need only a single dose, and frequency of administration should be dictated by patient response up to a maximum of four times daily.

Glycopyrrolate Injection is not recommended for the treatment of peptic ulcer in pediatric patients (see PRECAUTIONS – Pediatric Use).

Pediatric Patients (see PRECAUTIONS - Pediatric Use)

Preanesthetic Medication

The recommended dose of Glycopyrrolate Injection in pediatric patients is 0.004 mg/kg intramuscularly, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.

Infants

(1 month to 2 years of age) may require up to 0.009 mg/kg.

Intraoperative Medication

Because of the long duration of action of Glycopyrrolate Injection if used as preanesthetic medication, additional Glycopyrrolate Injection for anticholinergic effect intraoperatively is rarely needed; in the event it is required the recommended pediatric dose is 0.004 mg/kg intravenously, not to exceed 0.1 mg in a single dose which may be repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.

Reversal of Neuromuscular Blockade

The recommended pediatric dose of Glycopyrrolate Injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe.

Peptic Ulcer

Glycopyrrolate Injection is not recommended for the treatment of peptic ulcer in pediatric patients (see PRECAUTIONS – Pediatric Use).

Diluent Compatibilities

Dextrose 5% and 10% in water, or saline, dextrose 5% in sodium chloride 0.45%, sodium chloride 0.9%, and Ringer’s Injection.

Diluent Incompatibilities

Lactated Ringer’s solution

Admixture Compatibilities

Physical Compatibility

This list does not constitute an endorsement of the clinical utility or safety of co-administration of glycopyrrolate with these drugs. Glycopyrrolate Injection is compatible for mixing and injection with the following injectable dosage forms: atropine sulfate, USP; Antilirium® (physostigmine salicylate); Benadryl® (diphenhydramine HCl); codeine phosphate, USP; Emete-Con® (benz-quinamide HCl); hydromorphone HCl, USP; Inapsine® (droperidol); Levo-Dromoran® (levorphanol tartrate); lidocaine, USP; meperidine HCl, USP; Mestinon® /Regonol® (pyridostigmine bromide); morphine sulfate, USP; Nubain® (nalbuphine HCl); Numorphan® (oxymorphone HCl); procaine HCl, USP; promethazine HCl, USP; Prostigmin® (neostigmine methylsulfate, USP); scopolamine HBr, USP; Stadol® (butorphanol tartrate); Sublimaze® (fentanyl citrate); Tigan® (trimethobenzamide HCl); and Vistaril® (hydroxyzine HCl). Glycopyrrolate Injection may be administered via the tubing of a running infusion of normal saline.

Admixture Incompatibilities

Physical Incompatibility

Since the stability of glycopyrrolate is questionable above a pH of 6.0 do not combine Glycopyrrolate Injection in the same syringe with Brevital® (methohexital Na); Chloromycetin® (chloramphenicol Na succinate); Dramamine® (dimenhydrinate); Nembutal® (pentobarbital Na); Pentothal® (thiopental Na); Seconal® (secobarbital Na); sodium bicarbonate (Abbott); Valium® (diazepam); Decadron® (dexamethasone Na phosphate); or Talwin® (pentazocine lactate). These mixtures will result in a pH higher than 6.0 and may result in gas production or precipitation.
Prochlorperazine Edisyl...

Prochlorperazine Edisylate

NOTE ON INJECTION: For intramuscular administration, inject deeply into the upper, outer quadrant of the buttock.

Subcutaneous administration is not advisable because of local irritation.

Stability

This solution should be protected from light. Slight yellowish discoloration will not alter potency. If markedly discolored, solution should be discarded.

Compatibility

It is recommended that Prochlorperazine Edisylate Injection not be mixed with other agents in the syringe.

Adults

(For children’s dosage and administration, see below.) Dosage should be increased more gradually in debilitated or emaciated patients.

Elderly Patients

In general, dosages in the lower range are sufficient for most elderly patients. Since they appear to be more susceptible to hypotension and neuromuscular reactions, such patients should be observed closely. Dosage should be tailored to the individual, response carefully monitored, and dosage adjusted accordingly. Dosage should be increased more gradually in elderly patients.

To Control Severe Nausea and Vomiting

Adjust dosage to the response of the individual. Begin with lowest recommended dosage.

IM Dosage

Initially 5 mg to 10 mg (1 to 2 mL) injected deeply into the upper, outer quadrant of the buttock. If necessary, repeat every 3 or 4 hours. Total IM dosage should not exceed 40 mg per day.

IV Dosage

2.5 mg to 10 mg (0.5 to 2 mL) by slow IV injection or infusion at a rate not to exceed 5 mg per minute. Prochlorperazine Edisylate Injection may be administered either undiluted or diluted in isotonic solution. A single dose of the drug should not exceed 10 mg; total IV dosage should not exceed 40 mg per day. When administered IV, do not use bolus injection. Hypotension is a possibility if the drug is given by IV injection or infusion.

Subcutaneous administration is not advisable because of local irritation.

Adult Surgery (for severe nausea and vomiting)

Total parenteral dosage should not exceed 40 mg per day. Hypotension is a possibility if the drug is given by IV injection or infusion.

IM Dosage

5 mg to 10 mg (1 to 2 mL) 1 to 2 hours before induction of anesthesia (repeat once in 30 minutes, if necessary), or to control acute symptoms during and after surgery (repeat once if necessary).

IV Dosage

5 mg to 10 mg (1 to 2 mL) as a slow IV injection or infusion 15 to 30 minutes before induction of anesthesia, or to control acute symptoms during or after surgery. Repeat once if necessary. Prochlorperazine may be administered either undiluted or diluted in isotonic solution, but a single dose of the drug should not exceed 10 mg. The rate of administration should not exceed 5 mg per minute. When administered IV, do not use bolus injection.

In Adult Psychiatric Disorders

Adjust dosage to the response of the individual and according to the severity of the condition. Begin with the lowest recommended dose. Although response ordinarily is seen within a day or two, longer treatment is usually required before maximal improvement is seen.

IM Dosage

For immediate control of adult schizophrenic patients with severe symptomatology, inject an initial dose of 10 mg to 20 mg (2 to 4 mL) deeply into the upper, outer quadrant of the buttock. Many patients respond shortly after the first injection. If necessary, however, repeat the initial dose every 2 to 4 hours (or, in resistant cases, every hour) to gain control of the patient. More than 3 or 4 doses are seldom necessary. After control is achieved, switch patient to an oral form of the drug at the same dosage level or higher. If, in rare cases, parenteral therapy is needed for a prolonged period, give 10 mg to 20 mg (2 to 4 mL) every 4 to 6 hours. Pain and irritation at the site of injection have seldom occurred.

Subcutaneous administration is not advisable because of local irritation.

Children

DO NOT USE IN PEDIATRIC SURGERY

Children seem more prone to develop extrapyramidal reactions, even on moderate doses. Therefore, use lowest effective dosage. Tell parents not to exceed prescribed dosage, since the possibility of adverse reactions increases as dosage rises.

Occasionally the patient may react to the drug with signs of restlessness and excitement; if this occurs, do not administer additional doses. Take particular precaution in administering the drug to children with acute illnesses or dehydration (see under PRECAUTIONS and Dystonia).

Severe Nausea and Vomiting in Children

Prochlorperazine should not be used in pediatric patients under 20 pounds in weight or two years of age. It should not be used in conditions for which children’s dosages have not been established. Dosage and frequency of administration should be adjusted according to the severity of the symptoms and the response of the patient. The duration of activity following intramuscular administration may last up to 12 hours. Subsequent doses may be given by the same route if necessary.

IM Dosage

Calculate each dose on the basis of 0.06 mg of the drug per lb of body weight; give by deep IM injection. Control is usually obtained with one dose.

Children with Schizophrenia

IM Dosage

For ages under 12, calculate each dose on the basis of 0.06 mg of prochlorperazine per lb of body weight; give by deep IM injection. Control is usually obtained with one dose. After control is achieved, switch the patient to an oral form of the drug at the same dosage level or higher.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Artiss

Artiss

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of ARTISS depends on the size of the surface to be covered. The approximate surface areas covered by each package size of ARTISS are:
Table 1. Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL
It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of ARTISS Kit (Freeze-Dried)

During preparation of ARTISS Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials:
-Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution
Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:
Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit. Excessive stirring (20 minutes or more) may compromise product quality. If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.
Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen)

During preparation of ARTISS (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT MICROWAVEDO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING

Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Approximate thawing times when using this method are:
Pack Size Room Temperature(In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes
Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes
Quick Thawing

Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Sterile Water Bath(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Non-Sterile Water Bath(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant. The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application. The wound bed will glisten in the area to which fibrin sealant has been applied. Any areas not covered by fibrin sealant will be clearly visible. The skin graft should be attached to the wound bed immediately after ARTISS has been sprayed. The surgeon has approximately 60 seconds to manipulate and position the graft prior to polymerization. To prevent adherence, wet gloves with normal saline before product contact.

After the graft has been applied, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.2)). Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions.
Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System. Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece.
If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A

Vials and pre-filled syringes are for single use only. Discard unused contents.
Clinimix E

Clinimix E

If a patient is unable to take oral nourishment for a prolonged period of time, institution of total parenteral nutrition should be considered.

The total daily dose of CLINIMIX E sulfite-free (Amino Acid with Electrolytes in Dextrose with Calcium) Injections depends on the patient’s metabolic requirement and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements.

Recommended Dietary Allowances1 of protein range from approximately 0.75 g/kg of body weight for adults to 1.68 g/kg for infants up to three months of age. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially. Daily amino acid doses of approximately 1.0 to 1.5 g/kg of body weight for adults with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance.

For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrates will be necessary to promote adequate patient response to therapy. The severity of the illness being treated is the primary consideration in determining proper dose level. Such higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation.

Care should be exercised to insure the maintenance of proper levels of serum potassium. Quantities of 60 to 180 mEq of potassium per day have been used with adequate clinical effect. It may be necessary to add quantities of this electrolyte to these admixed injections, depending primarily on the amount of carbohydrate administered to and metabolized by the patient.

Total daily fluid requirements can be met beyond the volume of amino acids solution by supplementing with noncarbohydrate or carbohydrate-containing electrolyte solutions.

Maintenance vitamins, additional electrolytes, and trace elements should be administered as required.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria.

Fat emulsion administration should be considered when prolonged (more than 5 days) parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat-free TPN.

Intravenous fat emulsions provide approximately 1.1 kcal per mL (10%), 2.0 kcal per mL (20%), or 3.0 kcal per mL (30%) and may be admixed along with amino acid with electrolytes/dextrose with calcium injections in the CLARITY Container to supplement caloric intake.

Depending upon the clinical condition of the patient, approximately 3 liters of solution may be administered per 24 hour period. When used postoperatively, the therapy should begin with 1000 mL on the first postoperative day. Thereafter, the dose may be increased to 3000 mL per day.

Do not administer unless seal between chambers is opened, other seals are intact, and solution is clear and thoroughly mixed.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

A slight yellow color does not alter the quality and efficacy of this product.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced.

Do not store solutions containing additives. These amino acid with electrolytes/dextrose with calcium injections should be used promptly after mixing. Any storage with additives should be under refrigeration and limited to a brief period of time, less than 24 hours.
1
Food and Nutrition Board National Academy of Sciences - National Research Council (Revised 1989).

Pediatric Use:

Use of CLINIMIX E sulfite-free (Amino Acid with Electrolytes in Dextrose with Calcium) Injections in pediatric patients is governed by the same considerations that affect the use of any amino acid solution in pediatrics. The amount administered is dosed on the basis of grams of amino acids/kg of body weight/day. Two to 3 g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Solution administrations by peripheral vein should not exceed twice normal serum osmolarity (718 mOsmol/L).

Central Vein Administration:

Hypertonic mixtures of amino acid with electrolytes/dextrose with calcium injections may be administered safely by continuous infusion through a central vein catheter with the tip located in the vena cava. In addition to meeting nitrogen needs, the administration rate is governed, especially during the first few days of therapy, by the patient’s tolerance to dextrose, as indicated by frequent determinations of urine and blood sugar levels. Daily intake of amino acid with electrolytes/dextrose with calcium injections should be increased gradually to the maximum required dose.

Sudden cessation in administration of these admixed injections may result in insulin reaction due to continued endogenous insulin production. Parenteral nutrition mixtures should be withdrawn slowly.

Peripheral Vein Administration:

For patients requiring parenteral nutrition in whom the central vein route is not indicated, low concentration amino acid with electrolytes/dextrose with calcium injections may be administered by peripheral vein. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).
Intralipid

Intralipid

Intralipid® 30% (A 30% I.V. Fat Emulsion) Pharmacy Bulk Package should be administered only as a part of a three-in-one or total nutrient admixture via peripheral vein or by central venous infusion.

Directions For Proper Use of Pharmacy Bulk Package

INTRALIPID® 30% (A 30% I.V. Fat Emulsion) PHARMACY BULK PACKAGE IS NOT INTENDED FOR DIRECT INFUSION. The container closure may be penetrated only once using a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). Once the closure is penetrated, the contents should be dispensed as soon as possible; the transfer of contents to suitable TPN admixture containers must be completed within 4 hours of closure penetration. The bag should be stored below 25°C (77°F) after the closure has been entered. Date and time of container entry should be noted in the area designated on the container label.

Admixtures made using Intralipid 30% should be used promptly. See MIXING GUIDELINES AND LIMITATIONS section for admixture storage recommendations.

Adult Patients

The initial infusion rate of the nutrient admixture in adults should be the equivalent of 0.1 g fat/minute for the first 15 to 30 minutes of infusion. If no untoward reactions occur (see ADVERSE REACTIONS section), the infusion rate of the nutrient admixture can be increased to be equivalent to 0.2 g fat/minute. For adults, the admixture should not contain more than 330 mL of Intralipid® 30% on the first day of therapy. If the patient has no untoward reactions, the dose can be increased on the following day. The daily dosage should not exceed 2.5 g of fat/kg of body weight (8.3 mL of Intralipid® 30% per kg). Intralipid® should make up no more than 60% of the total caloric input to the patient. Carbohydrate and a source of amino acids should comprise the remaining caloric input.

Pediatric Patients

The dosage for premature infants starts at 0.5 g fat/kg body weight/24 hours (1.7 mL) Intralipid® 30% and may be increased in relation to the infant’s ability to eliminate fat. The maximum dosage recommended by the American Academy of Pediatrics is 3 g fat/kg/24 hours3.

The initial rate of infusion of the nutrient admixture in older pediatric patients should be no more than 0.01 g fat/minute for the first 10 to 15 minutes. If no untoward reactions occur, the rate can be changed to permit infusion of 0.1 g of fat/kg/hour. The daily dosage should not exceed 3 g of fat/kg of body weight3. Intralipid® should make up no more than 60% of the total caloric input to the patient. Carbohydrate and a source of amino acids should comprise the remaining caloric input.

Essential Fatty Acid Deficiency

When Intralipid® is administered to correct essential fatty acid deficiency, eight to ten percent of the caloric input should be supplied by Intralipid® in order to provide adequate amounts of linoleic and linolenic acids. When EFAD occurs together with stress, the amount of Intralipid® needed to correct the deficiency may be increased.

Administration

See MIXING GUIDELINES AND LIMITATIONS section for information regarding mixing this fat emulsion with other parenteral fluids.

INTRALIPID® 30% (A 30% I.V. Fat Emulsion) is not for direct infusion. It must be infused as part of an admixture into a central or peripheral vein.

The flow rate of the admixture should be controlled with an infusion pump. Filters of less than 1.2 micron pore size must not be used with admixtures containing Intralipid® 30%. Conventional administration sets and TPN pooling bags contain polyvinyl chloride (PVC) components that have DEHP (diethyl hexyl phthalate) as a plasticizer. Fat-containing fluids such as Intralipid® extract DEHP from these PVC components. Therefore it may be advisable to use a non-DEHP administration set for infusing admixtures which contain Intralipid®.

Do not use any bag in which there appears to be an oiling out on the surface of the emulsion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

MIXING GUIDELINES AND LIMITATIONS

INTRALIPID® 30% PHARMACY BULK PACKAGE IS NOT INTENDED FOR DIRECT INFUSION. It must be combined with total parenteral nutrition (TPN) fluids so that the resulting admixture has a final concentration of not more than 20% fat (0.2 g fat per mL of admixture). The following table may be used as a guide:
Volume of Intralipid® 30% Required Minimum Volume of Dextrose/ Amino Acid Solutions Final Volume of Admixture Final fat Concentration 1 mL + 0.5 mL = 1.5 mL 20% 100 mL + 50 mL = 150 mL 20% 250 mL + 125 mL = 375 mL 20% 500 mL + 250 mL = 750 mL 20%
Investigations have been conducted which demonstrate the compatibility of Intralipid® 30% when properly mixed with either Novamine® (8.5%, 11.4% or 15%) or 8.5% Travasol® or 10% Travasol® Amino Acid Injections for use in Total Parenteral Nutrition (TPN) therapy. Because of the potential for life threatening events, caution should be taken to ensure that precipitates have not formed in any parenteral nutrition mixture. Perform all manipulations in a suitable work area, such as a laminar flow hood.

Failure to follow the Mixing Guidelines and Limitations below, including recommended storage temperature, storage time, order of mixing, etc., may result in an unstable admixture.

The following proper mixing sequence must be followed to minimize pH related problems by ensuring that typically acidic Dextrose Injections are not mixed with lipid emulsions alone:
Transfer Dextrose Injection to the TPN admixture Container Transfer Amino Acid Injection Transfer Intralipid® 30% (A 30% I.V. Fat Emulsion)
Note: Amino Acid Injection, Dextrose Injection and Intralipid® may be simultaneously transferred to the admixture container. Admixing should be accompanied by gentle agitation to avoid localized concentration effects.

These admixtures should be used promptly with storage under refrigeration (2-8°C) not to exceed 24 hours and must be completely used within 24 hours after removal from refrigeration.

It is essential that the admixture be prepared using strict aseptic techniques as this nutrient mixture is a good growth medium for microorganisms.

Additives other than those named above may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist. If in the informed judgement of the prescribing physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives (e.g., vitamins and minerals).

Additives must not be added directly to Intralipid® and in no case should Intralipid® be added to the TPN container first. Bags should be shaken gently after each addition to minimize localized concentration.

Supplemental electrolytes, trace metals or multivitamins may be required in accordance with the prescription of the attending physician.

The prime destabilizers of emulsions are excessive acidity (low pH) and inappropriate electrolyte content. Careful consideration should be given to additions of divalent cations (Ca++ and Mg++) which have been shown to cause emulsion instability. Amino acid solutions exert a buffering effect protecting the emulsion.

The admixture should be inspected carefully for “breaking or oiling out” of the emulsion. “Breaking or oiling out” is described as the separation of the emulsion and can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. The admixture should also be examined for particulates. The admixture must be discarded if any of the above is observed.
Bebulin Vh

Bebulin Vh

General

BEBULIN VH is intended for intravenous administration only.

As a general rule, 1 International Unit of Factor IX activity/kg will increase the plasma level of Factor IX by 0.8%.

Accordingly, the following formula is provided for dosage calculations
Number of Factor bodyweight desired Factor IX increase x 1.2 IX IU required = (kg) x (% of normal)
It must, however, be emphasized that the response to treatment will vary from patient to patient and that occasionally larger doses than those derived from the above formula will be required, particularly if treatment is delayed. Exact dosage determination should be based on localization and extent of hemorrhage, and the level of Factor IX to be achieved. It must be emphasized that particularly with severe hemorrhage and major surgery, close laboratory monitoring of the Factor IX level is required to determine proper dosage.

Management of Specific Types of Bleeding 14-18

Approximate Factor IX levels, typical initial doses, and the average duration of treatment are suggested in the table below. For minor bleeding a single dose will usually be sufficient, otherwise a second dose may be given after 24 hours. More severe hemorrhage will require the administration of several doses at approximately 24 hours intervals. For maintenance therapy, usually two thirds of the initial dose is infused.
* For patients predisposing to thrombosis see “PRECAUTIONS” section. Type of Bleeding
Approximate

Factor IX Level
(% Normal)
Typical Initial

Dose
(IU/kg)
Average Duration

of Treatment
(Days)
Minor

early hemarthrosis,minor epistaxis,
and gingival bleeding, mild hematuria 20 25-35 1
Moderate

severe joint bleeding, early hematoma,

major open

bleeding,

minor trauma,

minor hemoptysis
hematemesis,and melena,major hematuria 40 40-55
2 or

until adequate
wound healing
Majorsevere hematoma major trauma,

Severe hemoptysis,
Hematemesis, and melena ≥60* 60-70
2-3 or

until adequate
wound healing
Management of Surgical Procedures 14-18.

Dosage guidelines for surgical procedures are suggested below. The preoperative loading dose should be administered one hour prior to surgery. Depending on the type of surgery, replacement therapy has to be continued over one to several weeks until adequate wound healing is achieved. The average treatment interval will initially be 12 hours, while in the later postoperative period 24 hours is generally adequate.
* For patients predisposing to thrombosis see “PRECAUTIONS” section. N/A– Not Applicable.
Type of

Surgery
Day of Operation
Init. Postop. Period
(1st to 2nd Week)
Late Postop. Period

(from 3rd Week Onwards)

Approx.

Level

F IX

(% Normal)

Dose
(I.U./kg)
Approx.

Level

F IX
(% Normal)
Dose
(I.U./kg)
Approx.

Level

F IX

(% Normal)

Dose
(I.U./kg) Major
≥60*
70-95 60-20 70-35 20
35-25
Minor 40-60 50-60
40-20

55-25
N/A N/A
For tooth extraction the same initial dose as for minor surgery is recommended.

Generally, one infusion will be sufficient. In case of extraction of several teeth, replacement therapy for up to one week may be necessary using the same doses as for minor surgery 13-15

Long-Term Prophylactic Treatment

Prophylactic doses of 20-30 IU/kg administered once, or preferably up to twice a week have been shown to significantly reduce the frequency of spontaneous hemorrhage 13,16. It is, however, recommended that prophylactic dosage regimens be tailored to individual needs.

Reconstitution

BEBULIN VH should be reconstituted immediately before application. The solution does not contain a preservative and must be used within 3 hours after reconstitution.

For reconstitution proceed as follows:
Warm both diluent and concentrate in unopened vials to room temperature (not above 37 °C, 98 °F). Remove caps from both vials to expose central portions of the rubber stoppers. Cleanse exposed surface of the rubber stoppers with germicidal solution and allow to dry. Using aseptic technique, remove protective covering from one end of the double-ended needle and insert the exposed end through the diluent vial stopper. Remove protective covering from the other end of the double-ended needle, taking care not to touch the exposed end. Invert diluent vial over the concentrate vial, then insert free end of the needle through the concentrate vial stopper. Diluent will be drawn into the concentrate vial by vacuum. Disconnect the two vials by removing needle from the concentrate vial stopper. Gently agitate or rotate the concentrate vial until all material is dissolved.
Do not refrigerate after reconstitution!

Administration

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.

Intravenous Injection
After reconstituting the concentrate as described above, attach the enclosed filter needle to a sterile disposable syringe using aseptic technique. Insert filter needle through the concentrate vial stopper. Inject air and withdraw solution into the syringe. Remove and discard filter needle. Attach a suitable intravenous needle or infusion set with winged adapter. Administer the solution intravenously at a rate comfortable to the patient (maximum rate 2 mL per minute).
Feiba Nf

Feiba Nf

(See under Intravenous Injection or Infusion:).

Clinical trials1,2 demonstrated that the response to treatment with FEIBA may differ from patient to patient with no correlation to the patient’s inhibitor titer. Response may also vary between different types of hemorrhage (e.g. joint hemorrhage vs. CNS hemorrhage). As a general guideline, a dosage range of 50 to 100 Units of FEIBA NF per kg of body weight is recommended. However, care should be taken to distinguish between the following four indications, all of which have undergone careful clinical evaluation:

Joint Hemorrhage

In joint hemorrhage, a dose of 50 units per kg of body weight is recommended at 12-hour intervals, which may be increased to doses of 100 units per kg of body weight at 12-hour intervals.

Treatment should be continued until clear signs of clinical improvement appear, such as relief of pain, reduction of swelling or mobilization of the joint.

Mucous Membrane Bleeding

A dose of 50 units per kg of body weight is recommended to be given at 6-hour intervals under careful monitoring (visible bleeding site, repeated measurements of the patient’s hematocrit). If hemorrhage does not stop, the dose may be increased to 100 units per kg of body weight at 6-hour intervals. Two such administrations or 200 units per kg of body weight a day should not be exceeded.

Soft Tissue Hemorrhage

For serious soft tissue bleeding, such as retroperitoneal bleeding, doses of 100 units per kg of body weight at 12-hour intervals are recommended. A daily dosage of 200 units per kg of body weight should not be exceeded.

Other Severe Hemorrhages

Severe hemorrhages, such as CNS bleedings have been effectively treated with doses of 100 units per kg of body weight at 12-hour intervals. Sometimes, FEIBA NF may be indicated at 6-hour intervals until clear clinical improvement is achieved.

Reconstitution:
Allow the unopened vials of FEIBA NF (concentrate) and Sterile Water for Injection (diluent) to reach room temperature (not above 37ºC, 98ºF). Remove the caps from the concentrate and diluent vials to expose central portions of the rubber stoppers. Disinfect the rubber stoppers of both vials using a germicidal solution. Place the vials on an even surface and allow them to dry. Open the package of the BAXJECT II Hi-Flow device by peeling away the lid without touching the inside contents (Fig. A). Do not remove the transfer system from the package. Do not touch the clear spike. (Fig. B). Grip the BAXJECT II Hi-Flow device package at the edges and pull the package off the device (Fig. C). Do not remove the blue protective cap from the BAXJECT II Hi-Flow device. Do not touch the purple spike. Turn the system over so that the vial is on top. Press the purple spike of the BAXJECT II Hi-Flow device fully into the FEIBA NF vial. The vacuum will draw the diluent into the FEIBA NF vial (Fig. D). Swirl the entire system gently until the powder is dissolved. Make sure that the FEIBA NF has been dissolved completely.
Fig A

Fig B

Fig C

Fig D

Do not refrigerate after reconstitution!

After complete reconstitution of FEIBA NF, its injection or infusion should be commenced as promptly as practicable, but must be completed within three hours following reconstitution. The solution must be given by intravenous injection or intravenous drip infusion.

Intravenous Injection/Infusion:

Inspect for particulate matter and discoloration after reconstituting the concentrate as described under Reconstitution prior to administration. The appearance of the solution should be colorless to slightly yellowish and essentially free of visible particles.

Plastic Luer lock syringes are recommended for use with this product since protein such as FEIBA NF tends to stick to the surface of all-glass syringes.
Remove the blue protective cap from the BAXJECT II Hi-Flow device. Connect the syringe to the BAXJECT II Hi-Flow device (DO NOT DRAW AIR INTO THE SYRINGE) (Fig. E). (Fig. F). Disconnect the syringe, attach a suitable needle and inject or infuse intravenously as instructed under Rate of Administration.

Fig E

Fig F

Rate of Administration:

The maximum injection or infusion rate must not exceed 2 units per kg of body weight per minute. For a patient with a body weight of 75 kg, this corresponds to an infusion rate of 2.5-7.5 mL per minute depending on the number of units per vial (see label on vial).

Rate of Administration:

The maximum injection or infusion rate must not exceed 2 units per kg of body weight per minute. For a patient with a body weight of 75 kg, this corresponds to an infusion rate of 2.5-7.5 mL per minute depending on the number of units per vial (see label on vial).
Tisseel

Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:
Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL
It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Sterile Water Bath (Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Non-Sterile Water Bath (In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Incubator (In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Tisseel Frozen

Tisseel Frozen

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:
Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL
It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Sterile Water Bath (Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Non-Sterile Water Bath (In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Incubator (In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Tisseel

Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:
Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL
It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Sterile Water Bath (Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Non-Sterile Water Bath (In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Incubator (In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Tisseel

Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:
Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL
It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Sterile Water Bath (Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Non-Sterile Water Bath (In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Incubator (In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Gammagard Sd

Gammagard Sd

Primary Immunodeficiency Diseases

For patients with primary immunodeficiencies, monthly doses of approximately 300-600 mg/kg infused at 3 to 4 week intervals are commonly used.42,43 As there are significant differences in the half-life of IgG among patients with primary immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response. The minimum serum concentration of IgG necessary for protection varies among patients and has not been established by controlled clinical trials.

B-cell Chronic Lymphocytic Leukemia (CLL)

For patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell Chronic Lymphocytic Leukemia, a dose of 400 mg/kg every 3 to 4 weeks is recommended.

Kawasaki Syndrome

For patients with Kawasaki syndrome, either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.44

Idiopathic Thrombocytopenic Purpura (ITP)

For patients with acute or chronic Idiopathic Thrombocytopenic Purpura, a dose of 1 g/kg is recommended. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

No prospective data are presently available to identify a maximum safe dose, concentration, and rate of infusion in patients determined to be at increased risk of acute renal failure. In the absence of prospective data, the recommended doses should not be exceeded and the concentration and infusion rate selected should be the minimum level practicable. Reduction in dose, concentration, and/or rate of administration in patients at risk of acute renal failure has been proposed in the literature in order to reduce the risk of acute renal failure.45

Reconstitution: Use Aseptic Technique

When reconstitution is performed aseptically outside of a sterile laminar air flow hood, administration should begin as soon as possible, but not more than 2 hours after reconstitution.

When reconstitution is performed aseptically inside of a sterile laminar air flow hood, the reconstituted product may be either maintained in the original glass container or pooled into VIAFLEX bags and stored under constant refrigeration (2-8°C), for up to 24 hours. (The date and time of reconstitution/pooling should be recorded). If these conditions are not met, sterility of the reconstituted product cannot be maintained. Partially used vials should be discarded.

A. 5% Solution

Note: If refrigerated, allow GAMMAGARD S/D to reach room temperature before administration.

1. Remove bottle caps and clean stoppers with germicidal solution.

2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface. Use exposed end of transfer device to spike diluent bottle through center of the stopper.

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover. Do not touch spike.

4a. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent vial to minimize spilling out diluent.

CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents.

CAUTION: Do not shake. Avoid foaming.

Discard transfer device after single use per local guidelines.

B. 10% Solution

1. Follow step 1 as previously described in A.

2. To prepare a 10% solution, it is necessary to remove half of the volume of diluent. Table 2 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).

3. Using the residual diluent in the diluent vial, follow steps 2-6 as previously described in A.
Table 2 Required Diluent Volume to be Removed 5g 10g Concentration bottle bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 48 mL 96 mL
Rate of Administration

It is recommended that initially a 5% solution be infused at a rate of 0.5 mL/kg/Hr. If infusion at this rate and concentration causes the patient no distress, the administration rate may be gradually increased to a maximum rate of 4 mL/kg/Hr for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/Hr can be infused with the 10% concentration starting at 0.5 mL/kg/Hr. If no adverse effects occur, the rate can be increased gradually up to a maximum of 8 mL/kg/Hr.

In general, it is recommended that patients beginning therapy with IGIV or switching from one IGIV product to another be started at the lower rates of infusion and should be advanced to the maximal rate only after they have tolerated several infusions at intermediate rates of infusion. It is important to individualize rates for each patient. As noted in the WARNINGS section, patients who have underlying renal disease or who are judged to be at risk of developing thrombotic events should not be infused rapidly with any IGIV product.

Although there are no prospective studies demonstrating that any concentration or rate of infusion is completely safe, it is believed that risk may be decreased at lower rates of infusion.45 Therefore, as a guideline, it is recommended that these patients who are judged to be at risk of renal dysfunction or thrombotic complications be gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hr of a 10% or < 4mL/kg/hr of a 5% solution).

It is recommended that antecubital veins be used especially for 10% solutions, if possible. This may reduce the likelihood of the patient experiencing discomfort at the infusion site (see ADVERSE REACTIONS).

A rate of administration which is too rapid may cause flushing and changes in pulse rate and blood pressure. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

Drug Interactions

Admixtures of GAMMAGARD S/D, Immune Globulin Intravenous (Human), with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMMAGARD S/D be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with Immune Globulin Intravenous (Human) from other manufacturers.

Antibodies in immune globulin preparations may interfere with patient responses to live vaccines, such as those for measles, mumps, and rubella. The immunizing physician should be informed of recent therapy with Immune Globulin Intravenous (Human) so that appropriate precautions can be taken.

Administration

GAMMAGARD S/D should be administered as soon after reconstitution as possible, or as described in DOSAGE AND ADMINISTRATION.

The reconstituted material should be at room temperature during administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstituted material should be a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed.

Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.
Gammagard Sd

Gammagard Sd

Primary Immunodeficiency Diseases

For patients with primary immunodeficiencies, monthly doses of approximately 300-600 mg/kg infused at 3 to 4 week intervals are commonly used.42,43 As there are significant differences in the half-life of IgG among patients with primary immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response. The minimum serum concentration of IgG necessary for protection varies among patients and has not been established by controlled clinical trials.

B-cell Chronic Lymphocytic Leukemia (CLL)

For patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell Chronic Lymphocytic Leukemia, a dose of 400 mg/kg every 3 to 4 weeks is recommended.

Kawasaki Syndrome

For patients with Kawasaki syndrome, either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.44

Idiopathic Thrombocytopenic Purpura (ITP)

For patients with acute or chronic Idiopathic Thrombocytopenic Purpura, a dose of 1 g/kg is recommended. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

No prospective data are presently available to identify a maximum safe dose, concentration, and rate of infusion in patients determined to be at increased risk of acute renal failure. In the absence of prospective data, the recommended doses should not be exceeded and the concentration and infusion rate selected should be the minimum level practicable. Reduction in dose, concentration, and/or rate of administration in patients at risk of acute renal failure has been proposed in the literature in order to reduce the risk of acute renal failure.45

Reconstitution: Use Aseptic Technique

When reconstitution is performed aseptically outside of a sterile laminar air flow hood, administration should begin as soon as possible, but not more than 2 hours after reconstitution.

When reconstitution is performed aseptically inside of a sterile laminar air flow hood, the reconstituted product may be either maintained in the original glass container or pooled into VIAFLEX bags and stored under constant refrigeration (2-8°C), for up to 24 hours. (The date and time of reconstitution/pooling should be recorded). If these conditions are not met, sterility of the reconstituted product cannot be maintained. Partially used vials should be discarded.

A. 5% Solution

Note: If refrigerated, allow GAMMAGARD S/D to reach room temperature before administration.

1. Remove bottle caps and clean stoppers with germicidal solution.

2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface. Use exposed end of transfer device to spike diluent bottle through center of the stopper.

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover. Do not touch spike.

4a. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent vial to minimize spilling out diluent.

CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents.

CAUTION: Do not shake. Avoid foaming.

Discard transfer device after single use per local guidelines.

B. 10% Solution

1. Follow step 1 as previously described in A.

2. To prepare a 10% solution, it is necessary to remove half of the volume of diluent. Table 2 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).

3. Using the residual diluent in the diluent vial, follow steps 2-6 as previously described in A.
Table 2 Required Diluent Volume to be Removed 5g 10g Concentration bottle bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 48 mL 96 mL
Rate of Administration

It is recommended that initially a 5% solution be infused at a rate of 0.5 mL/kg/Hr. If infusion at this rate and concentration causes the patient no distress, the administration rate may be gradually increased to a maximum rate of 4 mL/kg/Hr for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/Hr can be infused with the 10% concentration starting at 0.5 mL/kg/Hr. If no adverse effects occur, the rate can be increased gradually up to a maximum of 8 mL/kg/Hr.

In general, it is recommended that patients beginning therapy with IGIV or switching from one IGIV product to another be started at the lower rates of infusion and should be advanced to the maximal rate only after they have tolerated several infusions at intermediate rates of infusion. It is important to individualize rates for each patient. As noted in the WARNINGS section, patients who have underlying renal disease or who are judged to be at risk of developing thrombotic events should not be infused rapidly with any IGIV product.

Although there are no prospective studies demonstrating that any concentration or rate of infusion is completely safe, it is believed that risk may be decreased at lower rates of infusion.45 Therefore, as a guideline, it is recommended that these patients who are judged to be at risk of renal dysfunction or thrombotic complications be gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hr of a 10% or < 4mL/kg/hr of a 5% solution).

It is recommended that antecubital veins be used especially for 10% solutions, if possible. This may reduce the likelihood of the patient experiencing discomfort at the infusion site (see ADVERSE REACTIONS).

A rate of administration which is too rapid may cause flushing and changes in pulse rate and blood pressure. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

Drug Interactions

Admixtures of GAMMAGARD S/D, Immune Globulin Intravenous (Human), with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMMAGARD S/D be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with Immune Globulin Intravenous (Human) from other manufacturers.

Antibodies in immune globulin preparations may interfere with patient responses to live vaccines, such as those for measles, mumps, and rubella. The immunizing physician should be informed of recent therapy with Immune Globulin Intravenous (Human) so that appropriate precautions can be taken.

Administration

GAMMAGARD S/D should be administered as soon after reconstitution as possible, or as described in DOSAGE AND ADMINISTRATION.

The reconstituted material should be at room temperature during administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstituted material should be a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed.

Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.
Gammagard Sd

Gammagard Sd

Primary Immunodeficiency Diseases

For patients with primary immunodeficiencies, monthly doses of approximately 300-600 mg/kg infused at 3 to 4 week intervals are commonly used.42,43 As there are significant differences in the half-life of IgG among patients with primary immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response. The minimum serum concentration of IgG necessary for protection varies among patients and has not been established by controlled clinical trials.

B-cell Chronic Lymphocytic Leukemia (CLL)

For patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell Chronic Lymphocytic Leukemia, a dose of 400 mg/kg every 3 to 4 weeks is recommended.

Kawasaki Syndrome

For patients with Kawasaki syndrome, either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.44

Idiopathic Thrombocytopenic Purpura (ITP)

For patients with acute or chronic Idiopathic Thrombocytopenic Purpura, a dose of 1 g/kg is recommended. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

No prospective data are presently available to identify a maximum safe dose, concentration, and rate of infusion in patients determined to be at increased risk of acute renal failure. In the absence of prospective data, the recommended doses should not be exceeded and the concentration and infusion rate selected should be the minimum level practicable. Reduction in dose, concentration, and/or rate of administration in patients at risk of acute renal failure has been proposed in the literature in order to reduce the risk of acute renal failure.45

Reconstitution: Use Aseptic Technique

When reconstitution is performed aseptically outside of a sterile laminar air flow hood, administration should begin as soon as possible, but not more than 2 hours after reconstitution.

When reconstitution is performed aseptically inside of a sterile laminar air flow hood, the reconstituted product may be either maintained in the original glass container or pooled into VIAFLEX bags and stored under constant refrigeration (2°-8°C), for up to 24 hours. (The date and time of reconstitution/pooling should be recorded). If these conditions are not met, sterility of the reconstituted product cannot be maintained. Partially used vials should be discarded.

A. 5% Solution
Note: Reconstitute immediately before use. If refrigerated, warm the Sterile Water for Injection, USP (diluent) and GAMMAGARD S/D, Immune Globulin Intravenous (Human) (dried concentrate), to room temperature. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers. Cleanse stoppers with germicidal solution. Remove protective covering from one end of double-ended needle and insert exposed needle through diluent stopper at its center. Remove protective covering from other end of double-ended needle. Invert diluent bottle over upright concentrate bottle, then rapidly insert free end of the needle through the concentrate bottle stopper at its center. The vacuum in the concentrate bottle will draw in the diluent. When diluent transfer is complete, remove empty diluent bottle from needle and then needle from concentrate bottle. Discard needle after single use. Thoroughly wet the dried material by tilting or inverting and gently rotating the bottle. Do not shake. Avoid foaming. Repeat gentle rotation as long as undissolved product is observed.
B. 10% Solution

Follow steps 1-4 as previously described in A.

5. To prepare a 10% solution, reconstitute with the appropriate volume of diluent by using a sterile hypodermic syringe and needle. Table 2 indicates the volume of diluent required for a 5% or 10% concentration. Using aseptic technique, draw required volume into a sterile hypodermic syringe and needle. The diluent is then injected into the concentrate bottle.
Table 2 Required Diluent Volume Concentration 0.5g Bottle 5% 10 mL 10% 5 mL
6. Discard any unused diluent after single use.

7. Thoroughly wet the dried material by tilting or inverting and gently rotating the bottle. Do not shake. Avoid foaming.

8. Repeat gentle rotation as long as undissolved product is observed.

Rate of Administration

It is recommended that initially a 5% solution be infused at a rate of 0.5 mL/kg/Hr. If infusion at this rate and concentration causes the patient no distress, the administration rate may be gradually increased to a maximum rate of 4 mL/kg/Hr for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/Hr can be infused with the 10% concentration starting at 0.5 mL/kg/Hr. If no adverse effects occur, the rate can be increased gradually up to a maximum of 8 mL/kg/Hr.

In general, it is recommended that patients beginning therapy with IGIV or switching from one IGIV product to another be started at the lower rates of infusion and should be advanced to the maximal rate only after they have tolerated several infusions at intermediate rates of infusion. It is important to individualize rates for each patient. As noted in the WARNINGS section, patients who have underlying renal disease or who are judged to be at risk of developing thrombotic events should not be infused rapidly with any IGIV product.

Although there are no prospective studies demonstrating that any concentration or rate of infusion is completely safe, it is believed that risk may be decreased at lower rates of infusion45. Therefore, as a guideline, it is recommended that these patients who are judged to be at risk of renal dysfunction or thrombotic complications be gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2 mL/kg/hr of a 10% or < 4 mL/kg/hr of a 5% solution).

It is recommended that antecubital veins be used especially for 10% solutions, if possible. This may reduce the likelihood of the patient experiencing discomfort at the infusion site (see ADVERSE REACTIONS).

A rate of administration which is too rapid may cause flushing and changes in pulse rate and blood pressure. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

Drug Interactions

Admixtures of GAMMAGARD S/D, Immune Globulin Intravenous (Human), with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMMAGARD S/D be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with Immune Globulin Intravenous (Human) from other manufacturers.

Antibodies in immune globulin preparations may interfere with patient responses to live vaccines, such as those for measles, mumps, and rubella. The immunizing physician should be informed of recent therapy with Immune Globulin Intravenous (Human) so that appropriate precautions can be taken.

Administration

.

GAMMAGARD S/D should be administered as soon after reconstitution as possible, or as described in DOSAGE AND ADMINISTRATION .

The reconstituted material should be at room temperature during administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstituted material should be a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed.

Intravenous Syringe Injection
Attach filter needle to a disposable syringe and draw back plunger to admit air into syringe. Insert needle into reconstituted GAMMAGARD S/D. Inject air into bottle and then withdraw the reconstituted material into the syringe. Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration .
Tisseel

Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:
Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL
It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Sterile Water Bath (Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Non-Sterile Water Bath (In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:
Pack Size Thawing/Warming Times 33°C to 37°C Incubator (In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Diclofenac Sodium

Diclofenac Sodium

Penicillin G Potassium Injection, USP should be administered by intravenous infusion. The usual dose recommendations are as follows:

Adult patients

     (*) Because of its short half-life, Penicillin G is administered in divided doses, usually       every 4-6 hours with the exception of meningococcal meningitis/septicemia, i.e., every 2 hours.

CLINICAL INDICATION

DOSAGE

Serious infections due to susceptible strains of streptococci (including S. pneumoniae) -septicemia, empyema, pneumonia, pericarditis, endocarditis and meningitis

12 to 24 million units/day depending on the infection and its severity administered in equally divided doses every 4-6 hours.

Serious infections due to susceptible strains of staphylococci - septicemia, empyema, pneumonia, pericarditis, endocarditis and meningitis

5 to 24 million units/day depending on the infection and its severity administered in equally divided doses every 4-6 hours.

Anthrax

Minimum of 8 million units/day in divided doses every 6 hours. Higher doses may be required depending on susceptibility of organism.

Actinomycosis    Cervicofacial disease    Thoracic and abdominal disease

1 to 6 million units/day(*)10 to 20 million units/day(*)

Clostridial infections    Botulism (adjunctive therapy to antitoxin)    Gas gangrene (debridement and/or surgery as indicated)    Tetanus (adjunctive therapy to human tetanus immune globulin)

20 million units/day(*)

Diphtheria (adjunctive therapy to antitoxin and for the prevention of the carrier state)

2 to 3 million units/day in divided doses for 10-12 days(*)

Erysipelothrix endocarditis

12 to 20 million units/day for 4-6 weeks(*)

Fusospirochetosis (severe infections of the oropharynx [Vincent’s], lower respiratory tract and genital area)

5 to 10 million units/day(*)

Listeria infections    Meningitis    Endocarditis

15 to 20 million units/day for 2 weeks(*)15 to 20 million units/day for 4 weeks(*)

Pasteurella infections including bacteremia and meningitis

4 to 6 million units/day for 2 weeks(*)

Haverhill fever; Rat-bite fever

12 to 20 million units/day for 3-4 weeks(*)

Disseminated gonococcal infections, such as meningitis endocarditis, arthritis, etc., caused by penicillin - susceptible organisms

10 million units/day(*); duration depends on the type of infection

Syphilis (neurosyphilis)

12 to 24 million units/day, as 2-4 MU every 4 hours for 10-14 days; many experts recommend additional therapy with Benzathine PCN G 2.4 MU IM weekly for 3 doses after completion of IV therapy

Meningococcal meningitis and/or septicemia

24 million units/day as 2 million units every 2 hours

Pediatric patients

This product should not be administered to patients requiring less than one million units per dose

(see Precautions-Pediatric Use).

CLINICAL INDICATION

DOSAGE

Serious infections, such as pneumonia and endocarditis, due to susceptible strains of streptococci (including S. pneumoniae) and meningococcus

150,000–300,000 units/kg/day divided in equal doses every 4-6 hours; duration depends on infecting organism and type of infection

Meningitis caused by susceptible strains of pneumococcus and meningococcus

250,000 units/kg/day divided in equal doses every 4 hours for 7-14 days depending on the infecting organism (maximum dose of 12-20 million units/day)

Disseminated Gonococcal Infections (penicillin-susceptible strains)

Weight less than 45 kg:

    Arthritis

100,000 units/kg/day in 4 equally divided doses for 7-10 days

    Meningitis

250,000 units/kg/day in equal doses every 4 hours for 10-14 days

    Endocarditis

250,000 units/kg/day in equal doses every 4 hours for 4 weeks

    Arthritis, meningitis, endocarditis

Weight 45 kg or greater: 10 million units/day in 4 equally divided doses with the duration of therapy depending on the type of infection

Syphilis (congenital and neurosyphilis) after the newborn period

200,000-300,000 units/kg/day (administered as 50,000 units/kg every 4-6 hours) for 10-14 days

Diphtheria (adjunctive therapy to antitoxin and for prevention of the carrier state)

150,000-250,000 units/kg/day in equal doses every 6 hours for 7-10 days

Rat-bite fever; Haverhill fever (with endocarditis caused by S. moniliformis)

150,000-250,000 units/kg/day in equal doses every 4 hours for 4 weeks

Renal Impairment: Penicillin G is relatively nontoxic, and dosage adjustments are generally required only in cases of severe renal impairment. The recommended dosage regimens are as follows:

Creatinine clearance less than 10 mL/min/1.73m2; administer a full loading dose (see recommended dosages in the tables above) followed by one-half of the loading dose every 8-10 hours.

Uremic patients with a creatinine clearance greater than 10 mL/min/1.73m2; administer a full loading dose (see recommended dosages in the tables above) followed by one-half of the loading dose every 4-5 hours. Additional dosage modifications should be made in patients with hepatic disease and renal impairment.

For most acute infections, treatment should be continued for at least 48 to 72 hours after the patient becomes asymptomatic. Antibiotic therapy for Group A β-hemolytic streptococcal infections should be maintained for at least 10 days to reduce the risk of rheumatic fever. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Cardioplegic

Cardioplegic

The following information is suggested as a guide and is subject to variation according to the preference and experience of the surgeon. It is required that 10 mL (840 mg) of 8.4% Sodium Bicarbonate Injection, USP (10 mEq each of sodium and bicarbonate) be added aseptically and thoroughly mixed with each 1000 mL of cardioplegic solution to adjust pH. Use 10 mL of Hospira1 List 4900, 8.4% Sodium Bicarbonate Injection, USP, to achieve the approximate pH of 7.8 when measured at room temperature. Use of any other Sodium Bicarbonate Injection may not achieve this pH due to the varying pH’s of Sodium Bicarbonate Injections. Due to its inherent instability with other components, sodium bicarbonate must be added just prior to administration. After this addition, the solution must be used within 24 hours. The solution should be cooled to 4°C prior to use. Following institution of cardiopulmonary bypass at perfusate temperatures of 28° to 30°C, and after cross-clamping of the ascending aorta, the buffered solution is administered by rapid infusion into the aortic root. The initial rate of infusion may be 300 mL/m2/minute (about 540 mL/min in a 5’ 8”, 70 kg adult with 1.8 square meters of surface area) given for a period of two to four minutes. Concurrent external cooling (regional hypothermia of the pericardium) may be accomplished by instilling a refrigerated (4°C) physiologic solution such as a Normosol®2 -R (balanced electrolyte replacement solution) or Ringer's Injection into the chest cavity.

Should myocardial electromechanical activity persist or recur, the solution may be reinfused at a rate of 300 mL/m2/min for a period of two minutes. Reinfusion of the solution may be repeated every 20 to 30 minutes or sooner if myocardial temperature rises above 15° to 20°C or returning cardiac activity is observed. The regional hypothermia solution around the heart also may be replenished continuously or periodically in order to maintain adequate hypothermia. Suction may be used to remove warmed infusates. An implanted thermistor probe may be used to monitor myocardial temperature.

The volumes of solution instilled into the aortic root may vary depending on the duration or type of open heart surgical procedure.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS.)
Sevoflurane

Sevoflurane

The concentration of sevoflurane, USP being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane, USP. The administration of general anesthesia must be individualized based on the patient’s response.

Replacement of Dessicated CO2 Absorbents

When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane, USP and CO2 absorbents is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters (see Precautions).

Pre-anesthetic Medication

No specific premedication is either indicated or contraindicated with sevoflurane, USP. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist.

Induction:

Sevoflurane, USP has a nonpungent odor and does not cause respiratory irritability; it is suitable for mask induction in pediatrics and adults.

Maintenance:

Surgical levels of anesthesia can usually be achieved with concentrations of 0.5-3% sevoflurane, USP with or without the concomitant use of nitrous oxide. Sevoflurane, USP can be administered with any type of anesthesia circuit.
Table 9: * Neonates are full-term gestational age. MAC in premature infants has not been determined. † In 1 - <3 year old pediatric patients, 60% N 2O/40% O 2 was used.
MAC Values for Adults and Pediatric Patients According to Age

Age of Patient (years) Sevoflurane inOxygen Sevoflurane in 65%N2O/35%O2 0 - 1 months * 3.3% 1 - <6 months 3.0% 6 months - <3 years 2.8% 2.0% † 3 - 12 2.5% 25 2.6% 1.4% 40 2.1% 1.1% 60 1.7% 0.9% 80 1.4% 0.7%
Directions for Filling Vaporizers

Utilize an adapter, as appropriate, when filling the vaporizer with sevoflurane
Forane

Forane

Premedication

Premedication should be selected according to the need of the individual patient, taking into account that secretions are weakly stimulated by FORANE (isoflurane, USP), and the heart rate tends to be increased. The use of anticholinergic drugs is a matter of choice.

Inspired Concentration

The concentration of isoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using:

a. Vaporizers calibrated specifically for isoflurane;

b. Vaporizers from which delivered flows can be calculated, such as vaporizers delivering a saturated vapor, which is then diluted. The delivered concentration from such a vaporizer may be calculated using the formula:

% isoflurane = 100 PVFV / FT(PA – PV)
Where: PA = Pressure of atmosphere PV = Vapor pressure of isoflurane FV = Flow of gas through vaporizer (mL/min) FT = Total gas flow (mL/min)
Isoflurane contains no stabilizer. Nothing in the agent alters calibration or operation of these vaporizers.

Induction

Induction with isoflurane in oxygen or in combination with oxygen-nitrous oxide mixtures may produce coughing, breath holding, or laryngospasm. These difficulties may be avoided by the use of a hypnotic dose of an ultra-short-acting barbiturate. Inspired concentrations of 1.5 to 3.0% isoflurane usually produce surgical anesthesia in 7 to 10 minutes.

Maintenance

Surgical levels of anesthesia may be sustained with a 1.0 to 2.5% concentration when nitrous oxide is used concomitantly. An additional 0.5 to 1.0% may be required when isoflurane is given using oxygen alone. If added relaxation is required, supplemental doses of muscle relaxants may be used.

The level of blood pressure during maintenance is an inverse function of isoflurane concentration in the absence of other complicating problems. Excessive decreases may be due to depth of anesthesia and in such instances may be corrected by lightening anesthesia.
Recombinate

Recombinate

Each vial of RECOMBINATE is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.

The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al4 and is supported by the data generated by 419 clinical pharmacokinetic studies with RECOMBINATE in 67 patients over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.

Examples (Assuming patient’s baseline Factor VIII level is at <1%):

(1) A dose of 1750 IU RECOMBINATE administered to a 70 kg patient, i.e. 25 IU/kg (1750 IU/70 kg), should be expected to cause a peak post-infusion Factor VIII increase of 25 IU/kg x 2 (IU/dL)/(IU/kg) = 50 IU/dL (50% of normal).

(2) A peak level of 70% is required in a 40 kg child. In this situation, the dose would be 70 IU/dL/[2(IU/dL)/(IU/kg)] x 40 kg = 1400 IU.

Recommended Dosage Schedule

Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.
Hemorrhage Degree of hemorrhage Required peak post infusion Factor VIII activity in the blood (as % of normal or IU/dL plasma) Frequency of Infusion Early hemarthrosis or muscle bleed or oral bleed 20-40 Begin infusion every 12 to 24 hours for one-three days until the bleeding episode is resolved (as indicated by pain), or healing is achieved. More extensive hemarthrosis, muscle bleed, or hematoma 30-60 Repeat infusion every 12 to 24 hours for (usually) three days or more until pain and disability are resolved. Life threatening bleeds such as head injury, throat bleed, severe abdominal pain 60-100 Repeat infusion every 8 to 24 hours until threat is resolved Surgery Type of Operation
Minor surgery, including tooth extraction
60-80 A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases. Major surgery 80-100 (pre- and post-operative) Repeat infusion every 8 to 24 hours depending on state of healing.
If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be determined and a sufficient dose of RECOMBINATE should be administered to achieve a satisfactory clinical response.

The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages. In presence of a low titer inhibitor, doses larger than those recommended may be necessary as per standard care.

Although dosage can be estimated by the calculations above, it is strongly recommended that whenever possible, appropriate laboratory tests including serial Factor VIII assays be performed on the patient’s plasma at suitable intervals to assure that adequate Factor VIII levels have been reached and are maintained. Patients should be evaluated for the development of Factor VIII inhibitors, if the expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose.

Reconstitution: Use Aseptic Technique
Bring RECOMBINATE, (dry factor concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature. Remove caps from concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place vials on a flat surface Remove protective covering from one end of double-ended needle and insert exposed needle through the center of the stopper. Remove protective covering from other end of double-ended needle. Invert diluent vial over the upright RECOMBINATE vial, then rapidly insert free end of the needle through the RECOMBINATE vial stopper at its center. The vacuum in the vial will draw in the diluent. Disconnect the two vials by removing needle from diluent vial stopper, then remove needle from RECOMBINATE vial. Swirl gently until RECOMBINATE is completely dissolved, otherwise active material will be removed by the filter needle. After reconstitution, the solution should be colorless to faint yellow, and substantially free from foreign particles.
NOTE: Do not refrigerate after reconstitution. (See Administration)

Administration: Use Aseptic Technique

RECOMBINATE is administered by intravenous (IV) injection after reconstitution.

Administer at room temperature.

RECOMBINATE should be administered not more than 3 hours after reconstitution.

Intravenous Syringe Injection

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be colorless to faint yellow in appearance. If not, do not use the solution and notify Baxter immediately.

Plastic syringes are recommended for use with this product since proteins such as RECOMBINATE tend to stick to the surface of glass syringes.
Attach filter needle to a disposable syringe and draw back plunger to admit air into the syringe. Insert the needle into reconstituted RECOMBINATE . Inject air into vial and then withdraw the reconstituted material into the syringe. Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration. If a patient is to receive more than one vial of RECOMBINATE, the contents of multiple vials may be drawn into the same syringe by drawing up each vial through a separate unused filter needle. Filter needles are intended to filter the contents of a single vial of RECOMBINATE only.
Rate of Administration

The rate of administration should be a rate that ensures the comfort of the patient. Preparations of RECOMBINATE can be administered at a rate of up to 5 mL per minute when reconstituted with 5 mL of sWFI.

The pulse rate should be determined before and during administration of RECOMBINATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.
Clinimix

Clinimix

If a patient is unable to take oral nourishment for a prolonged period of time, institution of total parenteral nutrition should be considered.

The total daily dose of CLINIMIX sulfite-free (Amino Acid in Dextrose) Injections depends on the patient’s metabolic requirement and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements.

Recommended Dietary Allowances 1 of protein range from approximately 0.75 g/kg of body weight for adults to 1.68 g/kg for infants up to three months of age. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially. Daily amino acid doses of approximately 1.0 to 1.5 g/kg of body weight for adults with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance.

For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrate will be necessary to promote adequate patient response to therapy. The severity of the illness being treated is the primary consideration in determining proper dose level. Such higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation.

Care should be exercised to insure the maintenance of proper levels of serum potassium. Quantities of 60 to 180 mEq of potassium per day have been used with adequate clinical effect. It may be necessary to add quantities of this electrolyte to these admixed injections, depending primarily on the amount of carbohydrate administered to and metabolized by the patient.

Patients receiving CLINIMIX sulfite-free (Amino Acid in Dextrose) Injections without electrolytes should be monitored frequently and their electrolyte requirements individualized.

Total daily fluid requirements can be met beyond the volume of amino acids solution by supplementing with noncarbohydrate or carbohydrate-containing electrolyte solutions.

Maintenance vitamins, additional electrolytes, and trace elements should be administered as required.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria.

Fat emulsion administration should be considered when prolonged (more than 5 days) parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat-free TPN.

Intravenous fat emulsions provide approximately 1.1 kcal per mL (10%), 2.0 kcal per mL (20%), or 3.0 kcal per mL (30%) and may be admixed along with amino acid/dextrose injections in the CLARITY Container to supplement caloric intake.

Depending upon the clinical condition of the patient, approximately 3 liters of solution may be administered per 24 hour period. When used postoperatively, the therapy should begin with 1000 mL on the first postoperative day. Thereafter, the dose may be increased to 3000 mL per day.

Do not administer unless seal between chambers is opened, other seals are intact, and solution is clear and thoroughly mixed.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

A slight yellow color does not alter the quality and efficacy of this product.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced.

Do not store solutions containing additives. These amino acid with electrolytes/dextrose with calcium injections should be used promptly after mixing. Any storage with additives should be under refrigeration and limited to a brief period of time, less than 24 hours.
1
Food and Nutrition Board National Academy of Sciences - National Research Council (Revised 1989).

Pediatric Use:

Use of CLINIMIX sulfite-free (Amino Acid in Dextrose) Injections in pediatric patients is governed by the same considerations that affect the use of any amino acid solution in pediatrics. The amount administered is dosed on the basis of grams of amino acids/kg of body weight/day. Two to 3 g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Solution administrations by peripheral vein should not exceed twice normal serum osmolarity (718 mOsmol/L).

Central Vein Administration:

Hypertonic mixtures of amino acid/dextrose injections may be administered safely by continuous infusion through a central vein catheter with the tip located in the vena cava. In addition to meeting nitrogen needs, the administration rate is governed, especially during the first few days of therapy, by the patient’s tolerance to dextrose, as indicated by frequent determinations of urine and blood sugar levels. Daily intake of amino acids in dextrose should be increased gradually to the maximum required dose.

Sudden cessation in administration of these admixed injections may result in insulin reaction due to continued endogenous insulin production. Parenteral nutrition mixtures should be withdrawn slowly.

Peripheral Vein Administration:

For patients requiring parenteral nutrition in whom the central vein route is not indicated, low concentration amino acid/dextrose injections may be administered by peripheral vein. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).
Gammagard

Gammagard

2.1 Dosage
Table 1 Dosage and Administration
Dose

Initial Infusion Rate

Maintenance Infusion Rate

Intravenous Administration

Primary Immunodeficiency

300 to 600 milligram/kg every 3 to 4 weeks based on clinical response

0.5 mL/kg/hr

(0.8 milligram/kg/min) for 30 minutes

Increase every 30 minutes (if tolerated) up to 5 mL/kg/hr (8 milligram/kg/min)

Multifocal Motor Neuropathy

Dose range 0.5 to 2.4 grams/kg/month based on clinical response (14)

0.5 mL/kg /hr

(0.8 milligram/kg/min)

Infusion rate may be increased if tolerated up to 5.4 mL/kg/hr (9 milligram/kg/min)

Subcutaneous Administration

Primary Immunodeficiency

Initial Dose is 1.37 × previous intravenous dose divided by # of weeks between intravenous doses.

Maintenance dose is based on clinical response and target IgG trough level (2.2).

40 kg BW and greater: 30 mL/site at 20 mL/hr/site.

Under 40 kg BW: 20 mL/site at 15 mL/hr/site.

40 kg BW and greater: 30 mL/site at 20 to 30 mL/hr/site.

Under 40 kg BW: 20 mL/site at 15 to 20 mL/hr/site.

Dose Adjustments for Intravenous Administration in Patients with PI

Adjust dose according to IgG levels and clinical response, as the frequency and dose of immune globulin may vary from patient to patient.

No randomized controlled clinical trials are available to determine an optimum trough serum IgG level for intravenous treatment. If a patient misses a dose, administer the missed dose as soon as possible, and then resume scheduled treatments every 3 or 4 weeks, as applicable.

Prior to switching from intravenous to subcutaneous treatment, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments. Start the initial subcutaneous dose approximately one week after the last intravenous infusion.

Dose Adjustments for Intravenous Administration in MMN

The dose may need to be adjusted to achieve the desired clinical response. In the clinical study, the dose ranged between 0.5 to 2.4 grams/kg/month (see Table 1). While receiving GAMMAGARD LIQUID, 9% of subjects in the clinical study experienced neurological decompensation that required an increase in dose. In order to avoid worsening of muscle weakness in patients, dose adjustment may be necessary.

Dose Adjustments for Subcutaneous Administration for PI only

Based on the results of clinical studies, the expected increase in serum IgG trough level while on weekly subcutaneous treatment, at the dose adjusted to provide a comparable AUC, is projected to be approximately 281 milligram/dL higher than the last trough level during prior stable intravenous treatment. To calculate the target trough IgG level for subcutaneous treatment, add 281 milligram/dL to the IgG trough level obtained after the last intravenous treatment.

To guide dose adjustment, calculate the difference between the patient’s target serum IgG trough level and the IgG trough level during subcutaneous treatment. Find this difference in the columns of Table 2 and the corresponding amount (in mL) by which to increase (or decrease) the weekly dose based on the patient's body weight. If the difference between measured and target trough levels is less than 100 milligram/dL then no adjustment is necessary. However, the patient's clinical response should be the primary consideration in dose adjustment.
Table 2 Change in Weekly Dose of GAMMAGARD LIQUID for Intended IgG Trough Level Adjustmenta
Difference between Measured and Target IgG Trough Levels

Body Weight

100 mg/dL

200 mg/dL

300 mg/dL

400 mg/dL

10 kg

2 mL

4 mL

6 mL

8 mL

20 kg

4 mL

8 mL

11 mL

15 mL

30 kg

6 mL

11 mL

17 mL

23 mL

40 kg

8 mL

15 mL

23 mL

30 mL

50 kg

9 mL

19 mL

28 mL

38 mL

60 kg

11 mL

23 mL

34 mL

45 mL

70 kg

13 mL

26 mL

40 mL

53 mL

80 kg

15 mL

30 mL

45 mL

60 mL

90 kg

17 mL

34 mL

51 mL

68 mL

100 kg

19 mL

38 mL

57 mL

75 mL

110 kg

21 mL

42 mL

62 mL

83 mL

120 kg

23 mL

45 mL

68 mL

91 mL

130 kg

25 mL

49 mL

74 mL

98 mL

140 kg

26 mL

53 mL

79 mL

106 mL

a Derived using a linear approximation to the nomogram method with a slope of 5.3 kg/dL.

Example 1: A patient with a body weight of 80 kg has a measured IgG trough level of 800 milligram/dL and the target trough level is 1000 milligram/dL. The desired target trough level difference is 200 milligram/dL (1000 milligram/dL minus 800 milligram/dL). The weekly dose of GAMMAGARD LIQUID should be increasedby 30 mL (3.0 gm).

Example 2: A patient with a body weight of 60 kg has a measured IgG trough of 1000 milligram/dL and the target trough level is 800 milligram/dL. The desired target trough level difference is 200 milligram/dL (800 milligram/dL minus 1000 milligram/dL). The weekly dose of GAMMAGARD LIQUID should be decreasedby 23 mL (2.3 gm).

2.2 Preparation and Handling
• Inspect the drug product visually for particulate matter and discoloration prior to administration. GAMMAGARD LIQUID is a clear or slightly opalescent, colorless or pale yellow solution. Do not use if the solution is cloudy, turbid, or if it contains particulates. • GAMMAGARD LIQUID vial is for single use only. Any vial that has been entered should be used promptly. Partially used vials should be discarded. GAMMAGARD LIQUID contains no preservative. • Allow refrigerated product to come to room temperature before use. DO NOT MICROWAVE. • Do not shake. • Do not mix with other products. • Do not use normal saline as a diluent. If dilution is desired, 5% dextrose in water (D5W) should be used as a diluent. • The infusion line may be flushed with normal saline. An in-line filter is optional. • Record the name and lot number of the product in the recipient's records.
2.3 Administration

Intravenous
Table 3 Infusion Rates for Intravenous Administration
PI

MMN

Initial

0.5 mL/kg/hr

(0.8 milligram/kg/min) for 30 minutes

Increasing rates of infusion starting at 0.5 mL/kg/h (0.8 milligram/kg/min)

Subsequent

Increase every 30 minutes (if tolerated) up to 5 mL/kg/hr (8 milligram/kg/min)

Increasing to a maximum rate of 5.4 mL/kg /hr if tolerated (9 milligram/kg/min)

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing, and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in recurrence of the symptoms.

Adverse reactions may occur more frequently in patients receiving immune globulin for the first time, upon switching brands or if there has been a long interval since the previous infusion2. In such cases, start at lower infusion rates and gradually increase as tolerated.

Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients over 65 years of age or judged to be at risk for renal dysfunction or thrombotic events, administer GAMMAGARD LIQUID at the minimum infusion rate practicable. In such cases, the maximal rate should be less than 3.3 milligram/kg/min (<2mL/kg/hr), and consider discontinuation of administration if renal function deteriorates [see Warnings and Precautions (5.2, 5.4) and Use In Specific Populations (8.5)].Subcutaneous for PI
Table 4 Infusion Rates for Subcutaneous Administration
40 kg BW and greater

Under 40 kg BW

Initial

30 mL/site at a rate of 20 mL/hr/site

20 mL/site at a rate of 15 mL/hr/site

Maintenance

30 mL/site at a rate of 20 to 30 mL/hr/site

20 mL/site at a rate of 15 to 20 mL/hr/site

Selection of Infusion Site: Suggested areas for subcutaneous infusion of GAMMAGARD LIQUID are abdomen, thighs, upper arms, or lower back. Infusion sites should be at least two inches apart, avoiding bony prominences. Rotate sites each week.

Volume per Site: The weekly dose (mL) should be divided by 30 or 20, based on patient weight above, to determine the number of sites required. Simultaneous subcutaneous infusion at multiple sites can be facilitated by use of a multi-needle administration set.

Rate of Infusion for Patients 40 kg and greater (88 lbs): If multiple sites are used, the rate set on the pump should be the rate per site multiplied by the number of sites (e.g., 30 mL x 4 sites = 120 mL/hr). The number of simultaneous sites should be limited to 8, or maximum infusion rate of 240 mL/hr. Rate of Infusion for Patients under 40 kg (88 lbs): If multiple sites are used, the rate set on the pump should be the rate per site multiplied by the number of sites (e.g., 20 mL x 3 sites = 60 mL/hr). The number of simultaneous sites should be limited to 8, or maximum infusion rate of 160 mL/hr.

Instructions for Subcutaneous Administration: Instruct patients to observe the following procedures:
1. Aseptic technique - Use aseptic technique when preparing and infusing GAMMAGARD LIQUID. 2. Assemble supplies - Set up a clean work area and gather all supplies necessary for the subcutaneous infusion: vial(s) of GAMMAGARD LIQUID, ancillary supplies, sharps container and pump. If GAMMAGARD LIQUID has already been pooled into a bag or a syringe, skip to Step 5. 3. Product preparation - Remove the protective cap from the vial to expose the center of the vial. Wipe the stopper with an alcohol pad and allow to dry. 4. Withdraw GAMMAGARD LIQUID from the vials - Attach a sterile syringe to a needle and draw air into the syringe barrel equal to the amount of product to be withdrawn. Inject the air into the vial and withdraw the desired volume of GAMMAGARD LIQUID. If multiple vials are required to achieve the desired dose, repeat this step. 5. Prepare the infusion pump and tubing - Follow the manufacturer’s instructions for preparing the pump and administration tubing, if needed. Be sure to prime the pump tubing to ensure that no air is left in the tubing and needle. 6. Select the infusion sites - Select the number of infusion sites depending on the volume of the total dose. See Administration (2.3) for recommended maximum volumes and rates. Potential sites for infusion include the back of arms, abdomen, thighs, and lower back (see Figure below). Ensure sites are at least 2 inches apart; avoid bony prominences. 7. Cleanse the infusion site(s) - Cleanse the infusion site(s) with an antiseptic skin preparation (e.g., alcohol pad) using a circular motion working from the center of the site and moving to the outside. Allow to dry. 8. Insert the needle - Choose the correct needle length to assure that GAMMAGARD LIQUID is delivered into the subcutaneous space. Grasp the skin and pinch at least one inch of skin between two fingers. Insert needle at a 90-degree angle with a darting motion into the subcutaneous tissue. Secure the needle. 9. Check for proper needle placement - Prior to the start of infusion, check each needle for correct placement to make sure that a blood vessel has not been punctured. Gently pull back on the attached syringe plunger and monitor for any blood return in the needle set. If you see any blood, remove and discard the needle set. Repeat priming and needle insertion steps in a different infusion site with a new needle set. 10. Secure the needle to the skin - Secure the needle(s) in place by applying a sterile protective dressing over the site. 11. Start infusion of GAMMAGARD LIQUID - Follow the manufacturer’s instructions to turn pump on. 12. Document the infusion - Remove the peel-off label with product lot number and expiration date from the GAMMAGARD LIQUID vial and place in treatment diary/log book to keep track of the product lots used. Keep the treatment diary/log book current by recording the time, date, dose, product label and any reactions after each infusion. 13. Remove needle set - After the infusion is complete, remove the needle set and gently press a small piece of gauze over the needle insertion site and cover with a protective dressing. Discard any unused solution and disposable supplies in accordance with local requirements.
2.1 Dosage
Table 1 Dosage and Administration
Dose

Initial Infusion Rate

Maintenance Infusion Rate

Intravenous Administration

Primary Immunodeficiency

300 to 600 milligram/kg every 3 to 4 weeks based on clinical response

0.5 mL/kg/hr

(0.8 milligram/kg/min) for 30 minutes

Increase every 30 minutes (if tolerated) up to 5 mL/kg/hr (8 milligram/kg/min)

Multifocal Motor Neuropathy

Dose range 0.5 to 2.4 grams/kg/month based on clinical response (14)

0.5 mL/kg /hr

(0.8 milligram/kg/min)

Infusion rate may be increased if tolerated up to 5.4 mL/kg/hr (9 milligram/kg/min)

Subcutaneous Administration

Primary Immunodeficiency

Initial Dose is 1.37 × previous intravenous dose divided by # of weeks between intravenous doses.

Maintenance dose is based on clinical response and target IgG trough level (2.2).

40 kg BW and greater: 30 mL/site at 20 mL/hr/site.

Under 40 kg BW: 20 mL/site at 15 mL/hr/site.

40 kg BW and greater: 30 mL/site at 20 to 30 mL/hr/site.

Under 40 kg BW: 20 mL/site at 15 to 20 mL/hr/site.

Dose Adjustments for Intravenous Administration in Patients with PI

Adjust dose according to IgG levels and clinical response, as the frequency and dose of immune globulin may vary from patient to patient.

No randomized controlled clinical trials are available to determine an optimum trough serum IgG level for intravenous treatment. If a patient misses a dose, administer the missed dose as soon as possible, and then resume scheduled treatments every 3 or 4 weeks, as applicable.

Prior to switching from intravenous to subcutaneous treatment, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments. Start the initial subcutaneous dose approximately one week after the last intravenous infusion.

Dose Adjustments for Intravenous Administration in MMN

The dose may need to be adjusted to achieve the desired clinical response. In the clinical study, the dose ranged between 0.5 to 2.4 grams/kg/month (see Table 1). While receiving GAMMAGARD LIQUID, 9% of subjects in the clinical study experienced neurological decompensation that required an increase in dose. In order to avoid worsening of muscle weakness in patients, dose adjustment may be necessary.

Dose Adjustments for Subcutaneous Administration for PI only

Based on the results of clinical studies, the expected increase in serum IgG trough level while on weekly subcutaneous treatment, at the dose adjusted to provide a comparable AUC, is projected to be approximately 281 milligram/dL higher than the last trough level during prior stable intravenous treatment. To calculate the target trough IgG level for subcutaneous treatment, add 281 milligram/dL to the IgG trough level obtained after the last intravenous treatment.

To guide dose adjustment, calculate the difference between the patient’s target serum IgG trough level and the IgG trough level during subcutaneous treatment. Find this difference in the columns of Table 2 and the corresponding amount (in mL) by which to increase (or decrease) the weekly dose based on the patient's body weight. If the difference between measured and target trough levels is less than 100 milligram/dL then no adjustment is necessary. However, the patient's clinical response should be the primary consideration in dose adjustment.
Table 2 Change in Weekly Dose of GAMMAGARD LIQUID for Intended IgG Trough Level Adjustmenta
Difference between Measured and Target IgG Trough Levels

Body Weight

100 mg/dL

200 mg/dL

300 mg/dL

400 mg/dL

10 kg

2 mL

4 mL

6 mL

8 mL

20 kg

4 mL

8 mL

11 mL

15 mL

30 kg

6 mL

11 mL

17 mL

23 mL

40 kg

8 mL

15 mL

23 mL

30 mL

50 kg

9 mL

19 mL

28 mL

38 mL

60 kg

11 mL

23 mL

34 mL

45 mL

70 kg

13 mL

26 mL

40 mL

53 mL

80 kg

15 mL

30 mL

45 mL

60 mL

90 kg

17 mL

34 mL

51 mL

68 mL

100 kg

19 mL

38 mL

57 mL

75 mL

110 kg

21 mL

42 mL

62 mL

83 mL

120 kg

23 mL

45 mL

68 mL

91 mL

130 kg

25 mL

49 mL

74 mL

98 mL

140 kg

26 mL

53 mL

79 mL

106 mL

a Derived using a linear approximation to the nomogram method with a slope of 5.3 kg/dL.

Example 1: A patient with a body weight of 80 kg has a measured IgG trough level of 800 milligram/dL and the target trough level is 1000 milligram/dL. The desired target trough level difference is 200 milligram/dL (1000 milligram/dL minus 800 milligram/dL). The weekly dose of GAMMAGARD LIQUID should be increasedby 30 mL (3.0 gm).

Example 2: A patient with a body weight of 60 kg has a measured IgG trough of 1000 milligram/dL and the target trough level is 800 milligram/dL. The desired target trough level difference is 200 milligram/dL (800 milligram/dL minus 1000 milligram/dL). The weekly dose of GAMMAGARD LIQUID should be decreasedby 23 mL (2.3 gm).

2.2 Preparation and Handling
• Inspect the drug product visually for particulate matter and discoloration prior to administration. GAMMAGARD LIQUID is a clear or slightly opalescent, colorless or pale yellow solution. Do not use if the solution is cloudy, turbid, or if it contains particulates. • GAMMAGARD LIQUID vial is for single use only. Any vial that has been entered should be used promptly. Partially used vials should be discarded. GAMMAGARD LIQUID contains no preservative. • Allow refrigerated product to come to room temperature before use. DO NOT MICROWAVE. • Do not shake. • Do not mix with other products. • Do not use normal saline as a diluent. If dilution is desired, 5% dextrose in water (D5W) should be used as a diluent. • The infusion line may be flushed with normal saline. An in-line filter is optional. • Record the name and lot number of the product in the recipient's records.
Flexbumin

Flexbumin

FLEXBUMIN 25% must be administered intravenously.
• Do not use if turbid. • Do not begin administration more than 4 hours after the container has been entered. • Monitor hemodynamic parameters in patients receiving FLEXBUMIN 25% and check for the risk of hypervolemia and cardiovascular overload.[see Precautions]. Hypervolemia can occur if the dosage and rate of infusion are not adjusted, giving consideration to the solution concentration and the patient’s clinical status. • Do not dilute with Sterile Water for Injection as this can cause hemolysis in recipients [see Contraindications]. • Do not mix with other medicinal products including blood and blood components. FLEXBUMIN 25% can be used concomitantly with other parenterals such as whole blood, plasma, saline, glucose or sodium lactate when deemed medically necessary. The addition of four volumes of normal saline or 5% glucose to 1 volume of FLEXBUMIN 25% gives a solution which is approximately isotonic and isosmotic with citrated plasma. • Do not mix with protein hydrolysates or solutions containing alcohol since these combinations can cause the proteins to precipitate. • Do not add supplementary medication. • Record the name and batch number of the product in order to maintain a link between the patient and the batch of the product. • Discard unused portion.
Recommended Dosages

Hypovolemic Shock

The dosage of FLEXBUMIN 25% must be individualized. Initial dosage range for adults is 100 to 200 mL and for children 2.5 to 5 mL per kilogram body weight. Repeat after 15 to 30 minutes if the response is not adequate. Administer albumin replacement in the form of 5% Albumin (Human) in patients with significant plasma volume deficits.

Upon administration of additional albumin or if hemorrhage occurs, hemodilution and anemia can occur. Supplemental administration of compatible red blood cells or compatible whole blood may be required to treat this condition.

Burns

The optimal therapeutic regimen for administration of crystalloid and colloid solutions after extensive burns has not been established. Determine the appropriate dose according to the patient’s condition and response to treatment when FLEXBUMIN 25% is administered after the first 24 hours following burns.

Hypoalbuminemia

Hypoalbuminemia is usually accompanied by a hidden extravascular albumin deficiency of equal magnitude. Consider total body albumin deficit when determining the amount of albumin necessary to reverse the hypoalbuminemia. Calculate the body albumin compartment to be 80 to 100 mL per kg of body weight when using the patient’s serum albumin concentration to estimate the deficit.5,6 Do not exceed a daily dose of 2 g of albumin per kilogram of body weight.

Hemolytic Disease of the Newborn

Administer FLEXBUMIN 25% prior to or during exchange transfusion at a dose of 1 g per kilogram body weight.12

Preparation for Administration
• Check the GALAXY container for minute leaks prior to use by squeezing the bag firmly. If leaks are found, discard solution as sterility can be impaired. • Do not add supplementary medication. • Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. FLEXBUMIN 25% is a transparent or slightly opalescent solution, which may have a greenish tint or may vary from a pale straw to an amber color. Do not use unless solution is clear of particulate matter and seal is intact.
CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.

Administration:
1. Suspend container from eyelet support. 2. Remove plastic protector from outlet port at bottom of container.3. 3. Attach administration set. Refer to complete directions accompanying set. Make certain that the administration set contains an adequate filter (15-micron or smaller).
Flexbumin

Flexbumin

FLEXBUMIN 20% must be administered intravenously.
• Do not use if turbid. • Do not begin administration more than 4 hours after the container has been entered. • Monitor hemodynamic parameters in patients receiving FLEXBUMIN 20% and check for the risk of hypervolemia and cardiovascular overload.[see Precautions]. Hypervolemia can occur if the dosage and rate of infusion are not adjusted, giving consideration to the solution concentration and the patient’s clinical status. • Do not dilute with Sterile Water for Injection as this can cause hemolysis in recipients [see Contraindications]. • Do not mix with other medicinal products including blood and blood components. FLEXBUMIN 20% can be used concomitantly with other parenterals such as whole blood, plasma, saline, glucose or sodium lactate when deemed medically necessary. The addition of four volumes of normal saline or 5% glucose to 1 volume of FLEXBUMIN 20% gives a solution which is approximately isotonic and isosmotic with citrated plasma. • Do not mix with protein hydrolysates or solutions containing alcohol since these combinations can cause the proteins to precipitate. • Do not add supplementary medication. • Record the name and batch number of the product in order to maintain a link between the patient and the batch of the product. • Discard unused portion.
Recommended Dosages

Hypovolemic Shock

The dosage of FLEXBUMIN 20% must be individualized. Initial dosage range for adults is 125 to 250 mL and for children 3 to 6 mL per kilogram body weight. Repeat after 15 to 30 minutes if the response is not adequate. Administer albumin replacement in the form of 5% Albumin (Human) in patients with significant plasma volume deficits.

Upon administration of additional albumin or if hemorrhage occurs, hemodilution and anemia can occur. Supplemental administration of compatible red blood cells or compatible whole blood may be required to treat this condition.

Burns

The optimal therapeutic regimen for administration of crystalloid and colloid solutions after extensive burns has not been established. Determine the appropriate dose according to the patient’s condition and response to treatment when FLEXBUMIN 20% is administered after the first 24 hours following burns.

Hypoalbuminemia

Hypoalbuminemia is usually accompanied by a hidden extravascular albumin deficiency of equal magnitude. Consider total body albumin deficit when determining the amount of albumin necessary to reverse the hypoalbuminemia. Calculate the body albumin compartment to be 80 to 100 mL per kg of body weight when using the patient’s serum albumin concentration to estimate the deficit.5,6 Do not exceed a daily dose of 2 g of albumin per kilogram of body weight.

Hemolytic Disease of the Newborn

Administer FLEXBUMIN 20% prior to or during exchange transfusion at a dose of 1 g per kilogram body weight.12

Preparation for Administration
• Check the GALAXY container for minute leaks prior to use by squeezing the bag firmly. If leaks are found, discard solution as sterility can be impaired. • Do not add supplementary medication. • Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. FLEXBUMIN 20% is a transparent or slightly opalescent solution, which may have a greenish tint or may vary from a pale straw to an amber color. Do not use unless solution is clear of particulate matter and seal is intact.
CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.

Administration:
1. Suspend container from eyelet support. 2. Remove plastic protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set. Make certain that the administration set contains an adequate filter (15-micron or smaller).
Lactated Ringers

Lactated Ringers

As directed by a physician.

Cautions: Warm in oven to not more than 50°C for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only.
Advate

Advate

For Intravenous Use after Reconstitution Only
Initiate treatment with ADVATE under the supervision of a physician experienced in the treatment of Hemophilia A. Each vial of ADVATE has the recombinant Factor VIII potency in International Units stated on the label. The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or percent normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by 2. The dosage and duration of treatment depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient's clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. [See Dosage and Administration (2.1) and (2.2)]
The expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formulas:

IU/dL (or % of normal) = [Total Dose (IU)/body weight (kg)] × 2 [IU/dL]/[IU/kg]

OR

Dose (International Unit) = body weight (kg) × Desired Factor VIII Rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL)

Examples (assuming patient's baseline Factor VIII level is < 1% of normal):
A dose of 1750 IU ADVATE administered to a 70 kg patient should be expected to result in a peak post-infusion Factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal). A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU.
Base thedose and frequency on the individual clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to ADVATE. Although you can estimate the dose by the calculations above, whenever possible, perform appropriate laboratory tests including serial Factor VIII activity assays (see Warnings and Precautions [5.4] and Pharmacokinetics [12.3]).

2.1 Control and Prevention of Bleeding Episodes

A guide for dosing in the treatment of bleeding episodes is provided in Table 1. The careful control of treatment dose is especially important in cases of life-threatening bleeding episodes.
Table 1 ADVATE Dosing for Treatment of Bleeding Episodes in Adults and Children * Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL) Type of Bleeding Episodes Required Peak Post-infusion Factor VIII Activity in the Blood(as % of Normal or IU/dL) Dosage and Frequency Necessary to Maintain the Therapeutic Plasma Level MinorEarly hemarthrosis, mild muscle bleeding, or mild oral bleeding episode. 20-40 10-20 International Units per kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for one to three days until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved. ModerateModerate bleeding into muscles, bleeding into the oral cavity, definite hemarthroses, and known trauma. 30-60 15-30 International Units per kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for three days or more until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved. MajorSignificant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma. 60-100 Initial dose 30-50 International Units per kg* Repeat dose 30-50 International Units per kg every 8 to 24 hours (6 to 12 hours for patients under the age of 6) until resolution of the bleeding episode has occurred.
2.2 Perioperative Management

A guide for dosing in perioperative management is provided in Table 2. The careful control of dose and duration of treatment is especially important in cases of major surgery.
Table 2 ADVATE Dosing for Perioperative Management in Adults and Children Type of Surgery Required Peak Post-infusion Factor VIII Activity in the Blood (% of Normal or IU/dL) Frequency of Infusion * Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Minor

Including tooth extraction
60-100 A single bolus infusion (30-50 International Units/kg*) beginning within one hour of the operation. Optional additional dosing every 12 to 24 hours as needed to control bleeding. For dental procedures, adjunctive therapy may be considered.
Major

Examples include intracranial, intra-abdominal, or intrathoracic surgery, joint replacement surgery
80-120(pre- and post-operative)
Preoperative bolus infusion: 40-60 International Units/kg*. Verify 100% activity has been achieved prior to surgery.

Maintenance bolus infusion (40-60 International Unit/kg*) repeat infusions every 8 to 24 hours (6 to 24 hours for patients under the age of 6), depending on the desired level of Factor VIII and state of wound healing.

2.3 Routine Prophylaxis

For prevention of bleeding episodes, doses between 20 to 40 International Units of Factor VIII per kg body weight every other day (3 to 4 times weekly) may be utilized. Alternatively, an every third day dosing regimen targeted to maintain FVIII trough levels ≥ 1% may be employed. Adjust dose based on the patient’s clinical response.1,2

2.4 Instruction for Use

Administer ADVATE by intravenous (IV) injection after reconstitution. Ask patients to follow the specific preparation and administration procedures provided by their physicians.

For instructions, ask patients to follow the recommendations in the FDA-approved patient labeling (see FDA-approved patient labeling [17]).

Perform reconstitution, product administration, and handling of the administration set and needles with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted ADVATE, in an appropriate container.

2.5 Preparation and Reconstitution

The procedures below are provided as general guidelines for the preparation and reconstitution of ADVATE. Always work on a clean surface and wash your hands before performing the following procedures:
Bring the ADVATE (dry factor concentrate) and Sterile Water for Injection, USP (diluent) to room temperature. Remove caps from the factor concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place the vials on a flat surface. Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B). Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike. Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully into the ADVATE vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the ADVATE vial. Swirl gently until ADVATE is completely dissolved. Do not refrigerate after reconstitution.
2.6 Administration

ADVATE is for intravenous use after reconstitution only.
Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless in appearance. If not, do not use the solution and notify Baxter immediately. Administer ADVATE at room temperature within 3 hours of reconstitution. Use plastic syringes with this product because proteins in the product tend to stick to the surface of glass syringes.
Use aseptic technique. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). Do not inject air. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F). Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Administration by Bolus Infusion. If a patient is to receive more than one vial of ADVATE, the contents of multiple vials may be drawn into the same syringe. Please note that the BAXJECT II device is intended for use with a single vial of ADVATE and Sterile Water for Injection, USP, only; therefore, reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device. Administer ADVATE over a period of ≤ 5 minutes (maximum infusion rate 10 mL/min). Determine the pulse rate before and during administration of ADVATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly. Figure A Figure B Figure C

Figure D Figure E Figure F
Artiss

Artiss

FOR TOPICAL USE ONLY – DO NOT INJECT.

The amount of ARTISS to be applied must be individualized by the treating physician based on the size of the surface to be covered. The approximate surface areas covered by each package size of ARTISS are:
Table 1. Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL
It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain a link between the patient and product batch.

2.1 Preparation of ARTISS Kit (Freeze-Dried)

During preparation of ARTISS Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials:
-Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution
Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:
Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit. Excessive stirring (20 minutes or more) may compromise product quality. If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.
Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen)

During preparation of ARTISS (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT MICROWAVEDO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING

Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Approximate thawing times when using this method are:
Pack Size Room Temperature(In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes
Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes
Quick Thawing

Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Sterile Water Bath(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Non-Sterile Water Bath(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

2.3 Method of Application

Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Ensure that parts of the body outside the desired application area are sufficiently covered to prevent tissue adherence at undesired site.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant. The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application. The wound bed will glisten in the area to which fibrin sealant has been applied.

Any areas not covered by fibrin sealant will be clearly visible.

The skin flap or graft should be attached to the wound bed immediately after ARTISS has been sprayed. The surgeon has up to 60 seconds to manipulate and position the flap or graft prior to polymerization. The initial amount of the product to be applied should be sufficient to cover the intended application area.

The application can be repeated, if necessary, to any small areas that may not have been previously treated. To prevent adherence, wet gloves with normal saline before product contact.

After the flap or graft has been positioned, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.3)). Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) are administered.
Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System. Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece.
If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A

Vials and pre-filled syringes are for single use only. Discard unused contents.
Artiss

Artiss

FOR TOPICAL USE ONLY – DO NOT INJECT.

The amount of ARTISS to be applied must be individualized by the treating physician based on the size of the surface to be covered. The approximate surface areas covered by each package size of ARTISS are:
Table 1. Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL
It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain a link between the patient and product batch.

2.1 Preparation of ARTISS Kit (Freeze-Dried)

During preparation of ARTISS Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials:
-Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution
Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:
Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit. Excessive stirring (20 minutes or more) may compromise product quality. If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.
Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen)

During preparation of ARTISS (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT MICROWAVEDO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING

Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Approximate thawing times when using this method are:
Pack Size Room Temperature(In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes
Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes
Quick Thawing

Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Sterile Water Bath(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Non-Sterile Water Bath(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

2.3 Method of Application

Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Ensure that parts of the body outside the desired application area are sufficiently covered to prevent tissue adherence at undesired site.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant.

The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application. The wound bed will glisten in the area to which fibrin sealant has been applied. .

Any areas not covered by fibrin sealant will be clearly visible.

The skin flap or graft should be attached to the wound bed immediately after ARTISS has been sprayed. The surgeon has up to 60 seconds to manipulate and position the flap or graft prior to polymerization. The initial amount of the product to be applied should be sufficient to cover the intended application area.

The application can be repeated, if necessary, to any small areas that may not have been previously treated. To prevent adherence, wet gloves with normal saline before product contact.

After the flap or graft has been positioned, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.3)). Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) are administered.
Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System. Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece.
If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A

Vials and pre-filled syringes are for single use only. Discard unused contents.
Artiss

Artiss

FOR TOPICAL USE ONLY – DO NOT INJECT.

The amount of ARTISS to be applied must be individualized by the treating physician based on the size of the surface to be covered. The approximate surface areas covered by each package size of ARTISS are:
Table 1. Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL
It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain a link between the patient and product batch.

2.1 Preparation of ARTISS Kit (Freeze-Dried)

During preparation of ARTISS Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials:
-Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution
Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:
Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit. Excessive stirring (20 minutes or more) may compromise product quality. If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.
Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen)

During preparation of ARTISS (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT MICROWAVEDO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING

Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options

Room Temperature Thawing

Approximate thawing times when using this method are:
Pack Size Room Temperature(In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes
Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes
Quick Thawing

Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Sterile Water Bath(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Non-Sterile Water Bath(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

2.3 Method of Application

Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Ensure that parts of the body outside the desired application area are sufficiently covered to prevent tissue adherence at undesired site.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant.

The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application. The wound bed will glisten in the area to which fibrin sealant has been applied.

Any areas not covered by fibrin sealant will be clearly visible.

The skin flap or graft should be attached to the wound bed immediately after ARTISS has been sprayed. The surgeon has up to 60 seconds to manipulate and position the flap or graft prior to polymerization. The initial amount of the product to be applied should be sufficient to cover the intended application area.

The application can be repeated, if necessary, to any small areas that may not have been previously treated. To prevent adherence, wet gloves with normal saline before product contact.

After the flap or graft has been positioned, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.3)). Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) are administered.
Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System. Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece.
If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A

Vials and pre-filled syringes are for single use only. Discard unused contents.
Sevoflurane

Sevoflurane

The concentration of sevoflurane, USP being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane, USP. The administration of general anesthesia must be individualized based on the patient’s response.

Replacement of Dessicated CO2 Absorbents

When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane, USP and CO2 absorbents is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters (see PRECAUTIONS).

Pre-anesthetic Medication

No specific premedication is either indicated or contraindicated with sevoflurane, USP. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist.

Induction:

Sevoflurane, USP has a nonpungent odor and does not cause respiratory irritability; it is suitable for mask induction in pediatrics and adults.

Maintenance:

Surgical levels of anesthesia can usually be achieved with concentrations of 0.5-3% sevoflurane, USP with or without the concomitant use of nitrous oxide. Sevoflurane, USP can be administered with any type of anesthesia circuit.
Table 9: MAC Values for Adults and Pediatric Patients According to Age * Neonates are full-term gestational age. MAC in premature infants has not been determined. † In 1 - <3 year old pediatric patients, 60% N 2O/40% O 2 was used.
Age of Patient
(years)
Sevoflurane
in Oxygen Sevoflurane in 65%N2O/35% O2 0 - 1 months * 3.3% 1 - <6 months 3.0% 6 months - <3 years 2.8% 2.0%† 3 - 12 2.5% 25 2.6% 1.4% 40 2.1% 1.1% 60 1.7% 0.9% 80 1.4% 0.7%
Directions for Filling Vaporizers

Utilize an adapter, as appropriate, when filling the vaporizer with sevoflurane
Sodium Chloride

Sodium Chloride

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition, concomitant treatment, and on the patient’s clinical and laboratory response to treatment.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless solution is clear and seal is intact.

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers. Discard any unused portion.
Feiba Nf

Feiba Nf

Treatment should be initiated and supervised by a physician experienced in the management of hemophilia.

Clinical trials 1, 2 demonstrated that the response to treatment with FEIBA may differ from patient to patient with no correlation to the patient’s inhibitor titer. Response may also vary between different types of hemorrhage (e.g. joint hemorrhage vs. CNS hemorrhage). As a general guideline, a dosage range of 50 to 100 Units of FEIBA NF, per kg of body weight is recommended. However, care should be taken to distinguish between the following four indications:
Dosing Guidelines by Type of Hemorrhage * Begin treatment with 50 units/kg. Dose may be increased to 100 units/kg if hemorrhage does not stop. † Patients receiving more than 100 units/kg of body weight of FEIBA NF must be monitored for the development of DIC and/or symptoms of acute coronary ischemia. High doses of FEIBA NF should be given only as long as absolutely necessary to stop bleeding. Indication Units/kg of Body Weight Recommended Dosing Interval Additional Information Joint Hemorrhage 50 - 100* 12 hours
Continue treatment until clear signs of clinical improvement appear (e.g., relief of pain, reduction of swelling or mobilization of the joint).
Two administrations of 100 units/kg a day or a daily total dose of 200 units/kg should not normally be exceeded†. Mucous Membrane Bleeding 50 – 100* 6 hours
Carefully monitor patient (i.e., examine for cecessation of visible bleeding) and perform repeated measurements of the patient’s hemoglobin/hematocrit.
Two administrations of 100 units/kg a day or a daily total dose of 200 units/kg should not be exceeded†. Soft Tissue Hemorrhage(e.g., retroperitoneal bleeding) 100 12 hours A daily total dose of 200 units/kg should not be exceeded†. Other Severe Hemorrhage(e.g., CNS bleeds) 100 6-12 hours
May be indicated at 6-hour intervals until clear clinical improvement is achieved.
Single doses of 100 units/kg body weight and a daily dose of 200 units/kg body weight should not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses†.
Reconstitution

FEIBA NF contains no preservatives. Aseptic technique should be used throughout the entire reconstitution process and the solution should then be used immediately.
Allow the unopened vials of FEIBA NF (concentrate) and Sterile Water for Injection (diluent) to reach room temperature (not above 37°C, 98°F). Remove caps from the concentrate and diluent vials to expose central portions of the rubber stoppers. Disinfect the rubber stoppers of both vials using a germicidal solution. Place the vials on an even surface and allow them to dry. Open the package of BAXJECT device by peeling away the lid without touching the inside (Fig. A). Do not remove the device from the package. Turn the package over and insert the plastic spike through diluent stopper. (Fig. B). Grip the package at its edge and pull the package off the device (Fig. B). Turn the system over, so that the vial is on top. Quickly insert the other plastic spike into the FEIBA NF stopper (Fig. C). The vacuum will draw the diluent into the FEIBA NF vial. Please make sure that the connection of the two vials should be done expeditiously to close the open fluid pathway created by the first insertion of the spike to the diluent vial. Swirl gently until FEIBA NF is completely dissolved. Make sure that FEIBA NF has been dissolved completely; otherwise, active material will not pass through the device filter.
Fig A

Fig B

Fig C

Do not refrigerate after reconstitution!

After complete reconstitution of FEIBA NF its injection or infusion should be commenced as promptly as practicable, but must be completed within three hours following reconstitution. The solution must be given by intravenous injection or intravenous drip infusion.

Rate of Administration:

The maximum injection or infusion rate must not exceed 2 units per kg of body weight per minute. For a patient with a body weight of 75 kg, this corresponds to an infusion rate of 2.5 - 7.5 mL per minute depending on the number of units per vial (see label on vial).

Intravenous Injection or Infusion:
Inspect for particulate matter and discoloration after reconstituting the concentrate as described under Reconstitution prior to administration. The appearance of the solution should be colorless to slightly yellowish and essentially free of visible particles. Do not use solutions that are cloudy or have deposits. Mixing of FEIBA NF with other products or substances must be avoided. It is advisable to flush venous access lines with isotonic saline prior to and after infusion of FEIBA NF. If devices other than those supplied with FEIBA NF are used, ensure use of an adequate filter. Plastic Luer lock syringes are recommended for use with this product since protein such as FEIBA NF tends to stick to the surface of all-glass syringes. Turn the BAXJECT device handle down towards the FEIBA NF concentrate vial and remove the cap attached to the syringe connection of the BAXJECT device (Fig. D). Draw air into the syringe, connect the syringe to the BAXJECT device, inject air into the concentrate vial (Fig. E). While keeping the syringe plunger in place, turn the system upside down (concentrate vial now on top). Draw the concentrate into the syringe by pulling the plunger back slowly (Fig. F). Turn the BAXJECT handle to its original position (facing side way). Disconnect the syringe, attach a suitable needle and inject or infuse intravenously as instructed under Rate of Administration.
.

Fig D

Fig E

Fig F
Artiss

Artiss

FOR TOPICAL USE ONLY – DO NOT INJECT.

The amount of ARTISS to be applied must be individualized by the treating physician based on the size of the surface to be covered. The approximate surface areas covered by each package size of ARTISS are:
Table 1. Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL
It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain link between the patient and product batch.

2.1 Preparation of ARTISS Kit (Freeze-Dried)

During preparation of ARTISS Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials:
-Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution
Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.
Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.
Notes:
Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit. Excessive stirring (20 minutes or more) may compromise product quality. If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.
Preparation of Thrombin Solution with FIBRINOTHERM
Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.
Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen)

During preparation of ARTISS (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°CDO NOT MICROWAVEDO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING

Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Approximate thawing times when using this method are:
Pack Size Room Temperature(In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes
Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes
Quick Thawing

Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Sterile Water Bath(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes
Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Non-Sterile Water Bath(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes
Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are:
Pack Size 33°C to 37°C Incubator(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes
Maintain the product at 33-37°C until use. If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

2.3 Method of Application

Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Ensure that parts of the body outside the desired application area are sufficiently covered to prevent tissue adherence at undesired site.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant.

The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application. The wound bed will glisten in the area to which fibrin sealant has been applied.

Any areas not covered by fibrin sealant will be clearly visible.

The skin flap or graft should be attached to the wound bed immediately after ARTISS has been sprayed. The surgeon has up to 60 seconds to manipulate and position the flap or graft prior to polymerization. The initial amount of the product to be applied should be sufficient to cover the intended application area.

The application can be repeated, if necessary, to any small areas that may not have been previously treated. To prevent adherence, wet gloves with normal saline before product contact.

After the flap or graft has been positioned, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.3)). Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) are administered.
Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System. Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece.
If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A

Vials and pre-filled syringes are for single use only. Discard unused contents.
Ribavirin

Ribavirin

There is currently no dosage information available for this product. We apologize for any inconvenience.
Lactated Ringers

Lactated Ringers

The volume of slushed solution required will vary with patient’s age, clinical condition, cooling effect desired and duration of cooling effect desired, according to physician’s instructions.
Maximum Strength Laxati...

Maximum Strength Laxative

For intravenous injection after reconstitution only.

2.1 Dose
• Dosage and duration of treatment depend on the severity of factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. • Each vial of ADVATE has the recombinant factor VIII potency in International Units (IU) stated on the label. The expected in vivo peak increase in factor VIII level expressed as IU/dL of plasma or percent of normal can be estimated using the following formulas:
IU/dL (or % of normal) = [total dose (IU)/body weight (kg)] x 2 [IU/dL]/[IU/kg]

OR

Required dose (International Units) = body weight (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)

Examples (assuming patient's baseline factor VIII level is < 1% of normal):
1. A dose of 1750 IU ADVATE administered to a 70 kg patient should be expected to result in a peak post-infusion factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal). 2. A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU. • Base the dose and frequency on the individual clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to ADVATE. Although the dose can be estimated by the calculations above, whenever possible, perform appropriate laboratory tests including serial factor VIII activity assays. [see Warnings and Precautions (5.3) and Clinical Pharmacology ( 12.3)]
Control and Prevention of Bleeding Episodes

A guide for dosing ADVATE for the control and prevention of bleeding episodes is provided in Table 1. The goal of treatment is to maintain a plasma factor VIII activity level at or above the plasma levels (in % of normal or in IU/dL) outlined in Table 1.
Table 1 Dosing for Control and Prevention of Bleeding Episodes
Type of Bleeding Episodes

Factor VIII Level Required (% of normal or IU/dL)

Dose1

(IU/kg)

Frequency of Doses (hours)

Duration of Therapy (days)

Minor Early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode.

20-40

10-20

12-24

(Every 8 to 24 hours for patients under the age of 6)

Until the bleeding is

resolved

(approximately 1 to 3

days).

Moderate Muscle bleeding, bleeding into the oral cavity, definite hemarthroses, and known trauma.

30-60

15-30

12-24

(Every 8 to 24 hours for patients under the age of 6)

Until the bleeding is

resolved

(approximately 3 days

or more).

Major Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma.

60-100

30-50

8-24

(Every 6 to 12 hours for patients under the age of 6)

Until bleeding is resolved.

Perioperative Management

A guide for dosing ADVATE during surgery (perioperative management) is provided in Table 2. The goal of treatment is to maintain a plasma factor VIII activity level at or above the plasma level (in % of normal or in IU/dL) outlined in Table 2.
Table 2 Dosing for Perioperative Management Type of Surgery Factor VIII Level Required (% of normal or IU/dL) Dose1 (IU/kg) Frequency of Doses (hours) Duration of Therapy (days)
Minor

Including tooth extraction

60-100

30-50

Single dose within one hour of the operation.

12-24 (as needed to control bleeding)

Single dose or repeat until bleeding is resolved.

For dental procedures, adjunctive therapy may be considered.

Major

Intracranial, intra-abdominal, or intrathoracic surgery, joint replacement surgery

80-120(pre- and post-operative)

40-60

One dose preoperative to achieve 100% activity.

Every 8-24 to keep factor VIII activity in desired range.

(Every 6 to 24 hours for patients under the age of 6)

Until healing is complete.

Routine Prophylaxis
• Use dose of 20 to 40 International Units of factor VIII per kg body weight every other day (3 to 4 times weekly). • Alternatively, use every third day dosing regimen targeted to maintain FVIII trough levels ≥ 1%. • Adjust dose based on the patient’s clinical response. 1,2
2.2 Preparation and Reconstitution

Preparation
• Do not remove ADVATE or diluent vials from the external housing. • Always work on a clean surface and wash your hands before performing the procedures. • Examine the packaging containing ADVATE to ensure no damage or peeling of the lid is evident. Do not use if the lid is not completely sealed on the blister. Do not remove ADVATE or diluent vials from the external housing.
Reconstitution
1. Allow the ADVATE package to reach room temperature. 2. Open the package by peeling away the lid. Remove ADVATE from the package and verify that the expiration date on the label has not passed and the potency unit number is same as expected. Inspect parenteral drug products for discoloration and particulate matter. The ADVATE powder should be white to off-white in color and the diluent free from foreign particles. Do not use if the criteria are not met. 3. Place the ADVATE on a flat surface with the diluent vial on top (Figure A). The diluent vial has a blue stripe. Do not remove the blue cap until instructed in a later step. 4. With one hand holding the ADVATE housing, press down firmly on the diluent vial with the other hand until the system is fully collapsed and the diluent flows down into the ADVATE vial (Figure B). Do not tilt the system until the transfer is complete. 5. Verify that diluent transfer is complete. Swirl gently until the powder is completely dissolved (Figure C). Do not shake. Do not refrigerate after reconstitution.
Figure A

Figure B

Figure C

2.3 Administration

For intravenous injection after reconstitution only.
• Inspect parenteral drug products for particulate matter and discoloration prior to administration. The solution should be clear and colorless in appearance. If not, do not use the solution and notify Baxter immediately. • Administer ADVATE at room temperature within 3 hours of reconstitution. • Use plastic syringes with this product because proteins in the product tend to stick to the surface of glass syringes.
1. Use aseptic technique.

2. Remove the blue cap from the housing. Connect the syringe to the system (Figure D). Do not inject air into the ADVATE.

3. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure E).

4. Disconnect the syringe, attach a suitable needle, and inject intravenously as instructed. If a patient is to receive more than one ADVATE-BAXJECT III system or a combination of an ADVATE-BAXJECT II and an ADVATE-BAXJECT III system, the contents may be drawn into the same syringe.

5. Administer ADVATE over a period of ≤5 minutes (maximum infusion rate 10 mL/min). Determine the pulse rate before and during administration of ADVATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.

Figure D

Figure E

2.1 Dose
• Dosage and duration of treatment depend on the severity of factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. • Each vial of ADVATE has the recombinant factor VIII potency in International Units (IU) stated on the label. The expected in vivo peak increase in factor VIII level expressed as IU/dL of plasma or percent of normal can be estimated using the following formulas:
IU/dL (or % of normal) = [total dose (IU)/body weight (kg)] x 2 [IU/dL]/[IU/kg]

OR

Required dose (International Units) = body weight (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)

Examples (assuming patient's baseline factor VIII level is < 1% of normal):
1. A dose of 1750 IU ADVATE administered to a 70 kg patient should be expected to result in a peak post-infusion factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal). 2. A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU. • Base the dose and frequency on the individual clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to ADVATE. Although the dose can be estimated by the calculations above, whenever possible, perform appropriate laboratory tests including serial factor VIII activity assays. [see Warnings and Precautions (5.3) and Clinical Pharmacology ( 12.3)]
Control and Prevention of Bleeding Episodes

A guide for dosing ADVATE for the control and prevention of bleeding episodes is provided in Table 1. The goal of treatment is to maintain a plasma factor VIII activity level at or above the plasma levels (in % of normal or in IU/dL) outlined in Table 1.
Table 1 Dosing for Control and Prevention of Bleeding Episodes
Type of Bleeding Episodes

Factor VIII Level Required (% of normal or IU/dL)

Dose1

(IU/kg)

Frequency of Doses (hours)

Duration of Therapy (days)

Minor Early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode.

20-40

10-20

12-24

(Every 8 to 24 hours for patients under the age of 6)

Until the bleeding is

resolved

(approximately 1 to 3

days).

Moderate Muscle bleeding, bleeding into the oral cavity, definite hemarthroses, and known trauma.

30-60

15-30

12-24

(Every 8 to 24 hours for patients under the age of 6)

Until the bleeding is

resolved

(approximately 3 days

or more).

Major Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma.

60-100

30-50

8-24

(Every 6 to 12 hours for patients under the age of 6)

Until bleeding is resolved.

Perioperative Management

A guide for dosing ADVATE during surgery (perioperative management) is provided in Table 2. The goal of treatment is to maintain a plasma factor VIII activity level at or above the plasma level (in % of normal or in IU/dL) outlined in Table 2.
Table 2 Dosing for Perioperative Management Type of Surgery Factor VIII Level Required (% of normal or IU/dL) Dose1 (IU/kg) Frequency of Doses (hours) Duration of Therapy (days)
Minor

Including tooth extraction

60-100

30-50

Single dose within one hour of the operation.

12-24 (as needed to control bleeding)

Single dose or repeat until bleeding is resolved.

For dental procedures, adjunctive therapy may be considered.

Major

Intracranial, intra-abdominal, or intrathoracic surgery, joint replacement surgery

80-120(pre- and post-operative)

40-60

One dose preoperative to achieve 100% activity.

Every 8-24 to keep factor VIII activity in desired range.

(Every 6 to 24 hours for patients under the age of 6)

Until healing is complete.

Routine Prophylaxis
• Use dose of 20 to 40 International Units of factor VIII per kg body weight every other day (3 to 4 times weekly). • Alternatively, use every third day dosing regimen targeted to maintain FVIII trough levels ≥ 1%. • Adjust dose based on the patient’s clinical response. 1,2
Gammagard Sd

Gammagard Sd

For Intravenous Use Only

2.1 Preparation and Handling

Instruction for Reconstitution:

Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.

Reconstitution:

1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers, and cleanse stoppers with germicidal solution.

To make a 5% solution: Use the full volume of the diluent bottle

To make a 10% solution: Remove half of the volume of the diluent bottle

Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1. Required Diluent Volume to be Removed Concentration 2.5 g bottle 5 g bottle 10 g bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 25 ml 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper.

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.

4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent.

CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed.

CAUTION: Do not shake. Avoid foaming.

Discard transfer device after single use per local guidelines.

Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Do not use if particulate matter and/or discoloration is observed.

Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.

Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood.

Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2 °C to 8 °C). Record the date and time of reconstitution/pooling. Discard partially used vials.

2.2 Dose

Primary Immunodeficiency (PI)

The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.

B-cell Chronic Lymphocytic Leukemia (CLL)

The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4

Idiopathic Thrombocytopenic Purpura (ITP)

The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

Kawasaki Syndrome

The recommended dose of GAMMAGARD S/D for patients with Kawasaki Syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.5,7,8

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).
Gammagard Sd

Gammagard Sd

For Intravenous Use Only

2.1 Preparation and Handling

Instruction for Reconstitution:

Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.

Reconstitution:

1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers, and cleanse stoppers with germicidal solution.

To make a 5% solution: Use the full volume of the diluent bottle

To make a 10% solution: Remove half of the volume of the diluent bottle

Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1. Required Diluent Volume to be Removed Concentration 2.5 g bottle 5 g bottle 10 g bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 25 ml 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper.

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.

4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent.

CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed.

CAUTION: Do not shake. Avoid foaming.

Discard transfer device after single use per local guidelines.

Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Do not use if particulate matter and/or discoloration is observed.

Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.

Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood.

Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2 °C to 8 °C). Record the date and time of reconstitution/pooling. Discard partially used vials.

2.2 Dose

Primary Immunodeficiency (PI)

The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.

B-cell Chronic Lymphocytic Leukemia (CLL)

The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4

Idiopathic Thrombocytopenic Purpura (ITP)

The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

Kawasaki Syndrome

The recommended dose of GAMMAGARD S/D for patients with Kawasaki Syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.5,7,8

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).
Gammagard Sd

Gammagard Sd

For Intravenous Use Only

2.1 Preparation and Handling

Instruction for Reconstitution:

Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.

Reconstitution:

1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers, and cleanse stoppers with germicidal solution.

To make a 5% solution: Use the full volume of the diluent bottle

To make a 10% solution: Remove half of the volume of the diluent bottle

Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1. Required Diluent Volume to be Removed Concentration 2.5 g bottle 5 g bottle 10 g bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 25 ml 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper.

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.

4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent.

CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed.

CAUTION: Do not shake. Avoid foaming.

Discard transfer device after single use per local guidelines.

Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Do not use if particulate matter and/or discoloration is observed.

Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.

Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood.

Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2 °C to 8 °C). Record the date and time of reconstitution/pooling. Discard partially used vials.

2.2 Dose

Primary Immunodeficiency (PI)

The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.

B-cell Chronic Lymphocytic Leukemia (CLL)

The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4

Idiopathic Thrombocytopenic Purpura (ITP)

The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

Kawasaki Syndrome

The recommended dose of GAMMAGARD S/D for patients with Kawasaki Syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.5,7,8

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).
Potassium Chloride In S...

Potassium Chloride In Sodium Chloride

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of final filter is recommended during administration of all parenteral solutions, where possible.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Allergena Zone 1

Allergena Zone 1

OSMITROL Injection (Mannitol Injection, USP) should be administered only by intravenous infusion. The total dosage, concentration, and rate of administration should be governed by the nature and severity of the condition being treated, fluid requirement, and urinary output. The usual adult dosage ranges from 20 to 100 g in a 24 hour period, but in most instances an adequate response will be achieved at a dosage of approximately 50 to 100 g in a 24 hour period. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 mL/hour. This outline of administration and dosage is only a general guide to therapy.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Test Dose: A test dose of mannitol should be given prior to instituting OSMITROL Injection (Mannitol Injection, USP) therapy for patients with marked oliguria, or those believed to have inadequate renal function. Such a test dose may be approximately 0.2 g/kg body weight (about 75 mL of a 20% solution or 100 mL of a 15% solution) infused in a period of three to five minutes to produce a urine flow of at least 30 to 50 mL/hour. If urine flow does not increase, a second test dose may be given; if there is an inadequate response, the patient should be reevaluated.

Prevention of Acute Renal Failure (Oliguria): When used during cardiovascular and other types of surgery, 50 to 100 g of mannitol as a 5, 10, or 15% solution may be given. The concentration will depend upon the fluid requirements of the patient.

Treatment of Oliguria: The usual dose for treatment of oliguria is 100 g administered as a 15 or 20% solution.

Reduction of Intraocular Pressure: A dose of 1.5 to 2.0 g/kg as a 20% solution (7.5 to 10 mL/kg) or as a 15% solution (10 to 13 mL/kg) may be given over a period as short as 30 minutes in order to obtain a prompt and maximal effect. When used preoperatively the dose should be given one to one and one-half hours before surgery to achieve maximal reduction of intraocular pressure before operation.

Reduction of Intracranial Pressure: Usually a maximum reduction in intracranial pressure in adults can be achieved with a dose of 0.25 g/kg given not more frequently than every six to eight hours. An osmotic gradient between the blood and cerebrospinal fluid of approximately 10 mOsmol will yield a satisfactory reduction in intracranial pressure.

Adjunctive Therapy for Intoxications: As an agent to promote diuresis in intoxications, 5%, 10%, 15% or 20% mannitol is indicated. The concentration will depend upon the fluid requirement and urinary output of the patient.

Measurement of glomerular filtration rate by creatinine clearance may be useful for determination of dosage.

All injections in VIAFLEX containers are intended for intravenous administration using sterile equipment.

The use of supplemental additive medication is not recommended.
Prevantics

Prevantics

Organophosphate Poisoning

Treatment should include general supportive care, atropinization, and decontamination, in addition to the use of PROTOPAM Chloride. Treatment is most effective if initiated immediately after poisoning. Administration of PROTOPAM Chloride should be carried out slowly and, preferably, by infusion. If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used. Generally, little is accomplished if PROTOPAM Chloride is given more than 36 hours after termination of exposure to the poison. When the poison has been ingested, it is particularly important to take into account the likelihood of continuing absorption from the lower bowel since this constitutes new exposure and fatal relapses have been reported after initial improvement. In such cases, additional doses of PROTOPAM Chloride may be needed every three to eight hours. In effect, the patient should be “titrated” with PROTOPAM Chloride as long as signs of poisoning recur. As in all cases of organophosphate poisoning, care should be taken to keep the patient under observation for at least 48 to 72 hours.

If dermal exposure has occurred, clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol as soon as possible.

Supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control, may be necessary in cases of severe organophosphate poisoning.

Atropine should be given as soon as possible after hypoxemia is improved. Atropine should not be given in the presence of significant hypoxia due to the risk of atropine-induced ventricular fibrillation. In adults, atropine may be given intravenously in doses of 2 to 4 mg. This should be repeated at 5- to 10-minute intervals until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching).

Some degree of atropinization should be maintained for at least 48 hours, and until any depressed blood cholinesterase activity is reversed.

Use of morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers should be avoided in patients with organophosphate poisoning (see PRECAUTIONS, Drug Interactions). Prolonged paralysis has been reported in patients when succinylcholine is given with drugs having anticholinesterase activity; therefore, it should be used with caution.

After the effects of atropine become apparent, PROTOPAM Chloride may be administered.

Symptoms Of Nerve Agent And Insecticide Poisoning

PROTOPAM Chloride dosing is based, in part, on the severity of symptoms of nerve agent intoxication. These symptoms include the following:

MILD symptoms:
• Blurred vision and sore eyes • Teary eyes* • Runny nose* • Increased salivation such as sudden drooling* • Chest tightness or difficulty breathing • Tremors throughout the body or muscular twitching • Nausea and vomiting • Involuntary respiratory secretions
SEVERE symptoms:
• Strange or confused behavior • Severe difficulty breathing or respiratory secretions • Severe muscular twitching and general weakness** • Involuntary urination and defecation* • Convulsions • Unconsciousness
Symptoms in INFANTS AND YOUNG CHILDREN:

* These symptoms are sometimes observed in healthy infants and young children. In this age group, these symptoms are less reliable than other symptoms listed. Symptoms must be considered collectively when nerve agent or pesticide exposure is known or suspected.

** Infants may become drowsy or unconscious, with muscle floppiness rather than muscle twitching, soon after exposure to nerve agents or pesticides.

ADULT DOSING

ADULT INTRAVENOUS DOSING:

Refer to the Preparation for Administration section for instructions on reconstitution and dilution of PROTOPAM Chloride that result in a 10-20 mg/mL solution for intravenous infusion.

Inject an initial dose of 1000 to 2000 mg of PROTOPAM Chloride, preferably as an infusion in 100 mL of normal saline, over a 15- to 30-minute period. If this is not practical or if pulmonary edema is present, the dose should be given slowly (over not less than five minutes) by intravenous injection, as a 50 mg/mL solution in water (e.g., 1000 mg in 20 mL). A second dose of 1000 to 2000 mg may be indicated after about one hour if muscle weakness has not been relieved. Additional doses may be given every 10-12 hours if muscle weakness persists.

Intravenous administration of PROTOPAM Chloride should be carried out slowly and, preferably, by continuous or intermittent infusion, since temporary worsening of cholinergic manifestations (i.e. tachycardia, cardiac arrest, laryngospasm, and muscle rigidity or paralysis) may occur if PROTOPAM Chloride is infused too rapidly. The intermittent infusion rate should not exceed 200 mg/minute. If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used.

Evidence suggests that a loading dose followed by continuous intravenous infusion of PROTOPAM Chloride may maintain therapeutic levels longer than traditional short intermittent infusions therapy (see Pharmacokinetics).

ADULT INTRAMUSCULAR DOSING:

Refer to the Preparation for Administration section for instructions on reconstitution of PROTOPAM Chloride that result in an approximate 300 mg/mL solution for intramuscular administration.

Intramuscular dosing in adults should be based on the severity of clinical symptoms.

MILD SYMPTOMS
• For treatment of mild symptoms, administer a 600 mg (2 mL) intramuscular dose of PROTOPAM Chloride. Wait 15 minutes for PROTOPAM Chloride to take effect. • If, after 15 minutes, mild symptoms persist, then administer a second 600 mg (2 mL) intramuscular dose of PROTOPAM Chloride. • If, after an additional 15 minutes, mild symptoms continue to persist, a third 600 mg (2 mL) dose of PROTOPAM Chloride may be administered for a total cumulative dose of 1800 mg. • If at any time after the first dose, the patient develops severe symptoms, administer two additional 600 mg intramuscular doses in rapid succession for a total cumulative dose of 1800 mg of PROTOPAM Chloride.
SEVERE SYMPTOMS
• For treatment of severe symptoms, administer three 600 mg intramuscular doses (3 doses of 2 mL each) in rapid succession for a total dose of 1800 mg of PROTOPAM Chloride.
PERSISTENT SYMPTOMS
• If symptoms persist after administering the complete 1800 mg regimen (3 injections of 600 mg each), the series may be repeated beginning approximately 1 hour after administration of the last injection.
PEDIATRIC DOSING (FOR PATIENTS 16 YEARS AND UNDER)

PEDIATRIC INTRAVENOUS DOSING

Refer to the Preparation for Administration section for instructions on reconstitution and dilution of PROTOPAM Chloride that result in 10-20 mg/mL solution for intravenous infusion.

PROTOPAM Chloride can be given as intermittent intravenous infusions or as a loading dose followed by continuous intravenous infusion, depending upon the patient’s clinical condition. The specific dose given should depend upon the severity of the symptoms.

Loading Dose Following By Continuous Infusion

Administer a loading dose of 20-50 mg/kg (not to exceed 2000 mg/dose) over 15-30 minutes followed by a continuous infusion of 10-20 mg/kg/hour.

Intermittent Infusion Dosing

Administer an initial intermittent infusion of 20-50 mg/kg (not to exceed 2000 mg/dose) over 15-30 minutes. A second dose of 20-50 mg/kg may be indicated after about one hour if muscle weakness has not been relieved. Repeat dosing is permissible every 10-12 hours as needed.

If it is not practical to administer intermittent or continuous intravenous infusions, or if pulmonary edema is present, the 20-50 mg/kg dose should be given slowly (over not less than five minutes) by intravenous injection as a 50 mg/mL solution in water (see Preparation for Administration section). Additional doses may be given every 10-12 hours if muscle weakness persists.

PEDIATRIC INTRAMUSCULAR DOSING

Refer to the Preparation for Administration section for instructions on reconstitution of PROTOPAM Chloride that result in an approximate 300 mg/mL solution for intramuscular administration.

Intramuscular injections in children should be administered in the anterolateral aspect of the thigh to avoid the nerve, artery and vein, as well as the femur.

Pharmacokinetic modeling using published data from the scientific literature was conducted to derive intramuscular dosing recommendations in the pediatric population. The specific intramuscular dose of PROTOPAM Chloride should depend upon the severity of the symptoms.

MILD SYMPTOMS
• For the treatment of mild symptoms, administer a weight-appropriate intramuscular dose (see Table 1 below) of PROTOPAM Chloride. Wait 15 minutes for PROTOPAM Chloride to take effect. • If, after 15 minutes, mild symptoms persist, then administer a second weight-appropriate intramuscular dose of PROTOPAM Chloride. • If after an additional 15 minutes, mild symptoms continue to persist, a third weight-appropriate intramuscular dose of PROTOPAM Chloride may be administered. • The three PROTOPAM Chloride injections together are considered a single course of treatment, and the total amount of PROTOPAM Chloride administered per course of treatment (i.e., 3 weight-appropriate injections) should not exceed the total amounts listed in Table 1 below. • If at any time after the first dose, the patient develops severe symptoms, administer two additional weight-appropriate intramuscular doses of PROTOPAM Chloride in rapid succession.
SEVERE SYMPTOMS
• For treatment of severe symptoms, administer the weight-appropriate intramuscular dose (see Table 1 below) of PROTOPAM Chloride as three injections, in rapid succession, into the patient’s anterolateral thigh (see Table 1 below).
PERSISTENT SYMPTOMS
• If symptoms persist after administering a complete course (3 injections of the weight-appropriate dose each), the series may be repeated beginning approximately 1 hour after administration of the last injection. Table 1: Pediatric Intramuscular Dosing Recommendations* * Dosing is based on an approximate 300 mg/mL solution. † During the treatment of mild symptoms, if at any time after the first dose, the patient develops severe symptoms, administer two additional weight-appropriate intramuscular doses of PROTOPAM Chloride in rapid succession. ‡ Additional courses of PROTOPAM Chloride may be administered beginning one hour after the last injection. A single course consists of three separate, weight-appropriate injections, administered either with 15 minute inter-injection observation periods for patients with mild symptoms, or all in rapid succession for patients with severe symptoms. § Weight of 40 kg corresponds to approximately the 50th percentile for a 12 year old child per the weight-for-age percentile growth charts published by the Centers for Disease Control and Prevention in 2000. ¶ Adult Dose Per Injection is 600 mg; Total Adult Dose per Three-Injection Course is 1800 mg.
Weight in kg

Dose Per Injection†

Total Dose per Three-Injection Course‡

< 40kg

15 mg/kg

45 mg/kg

≥ 40 kg§

Use Adult Dosing Recommendations¶

Use Adult Dosing Recommendations

Anticholinesterase Overdosage

As an antagonist to such anticholinesterases as neostigmine, pyridostigmine, and ambenonium, which are used in the treatment of myasthenia gravis, PROTOPAM Chloride may be given in a dosage of 1000 to 2000 mg intravenously followed by increments of 250 mg every five minutes.

Preparation for Administration

PROTOPAM Chloride is supplied as 1000 mg single-dose vials for injection.

For INTRAVENOUS infusion: Reconstitute a single PROTOPAM Chloride 1000 mg vial by adding 20 mL of Sterile Water for Injection, USP, which results in a 50 mg/mL concentration.

The solution should further be diluted with Normal Saline for Injection, USP to achieve a concentration of 10 to 20 mg/mL (e.g. 1000 mg in 100 mL or 2000 mg in 100 mL).

For fluid restricted patients or for rapid administration (over at least 5 min), a maximum concentration of 50 mg/mL may be used.

For INTRAMUSCULAR injection: Reconstitute a single PROTOPAM Chloride 1000 mg vial by adding 3.3 mL of Sterile Water for Injection, USP for an approximate concentration of 300 mg/mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard unused solution after a dose has been withdrawn.
Lidocaine Hydrochloride...

Lidocaine Hydrochloride And Dextrose

Therapy of ventricular arrhythmias is often initiated with a single IV bolus of 50 to 100 mg of lidocaine hydrochloride injection. Following acute treatment by bolus in patients in whom arrhythmias tend to recur and who are incapable of receiving oral antiarrhythmic agents, intravenous infusion of Lidocaine Hydrochloride and 5% Dextrose Injection, USP is administered continuously at the rate of 1 to 4 mg/min (20 to 50 mcg/kg/min in the average 70 kg adult). The 0.4% solution (4 mg/mL) can be given at a rate of 15 to 60 mL/hr (0.25 to 1 mL/min). The 0.8% solution (8 mg/mL) can be given at a rate of 7.5 to 30 mL/hr (0.12 to 0.5 mL/min). Precise dose is determined by patient response.

“Pharmacokinetic data indicate reduced elimination of lidocaine after prolonged infusion (24 hours) with resultant prolongation of the half-life to approximately three times that seen following a single administration. Failure to adjust the rate of infusion in keeping with this altered ability to eliminate lidocaine may result in toxic accumulation of the drug in the patient’s serum.” 1

Intravenous infusions of lidocaine hydrochloride must be administered under constant ECG monitoring to avoid potential overdosage and toxicity. Intravenous infusion should be terminated as soon as the patient’s basic cardiac rhythm appears to be stable or at the earliest signs of toxicity. It should rarely be necessary to continue intravenous infusions beyond 24 hours. As soon as possible and when indicated, patients should be changed to an oral antiarrhythmic agent for maintenance therapy.

Caution: When administering lidocaine hydrochloride by continuous infusion, it is advisable to closely monitor the infusion rate. Administer Lidocaine Hydrochloride and 5% Dextrose Injection, USP only with a calibrated infusion device.

Pediatric: Although controlled clinical studies to establish pediatric dosing schedules have not been conducted, the American Heart Association’s Standards and Guidelines recommends a bolus dose of 1 mg/kg followed by an infusion rate of 30 µg/kg/min.2

Lidocaine hydrochloride should not be added to blood transfusion assemblies.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

Because dosages of this drug are titrated to response, no additives should be made to Lidocaine Hydrochloride and 5% Dextrose Injection, USP.
1 LeLorier, et al., Pharmacokinetics of lidocaine after prolonged intravenous infusions in uncomplicated myocardial infarction, Ann Int. Med. 87:700-702. 2 American Heart Association, Standards and Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC), JAMA Vol. 244. No. 5: 453-509.
Protective And Moisturi...

Protective And Moisturizing Skin

Oxacillin Injection, USP supplied as a premixed frozen solution is to be administered as a continuous or intermittent intravenous infusion. The usual dose recommendation is as follows:

Adults

250-500 mg

I.V. every 4-6 hours (mild to moderate infections)

1 gram

I.V. every 4-6 hours (severe infections)

This container system may be inappropriate for the dosage requirements for children, infants and neonates. Other dosage forms may be more appropriate.

Bacteriologic studies to determine the causative organisms and their susceptibility to oxacillin should always be performed. Duration of therapy varies with the type of severity of infection as well as the overall condition of the patient; therefore, it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with oxacillin should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic, and cultures are negative. Treatment of endocarditis and osteomyelitis may require a longer duration of therapy.

Concurrent administration of oxacillin and probenecid increases and prolongs serum penicillin levels. Probenecid decreases the apparent volume of distribution and slows the rate of excretion by competitively inhibiting renal tubular secretion of penicillin. Penicillin-probenecid therapy is generally limited to those infections where very high serum levels of penicillin are necessary.

With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not add supplementary medication to Oxacillin Injection, USP.

Store in a freezer capable of maintaining a temperature of -20°C/-4°F or less.

Directions for Use of GALAXY Plastic Container

Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). [DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION]. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Mix after solution has reached room temperature. Check for minute leaks by squeezing bag firmly. If leaks are found, discard solution as sterility may be impaired. Do not use if the solution is cloudy or precipitated or if seals are not intact. The thawed solution is stable for 21 days under refrigeration or 48 hours at room temperature. Do not refreeze.

Use sterile equipment.

Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for intravenous administration
1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set.
Golfers Skin Broad Spec...

Golfers Skin Broad Spectrum Spf 30 Plus Sunscreen

Following suitable admixture of prescribed drugs, the dosage is usually dependent upon age, weight and clinical condition of the patient as well as laboratory determinations. See directions accompanying drugs.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not administer unless solution is clear and seal is intact.

Use of a final filter is recommended during administration of all parenteral solutions where possible.

The dosage selection and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/ hypoglycemia. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

70% Dextrose Injection, USP in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures. Additives may be incompatible with the fluid withdrawn from this container. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of the 70% Dextrose Injection, USP.
Adenocard

Adenocard

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

As directed by a physician. Dosage, rate and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not administer unless the solution is clear and seal is intact.

Additives may be incompatible with PLASMA-LYTE A Injection pH 7.4 (Multiple Electrolytes Injection, Type 1, USP). As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of PLASMA-LYTE A Injection pH 7.4 (Multiple Electrolytes Injection, Type 1, USP) is appropriate. After addition, check for a possible color change and/or the appearance of precipitates, insoluble complexes or crystals.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible must not be used.When introducing additives to PLASMA-LYTE A Injection pH 7.4 (Multiple Electrolytes Injection, Type 1, USP), aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.
Phentermine Hydrochlori...

Phentermine Hydrochloride

As directed by a physician. Dosage is dependent upon the age, weight, and clinical condition of the patient as well as laboratory determinations. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile equipment.

The dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low weight infants, because of the increased risk of hyperglycemia/hypoglycemia. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Additives may be incompatible. Complete information is not available.

Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Methylprednisolone

Methylprednisolone

DIANEAL peritoneal dialysis solutions are intended for intraperitoneal administration only.

The mode of therapy, frequency of treatment, formulation, exchange volume, duration of dwell, and length of dialysis should be selected by the physician responsible for and supervising the treatment of the individual patient. DIANEAL should be administered at a rate that is comfortable for the patient, generally over a period of 10-20 minutes for a single exchange.

Patients on continuous ambulatory peritoneal dialysis (CAPD) typically perform 4 cycles per day (24 hours). Patients on automated peritoneal dialysis (APD) typically perform 4-5 cycles at night and up to 2 cycles during the day. The fill volume depends on body size, usually from 2.0 to 2.5 liters per 1.73m2.

To avoid the risk of severe dehydration and hypovolemia and to minimize the loss of protein, it is advisable to select the peritoneal dialysis solution with the lowest level of osmolarity consistent with the fluid removal requirements for that exchange. As the patient’s body weight becomes closer to the ideal dry weight, lowering the dextrose concentration of DIANEAL is recommended. DIANEAL 4.25% dextrose-containing solution has the highest osmolarity of the DIANEAL solutions and using it for all exchanges may cause dehydration.

Solutions that are cloudy, discolored, contain visible particulate matter, or show evidence of leakage should not be used.

Following use, the drained fluid should be inspected for the presence of fibrin or cloudiness which may indicate the presence of peritonitis.

For single use only. Discard unused portion.

It is recommended that patients being placed on peritoneal dialysis and/or their caretaker(s) should be appropriately trained.

Addition of Potassium

Potassium is omitted from DIANEAL solutions because dialysis may be performed to correct hyperkalemia. In situations where there is a normal serum potassium level or hypokalemia, the addition of potassium chloride (up to a concentration of 4 mEq/L) may be indicated to prevent severe hypokalemia. The decision to add potassium chloride should be made by the physician after careful evaluation of serum potassium.

Addition of Insulin

Patients with insulin-dependent diabetes may require modification of insulin dosage following initiation of treatment with DIANEAL. Appropriate monitoring of blood glucose should be performed when initiating DIANEAL in diabetic patients and insulin dosage adjusted if needed (see Warnings).

Addition of Heparin

No human drug interaction studies with heparin were conducted. In vitro studies demonstrated no evidence of incompatibility of heparin with DIANEAL.

Addition of Antibiotics

No formal clinical drug interaction studies have been performed. In vitro studies of the following medications have demonstrated stability with DIANEAL: amphotericin B, ampicillin, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, clindamycin, deferoxamine, erythromycin, gentamicin, linezolid, mezlocillin, miconazole, moxifloxacin, nafcillin, ofloxacin, penicillin G, piperacillin, sulfamethoxazole/trimethoprim, ticarcillin, tobramycin, and vancomycin. However, aminoglycosides should not be mixed with penicillins due to chemical incompatibility.

Directions for Use

For complete CAPD and APD system preparation, see directions accompanying ancillary equipment.

Aseptic technique must be used throughout the peritoneal dialysis procedure.

Warming

For patient comfort, DIANEAL can be warmed to 37°C (98°F). Only dry heat should be used. It is best to warm solutions within the overwrap using a heating pad. Do not immerse DIANEAL in water for warming. Do not use a microwave oven to warm DIANEAL.

To Open

To open, tear the overwrap down at the slit and remove the solution container. Some opacity of the plastic, due to moisture absorption during the sterilization process, may be observed. This does not affect the solution quality or safety and may often leave a slight amount of moisture within the overwrap. The opacity should diminish gradually.

Inspect for Container Integrity

Inspect the bag connector to ensure the tip protector (pull ring, blue pull tip, or blue twist-off tip) is attached. Do not use if the tip protector is not attached to the connector. Inspect the DIANEAL container for signs of leakage and check for minute leaks by squeezing the container firmly. If the container has frangible(s), inspect that they are positioned correctly and are not broken. Do not use DIANEAL if the frangible(s) are broken or leaks are suspected as sterility may be impaired.

For DIANEAL in ULTRABAG, inspect the tubing and drain container for presence of solution. Small droplets are acceptable, but if solution flows past the frangible prior to use, do not use and discard the units.

Adding Medications

Some drug additives may be incompatible with DIANEAL. See DOSAGE AND ADMINISTRATION section for additional information. If the resealable rubber plug on the medication port is missing or partly removed, do not use the product if medication is to be added.
1. Put on mask. Clean and/or disinfect hands. 2. Prepare medication port site using aseptic technique. 3. Using a syringe with a 1-inch long, 25- to 19-gauge needle, puncture the medication port and inject additive. 4. Reposition container with container ports up and evacuate medication port by squeezing and tapping it. 5. Mix solution and additive thoroughly.
Administration instructions for CAPD therapy using ULTRABAG containers

(Products listed in Tables 1-2)

Put on mask. Clean and/or disinfect hands. Using aseptic technique;
1) Uncoil tubing and drain bag, ensuring that the transfer set is closed. 2) Immediately attach the solution container to patient connector (transfer set). 3) Break the connector (Y-set) frangible. 4) Remove the tip protector from connector of solution container. Do not reuse the solution or container once the tip protector is removed. 5) Clamp solution line and then break frangible near solution bag. Hang solution container and place the drainage container below the level of the abdomen. 6) Open transfer set to drain the solution from abdomen. If drainage cannot be established, contact your clinician. When drainage complete, close transfer set. 7) Remove clamp from solution line and flush new solution to flow into the drainage container for 5 seconds to prime the line. Clamp drain line after flush complete. 8) Open transfer set to fill. When fill complete, close transfer set. 9) Disconnect ULTRABAG from transfer set and apply MINICAP. 10) Upon completion of therapy, discard any unused portion.
Administration instructions for APD therapy using containers with pull rings or blue pull tips

(Products listed in Tables 3-5)

Put on mask. Clean and/or disinfect hands. Using aseptic technique;
1) Remove the tip protector from connector of solution container. Do not reuse the solution or container once the tip protector is removed. 2) Immediately attach the solution container to an appropriate automated peritoneal dialysis set. 3) Continue therapy as instructed in user manual or directions accompanying tubing sets for automated peritoneal dialysis. 4) Upon completion of therapy, discard any unused portion.
Administration instructions for APD therapy using containers with blue twist-off tips

(Products listed in Table 6)

Put on mask. Clean and/or disinfect hands. Using aseptic technique;
1) Place and fasten blue outlet port clamp on solution bag administration port, between the blue connector and the solution container. 2) Twist off the blue twist-off tip from connector of solution container. Once the blue twist-off tip has been removed do not reuse the solution or container. 3) Remove the blue twist-off tip from connector of solution container. Do not reuse the solution or container once the blue twist-off tip is removed. 4) Continue therapy as instructed in user manual or directions accompanying tubing sets for automated peritoneal dialysis. 5) Upon completion of therapy, discard any unused portion.
Bupivacaine Hydrochlori...

Bupivacaine Hydrochloride

Ifosfamide for Injection should be administered intravenously at a dose of 1.2 grams per m2 per day for 5 consecutive days. Treatment is repeated every 3 weeks or after recovery from hematologic toxicity.

In order to prevent bladder toxicity, Ifosfamide for Injection should be given with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day. Mesna should be used to reduce the incidence of hemorrhagic cystitis. Ifosfamide for Injection should be administered as a slow intravenous infusion lasting a minimum of 30 minutes. Studies of Ifosfamide for Injection in patients with hepatic or renal impairment have not been conducted [see Use in Specific Populations (8.6, 8.7)].

Injections are prepared for parenteral use by adding Sterile Water for Injection, USP or Bacteriostatic Water for Injection, USP (benzyl alcohol or parabens preserved), to the vial and shaking to dissolve. Before parenteral administration, the substance must be completely dissolved. Use the quantity of diluents shown below to constitute the product:

Dosage Strength

Quantity of Diluent

Final Concentration

1 gram

20 mL

50 mg per mL

3 grams

60 mL

50 mg per mL

Solutions of ifosfamide may be diluted further to achieve concentrations of 0.6 to 20 mg/mL in the following fluids:
5% Dextrose Injection, USP 0.9% Sodium Chloride Injection, USP Lactated Ringer's Injections, USP Sterile Water for Injection, USP
Because essentially identical stability results were obtained for Sterile Water admixtures as for the other admixtures (5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer’s Injection), the use of large volume parenteral glass bottles, VIAFLEX bags or PAB bags that contain intermediate concentrations or mixtures of excipients (e.g., 2.5% Dextrose Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection) is also acceptable.

Constituted or constituted and further diluted solutions of Ifosfamide for Injection should be refrigerated and used within 24 hours. Benzyl-alcohol-containing solutions can reduce the stability of ifosfamide.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Intralipid

Intralipid

There is currently no dosage information available for this product. We apologize for any inconvenience.
Cyclophosphamide

Cyclophosphamide

During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide should be administered in the morning.

2.1 Dosing for Malignant Diseases

Adults and Pediatric Patients Intravenous When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

Oral

Oral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.

When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide as well as that of the other drugs.

2.2 Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients

An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males [see Use in Specific Populations (8.4)].

2.3 Preparation, Handling and Administration

Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing Cyclophosphamide for Injection, USP (lyophilized powder), or bottles containing cyclophosphamide tablets. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide for Injection, USP (lyophilized powder), or bottles containing cyclophosphamide tablets. The coating of the cyclophosphamide tablets prevents direct contact of persons handling the tablets with the active substance. However, to prevent inadvertent exposure to the active substance, the cyclophosphamide tablets should not be cut, chewed, or crushed. Personnel should avoid exposure to broken tablets. If contact with broken tablets occurs, wash hands immediately and thoroughly.

Cyclophosphamide for Injection, USP

Intravenous Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide vials if there are signs of melting. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.

Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.

For Direct Intravenous Injection

Reconstitute Cyclophosphamide with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.
Table 1: Reconstitution for Direct Intravenous Injection Strength Volume of 0.9% Sodium Chloride
Cyclophosphamide
Concentration 500 mg 25 mL 1 g 50 mL 20 mg per mL 2 g 100 mL
For Intravenous Infusion

Reconstitution of Cyclophosphamide:Reconstitute Cyclophosphamide using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.
Table 2: Reconstitution in preparation for Intravenous Infusion Strength Volume of Diluent
Cyclophosphamide
Concentration 500 mg 25 mL 1 g 50 mL 20 mg per mL 2 g 100 mL
Dilution of Reconstituted Cyclophosphamide:Further dilute the reconstituted Cyclophosphamide solution to a minimum concentration of 2 mg per mL with any of the following diluents:
5% Dextrose Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP
To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.

Storage of Reconstituted and Diluted Cyclophosphamide Solution:

If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 3:
Table 3: Storage of Cyclophosphamide Solutions * Storage time is the total time cyclophosphamide is in solution including the time it is reconstituted in 0.9% Sterile Sodium Chloride Injection, USP or Sterile Water for Injection, USP. Diluent Storage Room Temperature Refrigerated Reconstituted Solution (Without Further Dilution) 0.9% Sodium Chloride Injection, USP up to 24 hrs Up to 6 days Sterile Water for Injection, USP Do not store; use immediately Diluted Solutions * 0.45% Sodium Chloride Injection, USP up to 24 hrs up to 6 days 5% Dextrose Injection, USP up to 24 hrs up to 36 hrs 5% Dextrose and 0.9% Sodium Chloride Injection, USP up to 24 hrs up to 36 hrs
Use of Reconstituted Solution for Oral Administration

Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF) Such preparations should be stored under refrigeration in glass containers and used within 14 days.
Mucus Relief Dm

Mucus Relief Dm

All injections in VIAFLO plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition, concomitant treatment, and on the patient’s clinical and laboratory response to treatment.

When other electrolytes or medicines are added to this solution, the dosage and the infusion rate will also be dictated by the dose regimen of the additions.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless the solution is clear and seal is intact.

Additives may be incompatible with Sodium Chloride Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Sodium Chloride Injection, USP is appropriate. After addition, check for unexpected color changes and/or the appearance of precipitates, insoluble complexes or crystals.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible must not be used. When introducing additives to Sodium Chloride Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers. Discard any unused portion.
Transderm Scop

Transderm Scop

Each Transderm Scōp® patch is formulated to deliver in-vivo approximately 1mg of scopolamine over 3 days. Only one patch should be worn at any time. Do not cut the patch.The patch should be applied only to the skin in the postauricular (hairless area behind one ear) area.

HandlingAfter the patch is applied on the dry skin behind the ear, the hands should be washed thoroughly with soap and water and dried. Upon removal, the patch should be discarded. To prevent any traces of scopolamine from coming into direct contact with the eyes, after administration of the patch, the hands and the application site should be washed thoroughly with soap and water and dried. [see How Supplied/Storage and Handling (16) and Patient Counseling Information (17)]

2.1 Initiation of Therapy

Motion Sickness
To prevent the nausea and vomiting associated with motion sickness, one Transderm Scōp® patch (formulated to deliver approximately 1mg of scopolamine over 3 days) should be applied to the hairless area behind one ear at least 4 hours before the antiemetic effect is required.
Post Operative Nausea and Vomiting
To prevent post operative nausea and vomiting, one Transderm Scōp® patch should be applied the evening before scheduled surgery, except for caesarian section. For caesarian section surgery, to minimize exposure of the newborn baby to the drug, apply the patch one hour prior to caesarian section
2.2 Continuation of Therapy

Should the patch become displaced, it should be discarded, and a fresh one placed on the hairless area behind the other ear.

Motion SicknessIf therapy is required for longer than 3 days, the first patch should be removed and a fresh one placed on the hairless area behind the other ear.

Post Operative Nausea and VomitingFor perioperative use, the patch should be kept in place for 24 hours following surgery at which time it should be removed and discarded.
Cyclophosphamide

Cyclophosphamide

During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide should be administered in the morning.

2.1 Dosing of Malignant Diseases

Adults and Pediatric Patients

Intravenous When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

Oral Oral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.

When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide as well as that of the other drugs.

2.2 Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients

An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males [see Use in Specific Populations (8.4)].

2.3 Preparation, Handling and Administration

Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing Cyclophosphamide for Injection, USP. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide for Injection, USP.

Cyclophosphamide for Injection, USP

Intravenous Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide vials if there are signs of melting. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.

Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.

For Direct Intravenous Injection

Reconstitute Cyclophosphamide with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.
Table 1: Reconstitution for Direct Intravenous Injection
Strength

Volume of 0.9% Sodium Chloride

Cyclophosphamide Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

For Intravenous Infusion

Reconstitution of Cyclophosphamide:Reconstitute Cyclophosphamide using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.
Table 2: Reconstitution in preparation for Intravenous Infusion
Strength

Volume of Diluent

Cyclophosphamide

Concentration

500 mg

25 mL

1 g

50 mL

20 mg per mL

2 g

100 mL

Dilution of Reconstituted Cyclophosphamide:Further dilute the reconstituted Cyclophosphamide solution to a minimum concentration of 2 mg per mL with any of the following diluents:
• 5% Dextrose Injection, USP • 5% Dextrose and 0.9% Sodium Chloride Injection, USP • 0.45% Sodium Chloride Injection, USP
To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.

Storage of Reconstituted and Diluted Cyclophosphamide Solution:

If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 3.
Table 3: Storage of Cyclophosphamide Solutions * Storage time is the total time cyclophosphamide is in solution including the time it is reconstituted in 0.9% Sterile Sodium Chloride Injection, USP or Sterile Water for Injection, USP.
Diluent

Storage

Room Temperature

Refrigerated

Reconstituted Solution (Without Further Dilution)

0.9% Sodium Chloride Injection, USP

up to 24 hrs

Up to 6 days

Sterile Water for Injection, USP

Do not store; use immediately

Diluted Solutions*

0.45% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

5% Dextrose Injection, USP

up to 24 hrs

up to 36 hrs

5% Dextrose and 0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 36 hrs

Use of Reconstituted Solution for Oral Administration

Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF). Such preparations should be stored under refrigeration in glass containers and used within 14 days.
Alendronate Sodium

Alendronate Sodium

2.1 Intravenous Dosing

MESNEX may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below.

MESNEX injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage weight by weight (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of ifosfamide. The total daily dose of MESNEX is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below in Table 1.
Table 1. Recommended Intravenous Dosing Schedule * The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of MESNEX to ifosfamide should be maintained.

0 Hours

4 Hours

8 Hours

Ifosfamide

1.2 g/m2

–

–

MESNEX Injection*

240 mg/m2

240 mg/m2

240 mg/m2

2.2 Intravenous and Oral Dosing

MESNEX may be given on a fractionated dosing schedule of a single bolus injection followed by two oral administrations of MESNEX tablets as outlined below.

MESNEX injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration. MESNEX tablets are given orally in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. The total daily dose of MESNEX is 100% of the ifosfamide dose. The recommended dosing schedule is outlined in Table 2.
Table 2. Recommended Intravenous and Oral Dosing Schedule * The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of MESNEX to ifosfamide should be maintained.

0 Hours

2 Hours

6 Hours

Ifosfamide

1.2 g/m2

–

–

MESNEX injection*

240 mg/m2

–

–

MESNEX tablets

–

480 mg/m2

480 mg/m2

The efficacy and safety of this ratio of intravenous and oral MESNEX has not been established as being effective for daily doses of ifosfamide higher than 2 g/m2.

Patients who vomit within two hours of taking oral MESNEX should repeat the dose or receive intravenous MESNEX.

2.3 Monitoring for Hematuria

Maintain adequate hydration and sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. If severe hematuria develops when MESNEX is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.

2.4 Preparation for Intravenous Administration and Stability

Preparation

Determine the volume of MESNEX injection for the intended dose.

Dilute the volume of MESNEX injection for the dose in any of the following fluids to obtain a final concentration of 20 mg/mL:
• 5% Dextrose Injection, USP • 5% Dextrose and 0.2% Sodium Chloride Injection, USP • 5% Dextrose and 0.33% Sodium Chloride Injection, USP • 5% Dextrose and 0.45% Sodium Chloride Injection, USP • 0.9% Sodium Chloride Injection, USP • Lactated Ringer’s Injection, USP
Stability

The MESNEX injection multidose vials may be stored and used for up to 8 days after initial puncture.

Store diluted solutions at 25°C (77°F). Use diluted solutions within 24 hours.

Do not mix MESNEX injection with epirubicin, cyclophosphamide, cisplatin, carboplatin, and nitrogen mustard.

The benzyl alcohol contained in MESNEX injection vials can reduce the stability of ifosfamide. Ifosfamide and MESNEX may be mixed in the same bag provided the final concentration of ifosfamide does not exceed 50 mg/mL. Higher concentrations of ifosfamide may not be compatible with MESNEX and may reduce the stability of ifosfamide.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any solutions which are discolored, hazy, or contain visible particulate matter should not be used.
Sodium Chloride

Sodium Chloride

All injections in AVIVA plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition, concomitant treatment, and on the patient’s clinical and laboratory response to treatment.

When other electrolytes or medicines are added to this solution, the dosage and the infusion rate will also be dictated by the dose regimen of the additions.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless solution is clear and seal is intact.

Additives may be incompatible with Sodium Chloride Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Sodium Chloride Injection, USP is appropriate. After addition, check for unexpected color changes and/or the appearance of precipitates, insoluble complexes or crystals.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible must not be used. When introducing additives to Sodium Chloride Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers. Discard any unused portion.
Good Neighbor Pharmacy ...

Good Neighbor Pharmacy Pain Relief All Day

• do not take more than directed • the smallest effective dose should be used • drink a full glass of water with each dose
Adults and children 12 years and older:
• take 1 caplet every 8 to 12 hours while symptoms last • for the first dose you may take 2 caplets within the first hour • do not exceed 2 caplets in any 8- to 12-hour period • do not exceed 3 caplets in a 24-hour period
Children under 12 years:
• ask a doctor
Shoprite Childrens Acet...

Shoprite Childrens Acetaminophen

During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide should be administered in the morning.

2.1 Dosing for Malignant Diseases

Adults and Pediatric PatientsIntravenous When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

OralOral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.

When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide as well as that of the other drugs.

2.2 Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients

An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males [see Use in Specific Populations (8.4)].

2.3 Preparation, Handling and Administration

Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing Cyclophosphamide for Injection, USP. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide for Injection, USP.

Cyclophosphamide for Injection, USP

Intravenous Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide vials if there are signs of melting. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.

Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.

For Direct Intravenous Injection

Reconstitute Cyclophosphamide with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.
Table 1: Reconstitution for Direct Intravenous Injection
Strength

Volume of0.9% Sodium Chloride

CyclophosphamideConcentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

For Intravenous Infusion

Reconstitution of Cyclophosphamide:Reconstitute Cyclophosphamide using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.
Table 2: Reconstitution in preparation for Intravenous Infusion
Strength

Volume ofDiluent

CyclophosphamideConcentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

Dilution of Reconstituted Cyclophosphamide:Further dilute the reconstituted Cyclophosphamide solution to a minimum concentration of 2 mg per mL with any of the following diluents:
• 5% Dextrose Injection, USP • 5% Dextrose and 0.9% Sodium Chloride Injection, USP • 0.45% Sodium Chloride Injection, USP
To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.

Storage of Reconstituted and Diluted Cyclophosphamide Solution:

If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 3.
Table 3: Storage of Cyclophosphamide Solutions * Storage time is the total time cyclophosphamide is in solution including the time it is reconstituted in 0.9% Sterile Sodium Chloride Injection, USP or Sterile Water for Injection, USP.
Diluent

Storage

Room Temperature

Refrigerated

Reconstituted Solution (Without Further Dilution)

0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

Sterile Water for Injection, USP

Do not store; use immediately

Diluted Solutions*

0.45% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

5% Dextrose Injection, USP

up to 24 hrs

up to 36 hrs

5% Dextrose and 0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 36 hrs

Use of Reconstituted Solution for Oral Administration

Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF). Such preparations should be stored under refrigeration in glass containers and used within 14 days.
Gammagard Sd

Gammagard Sd

For Intravenous Use Only

2.1 Preparation and Handling

Instruction for Reconstitution:

Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.

Reconstitution:

1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers and cleanse stoppers with germicidal solution.
To make a 5% solution: Use the full volume of the diluent bottle To make a 10% solution: Remove half of the volume of the diluent bottle

Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1 Required Diluent Volume to be Removed 5g 10g Concentration bottle bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.

4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent. CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed. CAUTION: Do not shake. Avoid foaming. Discard transfer device after single use per local guidelines.
Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed. Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter. Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood. Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2°C to 8°C). Record the date and time of reconstitution/pooling. Discard partially used vials.
2.2 Dose

Primary Immunodeficiency (PI)

The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.

B-cell Chronic Lymphocytic Leukemia (CLL)

The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4

Idiopathic Thrombocytopenic Purpura (ITP)

The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

Kawasaki Syndrome

The recommended dose of GAMMAGARD S/D for patients with Kawasaki syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses).5,7,8

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site [see Adverse Reactions (6)].

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrate up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) [see Warnings and Precautions (5.3)].

2.1 Preparation and Handling

Instruction for Reconstitution:

Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.

Reconstitution:

1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers and cleanse stoppers with germicidal solution.
To make a 5% solution: Use the full volume of the diluent bottle To make a 10% solution: Remove half of the volume of the diluent bottle

Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1 Required Diluent Volume to be Removed 5g 10g Concentration bottle bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.

4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.

Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent. CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed. CAUTION: Do not shake. Avoid foaming. Discard transfer device after single use per local guidelines.
Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed. Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter. Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood. Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2°C to 8°C). Record the date and time of reconstitution/pooling. Discard partially used vials.
2.2 Dose

Primary Immunodeficiency (PI)

The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.

B-cell Chronic Lymphocytic Leukemia (CLL)

The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4

Idiopathic Thrombocytopenic Purpura (ITP)

The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

Kawasaki Syndrome

The recommended dose of GAMMAGARD S/D for patients with Kawasaki syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses).5,7,8
Sodium Chloride Irrigan...

Sodium Chloride Irrigant

The volume of slushed solution required will vary with patient’s age, clinical condition, cooling effect desired and duration of cooling effect desired, according to physician’s instructions.
Gammagard Sd

Gammagard Sd

For Intravenous Use Only

2.1 Preparation and Handling

Instruction for Reconstitution:

Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.

Reconstitution:

1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers, and cleanse stoppers with germicidal solution.
To make a 5% solution: Use the full volume of the diluent bottle To make a 10% solution: Remove half of the volume of the diluent bottle

Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1 Required Diluent Volume to be Removed Concentration 2.5 g bottle 5 g bottle 10 g bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 25 ml 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.

3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper.

CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.

3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.

While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.

4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent. Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.

5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent.

CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.

5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.

6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed. CAUTION: Do not shake. Avoid foaming.

Discard transfer device after single use per local guidelines.
Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed. Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter. Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood. Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2°C to 8°C). Record the date and time of reconstitution/pooling. Discard partially used vials.
2.2 Dose

Primary Immunodeficiency (PI)

The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.

B-cell Chronic Lymphocytic Leukemia (CLL)

The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4

Idiopathic Thrombocytopenic Purpura (ITP)

The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

Kawasaki Syndrome

The recommended dose of GAMMAGARD S/D for patients with Kawasaki syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses).5,7,8

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site [see Adverse Reactions (6)].

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrate up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) [see Warnings and Precautions (5.3)].

2.3 Administration

Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.

The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.

It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site [see Adverse Reactions (6)].

Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.

There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrate up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) [see Warnings and Precautions (5.3)].
Protonix Delayed-releas...

Protonix Delayed-release

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless solution is clear and seal is intact.

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile equipment.

The dosage selection and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/ hypoglycemia. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Tachosil

Tachosil

For topical use on cardiovascular or hepatic tissue only
• Determine the number of patches to be applied by the size of the bleeding area. • Apply the yellow, active side of the patch to the bleeding area. • When applying TachoSil, do not exceed the maximum number of patches shown in Table 1 [see Warnings and Precautions (5.6)].
Table 1. Amount of Fibrinogen and Thrombin per Total Patch Size and Maximum Number of TachoSil Patches to be Applied

TachoSil Patch Size

Human Fibrinogen (mg)

Human Thrombin (Units)

Maximum Number of Patches to be Applied

3.7 inch x 1.9 inch(9.5 cm x 4.8 cm)

337.4

123.1

10

1.9 inch x 1.9 inch(4.8 cm x 4.8 cm)

170.5

62.2

14

1.2 inch x 1.0 inch(3.0 cm x 2.5 cm)

55.5

20.3

42

2.1 Preparation for Application

TachoSil comes ready to use in sterile packages and must be handled using sterile technique in aseptic conditions. Discard damaged packages as resterilization is not possible.
• When in the operating room, the outer aluminum foil pouch may be opened in a non-sterile environment (Fig. 1A). The inner sterile blister must be opened in a sterile environment (Fig. 1B). • Remove the TachoSil patch from the blister (Fig. 1C), which can be used as a container for pre-moistening of the patch, if needed. • Determine the size of patch(es) to be applied to the bleeding surface. Select the appropriate TachoSil patch so that it extends 1 to 2 cm beyond the margins of the wound. The patch can be cut to the correct size and shape if desired (Fig. 1D). If more than one patch is used, overlap patches by at least 1 cm. • Prior to application, cleanse the area to be treated to remove disinfectants and other fluids. The fibrinogen and thrombin proteins can be denatured by alcohol, iodine or heavy metal ions. If any of these substances have been used to clean the wound area, thoroughly irrigate the area before the application of TachoSil. • Apply TachoSil directly to the bleeding area either wet or dry. If applied wet, pre-moisten TachoSil in 0.9% saline solution for no more than one minute and then apply immediately. In the case of a wet tissue surface (e.g., oozing bleeding) TachoSil may be applied without pre-moistening.
Figure 1: Pictures illustrating steps for preparation for application of TachoSil

A

B

C

D

2.2 Method of Application

•     Cleanse surgical instruments and gloves with saline solution to reduce the adherence to the TachoSil patch. The white, inactive side of TachoSil may also adhere to surgical instruments (e.g., forceps) or gloves covered with blood due to the affinity of collagen to blood.

•     Apply the yellow, active side of the patch to the bleeding area (Fig. 2A) and hold in place with gentle pressure applied through moistened gloves or a moist pad for at least three minutes (Fig. 2B).

•     To avoid pulling the patch loose, first place a clean surgical instrument at one end of the patch before relieving the pressure (Fig. 2C). Gentle irrigation may also aid in removing the pre-moistened pad or gloved hand without removing TachoSil from the bleeding area.

•     Leave TachoSil in place once it adheres to organ tissue. Only remove unattached TachoSil patches (or part of) and replace with new patches.

•     TachoSil cannot be resterilized once removed from inner pouch. Discard unused, opened packages of TachoSil at the end of the procedure.

Figure 2: Pictures illustrating steps for method of application of TachoSil

A

B

C

Record patient name and TachoSil batch number every time that TachoSil is administered to a patient.

2.3 Retreatment

If not satisfied with the placement of the patch, or if bleeding still occurs during or after the specified duration of compression, repeat application procedure above. Do not remove already applied TachoSil.
Extraneal

Extraneal

2.1 Basic Dosing Information

EXTRANEAL is intended for intraperitoneal administration only. Not for intravenous injection. Administer as a single daily exchange for the long dwell in continuous ambulatory peritoneal dialysis or automated peritoneal dialysis. The recommended dwell time is 8- to 16- hours. Administer over a period of 10-20 minutes at a rate that is comfortable for the patient.

The mode of therapy, frequency of treatment, exchange volume, duration of dwell, and length of dialysis should be initiated and supervised by the prescribing physician experienced in the treatment of end-stage renal disease with peritoneal dialysis. It is recommended that patients being placed on peritoneal dialysis should be appropriately trained in a program that is under supervision of a physician.

2.2 Directions for Use

For complete CAPD and APD system preparation, see directions accompanying ancillary equipment.

Aseptic technique should be used throughout the peritoneal dialysis procedure.

For single use only.

Storage

Store in moisture barrier overwrap and in carton until ready to use [see How Supplied/Storage and Handling (16)].

Warming

For patient comfort, EXTRANEAL can be warmed to 37°C (98.6°F). Only dry heat should be used. It is best to warm solutions within the overwrap using a heating pad. Do not immerse EXTRANEAL in water for warming. Do not use a microwave oven to warm EXTRANEAL. Do not heat above 40°C (104°F).

To Open

To open, tear the overwrap down at the slit and remove the solution container. Some opacity of the plastic, due to moisture absorption during the sterilization process, may be observed. This does not affect the solution quality or safety and may often leave a slight amount of moisture within the overwrap.

Inspect for Container Integrity and Solution Appearance

Do not use EXTRANEAL if it is cloudy or discolored, if it contains particulate matter, or if the container is leaking.

Inspect the patient connector to ensure the pull ring is attached. Do not use if pull ring is not attached to the connector. Inspect the EXTRANEAL container for signs of leakage and check for minute leaks by squeezing the container firmly. If the container has frangible(s), inspect that they are positioned correctly and are not broken. Do not use EXTRANEAL if the frangible(s) are broken or leaks are suspected as sterility may be impaired.

For EXTRANEAL in UltraBag, inspect the tubing and drain container for presence of solution. Small droplets are acceptable, but if solution flows past the frangible prior to use, do not use and discard the units.

Adding Medications

The decision to add medication should be made by the physician after careful evaluation of the patient [see Drug Interactions (7), Clinical Pharmacology (12.3)].

If the re-sealable rubber plug on the medication port is missing or partly removed, do not use the product if medication is to be added.

To add a medication:
• Put on mask. Clean and/or disinfect hands. • Prepare medication port site using aseptic technique. • Using a syringe with a 1-inch long, 25- to 19-gauge needle, puncture the medication port and inject additive. • Reposition container with container ports up and evacuate medication port by squeezing and tapping it. • Mix solution and additive thoroughly.
Preparation for Administration
• Put on mask. Clean and/or disinfect hands. • Place EXTRANEAL on work surface. • For ULTRABAG system for manual exchange, uncoil tubing and drain bag. Ensure the patient transfer set is closed. Break the connector (Y-set) frangible. • Remove pull ring from connector of solution container. If continuous fluid flow from connector is observed, discard solution container. Once the pull ring has been removed, do not reuse the solution or container. • Immediately attach the solution container to patient connector (transfer set) or appropriate peritoneal dialysis set. • For AMBU-FLEX II, continue with therapy set-up as instructed in user manual or directions accompanying tubing sets for automated peritoneal dialysis. • For ULTRABAG, follow the below steps: • Clamp solution line and then break frangible near solution bag. Hang solution container and place the drainage container below the level of the abdomen. • Open transfer set to drain the solution from abdomen. If drainage cannot be established, contact your clinician. When drainage complete, close transfer set. • Remove clamp from solution line and flush new solution to flow into the drainage container for 5 seconds to prime the line. Clamp drain line after flush complete. • Open transfer set to fill. When fill complete, close transfer set. • Disconnect ULTRABAG from transfer set and apply MINICAP.
Completion of Therapy
• Following use, the drained fluid should be inspected for the presence of fibrin or cloudiness, which may indicate the presence of peritonitis. • Discard unused portion.
Aspirin

Aspirin

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

As directed by a physician. Dosage, rate and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not administer unless solution is clear and seal is intact.

Additives may be incompatible with PLASMA-LYTE 148 Injection (Multiple Electrolytes Injection, Type 1, USP). As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of PLASMA-LYTE 148 Injection (Multiple Electrolytes Injection, Type 1, USP) is appropriate. After addition, check for a possible color change and/or the appearance of precipitates, insoluble complexes or crystals.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible must not be used. When introducing additives to PLASMA-LYTE 148 Injection (Multiple Electrolytes Injection, Type 1, USP), aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.
Omeprazole

Omeprazole

Treatment of Anaerobic Bacterial Infections

The recommended dosage schedule for adults is:

Loading Dose

15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult).

Maintenance Dose

7.5 mg/kg infused over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose.

Parenteral therapy may be changed to oral metronidazole when conditions warrant, based upon the severity of the disease and the response of the patient to Metronidazole Injection, USP treatment. The usual adult oral dosage is 7.5 mg/kg every six hours (approximately 500 mg for a 7-kg adult).

A maximum of 4 g should not be exceeded during a 24-hour period.

The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract and endocardium may require longer treatment.

Dosage Adjustments

Patients with Severe Hepatic Impairment

For patients with severe hepatic impairment (Child-Pugh C), the metronidazole dose should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Patients Undergoing Hemodialysis

Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation. The clearance of metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of metronidazole cannot be separated from a hemodialysis session, supplementation of metronidazole dosage following a hemodialysis session should be considered, depending on the patient’s clinical situation (see CLINICAL PHARMACOLOGY).

Prophylaxis

For surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is:
a. 15 mg/kg infused over 30 to 60 minutes and completed approximately one hour before surgery; followed by b. 7.5 mg/kg infused over 30 to 60 minutes at 6 and 12 hours after the initial dose.
It is important that (1) administration of the initial preoperative dose be completed approximately one hour before surgery so that adequate drug levels are present in the serum and tissues at the time of initial incision, and (2) Metronidazole Injection, USP be administered, if necessary, at 6-hour intervals to maintain effective drug levels. Prophylactic use of Metronidazole Injection, USP should be limited to the day of surgery only, following the above guidelines.

Caution: Metronidazole Injection, USP is to be administered by slow intravenous drip infusion only, either as a continuous or intermittent infusion. Additives should not be introduced into Metronidazole Injection, USP. If used with a primary intravenous fluid system, the primary solution should be discontinued during metronidazole infusion. DO NOT USE EQUIPMENT CONTAINING ALUMINUM (e.g., NEEDLES, CANNULAE) THAT WOULD COME IN CONTACT WITH THE DRUG SOLUTION.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Amiodarone Hydrochlorid...

Amiodarone Hydrochloride

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition, concomitant treatment, and on the patient’s clinical and laboratory response to treatment.

When other electrolytes or medicines are added to this solution, the dosage and the infusion rate will also be dictated by the dose regimen of the additions.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless the solution is clear and seal is intact.

Additives may be incompatible with Sodium Chloride Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Sodium Chloride Injection, USP is appropriate. After addition, check for unexpected color changes and/or the appearance of precipitates, insoluble complexes or crystals.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible must not be used. When introducing additives to Sodium Chloride Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers. Discard any unused portion.
Suprane

Suprane

Only persons trained in the administration of general anesthesia should administer SUPRANE. Only a vaporizer specifically designed and designated for use with desflurane should be utilized for its administration. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available.

SUPRANE (desflurane, USP) is administered by inhalation. The administration of general anesthesia must be individualized based on the patient’s response. Hypotension and respiratory depression increase as anesthesia with SUPRANE is deepened. The minimum alveolar concentration (MAC) of SUPRANE decreases with increasing patient age. The MAC for SUPRANE is also reduced by concomitant N2O administration (see Table 1). The dose should be adjusted accordingly. The following table provides mean relative potency based upon age and effect of N2O in predominately ASA physical status I or II patients.

Benzodiazepines and opioids decrease the MAC of SUPRANE [see Drug Interactions (7.1, Table 3)]. SUPRANE also decreases the doses of neuromuscular blocking agents required [see Drug Interactions (7.2, Table 4)]. The dose should be adjusted accordingly.
Table 1
Effect of Age on Minimum Alveolar Concentration of Desflurane Mean ± SD (percent atmospheres)

Age

N

O2 100%

N

N2O 60%/40% O2

2 weeks

6

9.2 ± 0.0

-

-

10 weeks

5

9.4 ± 0.4

-

-

9 months

4

10.0 ± 0.7

5

7.5 ± 0.8

2 years

3

9.1 ± 0.6

-

-

3 years

-

-

5

6.4 ± 0.4

4 years

4

8.6 ± 0.6

-

-

7 years

5

8.1 ± 0.6

-

-

25 years

4

7.3 ± 0.0

4

4.0 ± 0.3

45 years

4

6.0 ± 0.3

6

2.8 ± 0.6

70 years

6

5.2 ± 0.6

6

1.7 ± 0.4

N = number of crossover pairs (using up-and-down method of quantal response)

2.1 Preanesthetic Medication

Issues such as whether or not to premedicate and the choice of premedication(s) must be individualized. In clinical studies, patients scheduled to be anesthetized with SUPRANE frequently received IV preanesthetic medication, such as opioid and/or benzodiazepine.

2.2 Induction

In adults, some premedicated with opioid, a frequent starting concentration was 3% SUPRANE, increased in 0.5-1.0% increments every 2 to 3 breaths. End-tidal concentrations of 4-11%, SUPRANE with and without N2O, produced anesthesia within 2 to 4 minutes. When SUPRANE was tested as the primary anesthetic induction agent, the incidence of upper airway irritation (apnea, breathholding, laryngospasm, coughing and secretions) was high. During induction in adults, the overall incidence of oxyhemoglobin desaturation (SpO2 < 90%) was 6% [see Adverse Reactions (6.1)].

After induction in adults with an intravenous drug such as thiopental or propofol, SUPRANE can be started at approximately 0.5-1 MAC, whether the carrier gas is O2 or N2O/O2.

Inspired concentrations of SUPRANE greater than 12% have been safely administered to patients, particularly during induction of anesthesia. Such concentrations will proportionately dilute the concentration of oxygen; therefore, maintenance of an adequate concentration of oxygen may require a reduction of nitrous oxide or air if these gases are used concurrently.

2.3 Maintenance

Surgical levels of anesthesia in adults may be maintained with concentrations of 2.5-8.5% SUPRANE with or without the concomitant use of nitrous oxide. In children, surgical levels of anesthesia may be maintained with concentrations of 5.2-10% SUPRANE with or without the concomitant use of nitrous oxide.

During the maintenance of anesthesia with inflow rates of 2 L/min or more, the alveolar concentration of SUPRANE will usually be within 10% of the inspired concentration [FA/FI, see Figure 2 in Clinical Pharmacology (12.3)].

During the maintenance of anesthesia, increasing concentrations of SUPRANE produce dose-dependent decreases in blood pressure. Excessive decreases in blood pressure may be due to depth of anesthesia and in such instances may be corrected by decreasing the inspired concentration of SUPRANE.

Concentrations of SUPRANE exceeding 1 MAC may increase heart rate. Thus with this drug, an increased heart rate may not serve reliably as a sign of inadequate anesthesia.

2.4 Maintenance of Anesthesia in Intubated Pediatric Patients

SUPRANE is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than SUPRANE, and tracheal intubation.

SUPRANE, with or without N2O, and halothane, with or without N2O were studied in three clinical trials of pediatric patients aged 2 weeks to 12 years (median 2 years) and ASA physical status I or II. The concentration of SUPRANE required for maintenance of general anesthesia is age-dependent [see Clinical Studies (14.5)].

Changes in blood pressure during maintenance of and recovery from anesthesia with SUPRANE/N2O/O2 are similar to those observed with halothane/N2O/O2. Heart rate during maintenance of anesthesia is approximately 10 beats per minute faster with SUPRANE than with halothane. Patients were judged fit for discharge from post-anesthesia care units within one hour with both SUPRANE and halothane. There were no differences in the incidence of nausea and vomiting between patients receiving SUPRANE or halothane.

2.5 Recovery

The recovery from general anesthesia should be assessed carefully before patients are discharged from the post anesthesia care unit (PACU).

2.6 Use in Patients with Coronary Artery Disease

In patients with coronary artery disease, maintenance of normal hemodynamics is important to prevent myocardial ischemia. A rapid increase in desflurane concentration is associated with marked increase in pulse rate, mean arterial pressure and levels of epinephrine and norepinephrine. SUPRANE should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or patients where increases in heart rate or blood pressure are undesirable. It should be used with other medications, preferably intravenous opioids and hypnotics [see Clinical Studies (14.2)].

2.7 Neurosurgical Use

SUPRANE may produce a dose-dependent increase in cerebrospinal fluid pressure (CSFP) when administered to patients with intracranial space occupying lesions. SUPRANE should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) until cerebral decompression in patients with known or suspected increases in CSFP. Appropriate attention must be paid to maintain cerebral perfusion pressure [see Clinical Studies (14.4)].

2.8 Observations Related to Vaporizer Use

Yellow discoloration of SUPRANE sometimes accompanied by particulates, has been observed through the vaporizer sight glass or after draining the vaporizer. The presence of discoloration or particulates in these situations, does not alter the quality or efficacy of SUPRANE. If observed, refer to the respective vaporizer Instructions For Use (IFU) for recommended actions or contact Baxter Product Surveillance.
Suprane

Suprane

Only persons trained in the administration of general anesthesia should administer SUPRANE. Only a vaporizer specifically designed and designated for use with desflurane should be utilized for its administration. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available.

SUPRANE is administered by inhalation. The administration of general anesthesia must be individualized based on the patient’s response. Hypotension and respiratory depression increase as anesthesia with SUPRANE is deepened. The minimum alveolar concentration (MAC) of SUPRANE decreases with increasing patient age. The MAC for SUPRANE is also reduced by concomitant N2O administration (see Table 1). The dose should be adjusted accordingly. The following table provides mean relative potency based upon age and effect of N2O in predominately ASA physical status I or II patients.

Benzodiazepines and opioids decrease the MAC of SUPRANE [see Drug Interactions (7.1, Table 3)]. SUPRANE also decreases the doses of neuromuscular blocking agents required [see Drug Interactions (7.2, Table 4)]. The dose should be adjusted accordingly.
Table 1 N = number of crossover pairs (using up-and-down method of quantal response)
Effect of Age on Minimum Alveolar Concentration of Desflurane

Mean ± SD (percent atmospheres)

Age

N

O2 100%

N

N2O 60%/40% O2

2 weeks

6

9.2 ± 0.0

-

-

10 weeks

5

9.4 ± 0.4

-

-

9 months

4

10.0 ± 0.7

5

7.5 ± 0.8

2 years

3

9.1 ± 0.6

-

-

3 years

-

-

5

6.4 ± 0.4

4 years

4

8.6 ± 0.6

-

-

7 years

5

8.1 ± 0.6

-

-

25 years

4

7.3 ± 0.0

4

4.0 ± 0.3

45 years

4

6.0 ± 0.3

6

2.8 ± 0.6

70 years

6

5.2 ± 0.6

6

1.7 ± 0.4

2.1 Preanesthetic Medication

Issues such as whether or not to premedicate and the choice of premedication(s) must be individualized. In clinical studies, patients scheduled to be anesthetized with SUPRANE frequently received IV preanesthetic medication, such as opioid and/or benzodiazepine.

2.2 Induction

In adults, some premedicated with opioid, a frequent starting concentration was 3% SUPRANE , increased in 0.5-1.0% increments every 2 to 3 breaths. End-tidal concentrations of 4-11%, SUPRANE with and without N2O, produced anesthesia within 2 to 4 minutes. When SUPRANE was tested as the primary anesthetic induction agent, the incidence of upper airway irritation (apnea, breathholding, laryngospasm, coughing and secretions) was high. During induction in adults, the overall incidence of oxyhemoglobin desaturation (SpO2 < 90%) was 6% [see Adverse Reactions (6.1)].

After induction in adults with an intravenous drug such as thiopental or propofol, SUPRANE can be started at approximately 0.5-1 MAC, whether the carrier gas is O2 or N2O/O2.

Inspired concentrations of SUPRANE greater than 12% have been safely administered to patients, particularly during induction of anesthesia. Such concentrations will proportionately dilute the concentration of oxygen; therefore, maintenance of an adequate concentration of oxygen may require a reduction of nitrous oxide or air if these gases are used concurrently.

2.3 Maintenance

Surgical levels of anesthesia in adults may be maintained with concentrations of 2.5-8.5% SUPRANE with or without the concomitant use of nitrous oxide. In children, surgical levels of anesthesia may be maintained with concentrations of 5.2-10% SUPRANE with or without the concomitant use of nitrous oxide.

During the maintenance of anesthesia with inflow rates of 2 L/min or more, the alveolar concentration of SUPRANE will usually be within 10% of the inspired concentration [FA/FI, see Figure 2 in Clinical Pharmacology (12.3)].

During the maintenance of anesthesia, increasing concentrations of SUPRANE produce dose-dependent decreases in blood pressure. Excessive decreases in blood pressure may be due to depth of anesthesia and in such instances may be corrected by decreasing the inspired concentration of SUPRANE .

Concentrations of SUPRANE exceeding 1 MAC may increase heart rate. Thus with this drug, an increased heart rate may not serve reliably as a sign of inadequate anesthesia.

2.4 Maintenance of Anesthesia in Intubated Pediatric Patients

SUPRANE is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than SUPRANE, and tracheal intubation.

SUPRANE, with or without N2O, and halothane, with or without N2O were studied in three clinical trials of pediatric patients aged 2 weeks to 12 years (median 2 years) and ASA physical status I or II. The concentration of SUPRANE required for maintenance of general anesthesia is age-dependent [see Clinical Studies (14.5)].

Changes in blood pressure during maintenance of and recovery from anesthesia with SUPRANE /N2O/O2 are similar to those observed with halothane/N2O/O2. Heart rate during maintenance of anesthesia is approximately 10 beats per minute faster with SUPRANE than with halothane. Patients were judged fit for discharge from post-anesthesia care units within one hour with both SUPRANE and halothane. There were no differences in the incidence of nausea and vomiting between patients receiving SUPRANE or halothane.

2.5 Recovery

The recovery from general anesthesia should be assessed carefully before patients are discharged from the post anesthesia care unit (PACU).

2.6 Use in Patients with Coronary Artery Disease

In patients with coronary artery disease, maintenance of normal hemodynamics is important to prevent myocardial ischemia. A rapid increase in desflurane concentration is associated with marked increase in pulse rate, mean arterial pressure and levels of epinephrine and norepinephrine. SUPRANE should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or patients where increases in heart rate or blood pressure are undesirable. It should be used with other medications, preferably intravenous opioids and hypnotics [see Clinical Studies (14.2)].

2.7 Neurosurgical Use

SUPRANE may produce a dose-dependent increase in cerebrospinal fluid pressure (CSFP) when administered to patients with intracranial space occupying lesions. SUPRANE should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) until cerebral decompression in patients with known or suspected increases in CSFP. Appropriate attention must be paid to maintain cerebral perfusion pressure [see Clinical Studies (14.4)].

2.8 Observations Related to Vaporizer Use

Yellow discoloration of SUPRANE sometimes accompanied by particulates, has been observed through the vaporizer sight glass or after draining the vaporizer. The presence of discoloration or particulates in these situations, does not alter the quality or efficacy of SUPRANE. If observed, refer to the respective vaporizer Instructions For Use (IFU) for recommended actions or contact Baxter Product Surveillance.
Suprane

Suprane

Only persons trained in the administration of general anesthesia should administer SUPRANE. Only a vaporizer specifically designed and designated for use with desflurane should be utilized for its administration. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available.

SUPRANE is administered by inhalation. The administration of general anesthesia must be individualized based on the patient’s response. Hypotension and respiratory depression increase as anesthesia with SUPRANE is deepened. The minimum alveolar concentration (MAC) of SUPRANE decreases with increasing patient age. The MAC for SUPRANE is also reduced by concomitant N2O administration (see Table 1). The dose should be adjusted accordingly. The following table provides mean relative potency based upon age and effect of N2O in predominately ASA physical status I or II patients.

Benzodiazepines and opioids decrease the MAC of SUPRANE [see Drug Interactions (7.1, Table 3)]. SUPRANE also decreases the doses of neuromuscular blocking agents required [see Drug Interactions (7.2, Table 4)]. The dose should be adjusted accordingly.
Table 1
Effect of Age on Minimum Alveolar Concentration of Desflurane

Mean ± SD (percent atmospheres)

Age

N

O2 100%

N

N2O 60%/40% O2

2 weeks

6

9.2 ± 0.0

-

-

10 weeks

5

9.4 ± 0.4

-

-

9 months

4

10.0 ± 0.7

5

7.5 ± 0.8

2 years

3

9.1 ± 0.6

-

-

3 years

-

-

5

6.4 ± 0.4

4 years

4

8.6 ± 0.6

-

-

7 years

5

8.1 ± 0.6

-

-

25 years

4

7.3 ± 0.0

4

4.0 ± 0.3

45 years

4

6.0 ± 0.3

6

2.8 ± 0.6

70 years

6

5.2 ± 0.6

6

1.7 ± 0.4

N = number of crossover pairs (using up-and-down method of quantal response)

2.1 Preanesthetic Medication

Issues such as whether or not to premedicate and the choice of premedication(s) must be individualized. In clinical studies, patients scheduled to be anesthetized with SUPRANE frequently received IV preanesthetic medication, such as opioid and/or benzodiazepine.

2.2 Induction

In adults, some premedicated with opioid, a frequent starting concentration was 3% SUPRANE, increased in 0.5-1.0% increments every 2 to 3 breaths. End-tidal concentrations of 4-11%, SUPRANE with and without N2O, produced anesthesia within 2 to 4 minutes. When SUPRANE was tested as the primary anesthetic induction agent, the incidence of upper airway irritation (apnea, breathholding, laryngospasm, coughing and secretions) was high. During induction in adults, the overall incidence of oxyhemoglobin desaturation (SpO2 < 90%) was 6% [see Adverse Reactions (6.1)].

After induction in adults with an intravenous drug such as thiopental or propofol, SUPRANE can be started at approximately 0.5-1 MAC, whether the carrier gas is O2 or N2O/O2.

Inspired concentrations of SUPRANE greater than 12% have been safely administered to patients, particularly during induction of anesthesia. Such concentrations will proportionately dilute the concentration of oxygen; therefore, maintenance of an adequate concentration of oxygen may require a reduction of nitrous oxide or air if these gases are used concurrently.

2.3 Maintenance

Surgical levels of anesthesia in adults may be maintained with concentrations of 2.5-8.5% SUPRANE with or without the concomitant use of nitrous oxide. In children, surgical levels of anesthesia may be maintained with concentrations of 5.2-10% SUPRANE with or without the concomitant use of nitrous oxide.

During the maintenance of anesthesia with inflow rates of 2 L/min or more, the alveolar concentration of SUPRANE will usually be within 10% of the inspired concentration [FA/FI, see Figure 2 in Clinical Pharmacology (12.3)].

During the maintenance of anesthesia, increasing concentrations of SUPRANE produce dose-dependent decreases in blood pressure. Excessive decreases in blood pressure may be due to depth of anesthesia and in such instances may be corrected by decreasing the inspired concentration of SUPRANE.

Concentrations of SUPRANE exceeding 1 MAC may increase heart rate. Thus with this drug, an increased heart rate may not serve reliably as a sign of inadequate anesthesia.

2.4 Maintenance of Anesthesia in Intubated Pediatric Patients

SUPRANE is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than SUPRANE, and tracheal intubation.

SUPRANE, with or without N2O, and halothane, with or without N2O were studied in three clinical trials of pediatric patients aged 2 weeks to 12 years (median 2 years) and ASA physical status I or II. The concentration of SUPRANE required for maintenance of general anesthesia is age-dependent [see Clinical Studies (14.5)].

Changes in blood pressure during maintenance of and recovery from anesthesia with SUPRANE /N2O/O2 are similar to those observed with halothane/N2O/O2. Heart rate during maintenance of anesthesia is approximately 10 beats per minute faster with SUPRANE than with halothane. Patients were judged fit for discharge from post-anesthesia care units within one hour with both SUPRANE and halothane. There were no differences in the incidence of nausea and vomiting between patients receiving SUPRANE or halothane.

2.5 Recovery

The recovery from general anesthesia should be assessed carefully before patients are discharged from the post anesthesia care unit (PACU).

2.6 Use in Patients with Coronary Artery Disease

In patients with coronary artery disease, maintenance of normal hemodynamics is important to prevent myocardial ischemia. A rapid increase in desflurane concentration is associated with marked increase in pulse rate, mean arterial pressure and levels of epinephrine and norepinephrine. SUPRANE should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or patients where increases in heart rate or blood pressure are undesirable. It should be used with other medications, preferably intravenous opioids and hypnotics [see Clinical Studies (14.2)].

2.7 Neurosurgical Use

SUPRANE may produce a dose-dependent increase in cerebrospinal fluid pressure (CSFP) when administered to patients with intracranial space occupying lesions. SUPRANE should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) until cerebral decompression in patients with known or suspected increases in CSFP. Appropriate attention must be paid to maintain cerebral perfusion pressure [see Clinical Studies (14.4)].

2.8 Observations Related to Vaporizer Use

Yellow discoloration of SUPRANE sometimes accompanied by particulates, has been observed through the vaporizer sight glass or after draining the vaporizer. The presence of discoloration or particulates in these situations, does not alter the quality or efficacy of SUPRANE. If observed, refer to the respective vaporizer Instructions For Use (IFU) for recommended actions or contact Baxter Product Surveillance.
Amiodarone Hydrochlorid...

Amiodarone Hydrochloride

IFEX should be administered intravenously at a dose of 1.2 grams per m2 per day for 5 consecutive days. Treatment is repeated every 3 weeks or after recovery from hematologic toxicity.

In order to prevent bladder toxicity, IFEX should be given with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day. Mesna should be used to reduce the incidence of hemorrhagic cystitis. IFEX should be administered as a slow intravenous infusion lasting a minimum of 30 minutes. Studies of IFEX in patients with hepatic or renal impairment have not been conducted [see Use in Specific Populations (8.6, 8.7)].

Injections are prepared for parenteral use by adding Sterile Water for Injection, USP or Bacteriostatic Water for Injection, USP (benzyl alcohol or parabens preserved), to the vial and shaking to dissolve. Before parenteral administration, the substance must be completely dissolved. Use the quantity of diluents shown below to constitute the product:

Dosage Strength

Quantity of Diluent

Final Concentration

1 gram

20 mL

50 mg per mL

3 grams

60 mL

50 mg per mL

Solutions of ifosfamide may be diluted further to achieve concentrations of 0.6 to 20 mg/mL in the following fluids:

5% Dextrose Injection, USP

0.9% Sodium Chloride Injection, USP

Lactated Ringer’s Injections, USP

Sterile Water for Injection, USP

Because essentially identical stability results were obtained for Sterile Water admixtures as for the other admixtures (5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer’s Injection), the use of large volume parenteral glass bottles, VIAFLEX bags or PAB bags that contain intermediate concentrations or mixtures of excipients (e.g., 2.5% Dextrose Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection) is also acceptable.

Constituted or constituted and further diluted solutions of IFEX should be refrigerated and used within 24 hours. Benzyl-alcohol-containing solutions can reduce the stability of ifosfamide.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Bebulin

Bebulin

For intravenous administration only

One International Unit (IU) of Factor IX activity/kg will increase the plasma level of Factor IX by 0.8%. Accordingly, the following formula is provided for dosage calculations:

Number of Factor IX IU required = bodyweight (kg) x desired Factor IX increase (% of normal) x 1.2.

The response to treatment will vary from patient to patient. Exact dosage determination should be based on localization and extent of hemorrhage, and the level of Factor IX to be achieved. Close laboratory monitoring of the Factor IX level is required to determine proper dosage, particularly with severe hemorrhage and major surgery. Larger doses than those derived from the above formula may be required; particularly if treatment is delayed.

Management of Bleeding 7-11

Approximate desired Factor IX levels, typical initial doses, and the average duration of treatment are suggested in Table 3. For minor bleeding, a single dose will usually be sufficient; otherwise a second dose may be given after 24 hours. More severe hemorrhage will require several doses at approximately 24-hours intervals. For maintenance therapy, usually two thirds of the initial dose is infused.
Table 3 Management of Specific Types of Bleeding * For patients predisposing to thrombosis see Precautions section. Type of Bleeding
ApproximateDesired Factor IX Level
(% Normal)
Typical InitialDose
(International Units/kg)
Average Durationof Treatment
(Days)
Minor Early hemarthrosis,minor epistaxis,
and gingival bleeding, mild hematuria 20 25-35 1
Moderate Severe joint bleeding, early hematoma, major open bleeding, minor trauma, minor hemoptysis,
hematemesis,and melena,major hematuria 40 50-65
2 or until adequate
wound healing
Major Severe hematoma major trauma, Severe hemoptysis,
hematemesis, and melena ≥60* 75-90
2-3 or until adequate
wound healing
Management of Surgical Procedures 7-11

Dosage guidelines for surgical procedures are suggested in Table 4. Administer preoperative loading dose one hour prior to surgery. Depending on the type of surgery, continue replacement therapy over one to several weeks until adequate wound healing is achieved. The average treatment interval will initially be 12 hours, while in the later postoperative period, 24 hours is adequate.
Table 4 Management of Surgical Procedures * N/A– Not Applicable. † For patients predisposing to thrombosis see Precautions section.
Type ofSurgery
Day of Operation
Init. Postop. Period
(1st to 2nd Week)
Late Postop. Period(from 3rd Week Onwards)

Approx. Level Factor IX

(% Normal)

Dose
(IU/kg)
Approx. Level Factor IX
(% Normal)
Dose
(IU/kg)
Approx. Level Factor IX

(% Normal)

Dose
(IU/kg) Minor 40-60 50-75
20-40

25-65
N/A* N/A* Major
≥60†
75-90 20-60 25-75 20 25-35
For tooth extraction, the same initial dose as for minor surgery is recommended and one infusion should be sufficient. In case of extraction of several teeth, replacement therapy for up to one week may be necessary using the same doses as for minor surgery8-11.

Reconstitution
Do not mix BEBULIN with other medicinal products or solvents, other than the enclosed sterilized water for injection. Administer BEBULIN within 3 hours after reconstitution as the solution does not contain a preservative. Do not refrigerate after reconstitution. Warm unopened vials of both diluent and concentrate to room temperature (not to exceed 37°C, 98°F). Remove caps from both vials to expose central portions of the rubber stoppers. Cleanse exposed surface of the rubber stoppers with germicidal solution and allow to dry. Using aseptic technique, remove protective covering from one end of the double-ended needle and insert the exposed end through the diluent vial stopper. Remove protective covering from the other end of the double-ended needle. Do not touch the exposed end. Invert diluent vial over the concentrate vial, then insert free end of the needle through the concentrate vial stopper. Diluent will be drawn into the concentrate vial by vacuum. Disconnect the two vials by removing needle from the concentrate vial stopper. Gently agitate or rotate the concentrate vial until all material is dissolved.
Administration

For Intravenous Administration Only.
Parenteral drug products should be inspected for particulate matter and discoloration prior to administration. The reconstituted product should be colorless to slightly yellowish and clear to slightly turbid solution. Do not administer if particulate matter or discoloration is found and notify Baxter immediately. Record the name of the patient and batch number of the product in order to maintain a link between the patient and the batch of the product. After reconstituting the concentrate as described above, attach the enclosed filter needle to a sterile disposable syringe using aseptic technique. Insert filter needle through the concentrate vial stopper. Inject air and withdraw solution into the syringe. Remove and discard filter needle. Attach a suitable intravenous needle or infusion set with winged adapter. Administer the solution intravenously at a rate comfortable to the patient. The infusion rate should not exceed 2 mL per minute.
Clinolipid

Clinolipid

2.1 Use of an Inline Filter

Fragments of the administration port membrane could be dislodged into the bag after spiking. Use a 1.2 micron inline filter during administration of CLINOLIPID injection (alone or as part of an admixture) to remove particulate matter or micro-precipitate contamination during administration of CLINOLIPID injection (alone or as part of an admixture). Particulate matter > 5 microns has the capability of obstructing blood flow through capillaries, which could lead to embolism and vascular occlusion. Do not use filters of less than 1.2 micron pore size with lipid emulsions.

2.2 Important Administration Instructions

Before opening the overwrap, check the color of the oxygen indicator. Compare color of the indicator to the reference color printed next to the OK symbol depicted in the printed area of the indicator label. Do not use the product if the color of the oxygen absorber/indicator does not correspond to the reference color printed next to the OK symbol.

After opening the bag, use the contents immediately and do not store for a subsequent infusion.

Visually inspect that the emulsion is a homogeneous liquid with a milky appearance. Inspect for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not connect flexible bags in series to avoid air embolism due to possible residual gas contained in the primary bag.

Air embolism can result if residual gas in the bag is not fully evacuated prior to administration if the flexible bag is pressurized to increase flow rates.

Use of a vented intravenous administration set with the vent in the open position could result in air embolism.

If CLINOLIPID injection is mixed with dextrose and/or amino acid solutions, check the compatibility before administration by inspecting the mixture closely for the presence of precipitates. Formation of precipitates could result in vascular occlusion.

When infused alone, CLINOLIPID injection can be administered via central or peripheral vein. When administered with dextrose and amino acids, the choice of a central or peripheral venous route should depending on the osmolarity of the final infusate.

Do not use administration sets and lines that contain di-2-ehtylhexyl phthalate (DEHP).

2.3 Mixing Guidelines

Prepare the admixture using strict aseptic techniques to avoid microbial contamination.

Do not add additives directly to CLINOLIPID injection. Do not add CLINOLIPID injection to the total parenteral nutrition container first; destabilization of the lipid may occur from such an admixture.

Do not use the EXACTAMIX Inlet H938173 with an EXACTAMIX compounder to transfer CLINOLIPID injection. This inlet spike has been associated with dislodgement of the administration port membrane into the CLINOLIPID injection bag.

The following proper mixing sequence must be followed to minimize pH related problems by ensuring that typically acidic Dextrose Injections are not mixed with lipid emulsions alone:
Transfer Dextrose Injection to the Total Parenteral Nutrition Admixture Container Transfer Amino Acid Injection Transfer Lipid Emulsion
Amino Acid Injection, Dextrose Injection and Lipid Emulsions may be simultaneously transferred to the admixture container. Use gentle agitation during admixing to minimize localized concentration effects; shake bags gently after each addition.

The prime destabilizers of emulsions are excessive acidity (such as a pH below 5) and inappropriate electrolyte content. Give careful consideration to additions of divalent cations (Ca++ and Mg++), which have been shown to cause emulsion instability. Amino acid solutions exert buffering effects that protect the emulsion.

Inspect the admixture closely for separation of the emulsion. This can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. The admixture should also be examined for particulates. Discard the admixture if any of the above is observed.

2.4 Dosing Considerations

The dosing of CLINOLIPID injection depends on energy expenditure, the patient’s clinical status, body weight, tolerance, and ability to metabolize CLINOLIPID injection, as well as additional energy given orally/enterally to the patient. For complete parenteral nutrition, concomitant supplementation with amino acids, carbohydrates, electrolytes, vitamins, and trace elements is necessary.

Prior to administration of CLINOLIPID injection, correct severe water and electrolyte disorders, severe fluid overload states, and severe metabolic disorders. Before starting the infusion, obtain serum triglyceride levels to establish the baseline value. In patients with elevated triglyceride levels, initiate CLINOLIPID injection at a lower dose, and advance in smaller increments, checking the triglyceride levels prior to each adjustment.

Adjust the administration flow rate by taking into account the dose being administered, the daily volume intake, and the duration of the infusion [see Overdosage (10)].

The recommended duration of infusion for a parenteral nutrition bag is between 12 and 24 hours, depending on the clinical situation. Treatment with parenteral nutrition may be continued for as long as is required by the patient’s condition.

The maximum daily dose of CLINOLIPID injection should be based on individual total nutritional requirements and patient tolerance. The usual lipid dosage is 1 to 1.5 g/kg/day (equal to 5 to 7.5 mL/kg/day of CLINOLIPID 20%) 1. The daily dose should not exceed 2.5 g/kg/day. The initial infusion rate should not exceed 0.1 g (equal to 0.5 mL) per minute for the first 15 to 30 minutes. If tolerated, gradually increase until reaching the required rate after 30 minutes.
Intralipid

Intralipid

Intralipid® 20% (A 20% I.V. Fat Emulsion) Pharmacy Bulk Package should be administered only as a part of a three-in-one or total nutrient admixture via peripheral vein or by central venous infusion.

Directions For Proper Use of Pharmacy Bulk Package.

INTRALIPID® 20% PHARMACY BULK PACKAGE IS NOT INTENDED FOR DIRECT INFUSION. The container closure may be penetrated only once using a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). Once the closure is penetrated, the contents should be dispensed as soon as possible; the transfer of contents to suitable TPN admixture containers must be completed within 4 hours of closure penetration. The bag should be stored below 25°C (77°F) after the closure has been entered. Date and time of container entry should be noted in the area designated on the container label.

Admixtures made using Intralipid® 20% should be used promptly. See MIXING GUIDELINES AND LIMITATIONS section for admixture storage recommendations.

Adult Patients

The initial infusion rate of the nutrient admixture in adults should be 0.1 g fat/minute for the first 15 to 30 minutes of infusion. If no untoward reactions occur (see ADVERSE. REACTIONS section), the infusion rate can be increased to 0.2 g fat/minute. For adults, the admixture should not contain more than 500 mL of Intralipid® 20% on the first day of therapy. If the patient has no untoward reactions, the dose can be increased on the following day. The daily dosage should not exceed 2.5 g of fat/kg of body weight (12.5 mL of Intralipid® 20% per kg). Intralipid® should make up no more than 60% of the total caloric input to the patient. Carbohydrate and a source of amino acids should comprise the remaining caloric input.

Pediatric Patients

The dosage for premature infants starts at 0.5 g fat/kg body weight/24 hours (2.5 mL Intralipid® 20%) and may be increased in relation to the infant’s ability to eliminate fat. The maximum dosage recommended by the American Academy of Pediatrics is 3 g fat/kg/24 hours3

The initial rate of infusion in older pediatric patients should be no more than 0.01 g fat/minute for the first 10 to 15 minutes. If no untoward reactions occur, the rate can be changed to permit infusion of 0.1 g of fat/kg/hour. The daily dosage should not exceed 3 g of fat/kg of body weight3 Intralipid® should make up no more than 60% of the total caloric input to the patient. Carbohydrate and a source of amino acids should comprise the remaining caloric input.

Essential Fatty Acid Deficiency

When Intralipid® is administered to correct essential fatty acid deficiency, eight to ten percent of the caloric input should be supplied by Intralipid® in order to provide adequate amounts of linoleic and linolenic acids. When EFAD occurs together with stress, the amount of Intralipid® needed to correct the deficiency may be increased.

Administration

See MIXING GUIDELINES AND LIMITATIONS section for information regarding mixing this fat emulsion with other parenteral fluids.

INTRALIPID® 20% (A 20% I.V. FAT EMULSION) PHARMACY BULK PACKAGE IS NOT INTENDED FOR DIRECT INFUSION. It must be infused as part of an admixture into a central or peripheral vein.

The flow rate of the admixture should be controlled with an infusion pump. Filters of less than 1.2 micron pore size must not be used with admixtures containing Intralipid® 20%. Conventional administration sets and TPN pooling bags contain polyvinyl chloride (PVC) components that have DEHP (diethyl hexyl phthalate) as a plasticizer. Fat-containing fluids such as Intralipid® extract DEHP from these PVC components. Therefore it may be advisable to use a non-DEHP administration set for infusing admixtures which contain Intralipid®.

Do not use any bag in which there appears to be an oiling out on the surface of the emulsion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. whenever solution and container permit.

MIXING GUIDELINES AND LIMITATIONS

Investigations have been conducted which demonstrate the compatibility of Intralipid® 20% when properly mixed with either Novamine® (8.5%, 11.4% or 15%) or 8.5% Travasol® or 10% Travasol® Amino Acid Injections without Electrolytes for use in TPN therapy. Because of the potential for life threatening events, caution should be taken to ensure that precipitates have not formed in any parenteral nutrition mixture.

Perform all manipulations in a suitable work area, such as a laminar flow hood.

Failure to follow the Mixing Guidelines and Limitations below, including recommended storage temperature, storage time. order of mixing, etc., may result in an unstable admixture.

The following proper mixing sequence must be followed to minimize pH related problems by ensuring that typically acidic Dextrose Injections are not mixed with lipid emulsions alone:
Transfer Dextrose Injection to the TPN (Total Parenteral Nutrition) Admixture Container Transfer Amino Acid Injection Transfer Intralipid® 20%
Note: Amino Acid Injection, (Novamine® 8.5, 11.4 or 15% or 8.5 Travasol® 8.5 or 15% without electrolytes), Dextrose Injection and Intralipid® 20% may be simultaneously transferred to the admixture container using an automatic mixer. Admixing should be accompanied by gentle agitation to avoid localized concentration effects.

These admixtures should be used promptly with storage under refrigeration (2-8°C) not to exceed 24 hours and must be completely used within 24 hours after removal from refrigeration.

It is essential that the admixture be prepared using strict aseptic techniques as this nutrient mixture is a good growth medium for microorganisms.

Additives other than those named above may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives (e.g., vitamins and minerals). Additives must not be added directly to Intralipid® 20% (A 20% I.V. Fat Emulsion) Pharmacy Bulk Package and in no case should Intralipid® 20% be added to the TPN container first. Bags should be shaken gently after each addition to minimize localized concentration.

Supplemental electrolytes, trace metals or multivitamins may be required in accordance with the prescription of the attending physician.

The prime destabilizers of emulsions are excessive acidity (low pH) and inappropriate electrolyte content. Careful consideration should be given to addition of divalent cations (Ca++ and Mg++) which have been shown to cause emulsion instability. Amino acid solutions exert a buffering effect protecting the emulsion.

The admixture should be inspected carefully for “breaking or oiling out” of the emulsion. “Breaking or oiling out” is described as the separation of the emulsion and can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. The admixture should also be examined for particulates. The admixture must be discarded if any of the above is observed.
Recombinate

Recombinate

Each vial of RECOMBINATE is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.

The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al4 and is supported by the data generated by 419 clinical pharmacokinetic studies with RECOMBINATE in 67 patients over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.

Examples (Assuming patient’s baseline Factor VIII level is at <1%):
(1) A dose of 1750 IU RECOMBINATE administered to a 70 kg patient, i.e. 25 IU/kg (1750 IU/70 kg), should be expected to cause a peak post-infusion Factor VIII increase of 25 IU/kg x 2 (IU/dL)/(IU/kg) = 50 IU/dL (50% of normal). (2) A peak level of 70% is required in a 40 kg child. In this situation, the dose would be 70 IU/dL/[2(IU/dL)/(IU/kg)] x 40 kg = 1400 IU.
Recommended Dosage Schedule

Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.
Hemorrhage Degree of Hemorrhage Required peak post-infusion Factor VIII activity in the blood (as % of normal or IU/dL plasma) Frequency of Infusion Early hemarthrosis or muscle bleed or oral bleed 20-40 Begin infusion every 12 to 24 hours for one-three days until the bleeding episode is resolved (as indicated by pain), or healing is achieved. More extensive hemarthrosis, muscle bleed, or hematoma 30-60 Repeat infusion every 12 to 24 hours for (usually) three days or more until pain and disability are resolved. Life threatening bleeds such as head injury, throat bleed, severe abdominal pain 60-100 Repeat infusion every 8 to 24 hours until threat is resolved Surgery Type of Operation Minor surgery, including tooth extraction 60-80 A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases. Major surgery 80-100 (pre- and post-operative) Repeat infusion every 8 to 24 hours depending on state of healing.
If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be determined and a sufficient dose of RECOMBINATE should be administered to achieve a satisfactory clinical response.

The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages. In presence of a low titer inhibitor, doses larger than those recommended may be necessary as per standard care.

Although dosage can be estimated by the calculations above, it is strongly recommended that whenever possible, appropriate laboratory tests including serial Factor VIII assays be performed on the patient’s plasma at suitable intervals to assure that adequate Factor VIII levels have been reached and are maintained.

Patients should be evaluated for the development of Factor VIII inhibitors, if the expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose.

Reconstitution: Use Aseptic Technique
Bring RECOMBINATE (dry factor concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature. Remove caps from concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place vials on a flat surface. Open the BAXJECT II device package by peeling away the lid, without touching the inside. Do not remove the device from the package. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper. Grip the BAXJECT II package at its edge and pull the package off the device. Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike. Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the RECOMBINATE vial stopper by pushing straight down. The vacuum will draw the diluent into the RECOMBINATE vial. Swirl gently until RECOMBINATE is completely dissolved. After reconstitution, the solution should be colorless to faint yellow, and substantially free from foreign particles.
NOTE: Do not refrigerate after reconstitution. (SeeAdministration)

Administration: Use Aseptic Technique

RECOMBINATE is administered by intravenous (IV) injection after reconstitution.

Administer at room temperature. RECOMBINATE should be administered not more than 3 hours after reconstitution.

Intravenous Syringe Injection

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be colorless to faint yellow in appearance. If not, do not use the solution and notify Baxter immediately.

Plastic syringes are recommended for use with this product since proteins such as RECOMBINATE tend to stick to the surface of glass syringes.
Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device. DO NOT INJECT AIR. Turn over the connected vials so that the RECOMBINATE vial is on top. Draw the factor concentrate into the syringe by pulling the plunger back slowly. Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration . If a patient is to receive more than one vial of RECOMBINATE, the contents of multiple vials may be drawn into the same syringe. Please note that the BAXJECT II device is intended for use with a single vial of RECOMBINATE and Sterile Water for Injection only, therefore reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.
Rate of Administration

The rate of administration should be a rate that ensures the comfort of the patient. Preparations of RECOMBINATE can be administered at a rate of up to 5 mL per minute when reconstituted with 5 mL of sWFI.

The pulse rate should be determined before and during administration of RECOMBINATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.
Rixubis

Rixubis

For intravenous use after reconstitution only.
Each vial of RIXUBIS has the recombinant Factor IX (rFIX) potency in international units stated on the vial. Initiate treatment under the supervision of a physician experienced in the treatment of hemophilia. Dosage and duration of treatment with RIXUBIS depend on the severity of factor IX deficiency, the location and extent of bleeding, the patient’s clinical condition, age, and pharmacokinetic parameters of factor IX, such as incremental recovery and half-life. Dosing of RIXUBIS may differ from that of plasma-derived factor IX products [see Clinical Pharmacology (12)]. Subjects at the low end of the observed factor IX recovery range may require dose adjustment of RIXUBIS. Monitor patients using a factor IX activity assay to ensure that the desired factor IX activity plasma level has been attained. If necessary, adjust the dose and the frequency of repeated infusions as appropriate. Evaluate the patient for the development of factor IX inhibitors if the expected factor IX activity plasma levels are not attained or if bleeding is not controlled with an appropriate dose [see Warnings and Precautions (5.2)].
2.1 Dosing Guidelines

Calculating Initial Dose

The initial dose of RIXUBIS is calculated based on the empirical finding that one international unit of RIXUBIS per kg body weight is expected to increase the circulating level of factor IX by 0.9 international units/dL of plasma (0.9% of normal) in adult patients.

A guide for calculating the initial dose of RIXUBIS for treatment of bleeding episodes is as follows:

Initial Dose = body weight (kg) x desired factor IX increase (% of normal or IU/dL) x reciprocal of observed recovery (IU/kg per IU/dL)

Incremental Recovery in Previously Treated Patients (PTPs)

Base the calculation of the dose on the patient’s individual incremental recovery using serial factor IX activity assays, due to the wide range of inter-individual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics, in particular incremental recovery and half-life.

For an incremental recovery of 0.9 international units/dL of plasma (0.9% of normal), the dose is calculated as follows:

Dose (international units) = body weight (kg) x desired factor IX increase (% of normal or IU/dL) x 1.1 dL/kg

Examples (assuming patient’s baseline factor IX level is <1% of normal):
A dose of 4550 international units of RIXUBIS, administered to a 70 kg patient, should be expected to result in a peak post-infusion factor IX increase of 4550 international units x {[0.9 IU/dL]/[IU/kg]}/[70 kg] = 58.5 international units/dL (58.5 % of normal). A peak level of 70% is required in a 60 kg patient. The appropriate dose would be 60 kg x 70 international units/dL/{[0.9 IU/dL]/[IU/kg]} = 4667 international units.
2.2 Control and Prevention of Bleeding Episodes and Perioperative Management

A guide for dosing RIXUBIS in the control and prevention of bleeding episodes and perioperative management is provided in Table 1 and Table 2, respectively. Ensure the factor IX activity level is achieved and maintained in the corresponding period.
Table 1 Dosing for Control and Prevention of Bleeding Episodes Adapted from Roberts and Eberst1 Type of Bleeding Episodes Circulating Factor IX Level Required (% or IU/dL) Dosing Interval (hours) Duration of Therapy (days)
Minor
Uncomplicated hemarthrosis, superficial muscular or soft tissue 20-30 12-24 At least 1 day, until healing is achieved
Moderate
Intramuscular or soft tissue with dissection, mucous membranes, hematuria 25-50 12-24 2-7 days, until bleeding stops and healing is achieved
Major

Pharyngeal, retropharyngeal,
retroperitoneal, CNS 50-100 12-24 7-10 days, until bleeding stops and healing is achieved Table 2 Dosing for Perioperative Management Type of Surgery Circulating Factor IX Level Required (% or IU/dL) Dosing Interval (hours) Duration of Therapy (days) Minore.g., tooth extraction 30-60 24 At least 1 day, until healing is achieved Majore.g., intracranial, intraabdominal, intrathoracic, joint replacement 80-100 8-24 7-10 days, until bleeding stops and healing is achieved
2.3 Routine Prophylaxis

The dose for previously treated patients (PTPs) is 40 to 60 international units per kg twice weekly. Titration of dose may be necessary depending upon the individual patient’s age, bleeding pattern, and physical activity.

2.4 Preparation and Reconstitution

The procedures below are provided as general guidelines for the preparation and reconstitution of RIXUBIS. Always work on a clean surface and wash hands before performing the following procedures:
Use aseptic technique during reconstitution procedure. Allow the RIXUBIS vial (dry factor concentrate) and Sterile Water for Injection, USP vial (diluent) to reach room temperature. Remove caps from the factor concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place the vials on a flat surface. Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package. Note that the BAXJECT II device is intended for use with a single vial of RIXUBIS and Sterile Water for Injection, USP only; therefore, reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B). Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike. Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully into the RIXUBIS vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the RIXUBIS vial. Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. Use within 3 hours of reconstitution.
2.5 Administration

For intravenous bolus infusion only.
The safety and efficacy of RIXUBIS administration by continuous infusion has not been established. Inspect parenteral drug products for particulate matter and discoloration prior to administration. The solution should be clear and colorless in appearance. Do not use RIXUBIS if you notice any particulates or turbidity in the solution and notify Baxter. Perform product administration and handling of the administration set and needles with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single-use. Administer RIXUBIS at room temperature and within 3 hours of reconstitution. Discard any unused product.

1. Use a plastic syringe with this product.

2. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). Do not inject air.

3. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F).

4. Disconnect the syringe; attach a suitable needle and inject intravenously by bolus infusion. If a patient is to receive more than one vial of RIXUBIS, the contents of multiple vials may be drawn into the same syringe.

5. Maximum infusion rate of 10mL/min.

2.1 Dosing Guidelines

Calculating Initial Dose

The initial dose of RIXUBIS is calculated based on the empirical finding that one international unit of RIXUBIS per kg body weight is expected to increase the circulating level of factor IX by 0.9 international units/dL of plasma (0.9% of normal) in adult patients.

A guide for calculating the initial dose of RIXUBIS for treatment of bleeding episodes is as follows:

Initial Dose = body weight (kg) x desired factor IX increase (% of normal or IU/dL) x reciprocal of observed recovery (IU/kg per IU/dL)

Incremental Recovery in Previously Treated Patients (PTPs)

Base the calculation of the dose on the patient’s individual incremental recovery using serial factor IX activity assays, due to the wide range of inter-individual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics, in particular incremental recovery and half-life.

For an incremental recovery of 0.9 international units/dL of plasma (0.9% of normal), the dose is calculated as follows:

Dose (international units) = body weight (kg) x desired factor IX increase (% of normal or IU/dL) x 1.1 dL/kg

Examples (assuming patient’s baseline factor IX level is <1% of normal):
A dose of 4550 international units of RIXUBIS, administered to a 70 kg patient, should be expected to result in a peak post-infusion factor IX increase of 4550 international units x {[0.9 IU/dL]/[IU/kg]}/[70 kg] = 58.5 international units/dL (58.5 % of normal). A peak level of 70% is required in a 60 kg patient. The appropriate dose would be 60 kg x 70 international units/dL/{[0.9 IU/dL]/[IU/kg]} = 4667 international units.
2.2 Control and Prevention of Bleeding Episodes and Perioperative Management

A guide for dosing RIXUBIS in the control and prevention of bleeding episodes and perioperative management is provided in Table 1 and Table 2, respectively. Ensure the factor IX activity level is achieved and maintained in the corresponding period.
Table 1 Dosing for Control and Prevention of Bleeding Episodes Adapted from Roberts and Eberst1 Type of Bleeding Episodes Circulating Factor IX Level Required (% or IU/dL) Dosing Interval (hours) Duration of Therapy (days)
Minor
Uncomplicated hemarthrosis, superficial muscular or soft tissue 20-30 12-24 At least 1 day, until healing is achieved
Moderate
Intramuscular or soft tissue with dissection, mucous membranes, hematuria 25-50 12-24 2-7 days, until bleeding stops and healing is achieved
Major

Pharyngeal, retropharyngeal,
retroperitoneal, CNS 50-100 12-24 7-10 days, until bleeding stops and healing is achieved Table 2 Dosing for Perioperative Management Type of Surgery Circulating Factor IX Level Required (% or IU/dL) Dosing Interval (hours) Duration of Therapy (days) Minore.g., tooth extraction 30-60 24 At least 1 day, until healing is achieved Majore.g., intracranial, intraabdominal, intrathoracic, joint replacement 80-100 8-24 7-10 days, until bleeding stops and healing is achieved
2.3 Routine Prophylaxis

The dose for previously treated patients (PTPs) is 40 to 60 international units per kg twice weekly. Titration of dose may be necessary depending upon the individual patient’s age, bleeding pattern, and physical activity.

2.4 Preparation and Reconstitution

The procedures below are provided as general guidelines for the preparation and reconstitution of RIXUBIS. Always work on a clean surface and wash hands before performing the following procedures:
Use aseptic technique during reconstitution procedure. Allow the RIXUBIS vial (dry factor concentrate) and Sterile Water for Injection, USP vial (diluent) to reach room temperature. Remove caps from the factor concentrate and diluent vials. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place the vials on a flat surface. Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package. Note that the BAXJECT II device is intended for use with a single vial of RIXUBIS and Sterile Water for Injection, USP only; therefore, reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B). Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike. Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully into the RIXUBIS vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the RIXUBIS vial. Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. Use within 3 hours of reconstitution.
2.5 Administration

For intravenous bolus infusion only.
The safety and efficacy of RIXUBIS administration by continuous infusion has not been established. Inspect parenteral drug products for particulate matter and discoloration prior to administration. The solution should be clear and colorless in appearance. Do not use RIXUBIS if you notice any particulates or turbidity in the solution and notify Baxter. Perform product administration and handling of the administration set and needles with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single-use. Administer RIXUBIS at room temperature and within 3 hours of reconstitution. Discard any unused product.

1. Use a plastic syringe with this product.

2. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). Do not inject air.

3. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F).

4. Disconnect the syringe; attach a suitable needle and inject intravenously by bolus infusion. If a patient is to receive more than one vial of RIXUBIS, the contents of multiple vials may be drawn into the same syringe.

5. Maximum infusion rate of 10mL/min.
Lactated Ringers

Lactated Ringers

As directed by a physician. Dosage, rate and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless the solution is clear and seal is intact.

When making additions to Lactated Ringer’s Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

Additives may be incompatible with Lactated Ringer’s Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition, by checking for a possible color change and/or the appearance of precipitates, insoluble complexes, or crystals. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Lactated Ringer’s Injection, USP is appropriate.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible should not be used.
Lactated Ringers

Lactated Ringers

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

All injections in AVIVA plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless the solution is clear and seal is intact.

When making additions to Lactated Ringer’s Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

Additives may be incompatible with Lactated Ringer’s Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition, by checking for a possible color change and/or the appearance of precipitates, insoluble complexes, or crystals. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Lactated Ringer’s Injection, USP is appropriate.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible should not be used.
Tisseel

Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT

Vials and pre-filled syringes are for single use only. Discard any unused product.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers.

Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes and transfer devices for reconstituting Sealer Protein and Thrombin solutions and for application to prevent clotting.

The product must be used within 4 hours after reconstitution.

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

See FIBRINOTHERM manual for complete operating instructions. If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance.
Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter ring(s), and allow the vials to warm for up to 5 minutes (room temperature product will take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the caps from the Sealer Protein Concentrate and the Fibrinolysis Inhibitor Solution vials. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the product is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution is complete when no undissolved particles are visible.
Notes:

-If the Sealer Protein Concentrate has not fully dissolved within 20 minutes discard the vial and prepare a fresh kit.

-Keep the Sealer Protein Solution at 37°C without stirring. Stir shortly before drawing up the solution to ensure homogeneity.

Preparation of Thrombin Solution with FIBRINOTHERM

To reconstitute the Thrombin (Human) with the Calcium Chloride Solution; follow steps 1-3 under Preparation of Sealer Protein with FIBRINOTHERM utilizing the Thrombin and Calcium Chloride vials.

Transferring to the Sterile Field

For transfer of the Sealer Protein and Thrombin Solutions to the sterile field, the circulating nurse should disinfect the tops of the vials with a germicidal solution and allow to dry. The scrub nurse should withdraw the sterile solutions while the circulating nurse holds the non-sterile vials. Slowly withdraw the solution, by firm constant aspiration, to reduce the risk of large air bubbles.

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency) to 33-37ºC.

Do not remove the protective syringe cap until use.

Sterile Water Bath (Quick Thawing): Transfer inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath ensuring the syringe is completely immersed in the water. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Non-Sterile Water Bath: Maintain the pre-filled syringe in pouches and place into a water bath outside the sterile field ensuring the pouches remain submerged. Remove from the water bath after thawing and warming, dry the external pouch and transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Incubator: Maintain the pre-filled syringe in pouches and place into an incubator. Remove from the incubator after thawing and warming. Transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.
Table 1: Approximate Water Bath or Incubator Thawing and Warming Times Pack Size
Sterile Water Bath(Pouches Removed)
33 - 37°C
Non-Sterile Water Bath

(In Pouches)
33 - 37°C
Incubator

(In Pouches)
33 - 37°C 2 mL 5 minutes 30 minutes 40 minutes 4 mL 5 minutes 40 minutes 85 minutes 10 mL 12 minutes 80 minutes 105 minutes
Room Temperature Thawing: Unopened pouches can be stored for up to 48 hours at room temperature (15-25°C). Before use, warm the product to 33-37ºC and apply immediately. The total thawing and warming time cannot exceed 48 hours.

Table 2: Approximate Room Temperature Thawing Times Pack Size
Room Temperature

(In Pouches)
15 – 25oC 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes

Table 3: Approximate Water Bath or Incubator Warming Times for Thawed Product Pack Size
Sterile Water Bath(Pouches Removed)
33 – 37°C
Non-Sterile Water Bath

(In Pouches)
33 – 37°C
Incubator

(In Pouches)
33 – 37°C 2 mL 2 minutes 16 minutes 20 minutes 4 mL 2 minutes 21 minutes 43 minutes 10 mL 6 minutes 43 minutes 52 minutes
2.3 Method of Application

Dry the site of application as much as possible.

Apply TISSEEL as a thin layer by dripping or spraying using a cannula or spray set. The treating physician will determine the amount of TISSEEL to be applied based on the surface to be covered. Ensure that the amount applied is sufficient to entirely cover the intended application area. The approximate surface areas covered by each package size of TISSEEL are listed in Table 4:
Table 4: Surface Area Coverage
Required package size of
TISSEEL Maximum coverage using spray Maximum coverage using cannula
2 mL

4 mL
10 mL
100 cm2

200 cm2
500 cm2
8 cm2

16 cm2
40 cm2
Avoid application beyond the intended area. Allow at least 2 minutes after application to achieve sufficient polymerization. If repeat application is needed, dry the site as much as possible before reapplying. Reapply after removing residues from the prior application or before polymerization takes place since TISSEEL may not adhere firmly to a polymerized layer.

In cases where very small volumes (1-2 drops) are required, expel and discard the first several drops from the application cannula immediately before application to ensure administration of adequately mixed TISSEEL.

Exercise caution when applying TISSEEL using pressurized gas (see Warnings and Precautions (5.2)).

Record the product name, batch number and patient information for traceability purposes.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece (Y connector) and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Azithromycin

Azithromycin

[see Indications and Usage (1) and Clinical Pharmacology (12.3)]

2.1 Community-Acquired Pneumonia

The recommended dose of AZITHROMYCIN for injection for the treatment of adult patients with community-acquired pneumonia due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by azithromycin by the oral route at a single, daily dose of 500 mg, administered as two 250-mg tablets to complete a 7- to 10-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.

2.2 Pelvic Inflammatory Disease

The recommended dose of AZITHROMYCIN for injection for the treatment of adult patients with pelvic inflammatory disease due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for one or two days. Intravenous therapy should be followed by azithromycin by the oral route at a single, daily dose of 250 mg to complete a 7-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.

2.3 Preparation of the Solution for Intravenous administration

The infusate concentration and rate of infusion for AZITHROMYCIN for injection should be either 1 mg/mL over 3 hours or 2 mg/mL over 1 hour. AZITHROMYCIN for injection should not be given as a bolus or as an intramuscular injection.

Reconstitution

Prepare the initial solution of AZITHROMYCIN for injection by adding 4.8 mL of Sterile Water for Injection to the 500 mg vial, and shaking the vial until all of the drug is dissolved. Since AZITHROMYCIN for injection is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of Sterile Water is dispensed. Each mL of reconstituted solution contains 100 mg azithromycin. Reconstituted solution is stable for 24 hours when stored below 30°C (86°F).

Parenteral drug products should be inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded.

Dilute this solution further prior to administration as instructed below.

Dilution

To provide azithromycin over a concentration range of 1.0–2.0 mg/mL, transfer 5 mL of the 100 mg/mL azithromycin solution into the appropriate amount of any of the diluents listed below:

Normal Saline (0.9% sodium chloride)1/2 Normal Saline (0.45% sodium chloride)5% Dextrose in WaterLactated Ringer's Solution5% Dextrose in 1/2 Normal Saline (0.45% sodium chloride) with 20 mEq KCl5% Dextrose in Lactated Ringer's Solution5% Dextrose in 1/3 Normal Saline (0.3% sodium chloride)5% Dextrose in 1/2 Normal Saline (0.45% sodium chloride)Normosol®-M in 5% DextroseNormosol®-R in 5% Dextrose

When used with the Vial-Mate® drug reconstitution device, please reference the Vial-Mate® instructions for assembly and reconstitution.
Final Infusion Solution Concentration (mg/mL) Amount of Diluent (mL) 1.0 mg/mL 500 mL 2.0 mg/mL 250 mL
Other intravenous substances, additives, or medications should not be added to AZITHROMYCIN for injection, or infused simultaneously through the same intravenous line.

Storage

When diluted according to the instructions (1.0 mg/mL to 2.0 mg/mL), AZITHROMYCIN for injection is stable for 24 hours at or below room temperature 30°C (86°F), or for 7 days if stored under refrigeration 5°C (41°F).
Aralast Np

Aralast Np

For Intravenous Use Only

2.1 Dosage
Dose ranging studies using efficacy endpoints have not been performed. Administer 60 mg/kg body weight of ARALAST NP once weekly by intravenous infusion.
2.2 Reconstitution

1. Use aseptic technique

2. Allow ARALAST NP and diluent to reach room temperature before reconstitution.

3. Remove caps from the diluent and product vials.

4. Swab the exposed stopper surfaces with alcohol.

5. Remove cover from one end of the double-ended transfer needle. Insert the exposed end of the needle through the center of the stopper in the diluent vial.

6. Remove plastic cap from the other end of the double-ended transfer needle now seated in the stopper of the diluent vial. To reduce any foaming, invert the vial of diluent and insert the exposed end of the needle through the center of the stopper in the product vial at an angle, making certain that the diluent vial is always above the product vial. The angle of insertion directs the flow of diluent against the side of the product vial. Refer to Figure below. The vacuum in the vial is sufficient to allow transfer of all of the diluent.

7. Disconnect the two vials by removing the diluent vial from the transfer needle. This allows any remaining low pressure in the product vial to equalize. Next, remove the double-ended transfer needle from the product vial and discard the needle into the appropriate safety container.

8. Let the vial stand until most of the contents is in solution, then GENTLY swirl until the powder is completely dissolved. Reconstitution requires no more than five minutes for a 0.5 gram vial and no more than 10 minutes for a 1 gram vial.

Note: Do not shake the content of the vial. Do not invert the vial until ready to withdraw content.

9. Reconstituted product is a colorless or slightly yellow to yellow-green solution.

10. A few small visible particles may occasionally remain in the reconstituted product. These will be removed by the sterile 20 micron filter supplied with the product.

2.3 Administration

For intravenous infusion

1. Inspect the reconstituted product visually for particulate matter and discoloration prior to administration.

2. Several vials may be pooled into an empty, sterile intravenous solution container using aseptic technique and a sterile 20 micron filter supplied with the product.

3. Administer ARALAST NP within three hours after reconstitution to reduce the risk of harmful microbial growth. Discard any unused contents.

4. Administer ARALAST NP alone, without mixing with other agents or diluting solutions.

Infusion Rate
Administer ARALAST NP at a rate not to exceed 0.2 mL per kg body weight per minute, and as determined by the response and comfort of the patient. Reduce the infusion rate or halt the infusion if adverse reactions occur. Resume the infusion at a rate tolerated by the patient after symptoms subside.
2.3 Administration

For intravenous infusion

1. Inspect the reconstituted product visually for particulate matter and discoloration prior to administration.

2. Several vials may be pooled into an empty, sterile intravenous solution container using aseptic technique and a sterile 20 micron filter supplied with the product.

3. Administer ARALAST NP within three hours after reconstitution to reduce the risk of harmful microbial growth. Discard any unused contents.

4. Administer ARALAST NP alone, without mixing with other agents or diluting solutions.

Infusion Rate
Administer ARALAST NP at a rate not to exceed 0.2 mL per kg body weight per minute, and as determined by the response and comfort of the patient. Reduce the infusion rate or halt the infusion if adverse reactions occur. Resume the infusion at a rate tolerated by the patient after symptoms subside.
Tisseel

Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT

Vials and pre-filled syringes are for single use only. Discard any unused product.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers.

Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes and transfer devices for reconstituting Sealer Protein and Thrombin solutions and for application to prevent clotting.

The product must be used within 4 hours after reconstitution.

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

See FIBRINOTHERM manual for complete operating instructions. If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance.
Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter ring(s), and allow the vials to warm for up to 5 minutes (room temperature product will take less time).
Preparation of Sealer Protein Solution with FIBRINOTHERM
Remove the caps from the Sealer Protein Concentrate and the Fibrinolysis Inhibitor Solution vials. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the product is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution is complete when no undissolved particles are visible.
Notes:

-If the Sealer Protein Concentrate has not fully dissolved within 20 minutes discard the vial and prepare a fresh kit.

-Keep the Sealer Protein Solution at 37°C without stirring. Stir shortly before drawing up the solution to ensure homogeneity.

Preparation of Thrombin Solution with FIBRINOTHERM

To reconstitute the Thrombin (Human) with the Calcium Chloride Solution; follow steps 1-3 under Preparation of Sealer Protein with FIBRINOTHERM utilizing the Thrombin and Calcium Chloride vials.

Transferring to the Sterile Field

For transfer of the Sealer Protein and Thrombin Solutions to the sterile field, the circulating nurse should disinfect the tops of the vials with a germicidal solution and allow to dry. The scrub nurse should withdraw the sterile solutions while the circulating nurse holds the non-sterile vials. Slowly withdraw the solution, by firm constant aspiration, to reduce the risk of large air bubbles.

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency) to 33-37ºC.

Do not remove the protective syringe cap until use.

Sterile Water Bath (Quick Thawing): Transfer inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath ensuring the syringe is completely immersed in the water. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Non-Sterile Water Bath: Maintain the pre-filled syringe in pouches and place into a water bath outside the sterile field ensuring the pouches remain submerged. Remove from the water bath after thawing and warming, dry the external pouch and transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Incubator: Maintain the pre-filled syringe in pouches and place into an incubator. Remove from the incubator after thawing and warming. Transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.
Table 1: Approximate Water Bath or Incubator Thawing and Warming Times Pack Size
Sterile Water Bath(Pouches Removed)
33 - 37°C
Non-Sterile Water Bath

(In Pouches)
33 - 37°C
Incubator

(In Pouches)
33 - 37°C 2 mL 5 minutes 30 minutes 40 minutes 4 mL 5 minutes 40 minutes 85 minutes 10 mL 12 minutes 80 minutes 105 minutes
Room Temperature Thawing: Unopened pouches can be stored for up to 48 hours at room temperature (15-25°C). Before use, warm the product to 33-37ºC and apply immediately. The total thawing and warming time cannot exceed 48 hours.

Table 2: Approximate Room Temperature Thawing Times Pack Size
Room Temperature

(In Pouches)
15 – 25oC 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes

Table 3: Approximate Water Bath or Incubator Warming Times for Thawed Product Pack Size
Sterile Water Bath(Pouches Removed)
33 – 37°C
Non-Sterile Water Bath

(In Pouches)
33 – 37°C
Incubator

(In Pouches)
33 – 37°C 2 mL 2 minutes 16 minutes 20 minutes 4 mL 2 minutes 21 minutes 43 minutes 10 mL 6 minutes 43 minutes 52 minutes
2.3 Method of Application

Dry the site of application as much as possible.

Apply TISSEEL as a thin layer by dripping or spraying using a cannula or spray set. The treating physician will determine the amount of TISSEEL to be applied based on the surface to be covered. Ensure that the amount applied is sufficient to entirely cover the intended application area. The approximate surface areas covered by each package size of TISSEEL are listed in Table 4:
Table 4: Surface Area Coverage
Required package size of
TISSEEL Maximum coverage using spray Maximum coverage using cannula
2 mL

4 mL
10 mL
100 cm2

200 cm2
500 cm2
8 cm2

16 cm2
40 cm2
Avoid application beyond the intended area. Allow at least 2 minutes after application to achieve sufficient polymerization. If repeat application is needed, dry the site as much as possible before reapplying. Reapply after removing residues from the prior application or before polymerization takes place since TISSEEL may not adhere firmly to a polymerized layer.

In cases where very small volumes (1-2 drops) are required, expel and discard the first several drops from the application cannula immediately before application to ensure administration of adequately mixed TISSEEL.

Exercise caution when applying TISSEEL using pressurized gas (see Warnings and Precautions (5.2)).

Record the product name, batch number and patient information for traceability purposes.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):
Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece (Y connector) and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET
Potassium Chloride In L...

Potassium Chloride In Lactated Ringers And Dextrose

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

The infusion rate should not exceed the patient’s ability to utilize glucose in order to avoid hyperglycemia.

As reported in the literature, the dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low weight infants, because of the increased risk of hyperglycemia/hypoglycemia (See PRECAUTIONS, Pediatric Use).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless the solution is clear and the seal is intact.

When making additions to Potassium Chloride in Lactated Ringer’s and 5% Dextrose Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

Additives may be incompatible with Potassium Chloride in Lactated Ringer’s and 5% Dextrose Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition, by checking for a possible color change and/or the appearance of precipitates, insoluble complexes, or crystals. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Potassium Chloride in Lactated Ringer’s and 5% Dextrose Injection, USP is appropriate.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible should not be used.
Lactated Ringers And De...

Lactated Ringers And Dextrose

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

The infusion rate should not exceed the patient’s ability to utilize glucose in order to avoid hyperglycemia.

As reported in the literature, the dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low weight infants, because of the increased risk of hyperglycemia/hypoglycemia (See PRECAUTIONS, Pediatric Use).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not administer unless the solution is clear and the seal is intact.

When making additions to Lactated Ringer’s and 5% Dextrose Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

Additives may be incompatible with Lactated Ringer’s and 5% Dextrose Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition, by checking for a possible color change and/or the appearance of precipitates, insoluble complexes, or crystals. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Lactated Ringer’s and 5% Dextrose Injection, USP is appropriate.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible should not be used.
Sodium Lactate

Sodium Lactate

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and dependent upon the indication for use, patient's age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not administer unless the solution is clear and seal is intact.

When making additions to Sodium Lactate Injection, USP, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

Additives may be incompatible with Sodium Lactate Injection, USP. As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition, by checking for a possible color change and/or the appearance of precipitates, insoluble complexes, or crystals. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Sodium Lactate Injection, USP is appropriate.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible should not be used.
Ringers

Ringers

As directed by a physician.

Cautions: Warm in oven to not more than 50°C for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only.
Glassia

Glassia

For intravenous use only.

2.1 Dosage
Administer 60 mg/kg body weight of GLASSIA once weekly by intravenous infusion. Dose ranging studies using efficacy endpoints have not been performed.
2.2 Preparation
Use aseptic technique. Allow the product to reach room temperature prior to infusing and administer within three hours of entering the vials. Inspect the vial of GLASSIA. The solution should be clear and colorless to yellow-green and may contain a few protein particles. Do not use if the product is cloudy. Infuse directly from the vial or, alternatively for large dose, pool vials into an empty, sterile container for intravenous infusion using the supplied filter needle. In the latter case, use a vented filter spike (not supplied) to withdraw the material from the vial and then use the supplied 5 micron filter needle to transfer the product into the intravenous infusion container.
2.3 Administration

For intravenous infusion only.
Use aseptic technique. Inspect parenteral products visually for particulate matter and discoloration prior to administration whenever solution and container permit. Administer GLASSIA alone. Do not mix with other agents or diluting solutions. When infusing directly from the vials, use a vented filter spike (not supplied). If the contents of vials have been pooled to a sterile intravenous container, use an appropriate intravenous administration set. Always use a 5 micron in-line filter (not supplied) during infusion. Administer GLASSIA within three hours of entering the vials to avoid the potential ill effect of any inadvertent microbial contamination. Administer GLASSIA at room temperature through an appropriate intravenous administration set at a rate not to exceed 0.2 mL/kg body weight per minute, and as determined by the response and comfort of the patient. The recommended dosage of 60 mg/kg at a rate of 0.2 mL/kg/min will take approximately 15 minutes to infuse. Monitor the infusion rate closely during administration and observe the patient for signs of infusion related reactions. If infusion related adverse reactions occur, reduce the rate or interrupt the infusion as appropriate until the symptoms subside. Resume the infusion at a rate tolerated by the patient, except in the case of severe reaction. Following administration, discard all open vials, unused solution and administration equipment.
Tis-u-sol

Tis-u-sol

As directed by a physician.

Cautions: Warm in oven to not more than 50°C for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only.
Nifedipine

Nifedipine

2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

BREVIBLOC is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.
Table 1 Step-Wise Dosing
Step

Action

1

Optional loading dose (500 mcg per kg over 1 minute), then 50 mcg per kg per min for 4 min

2

Optional loading dose if necessary, then 100 mcg per kg per min for 4 min

3

Optional loading dose if necessary, then 150 mcg per kg per min for 4 min

4

If necessary, increase dose to 200 mcg per kg per min

In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.

The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.

Maintenance infusions may be continued for up to 48 hours.

2.2 Intraoperative and Postoperative Tachycardia and Hypertension

In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.

Immediate Control
• Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary. • Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.
Gradual Control
• Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes. • Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.
Maximum Recommended Doses
• For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases. • For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
2.3 Transition from BREVIBLOC Injection Therapy to Alternative Drugs

After patients achieve adequate control of the heart rate and a stable clinical status, transition to alternative antiarrhythmic drugs may be accomplished.

When transitioning from BREVIBLOC to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of BREVIBLOC as follows:
• Thirty minutes following the first dose of the alternative drug, reduce the BREVIBLOC infusion rate by one-half (50%). • After administration of the second dose of the alternative drug, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue the BREVIBLOC infusion.
2.4 Directions for Use

BREVIBLOC injection is available in a pre-mixed bag and ready-to-use vial. BREVIBLOC is not compatible with Sodium Bicarbonate (5%) solution (limited stability) or furosemide (precipitation).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Premixed Bag
• The medication port is to be used solely for withdrawing an initial bolus from the bag. • Use aseptic technique when withdrawing the bolus dose. • Do not add any additional
Figure 1: Two-Port INTRAVIA Bag

Figure 1: Two-Port INTRAVIA Bag
• medications to the bag.
Figure 1: Two-Port INTRAVIA Bag

Ready-to-Use Vial

The Ready-to-use Vial may be used to administer a loading dosage by hand-held syringe while the maintenance infusion is being prepared[see How Supplied/Storage and Handling (16.2)].

Compatibility with Commonly Used Intravenous Fluids

BREVIBLOC was tested for compatibility with ten commonly used intravenous fluids at a final concentration of 10 mg esmolol hydrochloride per mL. BREVIBLOC was found to be compatible with the following solutions and was stable for at least 24 hours at controlled room temperature or under refrigeration:
• Dextrose (5%) Injection, USP • Dextrose (5%) in Lactated Ringer’s Injection • Dextrose (5%) in Ringer’s Injection • Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP • Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP • Lactated Ringer’s Injection, USP • Potassium Chloride (40 mEq/liter) in Dextrose (5%) Injection, USP • Sodium Chloride (0.45%) Injection, USP • Sodium Chloride (0.9%) Injection, USP
Sterile Water Irrigant

Sterile Water Irrigant

As directed by a physician.

Cautions: Warm in oven to not more than 50°C for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only.
Sodium Chloride Irrigan...

Sodium Chloride Irrigant

As directed by a physician.

Cautions: Warm in oven to not more than 50°C for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only.
Cefazolin

Cefazolin

Usual Adult Dosage:
* In rare instances, doses of up to 12 grams of Cefazolin Injection per day have been used. Type of Infection Dose Frequency Moderate to severe infections 500 mg to 1 gram every 6 to 8 hrs. Mild infections caused by susceptible gram-positive cocci 250 mg to 500 mg every 8 hours Acute, uncomplicated urinary tractinfections 1 gram every 12 hours Pneumococcal pneumonia 500 mg every 12 hours Severe, life-threatening infections (e.g.,endocarditis, septicemia)* 1 gram to 1.5 grams every 6 hours
Perioperative Prophylactic Use

To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are:
1 gram IV administered ½ hour to 1 hour prior to start of surgery. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV during surgery (administration modified depending on the duration of the operative procedure). 500 mg to 1 gram IV every 6 to 8 hours for 24 hours postoperatively.
It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms.

In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin may be continued for 3 to 5 days following the completion of surgery.

Dosage Adjustment for Patients With Reduced Renal Function

Cefazolin Injection may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg % or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3.0 mg % can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg % should be given ½ the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg % or greater should be given ½ the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Patients undergoing peritoneal dialysis: See CLINICAL PHARMACOLOGY.
Vancomycin Hydrochlorid...

Vancomycin Hydrochloride

Vancomycin Injection, USP in the GALAXY plastic container (PL 2040) is intended for intravenous use only.

Vancomycin in the GALAXY Container (PL 2040 Plastic) is not to be administered orally. An infusion rate of 10 mg/min or less is associated with fewer infusion-related events (see ADVERSE REACTIONS). Infusion related events may occur, however, at any rate or concentration.

Patients With Normal Renal Function

Adults

The usual daily intravenous dose is 2 g divided either as 500 mg every 6 hours or 1 g every 12 hours. Each dose should be administered at no more than 10 mg/min or over a period of at least 60 minutes, whichever is longer. Other patient factors, such as age or obesity, may call for modification of the usual intravenous daily dose.

Pediatric patients

The usual intravenous dosage of vancomycin is 10 mg/kg per dose given every 6 hours. Each dose should be administered over a period of at least 60 minutes. Close monitoring of serum concentrations of vancomycin may be warranted in these patients.

Neonates

In pediatric patients up to the age of 1 month, the total daily intravenous dosage may be lower. In neonates, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the 1st week of life and every 8 hours thereafter up to the age of 1 month. Each dose should be administered over 60 minutes. In premature infants, vancomycin clearance decreases as postconceptional age decreases. Therefore, longer dosing intervals may be necessary in premature infants. Close monitoring of serum concentrations of vancomycin is recommended in these patients.

Patients With Impaired Renal Function and Elderly Patients

Dosage adjustment must be made in patients with impaired renal function. In the elderly, greater dosage reductions than expected may be necessary because of decreased renal function. Measurement of vancomycin serum concentrations can be helpful in optimizing therapy, especially in seriously ill patients with changing renal function. Vancomycin serum concentrations can be determined by use of microbiologic assay, radioimmunoassay, fluorescence polarization immunoassay, fluorescence immunoassay, or high-pressure liquid chromatography. If creatinine clearance can be measured or estimated accurately, the dosage for most patients with renal impairment can be calculated using the following table. The dosage of vancomycin per day in mg is about 15 times the glomerular filtration rate in mL/min:

DOSAGE TABLE FOR VANCOMYCININ PATIENTS WITH IMPAIRED RENAL FUNCTION(Adapted from Moellering et al)4

Creatinine Clearance mL/min

Vancomycin Dose mg/24 h

100

1,545

90

1,390

80

1,235

70

1,080

60

925

50

770

40

620

30

465

20

310

10

155

The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency. The table is not valid for functionally anephric patients. For such patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations. The dose required to maintain stable concentrations is 1.9 mg/kg/24 h. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1,000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1,000 mg every 7 to 10 days has been recommended.

When only the serum creatinine concentration is known, the following formula (based on sex, weight, and age of the patient) may be used to calculate creatinine clearance. Calculated creatinine clearances (mL/min) are only estimates. The creatinine clearance should be measured promptly.

Men:

Weight (kg) x (140 – age in years)

72 x serum creatinine concentration (mg/dL)

Women:

0.85 x above value

The serum creatinine must represent a steady state of renal function. Otherwise, the estimated value for creatinine clearance is not valid. Such a calculated clearance is an overestimate of actual clearance in patients with conditions: (1) characterized by decreasing renal function, such as shock, severe heart failure, or oliguria; (2) in which a normal relationship between muscle mass and total body weight is not present, such as obese patients or those with liver disease, edema, or ascites; and (3) accompanied by debilitation, malnutrition, or inactivity. The safety and efficacy of vancomycin administration by the intrathecal (intralumbar or intraventricular) routes have not been established.

Intermittent infusion is the recommended method of administration.

Directions for use of Vancomycin Injection, USP in GALAXY plastic container (PL 2040)

Vancomycin Injection, USP in GALAXY plastic container (PL 2040) is for intravenous administration only.

Storage

Store in a freezer capable of maintaining a temperature at or below -20°C (-4°F).

Thawing of Plastic Containers:
1. Thaw frozen containers at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. 2. Check for minute leaks by squeezing the bag firmly. If leaks are detected, discard solution because sterility may be impaired. 3. DO NOT ADD SUPPLEMENTARY MEDICATION. 4. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded. 5. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature (25°C/77°F) or for 30 days when stored under refrigeration (5°C/41°F). 6. Do not refreeze thawed antibiotics.
Preparation for Intravenous Administration:
1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set. 4. Use sterile equipment.
Caution: Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Rx only.
Mestinon

Mestinon

2.1 Adults and Pediatric Population

The recommended adult and pediatric dosages and routes of administration are outlined in Table 1. Cefepime Injection should be administered intravenously over approximately 30 minutes.
Table 1: Recommended Dosage Schedule for Cefepime Injection in Patients with CrCL Greater Than 60 mL/min* Site and Type of Infection Dose Frequency Duration (days) * Adjust dose in patients with CrCL less than or equal to 60 mL/min ( 2.3) † including cases associated with concurrent bacteremia ‡ For Pseudomonas aeruginosa, use 2 g IV every 8 hours (50 mg per kg per dose in pediatric patients 2 months up to 16 years. Ω § or until resolution of neutropenia. In patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be re-evaluated frequently.
Adults

Moderate to Severe Pneumonia due to S. pneumoniae†, P. aeruginosa‡, K. pneumoniae, or Enterobacter species

1-2 g IV

Every 8-12 hours

10

Empiric therapy for febrile neutropenic patients [see Indications and Usage (1) and Clinical Studies (14)]

2 g IV

Every 8 hours

7§

Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli, K. pneumoniae, or P. mirabilis†

0.5-1 g IV

Every 12 hours

7-10

Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli or K. pneumoniae†

2 g IV

Every 12 hours

10

Moderate to Severe Uncomplicated Skin and Skin Structure Infections due to S. aureus or S. pyogenes

2 g IV

Every 12 hours

10

Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by E. coli, viridans group streptococci, P. aeruginosa‡, K. pneumoniae, Enterobacter species, or B. fragilis. [see Clinical Studies (14)]

2 g IV

Every 8-12 hours

7-10

Pediatric Patients (2 months up to 16 years)

The maximum dose for pediatric patients should not exceed the recommended adult dose. The usual recommended dosage in pediatric patients up to 40 kg in weight for uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, and pneumonia‡ is 50 mg per kg per dose, administered every 12 hours (50 mg per kg per dose, every 8 hours for febrile neutropenic patients), for durations as given above.Cefepime Injection in GALAXY Container should be used only in pediatric patients who require the entire 1 or 2 g dose and not any fraction thereof.

2.2 Patients with Hepatic Impairment

No adjustment is necessary for patients with hepatic impairment.

2.3 Patients with Renal Impairment

In patients with creatinine clearance less than or equal to 60 mL/min, the dose of Cefepime Injection should be adjusted to compensate for the slower rate of renal elimination. The recommended initial dose of Cefepime Injection should be the same as in patients with normal renal function except in patients undergoing hemodialysis. The recommended doses of Cefepime Injection in patients with renal impairment are presented in Table 2.

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)1 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:

Males: Creatinine Clearance (mL/min) =

Weight (kg) x (140 – age)

72 x serum creatinine (mg/dL)

Females: 0.85 x above value
Table 2: Recommended Dosing Schedule for Cefepime Injection in Adult Patients (Normal Renal Function, Renal Impairment, and Hemodialysis) Creatinine Clearance (mL/min) Recommended Maintenance Schedule * On hemodialysis days, Cefepime Injection should be administered following hemodialysis. Whenever possible, Cefepime Injection should be administered at the same time each day.
Greater than 60 (Normal recommended dosing schedule)

500 mg every12 hours

1 g every12 hours

2 g every12 hours

2 g every8 hours

30–60

500 mg every24 hours

1 g every24 hours

2 g every24 hours

2 g every12 hours

11–29

500 mg every24 hours

500 mg every24 hours

1 g every24 hours

2 g every24 hours

Less than 11

250 mg every24 hours

250 mg every24 hours

500 mg every24 hours

1 g every24 hours

CAPD

500 mg every48 hours

1 g every48 hours

2 g every48 hours

2 g every48 hours

Hemodialysis*

1 g on day 1, then 500 mg every 24 hours thereafter

1 g every24 hours

In patients undergoing continuous ambulatory peritoneal dialysis, Cefepime Injection may be administered at normally recommended doses at a dosage interval of every 48 hours (see Table 2).

In patients undergoing hemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. The dosage of Cefepime Injection for hemodialysis patients is 1 g on Day 1 followed by 500 mg every 24 hours for the treatment of all infections except febrile neutropenia, which is 1 g every 24 hours. Cefepime Injection should be administered at the same time each day following the completion of hemodialysis on hemodialysis days (see Table 2).

Data in pediatric patients with impaired renal function are not available; however, since cefepime pharmacokinetics are similar in adults and pediatric patients [see Clinical Pharmacology (12)], changes in the dosing regimen proportional to those in adults (see Table 1 and Table 2) are recommended for pediatric patients.

2.4 Directions for Use of Cefepime Injection in GALAXY Container

Cefepime Injection in GALAXY Container (PL 2040 Plastic) is for intravenous administration using sterile equipment after thawing to room temperature.

Thawing of Plastic Container

Thaw frozen container at room temperature 25°C (77°F) or under refrigeration 5°C (41°F). Do not force thaw by immersion in water baths or by microwave irradiation. [See How Supplied/Storage and Handling (16).]

Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.

Do not add supplementary medication.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.

Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for intravenous administration.
• Suspend container from eyelet support. • Remove protector from outlet port at bottom of container. • Attach administration set. Refer to complete directions accompanying set.
Cefepime Injection should be administered intravenously over approximately 30 minutes.

Intermittent intravenous infusion with a Y-type administration set can be accomplished with compatible solutions. However, during infusion of Cefepime Injection, it is desirable to discontinue the other solution.

Solutions of cefepime, like those of most beta-lactam antibiotics, should not be added to solutions of ampicillin at a concentration greater than 40 mg per mL, and should not be added to metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate or aminophylline because of potential interaction. However, if concurrent therapy with cefepime is indicated, each of these antibiotics can be administered separately.
Fluconazole

Fluconazole

Dosage and Administration in Adults

SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.

The daily dose of Fluconazole Injection, USP for the treatment of infections should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.

Oropharyngeal candidiasis The recommended dosage of Fluconazole Injection, USP for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis The recommended dosage of Fluconazole Injection, USP for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.

Systemic Candida infections For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.

Urinary tract infections and peritonitis For the treatment of Candida urinary tract infections and peritonitis, daily doses of 50-200 mg have been used in open, noncomparative studies of small numbers of patients.

Cryptococcal meningitis The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10-12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of Fluconazole Injection, USP for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily.

Prophylaxis in patients undergoing bone marrow transplantation The recommended Fluconazole Injection, USP daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start Fluconazole Injection, USP prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:
* Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. Pediatric Patients Adults 3 mg/kg 100 mg 6 mg/kg 200 mg 12* mg/kg 400 mg
Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY.) Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available.

Oropharyngeal candidiasis The recommended dosage of Fluconazole Injection, USP for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis For the treatment of esophageal candidiasis, the recommended dosage of Fluconazole Injection, USP in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following the resolution of symptoms.

Systemic Candida infections For the treatment of candidemia and disseminated Candida infections, daily doses of 6-12 mg/kg/day have been used in an open, noncomparative study of a small number of children.

Cryptococcal meningitis For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10-12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of Fluconazole Injection, USP is 6 mg/kg once daily.

Dosage In Patients With Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. In patients with impaired renal function who will receive multiple doses of Fluconazole Injection, USP, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:
Creatinine Clearance (mL/min) Percent of Recommended Dose >50 100% ≤50 (no dialysis) 50% Regular dialysis 100% after each dialysis
These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.

When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults:
Males: Weight (kg) x (140 - age)
72 x serum creatinine (mg/100 mL)
Females: 0.85 x above value
Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children:
K x linear length or height (cm) serum creatinine (mg/100 mL)
(Where K=0.55 for children older than 1 year and 0.45 for infants.)

Administration

Fluconazole Injection, USP is administered by intravenous infusion. Fluconazole has been used safely for up to fourteen days of intravenous therapy. The intravenous infusion of Fluconazole Injection, USP should be administered at a maximum rate of approximately 200 mg/hour, given as a continuous infusion.

Fluconazole Injection, USP in INTRAVIA plastic containers is intended only for intravenous administration using sterile equipment.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not use if the solution is cloudy or precipitated or if the seal is not intact.
Famotidine

Famotidine

In some hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, Famotidine Injection may be administered until oral therapy can be instituted.

The recommended dosage for Famotidine Injection in adult patients is 20 mg intravenously q 12 h.

The doses and regimen for parenteral administration in patients with GERD have not been established.

Dosage for Pediatric Patients <1 year of age Gastroesophageal Reflux Disease (GERD)

See PRECAUTIONS, Pediatric Patients <1 year of age.

The use of intravenous famotidine in pediatric patients <1 year of age with GERD has not been adequately studied.

Dosage for Pediatric Patients 1–16 years of age

See PRECAUTIONS, Pediatric Patients 1-16 years of age.

The studies described in PRECAUTIONS, Pediatric Patients 1–16 years of age suggest that the starting dose in pediatric patients 1-16 years of age is 0.25 mg/kg intravenously (injected over a period of not less than two minutes or as a 15-minute infusion) q 12 h up to 40 mg/day.

While published uncontrolled clinical studies suggest effectiveness of famotidine in the treatment of peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or gastric pH determination and endoscopy. Published uncontrolled studies in pediatric patients 1-16 years of age have demonstrated gastric acid suppression with doses up to 0.5 mg/kg intravenously q 12 h.

Dosage Adjustments for Patients with Moderate or Severe Renal Insufficiency

In adult patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the elimination half-life of famotidine is increased. For patients with severe renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients. Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of Famotidine Injection may be reduced to half the dose, or the dosing interval may be prolonged to 36-48 hours as indicated by the patient’s clinical response.

Based on the comparison of pharmacokinetic parameters for famotidine in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.

Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas)

The dosage of famotidine in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult intravenous dose is 20 mg q 12 h. Doses should be adjusted to individual patient needs and should continue as long as clinically indicated. In some patients, a higher starting dose may be required. Oral doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.

Famotidine Injection

Famotidine Injection, supplied in GALAXY containers (PL 2501 Plastic), is a 50 mL iso-osmotic solution premixed with 0.9% sodium chloride for administration as an infusion over a 15-30 minute period.

This premixed solution is for intravenous use only using sterile equipment.
Nafcillin

Nafcillin

Nafcillin Injection, USP supplied as a premixed frozen solution is to be administered as an intravenous infusion. The usual I.V. dosage for adults is 500 mg every 4 hours. For severe infections, 1 g every 4 hours is recommended. Administer slowly over at least 30 to 60 minutes to minimize the risk of vein irritation and extravasation. Bacteriologic studies to determine the causative organisms and their susceptibility to nafcillin should always be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient; therefore, it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with nafcillin should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic, and cultures are negative. The treatment of endocarditis and osteomyelitis may require a longer duration of therapy.

Nafcillin-probenecid therapy is generally limited to those infections where very high serum levels of nafcillin are necessary.

No dosage alterations are necessary for patients with renal dysfunction, including those on hemodialysis. Hemodialysis does not accelerate nafcillin clearance from the blood.

For patients with hepatic insufficiency and renal failure, measurement of nafcillin serum levels should be performed and dosage adjusted accordingly.

With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not add supplementary medication to Nafcillin Injection, USP.

Store in a freezer capable of maintaining a temperature of -20°C (-4°F) or less.
Travasol

Travasol

If a patient is unable to take enteral nourishment for a prolonged period of time, institution of total parenteral nutrition (TPN) with exogenous calories should be considered.

The total daily dose of 10% TRAVASOL (Amino Acid) Injection depends on the patient’s metabolic requirement and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements.

Recommended Dietary Allowances* of protein range from approximately 0.75 g/kg of body weight for adults to 1.68 g/kg for infants. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially. Daily amino acid doses of approximately 1.0 to 1.5 g/kg of body weight for adults with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance.

For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrate will be necessary to promote adequate patient response to therapy. The severity of the illness being treated is the primary consideration in determining proper dose level. Such higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation.

For protein-sparing in well-nourished patients not receiving significant additional calories, amino acid dosages of 1.0 to 1.7 g/kg/day reduce nitrogen losses and spare body protein. If daily increases in BUN in the range of 10 to 15 mg% for more than three days should occur, then protein-sparing therapy should be discontinued and a regimen with full nonprotein calorie substrates should be adopted.

Care should be exercised to insure the maintenance of proper levels of serum potassium. Quantities of 60 to 180 mEq of potassium per day have been used with adequate clinical effect. It may be necessary to add quantities of this electrolyte to this injection, depending primarily on the amount of carbohydrate administered to and metabolized by the patient.

This injection provides a concentrated source of amino acids to meet the protein requirements of patients that are fluid restricted (e.g., renal failure). Acceptable total daily administration volumes are dependent upon the fluid balance requirements of the patient. Extreme care should be given to prevent fluctuations of blood osmolarity and serum electrolyte concentrations. Frequent and careful monitoring is mandatory when fluid restricted patients are receiving intravenous nutrition.

Patients receiving this injection should be monitored (carefully) and their electrolyte requirements individualized.

Total daily fluid requirements can be met beyond the volume of amino acid solutions by supplementing with noncarbohydrate or carbohydrate-containing electrolyte solutions.

*Food and Nutrition Board National Academy of Sciences – National Research Council (Revised 1989)

Maintenance vitamins, additional electrolytes and trace elements should be administered as required.

Fat emulsion coadministration should be considered when prolonged parenteral nutrition (more than 5 days) is required in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat free total parenteral nutrition.

Pediatric Use:

Use of 10% TRAVASOL (Amino Acid) Injection in pediatric patients is governed by the same considerations that affect the use of any amino acid solution in pediatrics. The amount administered is dosed on the basis of grams of amino acids/kg of body weight/day. Two to three g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Solutions administered by peripheral vein should not exceed twice normal serum osmolarity (718 mOsmol/L).

Central Vein Administration:

Hypertonic mixtures of amino acids and dextrose may be administered safely by continuous infusion through a central vein catheter with the tip located in the vena cava. In addition to meeting nitrogen needs, the administration rate is governed, especially during the first few days of therapy, by the patient’s tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of urine and blood sugar levels.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria.

Parenteral nutrition may be started with infusates containing lower concentrations of dextrose; dextrose content may be gradually increased to estimated caloric needs as the patient's glucose tolerance increases.

Sudden cessation in administration of concentrated dextrose solution may result in insulin reaction due to continued endogenous insulin production. Such solutions should be withdrawn slowly.

Peripheral Vein Administration:

For patients requiring parenteral nutrition in whom the central vein route is not indicated, this injection can be mixed with low concentration dextrose solutions and administered by peripheral vein in conjunction with or without fat emulsions. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).

Intravenous fat emulsions provide approximately 1.1 kcal/mL (10%) or 2.0 kcal/mL (20%) and may be administered along with amino acid-dextrose solutions by means of a short Y-connector near the infusion site to supplement caloric intake. Fat, however, should not be the sole caloric intake since studies have indicated that glucose is more nitrogen sparing in the stressed patient.

Protein-Sparing:

For well-nourished patients who require short-term parenteral support, 10% TRAVASOL (Amino Acid) Injection can be administered peripherally with or without carbohydrate calories. Such infusates can be prepared by dilution of this injection with Sterile Water for Injection or 5% Dextrose Injection to prepare isotonic or slightly hypertonic solutions which may be administered by peripheral vein.

Depending upon the clinical condition of the patient, approximately 3 liters of solution may be administered per 24 hour period. When used postoperatively, the therapy should begin with 1000 mL on the first postoperative day. Thereafter, the dose may be increased to 3000 mL per day.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.

Do not administer unless solution is clear and seal is intact.

A slight yellow color does not alter the quality and efficacy of the product.

10% TRAVASOL (Amino Acid) Injection in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures. Additives may be incompatible with the fluid withdrawn from this container. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of 10% TRAVASOL (Amino Acid) Injection.

Any storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.
Sodium Chloride Solutio...

Sodium Chloride Solution

As directed by a physician. See directions accompanying blood cell processing device.

Processing Solutions should be inspected visually for particulate matter and discoloration prior to use.
Dextrose

Dextrose

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless solution is clear and seal is intact.

All injections in AVIVA plastic containers are intended for intravenous administration using sterile equipment.

The dosage selection and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/ hypoglycemia. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Pentoxifylline

Pentoxifylline

Amiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of NEXTERONE is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:
Table 1: NEXTERONE PREMIXED INJECTION DOSE RECOMMENDATIONS: FIRST 24 HOURS
Loading infusions

First Rapid:

150 mg over the FIRST 10 minutes (15 mg/min).

Directly infuse NEXTERONE Premixed Injection (150 mg/100 mL; 1.5mg/mL) at a rate of 10mL/min.

Followed by Slow:

360 mg over the NEXT 6 hours (1 mg/min).

Directly infuse NEXTERONE Premixed Injection (360 mg/200 mL; 1.8 mg/mL) at a rate of 0.556 mL/min.

Maintenance infusion

540 mg over the REMAINING 18 hours (0.5 mg/min). Decrease the rate of the slow loading infusion to 0.5 mg/min. Directly infuse NEXTERONE Premixed Injection (360 mg/200 mL; 1.8 mg/mL) at a rate of 0.278 mL/min.

After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) by directly infusing NEXTERONE Premixed Injection (360 mg/200 mL; 1.8 mg/mL) at a rate of 0.278 mL/min. The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.

In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of NEXTERONE (infused over 10 minutes to minimize the potential for hypotension).

The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Do not exceed an initial infusion rate of 30 mg/min.

Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks.

Administer NEXTERONE, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration.

Intravenous amiodarone loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death [see Warnings and Precautions (5.3)].

Intravenous amiodarone concentrations greater than 3 mg/mL have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, do not exceed NEXTERONE concentrations of 2 mg/mL, unless a central venous catheter is used [see Adverse Reactions (6.2)].

NEXTERONE Premixed Injection is available in GALAXY containers as a single-use, ready-to-use, iso-osmotic solution in dextrose for intravenous administration. No further dilution is required. NEXTERONE Premixed Injection should not be combined with any product in the same intravenous line or premixed container. Do not add supplemental medication. Protect from light until ready to use.

NEXTERONE does not need to be protected from light during administration.

Since the premixed container is for single-use only, any unused portion should be discarded.

NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit, solution should be clear. Visually inspect the container. If the administration port protector is damaged, detached or not present, discard the container as the solution path sterility may be compromised. Check for minute leaks prior to use by squeezing the bag firmly. If leaks are detected, discard solution as sterility may be impaired.

CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.

Preparation of NEXTERONE Premixed Injection for administration:
1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set.
Admixture Incompatibility Amiodarone in D5W Injection forms precipitates with the drugs shown in Table 2. If co-administration of the following drugs is necessary, use separate intravenous administration lines.
Table 2: Y-SITE INJECTION INCOMPATIBILITY D5W = Dextrose 5% in Sterile Water, NS = Normal Saline
Drug

Vehicle

AmiodaroneConcentration

Aminophylline

D5W; NS

4 mg/mL

Amoxicillin Sodium-Clavulanic Acid

unknown

12.5 mg/mL

Ampicillin Sodium-Sulbactam Sodium

NS

6 mg/mL

Argatroban

D5W

1.8 mg/mL

Bivalirudin

D5W

4 mg/mL

Cefamandole Nafate

D5W

4 mg/mL

Cefazolin Sodium

D5W

4 mg/mL

Ceftazidime

D5W

6 mg/mL

Digoxin

D5W

6 mg/mL

Furosemide (10 mg/mL)

D5W

6 mg/mL

Mezlocillin Sodium

D5W

4 mg/mL

Heparin Sodium

D5W

--

Imipenem-Cilastin Sodium

D5W

6 mg/mL

Magnesium Sulfate (500 mg/mL)

D5W

6 mg/mL

Micafungin

NS

4 mg/mL

Piperacillin Sodium –Tazobactam Sodium

D5W

6 mg/mL

Potassium Phosphates

D5W

6 mg/mL

Sodium Bicarbonate

D5W

3 mg/mL

Sodium Nitroprusside

D5W

1.5, 6 and 15 mg/mL

Sodium Phosphates

D5W

6 mg/mL

Intravenous to Oral Transition Patients whose arrhythmias have been suppressed by NEXTERONE may be switched to oral amiodarone. The optimal dose for changing from intravenous to oral administration of amiodarone will depend on the dose of NEXTERONE already administered, as well as the bioavailability of oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone.

Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone [see Drug Interactions (7)].

Table 3 provides suggested doses of oral amiodarone to be initiated after varying durations of NEXTERONE administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone.
Table 3: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION * Assuming a 720 mg/day infusion (0.5 mg/min). † NEXTERONE is not intended for maintenance treatment.
Duration of NEXTERONE Infusion*

Initial Daily Dose ofOral Amiodarone

< 1 week

800-1600 mg

1-3 weeks

600-800 mg

> 3 weeks†

400 mg
Potassium Chloride In D...

Potassium Chloride In Dextrose And Sodium Chloride

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

The dosage selection and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Sodium Chloride

Sodium Chloride

As directed by a physician. Dosage is dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

All injections in Mini-Bag™ Plus containers are intended for intravenous administration using sterile equipment.

Do not remove unit from overwrap until ready for use. The overwrap is a moisture barrier.

To Open

Tear overwrap down side at slit and remove solution container. Visually inspect the container. If the port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity should diminish gradually.

Prior to use, check that the vial adaptor cover is intact. Check the solution container for minute leaks by squeezing inner bag firmly. If leaks are found or if the vial adaptor cover is not intact, discard product as sterility may be impaired.

To Assemble and Reconstitute

See other side for detailed instructions.

Additives may be incompatible.
Heparin Sodium And Sodi...

Heparin Sodium And Sodium Chloride

Heparin sodium is not effective by oral administration and Heparin Sodium and 0.9% Sodium Chloride Injection should not be given orally.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Maintenance of Catheter Patency

Although the rate for infusion of the 2 units/mL formulation is dependent upon age, weight, clinical condition of the patient and the procedure being employed, an infusion rate of 3 mL/hour has been found to be satisfactory.

Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy, regardless of the route of administration.

All injections in VIAFLEX Plus plastic containers are intended for administration using sterile equipment.

Because dosages of this drug are titrated to response, no additives should be made to Heparin Sodium and 0.9% Sodium Chloride Injection.
Potassium Chloride

Potassium Chloride

The dose and rate of administration are dependent upon the specific condition of each patient.

Administer intravenously only with a calibrated infusion device at a slow, controlled rate. Because pain associated with peripheral infusion of Potassium Chloride solution has been reported, whenever possible, administration via a central route is recommended for thorough dilution by the blood stream and avoidance of extravasation. Highest concentrations (300 and 400 mEq/L) should be exclusively administered via central route.

Recommended administration rates should not usually exceed 10 mEq/hour or 200 mEq for a 24 hour period if the serum potassium level is greater than 2.5 mEq/liter.

In urgent cases where the serum potassium level is less than 2.0 mEq/liter or where severe hypokalemia is a threat, (serum potassium level less than 2.0 mEq/liter and electrocardiographic changes and/or muscle paralysis) rates up to 40 mEq/hour or 400 mEq over a 24 hour period can be administered very carefully when guided by continuous monitoring of the EKG and frequent serum K+ determinations to avoid hyperkalemia and cardiac arrest.

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.Do not add supplementary medication.
Amoxicillin Extended-re...

Amoxicillin Extended-release

During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide should be administered in the morning.

2.1 Dosing for Malignant Diseases

Adults and Pediatric PatientsIntravenous When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

OralOral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.

When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide as well as that of the other drugs.

2.2 Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients

An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males [see Use in Specific Populations (8.4)].

2.3 Preparation, Handling and Administration

Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing Cyclophosphamide for Injection, USP. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide for Injection, USP.

Cyclophosphamide for Injection, USP

Intravenous Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide vials if there are signs of melting. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.

Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.

For Direct Intravenous Injection

Reconstitute Cyclophosphamide with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.
Table 1: Reconstitution for Direct Intravenous Injection
Strength

Volume of 0.9% Sodium Chloride

Cyclophosphamide Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

For Intravenous Infusion

Reconstitution of Cyclophosphamide:Reconstitute Cyclophosphamide using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.
Table 2: Reconstitution in preparation for Intravenous Infusion
Strength

Volume of Diluent

Cyclophosphamide Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

Dilution of Reconstituted Cyclophosphamide:Further dilute the reconstituted Cyclophosphamide solution to a minimum concentration of 2 mg per mL with any of the following diluents:
• 5% Dextrose Injection, USP • 5% Dextrose and 0.9% Sodium Chloride Injection, USP • 0.45% Sodium Chloride Injection, USP
To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.

Storage of Reconstituted and Diluted Cyclophosphamide Solution:

If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 3.
Table 3: Storage of Cyclophosphamide Solutions * Storage time is the total time cyclophosphamide is in solution including the time it is reconstituted in 0.9% Sterile Sodium Chloride Injection, USP or Sterile Water for Injection, USP.
Diluent

Storage

Room Temperature

Refrigerated

Reconstituted Solution (Without Further Dilution)

0.9% Sodium Chloride Injection, USP

up to 24 hrs

Up to 6 days

Sterile Water for Injection, USP

Do not store; use immediately

Diluted Solutions*

0.45% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

5% Dextrose Injection, USP

up to 24 hrs

up to 36 hrs

5% Dextrose and 0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 36 hrs

Use of Reconstituted Solution for Oral Administration

Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF). Such preparations should be stored under refrigeration in glass containers and used within 14 days.
Gentamicin Sulfate In S...

Gentamicin Sulfate In Sodium Chloride

Gentamicin Sulfate in 0.9% Sodium Chloride Injection is for intravenous use only.

The patient’s pretreatment body weight should be obtained for calculation of correct dosage. The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass. It is desirable to limit the duration of treatment with aminoglycosides to short term.

Patients with Normal Renal Function

Adults: The recommended dosage of Gentamicin Sulfate in 0.9% Sodium Chloride Injection for patients with serious infections and normal renal function is 3 mg/kg/day administered in three equal doses every eight hours (Table 1).

For patients with life-threatening infections, dosages up to 5 mg/kg/day may be administered in three or four equal doses. The dosage should be reduced to 3 mg/kg/day as soon as clinically indicated (Table 1).

It is desirable to measure both peak and trough serum concentrations of gentamicin to determine the adequacy and safety of the dosage. When such measurements are feasible, they should be carried out periodically during therapy to assure adequate but not excessive drug levels. For example, the peak concentration (at 30 to 60 minutes following cessation of infusion) is expected to be in the range of 4 to 6 mcg/mL. When monitoring peak concentrations, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided. When monitoring trough concentrations (just prior to the next dose), dosage should be adjusted so that levels above 2 mcg/mL are avoided. Determination of the adequacy of a serum level for a particular patient must take into consideration the susceptibility of the causative organism, the severity of the infection, and the status of the patient’s host-defense mechanisms.

In patients with extensive burns, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides. In such patients treated with gentamicin, measurement of serum concentrations is recommended as a basis for dosage adjustment.
Table 1. * The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass. † For q6h schedules, dosage should be recalculated. Dosage Schedule Guide for Adults With Normal Renal Function (Dosage at Eight-Hour Intervals) Patient’s Weight* Usual Dose for Serious Infections 1 mg/kg q8h (3 mg/kg/day) Dose for Life-Threatening Infections (Reduce as Soon as Clinically Indicated) 1.7 mg/kg q8h† (5 mg/kg/day) kg (lb) mg/dose q8h mg/dose q8h 40 ( 88) 40 66 45 ( 99) 45 75 50 (110) 50 83 55 (121) 55 91 60 (132) 60 100 65 (143) 65 108 70 (154) 70 116 75 (165) 75 125 80 (176) 80 133 85 (187) 85 141 90 (198) 90 150 95 (209) 95 158 100 (220) 100 166
Children: 6 to 7.5 mg/kg/day (2 to 2.5 mg/kg administered every eight hours).

Infants and Neonates: 7.5 mg/kg/day (2.5 mg/kg administered every eight hours).

Premature or Full-Term Neonates One Week of Age or Less: 5 mg/kg/day (2.5 mg/kg administered every 12 hours).

NOTE: For further information concerning the use of gentamicin in infants and children, see Pediatric Gentamicin Sulfate Injection product information.

The usual duration of treatment for all patients is seven to ten days. In difficult and complicated infections, a longer course of therapy may be necessary. In such cases monitoring of renal, auditory, and vestibular functions is recommended, since toxicity is more apt to occur with treatment extended for more than ten days. Dosage should be reduced if clinically indicated.

For Intravenous Administration

The intravenous administration of gentamicin may be particularly useful for treating patients with bacterial septicemia or those in shock. It may also be the preferred route of administration for some patients with congestive heart failure, hematologic disorders, severe burns, or those with reduced muscle mass. For intermittent intravenous administration in adults, a single dose of Gentamicin Sulfate in 0.9% Sodium Chloride Injection may be administered according to individual patient requirements from the appropriate premixed container. The solution may be infused over a period of one-half to two hours.

Gentamicin Sulfate Injection should not be physically premixed with other drugs, but should be administered separately in accordance with the recommended route of administration and dosage schedule.

Patients with Impaired Renal Function

Dosage must be adjusted in patients with impaired renal function to assure therapeutically adequate, but not excessive blood levels. Whenever possible, serum concentrations of gentamicin should be monitored. One method of dosage adjustment is to increase the interval between administration of the usual doses. Since the serum creatinine concentration has a high correlation with the serum half-life of gentamicin, this laboratory test may provide guidance for adjustment of the interval between doses. The interval between doses (in hours) may be approximated by multiplying the serum creatinine level (mg/100 mL) by 8. For example, a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 60 mg (1 mg/kg) every 16 hours (2 x 8).

In patients with serious systemic infections and renal impairment, it may be desirable to administer the antibiotic more frequently but in reduced dosage. In such patients, serum concentrations of gentamicin should be measured so that adequate, but not excessive levels result. A peak and trough concentration measured intermittently during therapy will provide optimal guidance for adjusting dosage. After the usual initial dose, a rough guide for determining reduced dosage at eight-hour intervals is to divide the normally recommended dose by the serum creatinine level (Table 2). For example, after an initial dose of 60 mg (1 mg/kg), a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 30 mg every eight hours (60 ÷ 2). It should be noted that the status of renal function may be changing over the course of the infectious process.

It is important to recognize that deteriorating renal function may require a greater reduction of dosage than that specified in the above guidelines for patients with stable renal impairment.

This container system may be inappropriate for the dosage requirements of children, infants, and neonates. Other dosage forms may be more appropriate.
Table 2 Dosage Adjustment Guide For Patients With Renal Impairment (Dosage at Eight-Hour Intervals After the Usual Initial Dose) Serum Creatinine (mg %) Approximate Creatinine Clearance (mL/min/1.73m²) Percent of Usual Doses Shown in Table 1 ≤1 >100 100 1.1 - 1.3 70 - 100 80 1.4 - 1.6 55 - 70 65 1.7 - 1.9 45 - 55 55 2 - 2.2 40 - 45 50 2.3 - 2.5 35 - 40 40 2.6 - 3 30 - 35 35 3.1 - 3.5 25 - 30 30 3.6 - 4 20 - 25 25 4.1 - 5.1 15 - 20 20 5.2 - 6.6 10 - 15 15 6.7 - 8 <10 10
In adults with renal failure undergoing hemodialysis, the amount of gentamicin removed from the blood may vary depending upon several factors including the dialysis method used. An eight hour hemodialysis may reduce serum concentrations of gentamicin by approximately 50%. The recommended dosage at the end of each dialysis period is 1 to 1.7 mg/kg depending upon the severity of infection.

In children, a dose of 2 mg/kg may be administered.

The above dosage schedules are not intended as rigid recommendations but are provided as guides to dosage when the measurement of gentamicin serum levels is not feasible.

A variety of methods are available to measure gentamicin concentrations in body fluids; these include microbiologic, enzymatic and radioimmunoassay techniques.

Gentamicin Sulfate in 0.9% Sodium Chloride Injection is a ready-to-use isotonic solution. No dilution or buffering is required.

If the prescribed dose is exactly 60, 80, or 100 mg use the appropriate container. If the prescribed dose is higher or lower than that of the supplied container adjustments can be made. If the dose is higher than the contents of a 100 mg container the additional amount should be removed from a container of gentamicin sulfate (60 mg/mL) and added to the 100 mg container. If the prescribed dose is less than that contained in a supplied container, use the container with the dose closest to (but above) the prescribed dose, removing and discarding an appropriate amount from it.

Do not use plastic containers in series connection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and container and seals are intact.

If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.

These solutions are intended for intravenous administration using sterile equipment. It is recommended that intravenous administration apparatus be replaced at least once every 24 hours.

Instructions for the Administration of Gentamicin Sulfate in 0.9% Sodium Chloride Injection.

This product is intended for use only as an IV secondary medication unit.

Use aseptic technique when removing contents from these units.

Do not add other drugs to Gentamicin Sulfate in 0.9% Sodium Chloride Injection.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.
Dopamine Hydrochloride ...

Dopamine Hydrochloride And Dextrose

Rate of Administration

Dopamine Hydrochloride and 5% Dextrose Injection, USP is administered intravenously through a suitable intravenous catheter or needle. An IV drip chamber or other suitable metering device is essential for controlling the rate of flow in drops/minute. Each patient must be individually titrated to the desired hemodynamic and/or renal response with dopamine hydrochloride. In titrating to the desired increase in systolic blood pressure, the optimum dosage rate for renal response may be exceeded, thus necessitating a reduction in rate after the hemodynamic condition is stabilized.

Administration of dopamine hydrochloride at rates greater than 50 mcg/kg/min has safely been used in advanced circulatory decompensation states. If unnecessary fluid expansion is of concern, use of a more concentrated solution may be preferred over increasing the flow rate of a less concentrated solution.

Suggested Regimen
When appropriate, increase blood volume with whole blood, plasma, or plasma expanders until central venous pressure is 10 to 15 cm H2O or pulmonary wedge pressure is 14 to 18 mm Hg. Begin infusion of Dopamine Hydrochloride and 5% Dextrose Injection, USP at doses of 2 to 5 mcg/kg/min in patients who are likely to respond to modest increments of heart force and renal perfusion.
In more seriously ill patients, begin administration of Dopamine Hydrochloride and 5% Dextrose Injection, USP at rates of 5 mcg/kg/min and increase gradually using 5 to 10 mcg/kg/min increments up to a rate of 20 to 50 mcg/kg/min as needed. If rates in excess of 50 mcg/kg/min are required, it is suggested that urine output be checked frequently. Should urine flow begin to decrease in the absence of hypotension, reduction of dopamine hydrochloride dosage should be considered. Reports have shown that more than 50% of the patients were satisfactorily maintained on doses of dopamine hydrochloride administered at rates of less than 20 mcg/kg/min. In patients who do not respond to these doses with adequate arterial pressures or urine flow, additional increments of dopamine hydrochloride may be given in an effort to produce an appropriate arterial pressure and central perfusion.
Treatment of all patients requires constant evaluation of therapy in terms of blood volume, augmentation of myocardial contractility and distribution of peripheral perfusion. Dosage of dopamine hydrochloride should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indices for decreasing or temporarily suspending the dosage. As with all potent intravenously administered drugs, care should be taken to control the rate of administration so as to avoid inadvertent administration of a bolus of drug.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use Dopamine Hydrochloride and 5% Dextrose Injection, USP if darker than slightly yellow or discolored in any other way.

All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

Drug additives should not be made to Dopamine Hydrochloride and 5% Dextrose Injection, USP.

Pediatric Dosing and Administration

In publications, the most common starting doses were 1-5 micrograms/kilograms/minute. Particularly in neonates, such low doses require considerable dilution of this product; careful consideration should be given to the use of this product in such circumstances. Dosing increments that were reported ranged from 2.5 to 5.0 micrograms/kilogram/minute. Usual maximum doses were 15-20 micrograms/kilogram/minute, with occasional use as great as 50 micrograms/kilogram/minute. The time course of dopamine kinetics is poorly defined. Increasing infusion rates (or dose) should be approached cautiously and only after it is apparent that hemodynamics (mainly systolic blood pressure) have stabilized with respect to the current dose and/or rate of infusion.

There have been occasional reports of vasospastic events when dopamine was infused through umbilical vessels. Due caution should be exercised if infusion of dopamine through umbilical vessels becomes necessary.
Dobutamine Hydrochlorid...

Dobutamine Hydrochloride In Dextrose

Recommended Dosage

Dobutamine Hydrochloride in 5% Dextrose Injection is administered intravenously through a suitable intravenous catheter or needle. A calibrated electronic infusion device is recommended for controlling the rate of flow in mL/hour or drops/minute.

Infusion of dobutamine should be started at a low rate (0.5-1.0 mcg/kg/min) and titrated at intervals of a few minutes, guided by the patient’s response, including systemic blood pressure, urine flow, frequency of ectopic activity, heart rate, and (whenever possible) measurements of cardiac output, central venous pressure, and/or pulmonary capillary wedge pressure. In reported trials, the optimal infusion rates have varied from patient to patient, usually 2-20 mcg/kg/min but sometimes slightly outside of this range. On rare occasions, infusion rates up to 40 mcg/kg/min have been required to obtain the desired effect.

Rates of infusion in mL/hour for dobutamine hydrochloride concentrations of 1,000, 2,000 and 4,000 mcg/mL are in Table 2.

This container system may be inappropriate for the dosage requirements of pediatric patients under 30 kg. Other dosage forms may be more appropriate.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Dobutamine Hydrochloride in 5% Dextrose Injection solutions may exhibit a pink color that, if present, will increase with time. This color change is due to slight oxidation of the drug, but there is no significant loss of potency.

The rate of administration and the duration of therapy should be adjusted according to the patient’s response, as determined by heart rate, presence of ectopic activity, blood pressure, urine flow, and, whenever possible, measurement of central venous or pulmonary wedge pressure and cardiac output.

Do not add supplementary medications to Dobutamine Hydrochloride in 5% Dextrose Injection. Do not administer Dobutamine Hydrochloride in 5% Dextrose Injection simultaneously with solutions containing sodium bicarbonate or strong alkaline solutions.
Lanoxin

Lanoxin

All injections in VIAFLEX plastic containers are intended for intravenous administration using sterile and nonpyrogenic equipment.

As directed by a physician. Dosage, rate, and duration of administration are to be individualized and dependent upon the indication for use, the patient’s age, weight, concomitant treatment and clinical condition of the patient as well as laboratory determinations.

The dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

After opening the container, the contents should be used immediately and should not be stored for a subsequent infusion. Do not reconnect any partially used containers.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless the solution is clear and the seal is intact.

Additives may be incompatible with PLASMA-LYTE 56 and 5% Dextrose Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of PLASMA-LYTE 56 and 5% Dextrose Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is appropriate. After addition, check for possible color change and/or the appearance of precipitates, insoluble complexes or crystals.

The instructions for use of the medication to be added and other relevant literature must be consulted. Additives known or determined to be incompatible must not be used. When introducing additives to PLASMA-LYTE 56 and 5% Dextrose Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP), aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.
Laxative Maximum Streng...

Laxative Maximum Strength

2.1 Preoperative Prophylactic Use in Adults
• Only use Cefazolin injection in patients who require the entire 2 gram dose and not any fraction of it. • Administer the entire 2 gram dose intravenously 1/2 hour to 1 hour prior to the start of surgery. • It is important that the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibacterial concentrations are present in the serum and tissues at the time of initial surgical incision.
2.2 Patients with Renal Impairment

Use Cefazolin injection only in patients whose creatinine clearance is greater than or equal to 35 mL/min and require the entire 2 gram dose and not any fraction of it.

2.3 Important Administration Instructions
• This premixed solution is for intravenous use only. • Administer Cefazolin injection intravenously over approximately 30 minutes. • Do not use plastic containers in series connections. Such use would result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Use only if solution is clear and container and seals are intact. • Do not introduce additives into the GALAXY Container.
2.4 Directions for Use of Cefazolin Injection
Thawing of Plastic Container • Thaw frozen container at room temperature (25°C/ 77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. • No further dilution is necessary. • Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired. • Do not add supplementary medication. • The container should be visually inspected. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded. • The thawed solution is stable for 30 days under refrigeration (5°C/41°F) and 48 hours at 25°C/77°F. Do not refreeze thawed antibacterial drugs. Preparation for Administration • Suspend container from support. • Remove protector from outlet port at bottom of container. • Attach Intravenous administration set to outlet port. Refer to the manufacturer’s instructions accompanying the administration set for complete directions.
Clinisol

Clinisol

Doses which achieve nitrogen equilibrium or positive balance are the most desirable. The dosage on the first day should be approximately half the anticipated optimal dosage and should be increased gradually to minimize glycosuria; similarly, withdrawal should be accomplished gradually to avoid rebound hypoglycemia.

Fat emulsion coadministration should be considered when prolonged (more than 5 days) parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD).

Pediatric Use:

Use of 15% CLINISOL - sulfite-free (Amino Acid) Injection in pediatric patients is governed by the same considerations that affect the use of any amino acid solution in pediatrics. The amount administered is dosed on the basis of grams of amino acids/kg of body weight/day. Two to three g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Solutions administered by peripheral vein should not exceed twice normal serum osmolarity (718 mOsmol/L).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

A slight yellow color does not alter the quality and efficacy of this product.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of 15% CLINISOL - sulfite-free (Amino Acid) Injection Pharmacy Bulk Package.

Central Vein Infusion

In unstressed adult patients with no unusual nitrogen losses, a minimum dosage of 0.1 gram nitrogen (4.2 mL of 15% CLINISOL - sulfite-free (Amino Acid) Injection Pharmacy Bulk Package) plus 4.4 grams (15 calories) of dextrose/fat emulsion per kilogram of body weight per day is required to achieve nitrogen balance and weight stability. For patients stressed by surgery, trauma or sepsis, and those with unusual nitrogen losses, the dosage required for maintenance may be as high as 0.3 to 0.4 grams of nitrogen (13 to 17 mL 15% CLINISOL - sulfite-free (Amino Acid) Injection Pharmacy Bulk Package) per kilogram of body weight per day, with proportionate increases in non-protein calories. Periodic assessment of nitrogen balance of the individual patient is the best indicator of proper dosage. Use of an infusion pump is advisable to maintain a steady infusion rate during central venous infusion.

Peripheral Infusion

In patients for whom central vein catheterization is not advisable, admixtures with 15% CLINISOL - sulfite-free (Amino Acid) Injection Pharmacy Bulk Package can be administered by peripheral vein. Dilution of 250 mL 15% CLINISOL - sulfite-free (Amino Acid) Injection Pharmacy Bulk Package in 750 mL of 10% dextrose will reduce the osmolarity to a level (718 mOsmol/L) which is more favorable to the maintenance of the integrity of the walls of the veins. If infused simultaneously, fat emulsion will provide a dilution effect upon the osmolarity, as well. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).
Prosol

Prosol

If a patient is unable to take enteral nourishment for a prolonged period of time, institution of total parenteral nutrition (TPN) with exogenous calories should be considered.

The total daily dose of 20% PROSOL – sulfite-free (Amino Acid) Injection depends on the patient’s metabolic requirement and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements.

Recommended Dietary Allowances* of protein range from approximately 0.75 g/kg of body weight for adults to 1.68 g/kg for infants. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially. Daily amino acid doses of approximately 1.0 to 1.5 g/kg of body weight for adults with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance.

For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrate may be necessary to promote adequate patient response to therapy. The severity of the illness being treated is the primary consideration in determining proper dose level. Such higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation.

For protein-sparing in well nourished patients not receiving significant additional calories, amino acid dosages of 1.0 to 1.7 g/kg/day reduce nitrogen losses and spare body protein. If daily increases in BUN in the range of 10 to 15 mg% for more than three days should occur, then protein-sparing therapy should be discontinued and a regimen with full nonprotein calorie substrates should be adopted.

*Food and Nutrition Board National Academy of Sciences - National Research Council (Revised 1989)

Care should be exercised to insure the maintenance of proper levels of serum potassium. Quantities of 60 to 180 mEq of potassium per day have been used with adequate clinical effect. It may be necessary to add quantities of this electrolyte to this injection, depending primarily on the amount of carbohydrate administered to and metabolized by the patient.

Total daily fluid requirements can be met beyond the volume of amino acid solutions by supplementing with noncarbohydrate or carbohydrate-containing electrolyte solutions.

Maintenance vitamins, additional electrolytes and trace elements should be administered as required.

Fat emulsion coadministration should be considered when prolonged parenteral nutrition (more than 5 days) is required in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat free total parenteral nutrition. Caution should be exercised in administering fat emulsions to patients with severe liver damage, pulmonary disease, anemia or blood coagulation disorders, or when there is danger of fat embolism.

Fat emulsion admixed into total parenteral formula may obscure the presence of precipitate formation.

Central Vein Administration:

Hypertonic mixtures of amino acids and dextrose may be administered safely by continuous infusion through a central venous catheter with the tip located in the vena cava. In addition to meeting nitrogen needs, the administration rate is governed, especially during the first few days of therapy, by the patient's tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of urine and blood sugar levels.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria.

Parenteral nutrition may be started with infusates containing lower concentrations of dextrose; dextrose content may be gradually increased to estimated caloric needs as the patient's glucose tolerance increases. Sudden cessation in administration of a concentrated dextrose solution may result in insulin reaction due to high levels of endogenous insulin. Such solutions should be withdrawn slowly.

Peripheral Vein Administration:

In patients requiring parenteral nutrition for whom the central vein route is not indicated, this injection can be mixed with low concentration dextrose solutions and administered by peripheral vein with or without fat emulsion.

Intravenous fat emulsion provides approximately 1.1 kcal/mL (10%) or 2.0 kcal/mL (20%) and may be administered along with amino acid-dextrose solutions by means of a short Y-connector near the infusion site to supplement caloric intake. Fat, however, should not be the sole caloric intake since studies have indicated that glucose is more nitrogen sparing in the stressed patient.

Protein-Sparing:

For well nourished patients who require short-term parenteral support, this injection can be administered peripherally with or without carbohydrate calories. Such infusates can be prepared by dilution of this injection with 5% Dextrose Injection and/or Sterile Water for Injection to prepare solutions which may be administered by peripheral vein, not to exceed twice normal serum osmolarity.

Depending upon the clinical condition of the patient, approximately 3 liters of solution may be administered per 24 hour period. When used postoperatively, the therapy should begin with 1000 mL the first postoperative day. Thereafter, the dose may be increased to 3000 mL per day.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible. Filters of less than 1.2 microns pore size must not be used with admixtures containing fat emulsions.

A slight yellow color does not alter the quality and efficacy of the product.

Do not use unless solution is clear and seal is intact.

20% PROSOL - sulfite-free (Amino Acid) Injection in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures. Additives may be incompatible with the fluid withdrawn from this container. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of 20% PROSOL - sulfite-free (Amino Acid) Injection.

Any storage of admixtures should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.
Divalproex Sodium

Divalproex Sodium

Following suitable admixture of prescribed drugs, the dosage is usually dependent upon the age, weight and clinical condition of the patient as well as laboratory determinations. See directions accompanying drugs.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible.

Do not administer unless solution is clear and seal is intact.

These admixed injections in VIAFLEX plastic containers are intended for intravenous administration using sterile equipment.

The dosage selection and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/ hypoglycemia. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in the informed judgement of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives.
Hemofil M

Hemofil M

For intravenous use only.

The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al,2 which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of HEMOFIL M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight.3

Examples:

(1) A dose of 1750 IU AHF administered to a 70 kg patient, i.e., 25 IU/kg (1750/70), should be expected to cause a peak post-infusion AHF increase of 25 x 2 = 50 IU/dL (50% of normal).

(2) A peak level of 70% is required in a 40 kg child. In this situation the dose would be 70/2 x 40 = 1400 IU.

Recommended Dosage Schedule

Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.

HEMORRHAGE

Degree of hemorrhage

Required peak post-infusion AHF activity in the blood (as % of normal or IU/dL plasma)

Frequency of infusion

Early hemarthrosis or muscle bleed or oral bleed

20-40

Begin infusion every 12 to 24 hours for one-three days until the bleeding episode as indicated by pain is resolved or healing is achieved.

More extensive hemarthrosis, muscle bleed, or hematoma

30-60

Repeat infusion every 12 to 24 hours for usually three days or more until pain and disability are resolved.

Life threatening bleeds such as head injury, throat bleed, severe abdominal pain

60-100

Repeat infusion every 8 to 24 hours until threat is resolved.

SURGERY

Type of operation

Minor surgery, including tooth extraction

60-80

A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases.

Major surgery

80-100 (pre- and post-operative)

Repeat infusion every 8 to 24 hours depending on state of healing.

If bleeding is not controlled with the prescribed dose, determine the plasma level of Factor VIII and administer a sufficient dose of HEMOFIL M to achieve a satisfactory clinical response.

Under certain circumstances (e.g., presence of a low titer inhibitor) doses larger than those recommended may be necessary as per standard care. In patients with high titer Factor VIII inhibitors, HEMOFIL M therapy may not be effective and other therapeutic options should be considered.

The dosage and duration of treatment depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life threatening hemorrhages.

Reconstitution: Use Aseptic Technique
1. Bring HEMOFIL M (dry concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature. 2. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers. 3. Cleanse stoppers with germicidal solution. 4. Remove protective covering from one end of double-ended needle and insert exposed needle through diluent stopper. 5. Remove protective covering from other end of double-ended needle. Invert diluent bottle over upright HEMOFIL M bottle, then rapidly insert free end of the needle through the HEMOFIL M bottle stopper at its center. The vacuum in the HEMOFIL M bottle will draw in the diluent. 6. Disconnect the two bottles by removing needle from diluent bottle stopper, then remove needle from HEMOFIL M bottle. Swirl gently until all material is dissolved. Be sure that HEMOFIL M is completely dissolved; otherwise active material will be removed by the filter.
Note: Do not refrigerate after reconstitution.

Administration: Use Aseptic Technique
• Intravenous administration only. • Administer at room temperature not more than 3 hours after reconstitution. • Record the name and batch number of the product in order to maintain a link between the patient and the batch of the product.
Intravenous Syringe Injection
• Visually inspect parenteral product for particulate matter and discoloration prior to administration. The solution should be colorless in appearance. Do not administer if particulate matter or discoloration is found. • Plastic syringes are recommended for use with this product. The ground glass surface of all-glass syringes tend to stick with solutions of this type.
1. Attach filter needle to a disposable syringe and draw back plunger to admit air into syringe.

2. Insert needle into reconstituted HEMOFIL M.

3. Inject air into bottle and then withdraw the reconstituted material into the syringe.

4. Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration.

5. If a patient is to receive more than one bottle of HEMOFIL M, the contents of two bottles may be drawn into the same syringe by drawing up each bottle through a separate unused filter needle. This practice lessens the loss of HEMOFIL M. Filter needles are intended to filter the contents of a single bottle of HEMOFIL M only.

Rate of Administration

Administer HEMOFIL M at a rate of up to 10 mL per minute. Infuse HEMOFIL M at a rate of administration that ensures the comfort of the patient. [see Precautions: Increase of Pulse Rate]
Premasol – Sulfit...

Premasol – Sulfite-free

The objective of nutritional management of infants and young children is the provision of sufficient amino acid and caloric support for protein synthesis and growth.

The total daily dose of 6% and 10% PREMASOL - sulfite-free (Amino Acid) Injections depends on daily protein requirements and on the patient's metabolic and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual protein requirements. Dosage should also be guided by the patient's fluid intake limits and glucose and nitrogen tolerances, as well as by metabolic and clinical response.

Recommendations for allowances of protein in infant nutrition have ranged from 2 to 4 grams of protein per kilogram of body weight per day (2.0 to 4.0 g/kg/day)1. The recommended dosage of PREMASOL - sulfite-free (Amino Acid) Injections is 2.0 to 2.5 grams of amino acids per kilogram of body weight per day (2.0 to 2.5 g/kg/day) for infants up to 10 kilograms. For infants and young children larger than 10 kilograms, the total dosage of amino acids should include the 20 to 25 grams/day for the first 10 kg of body weight plus 1.0 to 1.25 g/day for each kg of body weight over 10 kilograms.

Typically, PREMASOL - sulfite-free (Amino Acid) Injections are admixed with 50% or 70% Dextrose Injection USP supplemented with electrolytes and vitamins and administered continuously over a 24 hour period.

Total daily fluid intake should be appropriate for the patient's age and size. A fluid dose of 125 mL per kilogram body weight per day is appropriate for most infants on TPN. Although nitrogen requirements may be higher in severely hypercatabolic or depleted patients, provision of additional nitrogen may not be possible due to fluid intake limits, nitrogen, or glucose intolerance.

Cysteine is considered to be an essential amino acid in infants and young children. An admixture of cysteine hydrochloride to the TPN solution is therefore recommended. Based on clinical studies, the recommended dosage is 1.0 mmole of L-cysteine hydrochloride monohydrate per kilogram of body weight per day.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria. To prevent rebound hypoglycemia, a solution containing 5% dextrose should be administered when hypertonic dextrose solutions are abruptly discontinued.

Fat emulsion coadministration should be considered when prolonged (more than 5 days) parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat free TPN.

The provision of sufficient intracellular electrolytes, principally potassium, magnesium, and phosphate, is required for optimum utilization of amino acids. In addition, sufficient quantities of the major extracellular electrolytes sodium, calcium, and chloride, must be given. In patients with hyperchloremic or other metabolic acidoses, sodium and potassium may be added as the acetate salts to provide bicarbonate precursor. The electrolyte content of 6% and 10% PREMASOL - sulfite-free (Amino Acid) Injections must be considered when calculating daily electrolyte intake. Serum electrolytes, including magnesium and phosphorus, should be monitored frequently.

Appropriate vitamins, minerals and trace elements should also be provided.
1 Suskind RM: Textbook of Pediatric Nutrition, Raven Press, New York, 1981.
Central Venous Nutrition.

Hypertonic mixtures of amino acids and dextrose may be safely administered by continuous infusion through a central venous catheter with the tip located in the superior vena cava. Initial infusion rates should be slow, and gradually increased to the recommended 60-125 mL per kilogram of body weight per day. If administration rate should fall behind schedule, no attempt to “catch up” to planned intake should be made. In addition to meeting protein needs, the rate of administration, particularly during the first few days of therapy, is governed by the patient's glucose tolerance. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of glucose levels in blood and urine.

Peripheral Parenteral Nutrition.

For patients in whom the central venous route is not indicated and who can consume adequate calories enterally, PREMASOL - sulfite-free (Amino Acid) Injections may be administered by peripheral vein with or without parenteral carbohydrate calories. Such infusates can be prepared by dilution with Sterile Water for Injection or 5% -10% Dextrose Injection to prepare isotonic or slightly hypertonic solutions for peripheral infusion. It is essential that peripheral infusion be accompanied by adequate caloric intake.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

A slight yellow color does not alter the quality and efficacy of the product.

PREMASOL - sulfite-free (Amino Acid) Injections may be admixed with solutions which contain phosphate or which have been supplemented with phosphate. The presence of calcium and magnesium ions in an additive solution should be considered when phosphate is also present, in order to avoid precipitation.

Care must be taken to avoid incompatible admixtures. Consult with pharmacist.

Parenteral nutrition solutions should be used promptly after mixing. Any storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.

Directions for use of VIAFLEX plastic Pharmacy Bulk Package container

To Open

Tear overpouch across top at slit and remove solution container. Discard overpouch and sachet. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

For compounding only, not for direct infusion.

Preparation for Admixing
1. The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). 2. Suspend container from eyelet support. 3. Remove plastic protector from outlet port at bottom of container. 4. Attach solution transfer set. Refer to complete directions accompanying set. Note: The closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. 5. VIAFLEX containers should not be written on directly since ink migration has not been investigated. Affix accompanying label for date and time of entry. 6. Once container closure has been penetrated, withdrawal of contents should be completed without delay. After initial entry, maintain contents at room temperature (25°C/77°F) and dispense within 4 hours.
Intravenous fat emulsion should not be administered in polyvinyl chloride (PVC) containers that use di-2-ethylhexyl phthalate (DEHP) as a plasticizer, because the fat emulsion facilitates the leaching of DEHP from these containers.
Hyqvia

Hyqvia

For subcutaneous use only.

2.1 Dosage

Initiation of Treatment with HYQVIA
• For patients previously on another IgG treatment, administer the first dose approximately one week after the last infusion of their previous treatment. • Increase the dose and frequency from a 1-week dose to a 3- or 4-week dose (see ramp-up schedule in Table 1). • Initiating treatment at a full monthly dose was not evaluated in the clinical trial. Table 1 Initial Treatment Interval/Dosage Ramp-Up Schedule
Week

Infusion Number

Dose Interval

Example for 30 grams per 4 weeks

1

1st infusion

1-week-dose

7.5 grams

2

2nd infusion

2-week-dose

15 grams

3

No infusion

4

3rd infusion

3-week-dose

22.5 grams

5

No infusion

6

No infusion

7

4th infusion (if required)

4-week-dose

30 grams

For patients switching from Immune Globulin Intravenous (Human) [IGIV] treatment:

Administer HYQVIA at the same dose and frequency as the previous intravenous treatment, after the initial dose ramp-up.

For patients naïve to IgG treatment or switching from Immune Globulin Subcutaneous (Human) [IGSC]:

Administer HYQVIA at 300 to 600 mg/kg at 3 to 4 week intervals, after initial ramp-up.

Individualization of Dose

If HYQVIA is administered at the same dose and frequency, the serum IgG levels from HYQVIA should be comparable to serum IgG levels from intravenous treatment.

For dose adjustment:
• Calculate the difference between the patient's serum IgG trough level during HYQVIA treatment and the IgG trough level during the previous intravenous treatment. • Find this difference (in mg/dL) in the columns of Table 2 and the corresponding amount (in mL) by which to increase or decrease the dose based on the patient's body weight and desired change in IgG trough level. Table 2 Individualization in Volume Administered per Dosing Interval for Intended Change in IgG Trough Levela Difference in IgG Trough Levels Body Weight 100 mg/dL 200 mg/dL 300 mg/dL 400 mg/dL
10 kg

3 mL

6 mL

9 mL

12 mL

20 kg

6 mL

12 mL

18 mL

24 mL

30 kg

9 mL

18 mL

27 mL

36 mL

40 kg

12 mL

24 mL

36 mL

48 mL

50 kg

15 mL

30 mL

45 mL

61 mL

60 kg

18 mL

36 mL

55 mL

73 mL

70 kg

21 mL

42 mL

64 mL

85 mL

80 kg

24 mL

48 mL

73 mL

97 mL

90 kg

27 mL

55 mL

82 mL

109 mL

100 kg

30 mL

61 mL

91 mL

121 mL

110 kg

33 mL

67 mL

100 mL

133 mL

120 kg

36 mL

73 mL

109 mL

145 mL

130 kg

39 mL

79 mL

118 mL

158 mL

140 kg

42 mL

85 mL

127 mL

170 mL
aDerived using a slope of 3.3 kg/dL
Example 1: A patient with a body weight of 80 kg has a measured IgG trough level of 800 mg/dL and the reference trough level is 1000 mg/dL. The trough level difference is 200 mg/dL (1000 mg/dL minus 800 mg/dL). The dose of HYQVIA would be increased by 48 mL (4.8 grams) per dosing interval.

Example 2: A patient with a body weight of 60 kg has a measured IgG trough level of 1000 mg/dL and the reference trough level is 900 mg/dL. The trough level difference is -100 mg/dL (900 mg/dL minus 1000 mg/dL). The dose of HYQVIA would be decreased by 18 mL (1.8 grams) per dosing interval.

HYQVIA can be used to administer a full therapeutic dose in one site up to every four weeks. Adjust the frequency and number of infusion sites taking into consideration volume, total infusion time, and tolerability. Adjust the frequency as needed so that the patient receives the same weekly equivalent dose.

Example: When adjusting a dose of 30 grams administered every 3 weeks; administer 40 grams of HYQVIA every 4 weeks. If a higher trough level is required, relative to intravenous treatment at 3 or 4 week intervals, increase the dose or decrease the dosing interval. Evaluate the use ofa second site or infusing at shorter intervals when the volume of HYQVIA is greater than 600 mL.

If a patient misses a dose, administer the missed dose as soon as possible and then resume scheduled treatments as applicable.

If HYQVIA is administered at a different interval than the previous treatment, either intravenously or subcutaneously, then Table 2 should not be used and the dose of HYQVIA should be adjusted, if necessary, based on clinical response.

2.2 Administration

HYQVIA should be administered by a healthcare professional, caregiver or self-administered by the patient after appropriate training.
• Infusion requires an infusion pump capable of infusing a patient’s therapeutic dose at infusion rates up to 300 mL/hr/site. The pump must have the ability to titrate the flow rate up or down if required to improve tolerability. To ensure maximum flow rates, use a subcutaneous needle set that is 24 gauge and labeled for high flow rates. • Infuse the two components of HYQVIA sequentially, beginning with the Recombinant Human Hyaluronidase. • Initiate the infusion of the full dose of the Immune Globulin Infusion 10% (Human) through the same subcutaneous needle set within approximately 10 minutes of the Recombinant Human Hyaluronidase infusion. • For each full or partial vial of Immune Globulin Infusion 10% (Human) used, administer the entire contents of the Recombinant Human Hyaluronidase vial.
Selection of Infusion Site(s)

The suggested site(s) for the infusion of HYQVIA are the abdomen and thighs. If two sites are used, the two infusion sites should be on opposite sides of the body. Avoid bony prominences, or areas that are scarred, inflamed or infected.

Volume per Site

Administer up to 600 mL per site for patients greater than or equal to 40 kg and up to 300 mL per site for patients less than 40 kg.

A second site can be used at the discretion of the physician and patient based on tolerability and total volume. If a second site is used, administer half of total volume of the Recombinant Human Hyaluronidase of HYQVIA in each site.

Rate of Infusion

Administer the Recombinant Human Hyaluronidase of HYQVIA at an initial rate per site of approximately 1 to 2 mL per minute, or as tolerated.

Administer Immune Globulin Infusion 10% (Human) of HYQVIA at rates as shown in Table 3 for the initial infusions. If the patient tolerates these infusions at the full dose and maximum rate, adjust both the time intervals and number of rate changes of the ramp-up used for successive infusions at the discretion of the physician and patient.
Table 3 Immune Globulin Infusion 10% (Human) Infusion Rates
First 2 Infusions

Subsequent 2 or 3 Infusions

Subjects < 40 kg (< 88lbs)

Subjects ≥ 40 kg (≥ 88lbs)

Subjects < 40 kg (< 88lbs)

Subjects ≥ 40 kg (≥ 88lbs)

Intervals

Rate per site

Rate per site

Rate per site

Rate per site

Minutes

mL per hour

mL per hour

mL per hour

mL per hour
5 - 15
5

10

10

10
5 - 15
10

30

20

30
5 - 15
20

60

40

120
5 - 15
40

120

80

240

Remainder of infusion

80

240

160

300

2.3 Preparation and Handling
• Visually inspect both vials of HYQVIA for discoloration and particulate matter prior to administration. • The appearance of the Immune Globulin Infusion 10% (Human) of HYQVIA can vary from clear or slightly opalescent and colorless or pale yellow. • The appearance of the Recombinant Human Hyaluronidase of HYQVIA should be clear and colorless. • Do not use either component of HYQVIA if either solution is cloudy or has particulates. • Allow refrigerated product to come to room temperature before use. Do not apply heat or place in microwave. • Do not shake HYQVIA. • Do not mix the Recombinant Human Hyaluronidase and the Immune Globulin Infusion 10% (Human) of HYQVIA into the same container prior to administration. • Do not mix or administer components of HYQVIA with other products. Administer components of HYQVIA sequentially. Do not use either component alone. • Flush the infusion line with normal saline or Dextrose 5% in water (D5W) if required. • HYQVIA contains no preservative. Discard any unused product according to local standards for biohazard products
2.4 Instructions for Administration

Use aseptic technique when preparing and administering HYQVIA for infusion.

For more detail on steps, see accompanying Information for Patients.
1. Inspect the vials:Inspect for clarity, color, and expiration date(s) 2. Prepare for infusion: • Gather supplies: HYQVIA dual vial unit(s), ancillary supplies, sharps container and infusion pump (program pump per physician recommendation following manufacturer’s instructions). • Prepare a clean work area. • Wash hands. • If the Immune Globulin Infusion 10% (Human) and Recombinant Human Hyaluronidase are pooled into separate containers, skip to Step 5. 3. Prepare the Recombinant Human Hyaluronidase of HYQVIA (Labeled as HY): • Remove the protective cap. • Wipe each stopper with a sterile alcohol wipe and allow to dry. • Attach a syringe to a needle/needle-less transfer device (to prevent stopper push through or coring), inject air and then draw the full contents of each vial labeled “HY” into a single syringe, if possible. • Attach the syringe containing the Recombinant Human Hyaluronidase to the subcutaneous needle set and prime up to the needle hub. 4. Prepare Immune Globulin Infusion 10% (Human) of HYQVIA (Labeled as “IG”): • Wipe each stopper with a sterile alcohol wipe and allow to dry. • Transfer the vial(s) labeled “IG” using one of the following methods: • Pool into an infusion bag, using a transfer device per manufacturer’s directions. Attach and prime the pump administrating tubing; or- • Directly spike the vial using a vented pump administration tubing and prime as directed.
If using a syringe driver, transfer into syringe(s), preferably using a vented spike.
5. Prepare the infusion site(s): • Potential sites for infusion include the middle to upper abdomen and thigh. • Avoid: bony prominences, blood vessels, scars, or areas that are inflamed or infected. • If two sites are desired, a bifurcated needle set may be used on opposite sides of the body. • Rotate sites by choosing opposite sides of the body between successive infusions. • Cleanse the infusion site(s) with a sterile alcohol wipe beginning at the center of each infusion site and moving outward in a circular motion. Allow the infusion site(s) to dry. 6. Insert and secure the 24 gauge subcutaneous needle: • Pinch at least one inch of skin between two fingers. Insert the needle at a 90-degree angle into the subcutaneous tissue and secure the needle with sterile tape. • Check placement: gently pull back on the plunger of attached syringe and monitor for any blood return in the tubing. • If blood is seen in the tubing, remove and discard the needle and repeat steps 3, 5 and 6 with a new subcutaneous needle and infusion site. • Secure the needle in place with a sterile protective dressing. 7. Administer the Recombinant Human Hyaluronidase of HYQVIA:
Administer the entire Recombinant Human Hyaluronidase dose first. Start at a rate of 1 to 2 mL per minute per site and increase as tolerated. If more than one site is used, divide the contents equally between sites. At the end of infusion, disconnect the empty syringe and attach pump tubing/syringe containing the Immune Globulin Infusion 10% (Human) of HYQVIA to the same subcutaneous needle set.
8. Administer the Immune Globulin Infusion 10% (Human) of HYQVIA:
Within approximately 10 minutes of completing the infusion of the Recombinant Human Hyaluronidase of HYQVIA, start the variable rate program of the infusion pump to initiate the infusion of the full therapeutic dose of Immune Globulin Infusion 10% (Human) of HYQVIA. At the end of infusion, flush infusion tubing up to the needle with normal saline or Dextrose 5% in water (D5W), if required.
9. Remove subcutaneous needle(s) from the infusion site(s):
After the infusion is complete, remove the needle set and cover with a protective dressing. Discard any partially used vial(s) and disposable supplies in accordance with local requirements.
10. Document the infusion:
Remove the peel-off label from each Immune Globulin Infusion 10% (Human) vial of HYQVIA used and affix to the patient’s treatment record or infusion log. In addition, record the time, date, dose, infusion site location and any reactions after each infusion.

For self-administration, provide the patient with instructions and training for infusion in the home or other appropriate setting.
Glycine Solution

Glycine Solution

The volume of solution needed will vary with the nature and duration of the urologic procedure.

If desired, warm in overwrap to near body temperature in a water bath or oven heated to not more than 45°C.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Prostin E2

Prostin E2

The volume of solution needed will vary with the nature and duration of the arthroscopic procedure.

If desired, warm in overpouch to near body temperature in a water bath or oven heated to not more than 45º C.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Ceftriaxone

Ceftriaxone

Ceftriaxone Injection, USP is administered intravenously.

Do not further dilute ceftriaxone injection with products containing calcium, such as Ringer’s solution or Hartmann’s solution, because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS).

There have been no reports of an interaction between ceftriaxone and oral calcium-containing products.

Neonates

Hyperbilirubinemic neonates, especially prematures, should not be treated with Ceftriaxone Injection, USP (see CONTRAINDICATIONS).

Ceftriaxone is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see CONTRAINDICATIONS).

Pediatric Patients

For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams.

For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams.

In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

Adults

The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. For infections caused by Staphylococcus aureus (MSSA), the recommended daily dose is 2 to 4 grams, in order to achieve >90% target attainment. The total daily dose should not exceed 4 grams.

If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.

For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.

Generally, Ceftriaxone Injection, USP therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.

When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

No dosage adjustment is necessary for patients with impairment of renal or hepatic function.
Lactated Ringers

Lactated Ringers

The volume and/or rate of solution needed will vary with the nature and duration of the arthroscopic procedure.

This solution, as it is packaged, is not intended for IV administration or injection.

The container must not be vented (See Precautions).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless the solution is clear and the seal is intact. If particulate matter or discoloration is found, contact Baxter Customer Service

Aseptic technique should be used when applying this product.

The contents of an opened container should be used promptly to minimize the possibility of bacterial growth or pyrogen formation. Discard the unused portion of irrigating solution since no antimicrobial agent has been added.

When using Lactated Ringer’s Irrigation for pour irrigation, prevent contact of the fluid with the external surface of the container.

Lactated Ringer’s Irrigation is for single-patient use only.

Microwave heating of irrigation fluids is not recommended. If desired, Lactated Ringer’s Irrigation may be warmed in a water bath or oven to not more than 45° C while maintaining sterility. Lactated Ringer’s Irrigation that has been warmed must not be returned to storage.

Cetriaxone must not be mixed with calcium-containing solutions, including Lactated Ringer’s Irrigation.

Additives may be incompatible with Lactated Ringer’s Irrigation. Additives known or determined to be incompatible should not be used.

As with all parenteral solutions, compatibility of the additives with the solution must be assessed before addition, by checking for, for example, a possible color change and/or the appearance of precipitates, insoluble complexes, or crystals. Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Lactated Ringer’s Irrigation is appropriate.

The instructions for use of the medication to be added and other relevant literature must be consulted.

When making additions to Lactated Ringer’s Irrigation, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.
Sorbitol Irrigant

Sorbitol Irrigant

The volume of solution needed will vary with the nature and duration of the urologic procedure.

If desired, warm in overwrap to near body temperature in a water bath or oven heated to not more than 45°C.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Milrinone Lactate In De...

Milrinone Lactate In Dextrose

Milrinone should be administered with a loading dose followed by a continuous infusion (maintenance dose) according to the following guidelines:

Loading Dose

50 mcg/kg: Administer slowly over 10 minutes

Note: Milrinone (200 mcg/mL) in INTRAVIA Plastic Container is for intravenous infusion only.

Dosage recommendations using a 1 mg/mL concentration of milrinone are included for informational purposes only.

The table below shows the loading dose in milliliters (mL) of milrinone (1mg/mL) by patient body weight (kg).
Loading Dose (mL) Using 1 mg/mL Concentration Patient Body Weight (kg) kg 30 40 50 60 70 80 90 100 110 120 mL 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0
The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see appropriate package insert for diluents) may simplify the visualization of the injection rate.

Maintenance Dose
Infusion Rate Total Daily Dose (24 Hours) Minimum 0.375 mcg/kg/min 0.59 mg/kg Administer as a continuous intravenous infusion Standard 0.50 mcg/kg/min 0.77 mg/kg Maximum 0.75 mcg/kg/min 1.13 mg/kg
The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

Note: See "Dosage Adjustment in Renally Impaired Patients." Dosage may be titrated to the maximum hemodynamic effect and should not exceed 1.13 mg/kg/day. Duration of therapy should depend upon patient responsiveness.

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.
Milrinone Infusion Rate (mL/hr) Using 200 mcg/mL Concentration Maintenance Dose (mcg/kg/min) Patient Body Weight (kg) 30 40 50 60 70 80 90 100 110 120 0.375 3.4 4.5 5.6 6.8 7.9 9.0 10.1 11.3 12.4 13.5 0.400 3.6 4.8 6.0 7.2 8.4 9.6 10.8 12.0 13.2 14.4 0.500 4.5 6.0 7.5 9.0 10.5 12.0 13.5 15.0 16.5 18.0 0.600 5.4 7.2 9.0 10.8 12.6 14.4 16.2 18.0 19.8 21.6 0.700 6.3 8.4 10.5 12.6 14.7 16.8 18.9 21.0 23.1 25.2 0.750 6.8 9.0 11.3 13.5 15.8 18.0 20.3 22.5 24.8 27.0
Dosage Adjustment in Renally Impaired Patients

Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone. Reductions in infusion rate may be necessary in patients with renal impairment. For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table:
Creatinine Clearance(mL/min/1.73 m2) Infusion Rate(mcg/kg/min) 5 0.20 10 0.23 20 0.28 30 0.33 40 0.38 50 0.43
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Milrinone Lactate in 5% Dextrose Injection is a clear, colorless to pale yellow solution.

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