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Agila Specialties Private Limited Drugs

Vancomycin Hydrochlorid...

Vancomycin Hydrochloride

Infusion-related events are related to both the concentration and the rate of administration of vancomycin. Concentrations of no more than 5 mg/mL and rates of no more than 10 mg/min are recommended in adults (see also age-specific recommendations). In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used; use of such higher concentrations may increase the risk of infusion-related events. 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 six 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 premature infants and 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 (see following table).
DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION(Adapted from Moellering et al.4) Creatinine Clearance mL/min Vancomycin Dose mg/24 hr 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 hr. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1000 mg every 7 to 10 days has been recommended.

When only 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 in 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) route have not been established.

Intermittent infusion is the recommended method of administration.

COMPATIBILITY WITH OTHER DRUGS AND IV FLUIDS

The following diluents are physically and chemically compatible (with 4g/L vancomycin hydrochloride):

5% Dextrose Injection, USP

5% Dextrose Injection and 0.9% Sodium Chloride Injection, USP

Lactated Ringer’s Injection, USP

5% Dextrose and Lactated Ringer’s Injection

Normosol®-M and 5% Dextrose

0.9% Sodium Chloride Injection, USP

Isolyte® E

Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

Vancomycin solution has a low pH and may cause physical instability of other compounds.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE-NOT FOR DIRECT INFUSION

Pharmacy bulk packages are for use in pharmacy admixture service only in a suitable work area, such as a laminar flow hood. They should be hung by the integral hanger provided and suspended as a unit in the laminar flow hood. Using aseptic technique the container closure should be penetrated only one time after reconstitution utilizing a suitable sterile dispensing set which allows measured distribution of the contents. Use of a syringe and needle is not recommended as it may cause leakage. Swab vial stopper with an antiseptic solution.

Once the sterile dispensing set has been inserted into the container, withdrawal of the contents should be accomplished without delay. However, if this is not possible, a maximum time of 4 hours from the initial closure entry may be permitted for complete fluid transfer operations. Discard the container no later than 4 hours after initial closure puncture. The time limit should begin with introduction of solvent or diluent into Pharmacy package bottle.

PREPARATION AND STABILITY

10 g Pharmacy Bulk package bottle

At the time of use, reconstitute by adding 95 mL of Sterile Water for Injection, USP to the 10 g Pharmacy Bulk package bottle of dry, sterile vancomycin powder. The resultant solution will contain vancomycin equivalent to 500 mg/5 mL (1 g/10 mL). AFTER RECONSTITUTION FURTHER DILUTION IS REQUIRED.

Reconstituted solutions of vancomycin (500 mg/5 mL) must be further diluted in at least 100 mL of a suitable infusion solution. For doses of 1 gram (10 mL), at least 200 mL of solution must be used. The desired dose diluted in this manner should be administered by intermittent IV infusion over a period of at least 60 minutes.

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

For oral Administration

Oral vancomycin is used in treating antibiotic associated pseudomembranous colitis caused by C. difficile and for staphylococcal enterocolitis. Vancomycin is not effective by the oral route for other types of infections. The usual adult total daily dosage is 500 mg to 2 g given in 3 or 4 divided doses for 7 to 10 days. The total daily dose in children is 40 mg/kg of body weight in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g. The appropriate dose may be diluted in 1 oz of water and given to the patient to drink. Common flavoring syrups may added to the solution to improve the taste for oral administration. The diluted solution may be administered via a nasogastric tube.
Zoledronic Acid

Zoledronic Acid

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

2.1 Hypercalcemia of Malignancy

The maximum recommended dose of zoledronic acid injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal 12 mg/dL [3 mmol/L]) is 4 mg. The 4-mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients who receive zoledronic acid injection should have serum creatinine assessed prior to each treatment.

Dose adjustments of zoledronic acid injection are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine less than 400 μmol/L or less than 4.5 mg/dL).

Patients should be adequately rehydrated prior to administration of zoledronic acid injection [see Warnings And Precautions (5.2)].

Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of zoledronic acid injection. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia.

Retreatment with zoledronic acid injection 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. Renal function must be carefully monitored in all patients receiving zoledronic acid injection and serum creatinine must be assessed prior to retreatment with zoledronic acid injection [see Warnings And Precautions (5.2)].

2.2 Multiple Myeloma and Metastatic Bone Lesions of Solid Tumors

The recommended dose of zoledronic acid injection in patients with multiple myeloma and metastatic bone lesions from solid tumors for patients with creatinine clearance greater than 60 mL/min is 4 mg infused over no less than 15 minutes every 3 to 4 weeks. The optimal duration of therapy is not known.

Upon treatment initiation, the recommended zoledronic acid injection doses for patients with reduced renal function (mild and moderate renal impairment) are listed in Table 1. These doses are calculated to achieve the same AUC as that achieved in patients with creatinine clearance of 75 mL/min. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula [see Warnings And Precautions (5.2)].
Table 1: Reduced Doses for Patients with Baseline CrCl less than or equal to 60 mL/min * Doses calculated assuming target AUC of 0.66 (mg•hr/L) (CrCl = 75 mL/min) Baseline Creatinine Clearance (mL/min) Zoledronic acid injection Recommended Dose* greater than 60 4 mg 50 to 60 3.5 mg 40 to 49 3.3 mg 30 to 39 3 mg
During treatment, serum creatinine should be measured before each zoledronic acid injection dose and treatment should be withheld for renal deterioration. In the clinical studies, renal deterioration was defined as follows:

For patients with normal baseline creatinine, increase of 0.5 mg/dL

For patients with abnormal baseline creatinine, increase of 1 mg/dL

In the clinical studies, zoledronic acid injection treatment was resumed only when the creatinine returned to within 10% of the baseline value. zoledronic acid injection should be reinitiated at the same dose as that prior to treatment interruption.

Patients should also be administered an oral calcium supplement of 500 mg and a multiple vitamin containing 400 IU of Vitamin D daily.

2.3 Preparation of Solution

Zoledronic acid injection must not be mixed with calcium or other divalent cation-containing infusion solutions, such as Lactated Ringer's solution, and should be administered as a single intravenous solution in a line separate from all other drugs.

4 mg per 5 mL Single-Use Vial

Vials of zoledronic acid injection concentrate for infusion contain overfill allowing for the withdrawal of 5 mL of concentrate (equivalent to 4 mg zoledronic acid). This concentrate should immediately be diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP, following proper aseptic technique, and administered to the patient by infusion. Do not store undiluted concentrate in a syringe, to avoid inadvertent injection.

To prepare reduced doses for patients with baseline CrCl less than or equal to 60 mL/min, withdraw the specified volume of the zoledronic acid injection concentrate from the vial for the dose required (see Table 2).
Table 2: Preparation of Reduced Doses – Zoledronic acid injection concentrate Remove and Use Zoledronic Acid Injection Volume (mL) Dose (mg) 4.4 3.5 4.1 3.3 3.8 3
The withdrawn concentrate must be diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP.

If not used immediately after dilution with infusion media, for microbiological integrity, the solution should be refrigerated at 2°C to 8°C (36°F to 46°F). The refrigerated solution should then be equilibrated to room temperature prior to administration. The total time between dilution, storage in the refrigerator, and end of administration must not exceed 24 hours.

2.4 Method of Administration

Due to the risk of clinically significant deterioration in renal function, which may progress to renal failure, single doses of zoledronic acid injection should not exceed 4 mg and the duration of infusion should be no less than 15 minutes [see Warnings And Precautions (5.2)]. In the trials and in postmarketing experience, renal deterioration, progression to renal failure and dialysis, have occurred in patients, including those treated with the approved dose of 4 mg infused over 15 minutes. There have been instances of this occurring after the initial zoledronic acid injection dose.
Haloperidol Decanoate

Haloperidol Decanoate

Haloperidol decanoate injection, 50 mg/mL and haloperidol decanoate injection, 100 mg/mL should be administered by deep intramuscular injection. A 21 gauge needle is recommended. The maximum volume per injection site should not exceed 3 mL. DO NOT ADMINISTER INTRAVENOUSLY.

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

Haloperidol decanoate injection, 50 mg/mL and haloperidol decanoate injection, 100 mg/mL are intended for use in schizophrenic patients who require prolonged parenteral antipsychotic therapy. These patients should be previously stabilized on antipsychotic medication before considering a conversion to haloperidol decanoate, USP. Furthermore, it is recommended that patients being considered for haloperidol decanoate, USP therapy have been treated with, and tolerate well, short-acting haloperidol, USP in order to reduce the possibility of an unexpected adverse sensitivity to haloperidol, USP. Close clinical supervision is required during the initial period of dose adjustment in order to minimize the risk of overdosage or reappearance of psychotic symptoms before the next injection. During dose adjustment or episodes of exacerbation of symptoms of schizophrenia, haloperidol decanoate, USP therapy can be supplemented with short-acting forms of haloperidol, USP.

The dose of haloperidol decanoate injection, 50 mg/mL or haloperidol decanoate injection, 100 mg/mL should be expressed in terms of its haloperidol, USP content. The starting dose of haloperidol decanoate, USP should be based on the patient's age, clinical history, physical condition, and response to previous antipsychotic therapy. The preferred approach to determining the minimum effective dose is to begin with lower initial doses and to adjust the dose upward as needed. For patients previously maintained on low doses of antipsychotics (e.g. up to the equivalent of 10 mg/day oral haloperidol), it is recommended that the initial dose of haloperidol decanoate, USP be 10 to 15 times the previous daily dose in oral haloperidol equivalents; limited clinical experience suggests that lower initial doses may be adequate.

Initial Therapy

Conversion from oral haloperidol to haloperidol decanoate, USP can be achieved by using an initial dose of haloperidol decanoate, USP that is 10 to 20 times the previous daily dose in oral haloperidol equivalents.

In patients who are elderly, debilitated, or stable on low doses of oral haloperidol (e.g. up to the equivalent of 10 mg/day oral haloperidol), a range of 10 to 15 times the previous daily dose in oral haloperidol equivalents is appropriate for initial conversion.

In patients previously maintained on higher doses of antipsychotics for whom a low dose approach risks recurrence of psychiatric decompensation and in patients whose long-term use of haloperidol, USP has resulted in a tolerance to the drug, 20 times the previous daily dose in oral haloperidol equivalents should be considered for initial conversion, with downward titration on succeeding injections.

The initial dose of haloperidol decanoate, USP should not exceed 100 mg regardless of previous antipsychotic dose requirements. If, therefore, conversion requires more than 100 mg of haloperidol decanoate, USP as an initial dose, that dose should be administered in two injections, i.e. a maximum of 100 mg initially followed by the balance in 3 to 7 days.

Maintenance Therapy

The maintenance dosage of haloperidol decanoate, USP must be individualized with titration upward or downward based on therapeutic response. The usual maintenance range is 10 to 15 times the previous daily dose in oral haloperidol equivalents dependent on the clinical response of the patient.
HALOPERIDOL DECANOATE, USP DOSING RECOMMENDATIONS Patients Monthly 1st Month Maintenance Stabilized on low daily oral doses (up to 10 mg/day)Elderly or Debilitated 10-15 x Daily Oral Dose 10-15 x Previous Daily Oral Dose High doseDose Risk of relapse Tolerant to oral haloperidol 20 x Daily Oral Dose 10-15 x Previous Daily Oral Dose
Close clinical supervision is required during initiation and stabilization of haloperidol decanoate, USP therapy. Haloperidol decanoate, USP is usually administered monthly or every 4 weeks. However, variation in patient response may dictate a need for adjustment of the dosing interval as well as the dose (See CLINICAL PHARMACOLOGY).

Clinical experience with haloperidol decanoate, USP at doses greater than 450 mg per month has been limited.
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 injection 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.
Ampicillin Sodium

Ampicillin Sodium

This insert is for a Pharmacy Bulk Package and is intended for preparing IV admixtures only. Dosage recommendations for intramuscular are for informational purposes only.

Infections of the respiratory tract and soft tissues.

Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 25 mg to 50 mg/kg/day in equally divided doses at 6-to 8-hour intervals.

Infections of the gastrointestinal and genitourinary tracts (including those caused by Neisseria gonorrhoeae in females).

Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6-to 8-hour intervals.

In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

Urethritis in males due to N. gonorrhoeae.

Adults – Two doses of 500 mg each at an interval of 8 to 12 hours. Treatment may be repeated if necessary or extended if required. In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months.

The doses for the preceding infections may be given by either the intramuscular or intravenous route. A change to oral ampicillin may be made when appropriate.

Bacterial Meningitis

Adults and children – 150 mg to 200 mg/kg/day in equally divided doses every 3 to 4 hours. (Treatment may be initiated with intravenous drip therapy and continued with intramuscular injections.) The doses for other infections may be given by either the intravenous or intramuscular route.

Septicemia

Adults and children – 150 mg to 200 mg/kg/day. Start with intravenous administration for at least three days and continue with the intramuscular route every 3 to 4 hours.

Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10-days treatment is recommended for any infection caused by Group A beta-hemolytic streptococci to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis.

For Administration by Intravenous Infusion – Reconstitute as directed below (Directions for Proper Use of Pharmacy Bulk Package) prior to diluting with an intravenous solution.

IMPORTANT: This chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

Stability studies on ampicillin sodium at several concentrations in various intravenous solutions indicate the drug will lose less than 10% activity at the temperatures noted for the time periods stated.
Room Temperature (25°C) Diluent Concentrations Stability Periods Sterile Water for Injection up to 30 mg/mL 8 hours Sodium Chloride Injection USP, 0.9% up to 30 mg/mL 8 hours 5% Dextrose in Water 10 to 20 mg/mL 1 hour 5% Dextrose in Water up to 2 mg/mL 2 hours 5% Dextrose in 0.45% NaCl Injection up to 2 mg/mL 2 hours Lactated Ringer’s Solution up to 30 mg/mL 8 hours Refrigerated (4° C) Sterile Water for Injection 30 mg/mL 48 hours Sterile Water for Injection up to 20 mg/mL 72 hours Sodium Chloride Injection USP, 0.9% 30 mg/mL 24 hours Sodium Chloride Injection USP, 0.9% up to 20 mg/mL 48 hours Lactated Ringer’s Solution up to 30 mg/mL 24 hours 5% Dextrose in Water up to 20 mg/mL 1 hour 5% Dextrose and 0.45% NaCl Injection up to 10 mg/mL 1 hour
Only those solutions listed above should be used for the intravenous infusion of Ampicillin for Injection, USP. The concentrations should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of ampicillin is administered before the drug loses its stability in the solution in use.

Directions For Proper Use Of Pharmacy Bulk Package

This Pharmacy bulk Package bottle contains 10 grams ampicillin and is designed for use in the pharmacy in preparing IV admixtures.
Add 94 mL Sterile Water for Injection USP. The resulting solution will contain 100 milligrams ampicillin activity per mL, and is stable up to ONE HOUR at room temperature. Dilute further within ONE HOUR to a concentration of 5 mg to 10 mg per mL. See Table for suitable fluid. Use promptly. This chemical stability information in no way indicates that it would be acceptable practice to use this product well after preparation time. Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible. Using aseptic technique under laminar flow hood, the closure should be penetrated only one time after reconstitution using a suitable sterile dispensing set; which allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. After entry, use entire contents of Pharmacy bulk Package bottle promptly. The entire contents of the Pharmacy bulk Package bottle must be dispensed within ONE HOUR of reconstitution. The time limit should begin with the introduction of solvent in the Pharmacy bulk Package bottle. A plastic ball attached to the pharmacy bulk package provides a suitable hanging device while dispensing contents.
Use of this product is restricted to a suitable work area, such as a laminar flow hood. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Ampicillin Sodium And S...

Ampicillin Sodium And Sulbactam Sodium

The pharmacy bulk package is for preparation of solutions for IV infusion only. Ampicillin and Sulbactam for Injection should be administered by slow intravenous injection over at least 10 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 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:
TABLE 5: Ampicillin and Sulbactam for Injection, USP Dosage Guide For Patients With Renal Impairment Creatinine Clearance Ampicillin/Sulbactam Recommended (mL/min/1.73m2) Half-Life (Hours) Ampicillin and Sulbactam for Injection, USP Dosage ≥30 1 1.5 to 3 g q 6h to q 8h 15 to 29 5 1.5 to 3 g q 12h 5 to14 9 1.5 to 3 g q 24h
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.

COMPATIBILITY, RECONSTITUTION AND STABILITY

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam for Injection and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

Intravenous Administration

Directions for Proper Use of Pharmacy Bulk Package

Ampicillin and Sulbactam for Injection, USP sterile powder for intravenous use may be reconstituted with any of the compatible diluents described in this insert. Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. Ampicillin and Sulbactam concentrations between 3 and 45 mg (2 to 30 mg ampicillin/1 to 15 mg sulbactam/mL) are recommended for intravenous use.

The 15 gram bottle may be reconstituted with either 92 mL Sterile Water for Injection or 0.9% Sodium Chloride Injection. The diluent should be added in two separate aliquots in a suitable work area, such as a laminar flow hood. Add 50 mL of solution, shake to dissolve. Then add an additional 42 mL and shake. The solution should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. The resultant solution will have a final concentration of approximately 100 mg/mL ampicillin and 50 mg/mL sulbactam. The closure may be penetrated only one time after reconstitution, if needed, using a suitable sterile transfer device or dispensing set that allows for measured dispensing of the contents.

After reconstitution, use within two hours if stored at room temperature, or within four hours if stored under refrigeration.

Reconstituted Bulk Solution Should Not be Used For Direct Infusion

If the reconstituted bulk solution is stored for less than one hour at room temperature (20°C/68°F) prior to further dilution, the use periods indicated in Table 6 apply for the diluted solutions.

If the bulk solution is stored for one to two hours at room temperature (20°C/68°F) and then diluted with Sterile Water for Injection or 0.9% Sodium Chloride Injection to the following concentrations, the use periods indicated in Table 7 apply.

Any unused portions of solution that remain after the indicated time periods should be discarded.
TABLE 6: Diluent Maximum Concentration (mg/mL) Ampicillin and Sulbactam for Injection, USP (Ampicillin/Sulbactam) Use Periods Sterile Water for 45 (30/15) 8 hrs @ 21°C Injection 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 0.9% Sodium Chloride 45 (30/15) 8 hrs @ 21°C Injection 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 5% Dextrose Injection 30 (20/10) 2 hrs @ 21°C 30 (20/10) 4 hrs @ 4°C 3 (2/1) 2 hrs @ 21°C Lactated Ringer’s 45 (30/15) 8 hrs @ 21°C Injection 45 (30/15) 24 hrs @ 4°C M/6 Sodium Lactate 45 (30/15) 8 hrs @ 21°C Injection 45 (30/15) 12 hrs @ 4°C 5% Dextrose in 0.45% 3 (2/1) 4 hrs @ 21°C Saline 15 (10/5) 4 hrs @ 4°C 10% Invert Sugar 3 (2/1) 4 hrs @ 21°C 30 (20/10) 3 hrs @ 4°C Table 7: IV Solution Maximum Concentration (mg/mL) Ampicillin and Sulbactam for Injection, USP (Ampicillin/Sulbactam) Use Periods Sterile Water for 45 (30/15) 4 hrs @ 21°C Injection, USP 45 (30/15) 24 hrs @ 4°C 0.9% Sodium Chloride Injection, 45 (30/15) 4 hrs @ 21°C USP 45 (30/15) 24 hrs @ 4°C
Animal Pharmacology

While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in man.
Ampicillin

Ampicillin

Infections of the respiratory tract and soft tissues.

Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 25 mg to 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

Infections of the gastrointestinal and genitourinary tracts (including those caused by Neisseria gonorrhoeae in females).

Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

Urethritis in males due to N. gonorrhoeae.

Adults – Two doses of 500 mg each at an interval of 8 to 12 hours. Treatment may be repeated if necessary or extended if required. In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months.

The doses for the preceding infections may be given by either the intramuscular or intravenous route. A change to oral ampicillin may be made when appropriate.

Bacterial Meningitis

Adults and children – 150 mg to 200 mg/kg/day in equally divided doses every 3 to 4 hours. (Treatment may be initiated with intravenous drip therapy and continued with intramuscular injections.) The doses for other infections may be given by either the intravenous or intramuscular route.

Septicemia

Adults and children – 150 mg to 200 mg/kg/day. Start with intravenous administration for at least three days and continue with the intramuscular route every 3 to 4 hours.

Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10 days treatment is recommended for any infection caused by Group A beta-hemolytic streptococci to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis.

DIRECTIONS FOR USE

Use only freshly prepared solutions. Intramuscular and intravenous injections should be administered within one hour after preparation since the potency may decrease significantly after this period.

For Intramuscular Use – Dissolve contents of a vial with the amount of Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, listed in the table below:

Recommended Withdrawable Concentration NDC Label Claim Amount of Diluent volume (in mg/mL) 76126-026-10 250 mg 1 mL 1 mL 250 mg 76126-027-10 500 mg 1.8 mL 2 mL 250 mg 76126-028-10 1 gram 3.5 mL 4 mL 250 mg 76126-047-04 2 grams 6.8 mL 8 mL 250 mg
While Ampicillin for Injection, USP, 1 g and 2 g, are primarily for intravenous use, they may be administered intramuscularly when the 250 mg or 500 mg vials are unavailable. In such instances, dissolve in 3.5 or 6.8 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP respectively. The resulting solution will provide a concentration of 250 mg per mL.

Ampicillin for Injection USP, 125 mg is intended primarily for pediatric use. It also serves as a convenient dosage form when small parenteral doses of the antibiotic are required.

For Direct Intravenous Use – Add 5 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP to the 250 mg, and 500 mg vials and administer slowly over a 3- to 5- minute period. Ampicillin for Injection, USP 1 g or 2 g, may also be given by direct Intravenous administration. Dissolve in 7.4 or 14.8 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, respectively, and administer slowly over at least 10 to 15 minutes. CAUTION: More rapid administration may result in convulsive seizures.

For Administration by Intravenous Drip – Reconstitute as directed above (For Direct Intravenous Use) prior to diluting with Intravenous Solution. Stability studies on ampicillin sodium at several concentrations in various intravenous solutions indicate the drug will lose less than 10% activity at the temperatures noted for the time periods stated.

Room Temperature (25ºC) Diluent Concentrations Stability Periods Sterile Water for Injection USP up to 30 mg/mL 8 hours Sodium Chloride Injection USP, 0.9% up to 30 mg/mL 8 hours 5% Dextrose in Water 10 to 20 mg/mL 1 hour 5% Dextrose in Water up to 2 mg/mL 2 hours 5% Dextrose in 0.45% Sodium Chloride up to 2 mg/mL 2 hours Lactated Ringer’s Solution up to 30 mg/mL 8 hours Refrigerated (4°C) Diluent Concentrations Stability Periods Sterile Water for Injection USP 30 mg/mL 48 hours Sterile Water for Injection USP up to 20 mg/mL 72 hours Sodium Chloride Injection USP, 0.9% 30 mg/mL 24 hours Sodium Chloride Injection USP, 0.9% up to 20 mg/mL 48 hours Lactated Ringer’s Solution up to 30 mg/mL 24 hours 5% Dextrose in Water up to 20 mg/mL 1 hour 5% Dextrose and 0.45% Sodium Chloride up to 10 mg/mL 1 hour
Only those solutions listed above should be used for the intravenous infusion of Ampicillin for injection, USP. The concentrations should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of ampicillin is administered before the drug loses its stability in the solution in use.
Ampicillin Sodium And S...

Ampicillin Sodium And Sulbactam Sodium

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 to 15 minutes or can also be delivered, in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 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:
TABLE 5: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 Sulbactam for Injection Dosage ≥30 1 1.5 to 3 g q 6h to q 8h 15 to 29 5 1.5 to 3 g q 12h 5 to 14 9 1.5 to 3 g q 24h
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



COMPATIBILITY, RECONSTITUTION AND STABILITY

When concomitant therapy with aminoglycosides is indicated, ampicillin and sulbactam for injection and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

DIRECTIONS FOR USE

General Dissolution Procedures: Ampicillin and sulbactam for injection sterile powder for intravenous and intramuscular use may be reconstituted with any of the compatible diluents described in this insert. Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.

Preparation for Intravenous Use

1.5 g and 3 g Vials: Initially, the vials may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg ampicillin and sulbactam per mL (250 mg ampicillin/125 mg sulbactam per mL). An appropriate volume should then be immediately diluted with a suitable parenteral diluent to yield solutions containing 3 to 45 mg ampicillin and sulbactam per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL). Reconstitution of ampicillin and sulbactam for injection, at the specified concentrations, with these diluents provide stable solutions for the time periods indicated in the following table: (After the indicated time periods, any unused portions of solutions should be discarded.)
TABLE 6: Diluent Maximum Concentration (mg/mL) Ampicillin and Sulbactam Use Periods Sterile Water for Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 0.9% Sodium Chloride Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 5% Dextrose Injection 30 (20/10) 2 hrs @ 25°C 30 (20/10) 4 hrs @ 4°C 3 (2/1) 4 hrs @ 25°C Lactated Ringer’s Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 24 hrs @ 4°C M/6 Sodium Lactate Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 8 hrs @ 4°C 5% Dextrose in 0.45% Saline 3 (2/1) 4 hrs @ 25°C 15 (10/5) 4 hrs @ 4°C 10% Invert Sugar 3 (2/1) 4 hrs @ 25°C 30 (20/10) 3 hrs @ 4°C
Preparation for Intramuscular Injection

1.5 g and 3 g Standard Vials: Vials for intramuscular use may be reconstituted with Sterile Water for Injection USP, 0.5% Lidocaine Hydrochloride Injection USP or 2% Lidocaine Hydrochloride Injection USP. Consult the following table for recommended volumes to be added to obtain solutions containing 375 mg ampicillin and per mL (250 mg ampicillin/125 mg sulbactam per mL). Note: Use only freshly prepared solutions and administer within one hour after preparation.
TABLE 7: Ampicillin and Sulbactam for Injection Vial Size Volume of Diluent to be Added Withdrawal Volume* 1.5 g 3.2 mL 4 mL 3 g 6.4 mL 8 mL
*There is sufficient excess present to allow withdrawal and administration of the stated volumes.

Animal Pharmacology: While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in man.
Lidocaine Hydrochloride...

Lidocaine Hydrochloride

Table 1 (Recommended Dosages) summarizes the recommended volumes and concentrations of Lidocaine Hydrochloride Injection for various types of anesthetic procedures. The dosages suggested in this table are for normal healthy adults and refer to the use of epinephrine-free solutions. When larger volumes are required, only solutions containing epinephrine should be used except in those cases where vasopressor drugs may be contraindicated.

There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. Lidocaine Hydrochloride Injection, USP is not approved for this use (see WARNINGS and DOSAGE and ADMINISTRATION).

These recommended doses serve only as a guide to the amount of anesthetic required for most routine procedures. The actual volumes and concentrations to be used depend on a number of factors such as type and extent of surgical procedure, depth of anesthesia and degree of muscular relaxation required, duration of anesthesia required, and the physical condition of the patient. In all cases the lowest concentration and smallest dose that will produce the desired result should be given. Dosages should be reduced for children and for the elderly and debilitated patients and patients with cardiac and/or liver disease.

The onset of anesthesia, the duration of anesthesia and the degree of muscular relaxation are proportional to the volume and concentration (i.e., total dose) of local anesthetic used. Thus, an increase in volume and concentration of Lidocaine Hydrochloride Injection will decrease the onset of anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and increase the segmental spread of anesthesia. However, increasing the volume and concentration of Lidocaine Hydrochloride Injection may result in a more profound fall in blood pressure when used in epidural anesthesia. Although the incidence of side effects with lidocaine hydrochloride is quite low, caution should be exercised when employing large volumes and concentrations, since the incidence of side effects is directly proportional to the total dose of local anesthetic agent injected.

For intravenous regional anesthesia, only the 50 mL single dose vial containing lidocaine hydrochloride 0.5% injection should be used.

MAXIMUM RECOMMENDED DOSAGES

NOTE: The products accompanying this insert do not contain epinephrine.

Adults

For normal healthy adults, the maximum individual dose should not exceed 4.5 mg/kg (2 mg/lb) of body weight, and in general it is recommended that the maximum total dose does not exceed 300 mg.

The maximum recommended dose per 90 minute period of lidocaine hydrochloride for paracervical block in obstetrical patients and non-obstetrical patients is 200 mg total. One half of the total dose is usually administered to each side. Inject slowly, five minutes between sides. (See also discussion of paracervical block in PRECAUTIONS.)

Children

It is difficult to recommend a maximum dose of any drug for children, since this varies as a function of age and weight. For children over 3 years of age who have a normal lean body mass and normal body development, the maximum dose is determined by the child's age and weight. For example, in a child of 5 years weighing 50 lbs the dose of lidocaine hydrochloride should not exceed 75 to100 mg (1.5 to 2 mg/lb). The use of even more dilute solutions (i.e., 0.25-0.5%) and total dosages not to exceed 3 mg/kg (1.4 mg/lb) are recommended for induction of intravenous regional anesthesia in children.

In order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose should be used at all times. In some cases it will be necessary to dilute available concentrations with 0.9% sodium chloride injection in order to obtain the required final concentration.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. The Injection is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.
Table 1. Recommended Dosages Procedure Lidocaine Hydrochloride Injection, USP(without epinephrine) Conc (%) Vol (mL) Total Dose (mg) Infiltration Percutaneous 0.5 or 1 1-60 5-300 Intravenous regional 0.5 10-60 50-300 Peripheral Nerve Blocks, e.g., Brachial 1.5 15-20 225-300 Dental 2 1-5 20-100 Intercostal 1 3 30 Paravertebral 1 3-5 30-50 Pudendal (each side) 1 10 100 Paracervical Obstetrical analgesia (each side) 1 10 100 Sympathetic nerve blocks, e.g., Cervical (stellate ganglion) 1 5 50 Lumbar 1 5-10 50-100
THE ABOVE SUGGESTED CONCENTRATIONS AND VOLUMES SERVE ONLY AS A GUIDE. OTHER VOLUMES AND CONCENTRATIONS MAY BE USED PROVIDED THE TOTAL MAXIMUM RECOMMENDED DOSE IS NOT EXCEEDED.

STERILIZATION, STORAGE AND TECHNICAL PROCEDURES

Disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc.) should not be used for skin or mucous membrane disinfection as they have been related to incidents of swelling and edema. When chemical disinfection of multi-dose vials is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of USP grade, contain denaturants which are injurious to rubber and therefore are not to be used.
Sumatriptan

Sumatriptan

2.1 Dosing Information

The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is 6 mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 to 5 mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established.

The maximum cumulative dose that may be given in 24 hours is 12 mg, two 6 mg injections separated by at least 1 hour. A second 6 mg dose should only be considered if some response to a first injection was observed.

2.3 Administration of Doses of Sumatriptan Injection Other Than 4 or 6 mg

In patients receiving doses other than 4 or 6 mg, use the 6 mg single-dose vial. Visually inspect the vial for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted.
Ceftriaxone

Ceftriaxone

Ceftriaxone for injection may be administered intravenously or intramuscularly. However, the intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only. Ceftriaxone for injection should be administered intravenously by infusion over a period of 30 minutes.

Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to reconstitute ceftriaxone bottles or to further dilute a reconstituted bottle for IV administration 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 or interactions between intramuscular ceftriaxone and calcium- containing products (IV or oral).

NEONATES

Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone for injection (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 g.

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 g.

In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 g). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 g 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 g 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 g, in order to achieve >90% target attainment. The total daily dose should not exceed 4 g.

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 g administered intravenously 1/2 to 2 hours before surgery is recommended.

Generally, ceftriaxone 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.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE
PHARMACY BULK PACKAGE NOT FOR DIRECT INFUSION
RECONSTITUTED STOCK SOLUTION MUST BE TRANSFERRED AND FURTHER DILUTED FOR I.V. INFUSION

The 10 g bottle should be reconstituted with 95 mL of an appropriate IV diluent in a suitable work area such as a laminar flow hood. The resulting solution will contain approximately 100 mg/mL of ceftriaxone. The container closure may be penetrated only one time, utilizing a suitable sterile transfer device or dispensing set which allows measured distribution of the contents. (A sterile substance which must be reconstituted prior to use may require a separate closure entry). Use of this product is restricted to a suitable work area, such as a laminar flow hood.

The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum of 4 hours from initial closure entry is permitted to complete fluid transfer operations. If reconstitution is necessary, this time limit should begin with the introduction of solvent or diluent into the Pharmacy Bulk Package.

Unused portions of solutions held longer than the recommended time periods should be discarded.
RECONSTITUTED BULK SOLUTION SHOULD NOT BE USED FOR DIRECT INFUSION
Transfer individual dose to appropriate intravenous solutions as soon as possible following reconstitution of the bulk package. The stability of the solution that has been transferred into a container varies according to diluent, concentration and temperature (see COMPATIBILITY AND STABILITY). Concentrations between 10 mg/mL and 40 mg/mL are recommended; however, lower concentrations may be used if desired.

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® (metronidazole) formulation or using other diluents. Metronidazole at concentrations greater than 8 mg/mL will precipitate. Do not refrigerate the admixture as precipitation will occur.

*Registered trademark of G.D Searle & Co.

Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures. When any of these drugs are 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 or to further dilute a reconstituted pharmacy bulk package bottle for IV administration. Particulate formation can result.

Ceftriaxone for injection 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 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. Storage Diluent Room Temp. (25°C) Refrigerated (4°C) Sterile Water for Injection 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 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 of ceftriaxone for injection should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.
Mesna

Mesna

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.
Table1. Recommended Intravenous Dosing Schedule
1The 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.
0 Hours 4 Hours 8 Hours Ifosfamide 1.2 g/m2 – – Mesna injection1 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 mesna 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. Mesna 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.
Table 2. Recommended Intravenous and Oral Dosing Schedule
1The 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.
0 Hours 2 Hours 6 Hours Ifosfamide 1.2 g/m2 – – Mesna injection1 240 mg/m2 – – Mesna tablets – 480 mg/m2 480 mg/m2
The efficacy and safety of this ratio of intravenous and oral mesna 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 mesna 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.
Ketorolac Tromethamine

Ketorolac Tromethamine

DOSAGE AND ADMINISTRATION

Ketorolac Tromethamine Tablets
Ketorolac tromethamine tablets are indicated only as continuation therapy to ketorolac tromethamine injection, and the combined duration of use of ketorolac tromethamine injection and ketorolac tromethamine tablets is not to exceed 5 (five) days, because of the increased risk of serious adverse events. The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for ketorolac tromethamine injection (maximum 120 mg) (see DOSAGE AND ADMINISTRATION ).
Carefully consider the potential benefits and risks of ketorolac tromethamine and other treatment options before deciding to use ketorolac tromethamine. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. In adults, the combined duration of use of IV or IM dosing of ketorolac tromethamine and oral ketorolac tromethamine is not to exceed 5 days. In adults, the use of oral ketorolac tromethamine is only indicated as continuation therapy to IV or IM dosing of ketorolac tromethamine. See package insert for ketorolac tromethamine tablets for transition from IV or IM dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose oral ketorolac tromethamine.

Note:

Oral formulation should not be given as an initial dose

Use minimum effective dose for the individual patient

Total duration of treatment in adult patients: the combined duration of use of IV or IM dosing of ketorolac tromethamine and oral ketorolac tromethamine is not to exceed 5 days.

Ketorolac Tromethamine Injection

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 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

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.
Multiple-Dose Treatment (IV or IM)
Patients < 65 years of age : The recommended dose is 30 mg ketorolac tromethamine injection every 6 hours. The maximum daily dose for these populations should not exceed 120 mg. For patients ≥ 65 years of age, renally impaired patients (see WARNINGS ), and patients less than 50 kg (110 lbs): 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: 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.

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

Piperacillin And Tazobactam

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

2.1 Adult Patients

The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.

Piperacillin and tazobactam for injection should be administered by intravenous infusion over 30 minutes.

2.2 Nosocomial Pneumonia

Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18 g (16 g piperacillin/2 g tazobactam). The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.

2.3 Renal Impairment

In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:
Table 1: Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal-Impairment (As total grams piperacillin/tazobactam) * Creatinine clearance for patients not receiving hemodialysis † 0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days Renal Function (creatinine clearance, mL/min) All Indications (except nosocomial pneumonia) Nosocomial Pneumonia >40 mL/min 3.375 q 6 h 4.5 q 6 h 20 to 40 mL/min* 2.25 q 6 h 3.375 q 6 h <20 mL/min* 2.25 q 8 h 2.25 q 6 h Hemodialysis† 2.25 q 12 h 2.25 q 8 h CAPD 2.25 q 12 h 2.25 q 8 h
For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.

2.4 Pediatric Patients

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.

It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.

2.5 Reconstitution and Dilution of Powder Formulations

Single dose vials

Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.

2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

Compatible Reconstitution Diluents for Single Dose Vials

0.9% sodium chloride for injection

Sterile water for injection

Dextrose 5%

Bacteriostatic saline/parabens

Bacteriostatic water/parabens

Bacteriostatic saline/benzyl alcohol

Bacteriostatic water/benzyl alcohol

Reconstituted piperacillin and tazobactam for injection solutions for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

Compatible Intravenous Solutions for Single Dose Vials

0.9% sodium chloride for injection

sterile water for injectiona

Dextran 6% in saline

Dextrose 5%

Lactated Ringer's Solution is not compatible with Piperacillin and Tazobactam for Injection.

aMaximum recommended volume per dose of sterile water for injection is 50 mL.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates.

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

Stability of piperacillin and tazobactam for injection Powder Formulations Following Reconstitution

Piperacillin and tazobactam for injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents.

Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.

Piperacillin and tazobactam for injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.

2.7 Compatibility with Aminoglycosides

Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam for injection and aminoglycosides are recommended for separate administration. Piperacillin and tazobactam for injection and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated [see Drug Interactions (7.1)].

In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:
Table 2: Compatibility with Aminoglycosides * Diluent volumes apply only to single vials † The concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10 to 15 mg/kg/day in two daily doses for amikacin and 3 to 5 mg/kg/day in three daily doses for gentamicin). Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam has not been evaluated. See package insert for each aminoglycoside for complete Dosage and Administration instructions. Aminoglycoside Piperacillin and Tazobactam Dose (grams) Piperacillin and Tazobactam Diluent Volume* (mL) Aminoglycoside Concentration Range†(mg/mL) Acceptable Diluents Amikacin 2.25, 3.375,4.5 50, 100, 150 1.75 to 7.5 0.9% sodium chloride or 5% dextrose Gentamicin 2.253.3754.5 50,100150 0.7 to 3.32 0.9% sodium chloride or 5% dextrose
Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

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

Vancomycin Hydrochloride

Infusion-related events are related to both the concentration and the rate of administration of vancomycin. Concentrations of no more than 5 mg/mL and rates of no more than 10 mg/min are recommended in adults (see also age-specific recommendations). In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used; use of such higher concentrations may increase the risk of infusion-related events. 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 six 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 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 premature infants and 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 (see following table).
DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Meollering et al)4 Creatinine Clearance mL/min Vancomycin Dose mg/24 hr 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 hr. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1000 mg every 7 to 10 days has been recommended.

When only 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 in 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.

COMPATIBILITY WITH OTHER DRUGS AND IV FLUIDS

The following diluents are physically and chemically compatible (with 4g/L vancomycin hydrochloride):

5% Dextrose Injection, USP

5% Dextrose Injection and 0.9% Sodium Chloride Injection, USP

Lactated Ringer's Injection, USP

5% Dextrose and Lactated Ringer's Injection

Normosol®-M and 5% Dextrose

0.9% Sodium Chloride Injection, USP

Isolyte® E

Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

Vancomycin solution has a low pH and may cause physical instability of other compounds.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE-NOT FOR DIRECT INFUSION

Pharmacy bulk packages are for use in pharmacy admixture service only in a suitable work area, such as a laminar flow hood. They should be hung by the integral hanger provided and suspended as a unit in the laminar flow hood. Using aseptic technique the container closure should be penetrated only one time after reconstitution utilizing a suitable sterile dispensing set which allows measured distribution of the contents. Use of a syringe and needle is not recommended as it may cause leakage. Swab vial stopper with an antiseptic solution.

Once the sterile dispensing set has been inserted into the container, withdrawal of the contents should be accomplished without delay. However, if this is not possible, a maximum time of 4 hours from the initial closure entry may be permitted to complete fluid transfer operations. Discard the container no later than 4 hours after initial closure puncture. This time limit should begin with introduction of solvent or diluent into the Pharmacy Bulk Package bottle.

PREPARATION AND STABILITY

10 g Pharmacy Bulk Package bottle

At the time of use, reconstitute by adding 95 mL of Sterile Water for Injection, USP to the 10 g of Pharmacy Bulk Package bottle of dry, vancomycin powder. The resultant solution is a tan colored solution and will contain vancomycin equivalent to 500 mg/5 mL (1 g/10 mL). AFTER RECONSTITUTION FURTHER DILUTION IS REQUIRED.

Reconstituted solutions of vancomycin (500 mg/5 mL) must be further diluted in at least 100 mL of a suitable infusion solution. For doses of 1 gram (10 mL), at least 200 mL of solution must be used. The desired dose diluted in this manner should be administered by intermittent IV infusion over a period of at least 60 minutes.

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

For Oral Administration

Oral vancomycin is used in treating antibiotic-associated pseudomembranous colitis caused by C. difficile and for staphylococcal enterocolitis. Vancomycin is not effective by the oral route for other types of infections. The usual adult total daily dose is 500 mg to 2 g given in 3 or 4 divided doses for 7 to 10 days. The total daily dose in children is 40 mg/kg of body weight in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g. The appropriate dose may be diluted in 1 oz of water and given to the patient to drink. Common flavoring syrups may be added to the solution to improve the taste for oral administration. The diluted solution may be administered via a nasogastric tube.
Oxacillin

Oxacillin

The penicillinase-resistant penicillins are available for oral administration and for intramuscular and intravenous injection. The sodium salts of methicillin, oxacillin, and nafcillin may be administered parenterally and the sodium salts of cloxacillin, dicloxacillin, oxacillin, and nafcillin are available for oral use.

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.

Oral preparations of the penicillinase-resistant penicillins should not be used as initial therapy in serious, life-threatening infections (See PRECAUTIONS-General). Oral therapy with the penicillinase-resistant penicillins may be used to follow-up the previous use of a parenteral agent as soon as the clinical condition warrants. For intramuscular gluteal injections, care should be taken to avoid sciatic nerve injury.

With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis.
RECOMMENDED DOSAGES FOR OXACILLIN FOR INJECTION, USP Drug Adults Infants and Children < 40 kg (88 lbs) Other Recommendations Oxacillin 250 to 500 mg IM or IV every 4 to 6hours (mild to moderate infections) 50 mg/kg/day IM or IV in equally divideddoses every 6 hours (mild to moderate infections) 1 gram IM or IVevery 4 to 6 hours (severe infections) 100 mg/kg/day IM or IV in equally divided dosesevery 4 to 6 hours (severe infections) Premature and Neonates 25 mg/kg/day IM or IV
Directions for use

For Intramuscular Use

Use Sterile Water for Injection, USP. Add 5.7 mL to the 1 gram vial and 11.5 mL to the 2 gram vial. Shake well until a clear solution is obtained. After reconstitution, vials will contain 250 mg of active drug per 1.5 mL of solution. The reconstituted solution is stable for 3 days at 70°F or for one week under refrigeration (40° F).

For Direct Intravenous Use

Use Sterile Water for Injection, USP or Sodium Chloride Injection, USP. Add 10 mL to the 1 gram vial and 20 mL to the 2 gram vial. Withdraw the entire contents and administer slowly over a period of approximately10 minutes.

For Administration by Intravenous Drip

Reconstitute as directed above (For Direct Intravenous Use) prior to diluting with Intravenous Solution.
STABILITY PERIODS FOR OXACILLIN FOR INJECTION, USP Concentration mg/mL Sterile water for Injection 0.9% sodium chloride Injection, USP M/6 Molar Sodium Lactate Solution 5% Dextrose in water 5% Dextrose in 0.45% sodium chloride 10% Invert Sugar Injection, USP Lactated Ringers Solution ROOM TEMPERATURE (25° C) 10 to100 4 Days 4 Days 10 to 30 24 Hrs 24 Hrs 0.5 to 2 6 Hrs 6 Hrs 6 Hrs REFRIGERATION (4° C) 10 to 100 7 Days 7 Days 10 to 30 4 Days 4 Days 4 Days 4 days 4 Days FROZEN (-15° C) 50 to 100 30 Days 250/1.5 mL 30 Days 100 30 Days 10 to 100 30 Days 30 Days 30 Days 30 days 30 Days
Stability studies on oxacillin sodium at concentrations of 0.5 mg/mL and 2 mg/mL in various intravenous solutions listed below indicate the drug will lose less than 10% activity at room temperature (70°F) during a 6-hour period.

IV Solution

5% Dextrose in Normal Saline

10% D-Fructose in Water

10% D-Fructose in Normal Saline

Lactated Potassic Saline Injection

10% Invert Sugar in Normal Saline

10% Invert Sugar Plus 0.3% Potassium Chloride in Water

Travert 10% Electrolyte #1

Travert 10% Electrolyte #2

Travert 10% Electrolyte #3

Only those solutions listed above should be used for the intravenous infusion of oxacillin sodium. The concentration of the antibiotic should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of oxacillin is administered before the drug loses its stability in the solution in use.

If another agent is used in conjunction with oxacillin therapy, it should not be physically mixed with oxacillin but should be administered separately.

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 for injection, USP.

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