West-ward Pharmaceutical Corp

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West-ward Pharmaceutical Corp Drugs

Cefuroxime

Cefuroxime

The intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only. Dosing reference to the intramuscular route of administration is for informational purposes only.

Dosage:

Adults:

The usual adult dosage range for Cefuroxime for Injection is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750-mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5-gram dose every 8 hours is recommended.

In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with Cefuroxime for Injection. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of Cefuroxime for Injection.

In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged.

For preventive use during open heart surgery, a 1.5-gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.

Impaired Renal Function:

A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism (see Table 4).
Table 4. Dosage of Cefuroxime for Injection in Adults With Reduced Renal Function * Since Cefuroxime for Injection is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis. Creatinine Clearance mL/min) Dose Frequency
>20
750 mg-1.5 grams q8h
10-20
750 mg q12h <10 750 mg q24h*
When only serum creatinine is available, the following formula4 (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: Creatinine clearance (mL/min) = Weight (kg) x (140 - age)72 x serum creatinine (mg/dL)
Females: 0.85 x male value

NOTE: As with antibiotic therapy in general, administration of Cefuroxime for Injection should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients Above 3 Months of Age:

Administration of 50 to 100 mg/kg/day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to cefuroxime. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

In bone and joint infections, 150 mg/kg/day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of Cefuroxime for Injection.

In cases of bacterial meningitis, a larger dosage of Cefuroxime for Injection is recommended, 200 to 240 mg/kg/day intravenously in divided doses every 6 to 8 hours.

In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

Preparation of Solution and Suspension:

The directions for preparing Cefuroxime for Injection, Pharmacy Bulk Package, are summarized in Table 5.
THIS PHARMACY BULK PACKAGE IS NOT TO BE DISPENSED AS A UNIT FOR DIRECT INFUSION
For Intravenous Use:

The 7.5 gram pharmacy bulk package should be reconstituted with 77 mL of Sterile Water for Injection; the constituted solution occupies a volume of about 82.5 mL and contains approximately 750 mg of cefuroxime per 8 mL. Not for direct infusion. Disperse aliquots from the vial via a suitable dispersing device into infusion fluids under a laminar flow hood using aseptic technique. DISCARD VIALS 4 HOURS AFTER INITIAL ENTRY. Color changes in solution do not affect potency.
Table 5. Preparation of Solution * 8 mL of solution contains 750 mg of cefuroxime; 16 mL of solution contains 1.5 grams of cefuroxime. Strength Amount of Diluent to Be Added (mL) Volume to be Withdrawn Approximate Cefuroxime Concentration (mg/mL) 7.5-gram Pharmacy Bulk Package 77 (IV) Amount Needed*
95

Administration:

After constitution, Cefuroxime for Injection may be given intravenously or intramuscularly. However, the intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only.

Intravenous Administration:

The IV route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending.

For intermittent IV Infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Cefuroxime for Injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For continuous IV infusion, a solution of Cefuroxime for Injection may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection.

Solutions of Cefuroxime for Injection, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

However, if concurrent therapy with Cefuroxime for Injection and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for Administration:
Suspend container from eyelet support. Remove protector from outlet port at bottom of container. Attach administration set. Refer to complete directions accompanying set.
Cefuroxime

Cefuroxime

Dosage:

Adults:

The usual adult dosage range for Cefuroxime for Injection is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750 mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5 gram dose every 8 hours is recommended.

In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with Cefuroxime for Injection. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of Cefuroxime for Injection.

In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged.

For preventive use during open heart surgery, a 1.5 gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.

Impaired Renal Function:

A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism (see Table 4).
Table 4. Dosage of Cefuroxime for Injection in Adults With Reduced Renal Function *
Since Cefuroxime for Injection is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis.
Creatinine Clearance mL/min) Dose Frequency > 20 750 mg - 1.5 grams q8h 10 - 20 750 mg q12h < 10 750 mg q24h*
When only serum creatinine is available, the following formula4 (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: Creatinine clearance (mL/min) =

Weight (kg) x (140 - age)72 x serum creatinine (mg/dL)

Females: 0.85 x male value

Note: As with antibiotic therapy in general, administration of Cefuroxime for Injection should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients Above 3 Months of Age:

Administration of 50 to 100 mg/kg/day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to cefuroxime. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

In bone and joint infections, 150 mg/kg/day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of Cefuroxime for Injection.

In cases of bacterial meningitis, a larger dosage of Cefuroxime for Injection is recommended, 200 to 240 mg/kg/day intravenously in divided doses every 6 to 8 hours.

In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

Preparation of Solution and Suspension:

The directions for preparing Cefuroxime for Injection for both IV and IM use are summarized in Table 5.

For Intramuscular Use:

Each 750-mg vial of Cefuroxime for Injection should be constituted with 3 mL of Sterile Water for Injection. Shake gently to disperse and withdraw completely the resulting suspension for injection.

For Intravenous Use:

Each 750-mg vial should be constituted with 8.3 mL of Sterile Water for Injection. Withdraw completely the resulting solution for injection.

Each 1.5-gram vial should be constituted with 16 mL of Sterile Water for Injection, and the solution should be completely withdrawn for injection.
Table 5. Preparation of Solution * Note: Cefuroxime for Injection is a suspension at IM concentrations. Strength Amount of Diluent to be Added (mL) Volume to be Withdrawn Approximate Cefuroxime Concentration (mg/mL) 750-mg Vial 3 (IM) Total* 225 750-mg Vial 8.3 (IV) Total 90 1.5-gram Vial 16.0 (IV) Total
90

Administration:

After constitution, Cefuroxime for Injection may be given intravenously or by deep IM injection into a large muscle mass (such as the gluteus or lateral part of the thigh). Before injecting intramuscularly, aspiration is necessary to avoid inadvertent injection into a blood vessel.

Intravenous Administration:

The IV route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending.

For direct intermittent IV administration, slowly inject the solution into a vein over a period of 3 to 5 minutes or give it through the tubing system by which the patient is also receiving other IV solutions.

For direct intermittent IV infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Cefuroxime for Injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For continuous IV infusion, a solution of Cefuroxime for Injection may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection.

Solutions of Cefuroxime for Injection, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

However, if concurrent therapy with Cefuroxime for Injection and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Caution:

Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for Administration:

1. Suspend container from eyelet support.

2. Remove protector from outlet port at bottom of container.

3. Attach administration set. Refer to complete directions accompanying set.
Bumetanide

Bumetanide

Dosage should be individualized with careful monitoring of patient response.

Parenteral Administration

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

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

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

Miscibility and Parenteral Solutions

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

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

Sun Block Sprary

2.1           Hypertension

Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect.

Use with diuretics in adultsIf blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of lisinopril tablets.

The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.

Pediatric Patients 6 years of age and older with hypertension

For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m2, the recommended starting dose is 0.07 mg per kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology (12.3)].

Lisinopril tablets are not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2 [see Use in Specific Populations (8.4) and Clinical Studies (14.1)].

2.2           Heart Failure

The recommended starting dose for lisinopril tablets, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.

Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension [see Warnings and Precautions (5.4), and Drug Interactions (7.1)]. The appearance of hypotension after the initial dose of lisinopril tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

2.3           Reduction of Mortality in Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give lisinopril tablets 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least six weeks.

Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mmHg) during the first 3 days after the infarct [see Warnings and Precautions (5.4)]. If hypotension occurs (systolic blood pressure ≤ 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) lisinopril tablets should be withdrawn.

2.4           Dose in Patients with Renal Impairment

No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril tablets to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2.5 mg. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Sodium Ferric Gluconate...

Sodium Ferric Gluconate Complex In Sucrose

The dosage of sodium ferric gluconate complex in sucrose injection is expressed in terms of mg of elemental iron. Each 5 mL sterile, single dose vial contains 62.5 mg of elemental iron (12.5 mg/mL).

Do not mix sodium ferric gluconate complex in sucrose injection with other medications, or add to parenteral nutrition solutions for intravenous infusion. The compatibility of sodium ferric gluconate complex in sucrose injection with intravenous infusion vehicles other than 0.9% sodium chloride has not been evaluated. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever the solution and container permit. If diluted, use immediately.

Sodium ferric gluconate complex in sucrose injection treatment may be repeated if iron deficiency reoccurs.

2.1 Adult Dosage and Administration

The recommended dosage of sodium ferric gluconate complex in sucrose injection for the repletion treatment of iron deficiency in hemodialysis patients is 10 mL of sodium ferric gluconate complex in sucrose injection (125 mg of elemental iron). Sodium ferric gluconate complex in sucrose injection may be diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session. Sodium ferric gluconate complex in sucrose injection may also be administered undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session. For repletion treatment most patients may require a cumulative dose of 1000 mg of elemental iron administered over 8 dialysis sessions. Sodium ferric gluconate complex in sucrose injection has been administered at sequential dialysis sessions by infusion or by slow intravenous injection during the dialysis session itself.

Data from sodium ferric gluconate complex in sucrose injection postmarketing spontaneous reports indicate that individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events [see Adverse Reactions (6.2)].

2.2 Pediatric Dosage and Administration

The recommended pediatric dosage of sodium ferric gluconate complex in sucrose injection for the repletion treatment of iron deficiency in hemodialysis patients is 0.12 mL/kg sodium ferric gluconate complex in sucrose injection (1.5 mg/kg of elemental iron) diluted in 25 mL 0.9% sodium chloride and administered by intravenous infusion over 1 hour per dialysis session. The maximum dosage should not exceed 125 mg per dose.
Folic Acid

Folic Acid

Oral administration is preferred. Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid given orally. Parenteral administration is not advocated but may be necessary in some individuals (e.g., patients receiving parenteral or enteral alimentation). Doses greater than 0.1 mg should not be used unless anemia due to vitamin B12 deficiency has been ruled out or is being adequately treated with cobalamin. Daily doses greater than 1 mg do not enhance the hematologic effect, and most of the excess is excreted unchanged in the urine.

The usual therapeutic dosage in adults and children (regardless of age) is up to 1 mg daily. Resistant cases may require larger doses.

When clinical symptoms have subsided and the blood picture has become normal, a daily maintenance level should be used, e.g., 0.1 mg for infants and up to 0.3 mg for children under 4 years of age, 0.4 mg for adults and children 4 or more years of age, and 0.8 mg for pregnant and lactating women, but never less than 0.1 mg/day. Patients should be kept under close supervision and adjustment of maintenance level made if relapse appears imminent.

In the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection, the maintenance level may need to be increased.
Ondansetron

Ondansetron

Prevention of Chemotherapy-Induced Nausea and Vomiting:

Adult Dosing: The recommended I.V dosage of ondansetron injection, USP for adults is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. The recommended infusion rate should not be exceeded (see OVERDOSAGE).

With the three-dose (0.15 mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron injection, USP.

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

Vial: DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron injection, USP should be diluted in 50 mL of 5% dextrose injection or 0.9% sodium chloride injection before administration.

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

Dosing information for pediatric cancer patients 6 months to 48 months of age is approved for GlaxoSmithKline Corporation's ondansetron injection. However, due to GlaxoSmithKline's marketing exclusivity rights, this drug product is not labeled for use in this subpopulation of pediatric patients.

Vial: DILUTE BEFORE USE. Ondansetron injection, USP should be diluted in 50 mL of 5% dextrose injection or 0.9% sodium chloride injection before administration.

Geriatric Dosing: The dosage recommendation is the same as for the general population.

Prevention of Postoperative Nausea and Vomiting:

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

Vial: REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

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

Dosing information for pediatric surgical patients 1 month to 24 months of age is approved for Glaxo SmithKline Corporation's ondansetron injection. However, due to GlaxoSmithKline's marketing exclusivity rights, this drug product is not labeled for use in this subpopulation of pediatric patients.

Vial: REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Geriatric Dosing: The dosage recommendation is the same as for the general population.

Dosage Adjustment for Patients with Impaired Renal Function: The dosage recommendation is the same as for the general population. There is no experience beyond the first-day administration of ondansetron.

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

Stability: Ondansetron injection, USP is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following I.V. fluids: 0.9% sodium chloride injection, 5 % dextrose injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection, and 3% sodium chloride injection.

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

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

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

HOW SUPPLIED

ONDANSETRON INJECTION. USP, 2 mg/mL, is supplied as follows:
NDC 62778-027-01 2-mL single-dose vials (Carton of 5) NDC 62778-028-01 20-mL multidose vial (Carton of 1)
Store between 20° and 25°C (68° and 77°F). [See USP Controlled Room Temperature]. Protect from light.

REFERENCES:
Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit J Surg. 1973;60:646-649. Villikka K, Kivisto KT, Neuvonen PJ. The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999;65:377-381. De Witte JL. Schoenmaekers B, Sessler DI, et al. AnesthAnalg. 2001;92:1319-1321. Arcioni R, della Rocca M, RomanÒ R, et al. Anesth Analg. 2002;94:1553-1557.
Manufactured by:

HIKMA FARMACêUTICA (PORTUGAL), S.A.Estrada do Rio da MÒ, n0 8, 8A e 8B - Fervenca,2705 - 906 Terrugem SNTPORTUGAL

for:

WEST-WARD PHARMACEUTICAL Corp.465 Industrial Way WestEATONTOWN NJ 07724USA

Iss.: Sept.2006
Isosorbide Dinitrate

Isosorbide Dinitrate

As noted under CLINICAL PHARMACOLOGY multiple-dose studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for isosorbide dinitrate tablets must provide a daily dose-free interval to minimize the development of this tolerance. With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hours long.

As also noted under CLINICAL PHARMACOLOGY, the effects of the second and later doses have been smaller and shorter-lasting than the effects of the first.

Large controlled studies with other nitrates suggest that no dosing regimen with isosorbide dinitrate oral tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.

As with all titratable drugs, it is important to administer the minimum dose which produces the desired clinical effect. The usual starting dose of isosorbide dinitrate tablets is 5 mg to 40 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen.
Amoxicillin

Amoxicillin

Amoxicillin capsules may be given without regard to meals. However, food effect studies have not been performed with the 500 mg formulation.

Neonates and infants aged ≤ 12 weeks (≤ 3 months):

Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin is 30 mg/kg/day divided q12h.
Adults and pediatric patients >3 months:
* Dosing for infections caused by less susceptible organisms should follow the recommendations for severe infections.

† The children's dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations.
Infection Severity* Usual Usual Dose Adult Dose for Children >3 months† Ear/nose/throat Mild/Moderate 500 mg 25 mg/kg/day every 12 hours in divided doses or every 12 hours 250 mg or every 8 hours 20 mg/kg/day in divided doses every 8 hours Severe 875 mg 45 mg/kg/day every 12 hours in divided doses or every 12 hours 500 mg or every 8 hours 40 mg/kg/day in divided doses every 8 hours Lower respiratory Mild/Moderate 875 mg 45 mg/kg/day Tract or Severe every 12 hours in divided doses or every 12 hours 500 mg every or 8 hours 40 mg/kg/day in divided doses every 8 hours Skin/Skin Mild/Moderate 500 mg 25 mg/kg/day Structure every 12 hours in divided doses or every 12 hours 250 mg every or 8 hours 20 mg/kg/day in divided doses every 8 hours Severe 875 mg 45 mg/kg/day every 12 hours in divided doses or every 12 hours 500 mg every or 8 hours 40 mg/kg/day in divided doses every 8 hours Genitourinary Mild/Moderate 500 mg 25 mg/kg/day Tract every 12 hours in divided doses or every 12 hours 250 mg every or 8 hours 20 mg/kg/day in divided doses every 8 hours Severe 875 mg 45 mg/kg/day every 12 hours in divided doses or every 12 hours 500 mg or every 8 hours 40 mg/kg/day in divided doses every 8 hours Gonorrhea 3 grams Prepubertal Acute, as children: uncomplicated single oral dose 50 mg/kg ano-genital and amoxicillin combined with 25 mg/kg probenecid urethral infections as a single dose. in males and NOTE: SINCE females PROBENECID IS CONTRAINDICATED IN CHILDREN UNDER 2 YEARS. DO NOT USE THIS REGIMEN IN THESE CASES.
All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS - Laboratory Tests.)

Larger doses may be required for stubborn or severe infections.

General: It should be recognized that in the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisals are necessary. Smaller doses than those recommended above should not be used. Even higher doses may be needed at times. 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. Except for gonorrhea, treatment 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. It is recommended that there be at least 10 days' treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever.

H. pylori eradication to reduce the risk of duodenal ulcer recurrence:

Triple therapy: Amoxicillin/clarithromycin/lansoprazole

The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (q12h) for 14 days. (See INDICATIONS AND USAGE.)

Dual therapy: Amoxicillin/lansoprazole

The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (q8h) for 14 days. (See INDICATIONS AND USAGE.)

Please refer to clarithromycin and lansoprazole full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally impaired patients.

Dosing recommendations for adults with impaired renal function: Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of <30 mL/min. should not receive the 875-mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/minute glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

There are currently no dosing recommendations for pediatric patients with impaired renal function.
Hydrocortisone

Hydrocortisone

For oral administration

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.

The initial dosage varies from 20 to 240 mg a day depending on the disease being treated. In less severe diseases doses lower than 20 mg may suffice, while in severe diseases doses higher than 240 mg may be required. The initial dosage should be maintained or adjusted until the patient's response is satisfactory. If satisfactory clinical response does not occur after a reasonable period of time, discontinue hydrocortisone tablets and transfer the patient to other therapy.

After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response.

Patients should be observed closely for signs that might require adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.

If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.
Rosiglitazone Maleate

Rosiglitazone Maleate

The management of antidiabetic therapy should be individualized. All patients should start rosiglitazone maleate tablets at the lowest recommended dose. Further increases in the dose of rosiglitazone maleate tablets should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning and Warnings and Precautions (5.1) ].

Rosiglitazone maleate tablets may be administered at a starting dose of 4 mg either as a single daily dose or in 2 divided doses. For patients who respond inadequately following 8 to 12 weeks of treatment, as determined by reduction in fasting plasma glucose (FPG), the dose may be increased to 8 mg daily as monotherapy or in combination with metformin, sulfonylurea, or sulfonylurea plus metformin. Reductions in glycemic parameters by dose and regimen are described under Clinical Studies (14.1) . Rosiglitazone maleate tablets may be taken with or without food.

The total daily dose of rosiglitazone maleate tablets should not exceed 8 mg.

2.1 Monotherapy

The usual starting dose of rosiglitazone maleate tablets is 4 mg administered either as a single dose once daily or in divided doses twice daily. In clinical trials, the 4-mg twice-daily regimen resulted in the greatest reduction in FPG and hemoglobin A1c (HbA1c).

2.2 Combination With Sulfonylurea or Metformin

When rosiglitazone maleate tablets is added to existing therapy, the current dose(s) of the agent(s) can be continued upon initiation of therapy with rosiglitazone maleate tablets.

Sulfonylurea

When used in combination with sulfonylurea, the usual starting dose of Rosiglitazone maleate is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin

The usual starting dose of Rosiglitazone Maleate in combination with metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with Rosiglitazone Maleate.

2.3 Combination With Sulfonylurea Plus Metformin

The usual starting dose of rosiglitazone maleate tablets in combination with a sulfonylurea plus metformin is 4 mg administered as either a single dose once daily or divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

2.4 Specific Patient Populations

Renal Impairment

No dosage adjustment is necessary when Rosiglitazone maleate is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and Rosiglitazone maleate is also contraindicated in patients with renal impairment.

Hepatic Impairment

Liver enzymes should be measured prior to initiating treatment with rosiglitazone maleate. Therapy with rosiglitazone maleateshould not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy). After initiation of rosiglitazone maleate, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) .]

Pediatric

Data are insufficient to recommend pediatric use of rosiglitazone maleate [see Use in Specific Populations (8.4 )].

2.1 Monotherapy

The usual starting dose of rosiglitazone maleate tablets is 4 mg administered either as a single dose once daily or in divided doses twice daily. In clinical trials, the 4-mg twice-daily regimen resulted in the greatest reduction in FPG and hemoglobin A1c (HbA1c).

2.2 Combination With Sulfonylurea or Metformin

When rosiglitazone maleate tablets is added to existing therapy, the current dose(s) of the agent(s) can be continued upon initiation of therapy with rosiglitazone maleate tablets.

Sulfonylurea

When used in combination with sulfonylurea, the usual starting dose of Rosiglitazone maleate is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin

The usual starting dose of Rosiglitazone Maleate in combination with metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with Rosiglitazone Maleate.

Sulfonylurea

When used in combination with sulfonylurea, the usual starting dose of Rosiglitazone maleate is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin

The usual starting dose of Rosiglitazone Maleate in combination with metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with Rosiglitazone Maleate.

2.3 Combination With Sulfonylurea Plus Metformin

The usual starting dose of rosiglitazone maleate tablets in combination with a sulfonylurea plus metformin is 4 mg administered as either a single dose once daily or divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

2.4 Specific Patient Populations

Renal Impairment

No dosage adjustment is necessary when Rosiglitazone maleate is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and Rosiglitazone maleate is also contraindicated in patients with renal impairment.

Hepatic Impairment

Liver enzymes should be measured prior to initiating treatment with rosiglitazone maleate. Therapy with rosiglitazone maleateshould not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy). After initiation of rosiglitazone maleate, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) .]

Pediatric

Data are insufficient to recommend pediatric use of rosiglitazone maleate [see Use in Specific Populations (8.4 )].

Renal Impairment

No dosage adjustment is necessary when Rosiglitazone maleate is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and Rosiglitazone maleate is also contraindicated in patients with renal impairment.

Hepatic Impairment

Liver enzymes should be measured prior to initiating treatment with rosiglitazone maleate. Therapy with rosiglitazone maleateshould not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy). After initiation of rosiglitazone maleate, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) .]

Pediatric

Data are insufficient to recommend pediatric use of rosiglitazone maleate [see Use in Specific Populations (8.4 )].
Chlorothiazide

Chlorothiazide

Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.

Adults

For Edema

The usual adult dosage is 500 mg to 1000 mg once or twice a day. Many patients with edema respond to intermittent therapy, i.e., administration on alternate days or on three to five days each week. With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.

For Control of Hypertension

The usual adult starting dosage is 500 mg to 1000 mg a day as a single or divided dose. Dosage is increased or decreased according to blood pressure response. Rarely some patients may require up to 2000 mg a day in divided doses.

Infants and Children

For Diuresis and For Control of Hypertension

The usual pediatric dosage is 5 to 10 mg per pound (10 to 20 mg/kg) per day in single or two divided doses, not to exceed 375 mg per day in infants up to 2 years of age or 1000 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 15 mg per pound (30 mg/kg) per day in two divided doses may be required.
Risperidone

Risperidone

2.1 Schizophrenia

Adults

Usual Initial Dose

RISPERIDONE can be administered once or twice daily. Initial dosing is generally 2 mg/day. Dose increases should then occur at intervals not less than 24 hours, in increments of 1 - 2 mg/day, as tolerated, to a recommended dose of 4 to 8 mg/day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 to 16 mg/day [see Clinical Studies (14.1)]. However, doses above 6 mg/day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are generally not recommended. In a single study supporting once-daily dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg/day has not been evaluated in clinical trials.

Maintenance Therapy

While it is unknown how long a patient with schizophrenia should remain on RISPERIDONE, the effectiveness of RISPERIDONE 2 mg/day to 8 mg/day at delaying relapse was demonstrated in a controlled trial in patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Patients should be periodically reassessed to determine the need for maintenance treatment with an appropriate dose.

Adolescents

Due to Janssen Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia. Dosage and administration information for pediatric patients with schizophrenia, 13 to 17 years of age, is approved for Janssen Pharmaceuticals Corporation's risperidone drug product.

Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that after an interval off RISPERIDONE, the initial titration schedule should be followed.

Switching From Other Antipsychotics

There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to RISPERIDONE, or treating patients with concomitant antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some schizophrenic patients, more gradual discontinuation may be most appropriate for others. The period of overlapping antipsychotic administration should be minimized. When switching schizophrenic patients from depot antipsychotics, initiate RISPERIDONE therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be re-evaluated periodically.

2.2 Bipolar Mania

Usual Dose

Adults

RISPERIDONE should be administered on a once-daily schedule, starting with 2 mg to 3 mg per day. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments/decrements of 1 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1 to 6 mg per day [see Clinical Studies (14.2, 14.3)]. RISPERIDONE doses higher than 6 mg per day were not studied.

Pediatrics

Due to Janssen Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with bipolar mania. Dosage and administration information for the treatment of pediatric patients with bipolar disorder is approved for Janssen Pharmaceuticals Corporation's risperidone drug products.

Maintenance Therapy

There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with RISPERIDONE. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of RISPERIDONE in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use RISPERIDONE for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)

Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with irritability associated with autistic disorder. Dosage and administration information for the treatment of pediatric patients with irritability associated with autistic disorder, 5 to 16 years of age, is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.

2.4 Dosage in Special Populations

The recommended initial dose is 0.5 mg twice daily in patients who are elderly or debilitated, patients with severe renal or hepatic impairment, and patients either predisposed to hypotension or for whom hypotension would pose a risk. Dosage increases in these patients should be in increments of no more than 0.5 mg twice daily. Increases to dosages above 1.5 mg twice daily should generally occur at intervals of at least 1 week. In some patients, slower titration may be medically appropriate.

Elderly or debilitated patients, and patients with renal impairment, may have less ability to eliminate RISPERIDONE than normal adults. Patients with impaired hepatic function may have increases in the free fraction of risperidone, possibly resulting in an enhanced effect [see CLINICAL PHARMACOLOGY (12.3)]. Patients with a predisposition to hypotensive reactions or for whom such reactions would pose a particular risk likewise need to be titrated cautiously and carefully monitored [see WARNINGS AND PRECAUTIONS (5.2, 5.7, 5.16)]. If a once-daily dosing regimen in the elderly or debilitated patient is being considered, it is recommended that the patient be titrated on a twice-daily regimen for 2 to 3 days at the target dose. Subsequent switches to a once-daily dosing regimen can be done thereafter.

2.5 Co-Administration of RISPERIDONE with Certain Other Medications

Co-administration of carbamazepine and other enzyme inducers (e.g., phenytoin, rifampin, phenobarbital) with RISPERIDONE would be expected to cause decreases in the plasma concentrations of the sum of risperidone and 9-hydroxyrisperidone combined, which could lead to decreased efficacy of RISPERIDONE treatment. The dose of RISPERIDONE needs to be titrated accordingly for patients receiving these enzyme inducers, especially during initiation or discontinuation of therapy with these inducers [see Drug Interactions (7.11)].

Fluoxetine and paroxetine have been shown to increase the plasma concentration of risperidone 2.5-2.8 fold and 3-9 fold, respectively. Fluoxetine did not affect the plasma concentration of 9-hydroxyrisperidone. Paroxetine lowered the concentration of 9-hydroxyrisperidone by about 10%. The dose of RISPERIDONE needs to be titrated accordingly when fluoxetine or paroxetine is co-administered [see Drug Interactions (7.10)].
Promethazine Hydrochlor...

Promethazine Hydrochloride

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Cefuroxime

Dosage:

Adults:

The usual adult dosage range for Cefuroxime for Injection is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750 mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5 gram dose every 8 hours is recommended.

In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with Cefuroxime for Injection. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of Cefuroxime for Injection.

In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged.

For preventive use during open heart surgery, a 1.5 gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.

Impaired Renal Function:

A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism (see Table 4).
Table 4. Dosage of Cefuroxime for Injection in Adults With Reduced Renal Function *
Since Cefuroxime for Injection is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis.
Creatinine Clearance mL/min) Dose Frequency > 20 750 mg - 1.5 grams q8h 10 - 20 750 mg q12h < 10 750 mg q24h*
When only serum creatinine is available, the following formula4 (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: Creatinine clearance (mL/min) =

Weight (kg) x (140 - age)72 x serum creatinine (mg/dL)

Females: 0.85 x male value

Note: As with antibiotic therapy in general, administration of Cefuroxime for Injection should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients Above 3 Months of Age:

Administration of 50 to 100 mg/kg/day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to cefuroxime. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

In bone and joint infections, 150 mg/kg/day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of Cefuroxime for Injection.

In cases of bacterial meningitis, a larger dosage of Cefuroxime for Injection is recommended, 200 to 240 mg/kg/day intravenously in divided doses every 6 to 8 hours.

In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

Preparation of Solution and Suspension:

The directions for preparing Cefuroxime for Injection for both IV and IM use are summarized in Table 5.

For Intramuscular Use:

Each 750-mg vial of Cefuroxime for Injection should be constituted with 3 mL of Sterile Water for Injection. Shake gently to disperse and withdraw completely the resulting suspension for injection.

For Intravenous Use:

Each 750-mg vial should be constituted with 8.3 mL of Sterile Water for Injection. Withdraw completely the resulting solution for injection.

Each 1.5-gram vial should be constituted with 16 mL of Sterile Water for Injection, and the solution should be completely withdrawn for injection.
Table 5. Preparation of Solution * Note: Cefuroxime for Injection is a suspension at IM concentrations. Strength Amount of Diluent to be Added (mL) Volume to be Withdrawn Approximate Cefuroxime Concentration (mg/mL) 750-mg Vial 3 (IM) Total*
225
750-mg Vial 8.3 (IV) Total
90
1.5-gram Vial 16.0 (IV)
Total

90

Administration:

After constitution, Cefuroxime for Injection may be given intravenously or by deep IM injection into a large muscle mass (such as the gluteus or lateral part of the thigh). Before injecting intramuscularly, aspiration is necessary to avoid inadvertent injection into a blood vessel.

Intravenous Administration:

The IV route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending.

For direct intermittent IV administration, slowly inject the solution into a vein over a period of 3 to 5 minutes or give it through the tubing system by which the patient is also receiving other IV solutions.

For direct intermittent IV infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Cefuroxime for Injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For continuous IV infusion, a solution of Cefuroxime for Injection may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection.

Solutions of Cefuroxime for Injection, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

However, if concurrent therapy with Cefuroxime for Injection and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Caution:

Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for Administration:

1. Suspend container from eyelet support.

2. Remove protector from outlet port at bottom of container.

3. Attach administration set. Refer to complete directions accompanying set.
Cefuroxime

Cefuroxime

The intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only. Dosing reference to the intramuscular route of administration is for informational purposes only.

Dosage:

Adults:

The usual adult dosage range for Cefuroxime for Injection is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750-mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5-gram dose every 8 hours is recommended.

In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with Cefuroxime for Injection. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of Cefuroxime for Injection.

In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged.

For preventive use during open heart surgery, a 1.5-gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.

Impaired Renal Function:

A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism (see Table 4).
Table 4. Dosage of Cefuroxime for Injection in Adults With Reduced Renal Function * Since Cefuroxime for Injection is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis. Creatinine Clearance mL/min) Dose Frequency
>20
750 mg-1.5 grams q8h
10-20
750 mg q12h <10 750 mg q24h*
When only serum creatinine is available, the following formula4 (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: Creatinine clearance (mL/min) = Weight (kg) x (140 - age)72 x serum creatinine (mg/dL)
Females: 0.85 x male value

NOTE: As with antibiotic therapy in general, administration of Cefuroxime for Injection should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients Above 3 Months of Age:

Administration of 50 to 100 mg/kg/day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to cefuroxime. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

In bone and joint infections, 150 mg/kg/day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of Cefuroxime for Injection.

In cases of bacterial meningitis, a larger dosage of Cefuroxime for Injection is recommended, 200 to 240 mg/kg/day intravenously in divided doses every 6 to 8 hours.

In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

Preparation of Solution and Suspension:

The directions for preparing Cefuroxime for Injection, Pharmacy Bulk Package, are summarized in Table 5.
THIS PHARMACY BULK PACKAGE IS NOT TO BE DISPENSED AS A UNIT FOR DIRECT INFUSION
For Intravenous Use:

The 7.5 gram pharmacy bulk package should be reconstituted with 77 mL of Sterile Water for Injection; the constituted solution occupies a volume of about 82.5 mL and contains approximately 750 mg of cefuroxime per 8 mL. Not for direct infusion. Disperse aliquots from the vial via a suitable dispersing device into infusion fluids under a laminar flow hood using aseptic technique. DISCARD VIALS 4 HOURS AFTER INITIAL ENTRY. Color changes in solution do not affect potency.
Table 5. Preparation of Solution * 8 mL of solution contains 750 mg of cefuroxime; 16 mL of solution contains 1.5 grams of cefuroxime. Strength Amount of Diluent to Be Added (mL) Volume to Be Withdrawn Approximate Cefuroxime Concentration (mg/mL) 7.5 gram Pharmacy Bulk Package 77 (IV) Amount Needed*
95

Administration:

After constitution, Cefuroxime for Injection may be given intravenously or intramuscularly. However, the intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only.

Intravenous Administration:

The IV route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending.

For intermittent IV Infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Cefuroxime for Injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For continuous IV infusion, a solution of Cefuroxime for Injection may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection.

Solutions of Cefuroxime for Injection, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

However, if concurrent therapy with Cefuroxime for Injection and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for Administration:
Suspend container from eyelet support. Remove protector from outlet port at bottom of container. Attach administration set. Refer to complete directions accompanying set.
Metronidazole

Metronidazole

In elderly patients the pharmacokinetics of metronidazole may be altered and therefore monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Treatment of Anaerobic Infections

The recommended dosage schedule for adults is:

Loading Dose: 15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult). Maintenance Dose: 7.5 mg/kg infused over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose.

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

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

Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously. Close monitoring of plasma metronidazole levels2 and toxicity is recommended.

In patients receiving Metronidazole Injection, USP in whom gastric secretions are continuously removed by nasogastric aspiration, sufficient metronidazole may be removed in the aspirate to cause a reduction in serum levels.

The dose of Metronidazole Injection, USP should not be specifically reduced in anuric patients since accumulated metabolites may be rapidly removed by dialysis.

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

Prophylaxis

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

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

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

Ondansetron Hydrochloride And Dextrose

Prevention of Chemotherapy-Induced Nausea and Vomiting:

Adult Dosing:

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

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

Flexible Plastic Container:  REQUIRES NO DILUTION. Ondansetron in 5 % Dextrose Injection, 32 mg in 50 mL.

Pediatric Dosing:

On the basis of the available information (see CLINICAL TRIALS: Pediatric Studies and CLINICAL PHARMACOLOGY: Pharmacokinetics), the dosage in pediatric cancer patients 4 to 18 years of age should be three 0.15-mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy, subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron in 5 % Dextrose Injection. The drug should be infused intravenously over 15 minutes. Little information is available about dosage in pediatric cancer patients younger than 6 months of age.

Dosing information for pediatric cancer patients 6 months to 48 months of age is approved for GlaxoSmithKline Corporation’s ondansetron injection. However, due to GlaxoSmithKline’s marketing exclusivity rights, this drug product is not labeled for use in this subpopulation of pediatric patients.

Flexible Plastic Container:  REQUIRES NO DILUTION. Ondansetron in 5 % Dextrose Injection, 32 mg in 50 mL.

Geriatric Dosing:

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

Dosage Adjustment for Patients With Impaired Renal Function:

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

Dosage Adjustment for Patients With Impaired Hepatic Function:

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

Ondansetron in 5 % Dextrose Injection in Flexible Plastic Containers: Instructions for Use:

To Open: Tear outer wrap at notch and remove solution container. Check for minute leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.

Preparation for Administration:  Use aseptic technique.

1.       Close flow control clamp of administration set.

2.       Remove cover from outlet port at bottom of container.

3.       Insert piercing pin of administration set into port with a twisting motion until the pin

      is firmly seated. NOTE: See full directions on administration set carton.

4.       Suspend container from hanger.

5.       Squeeze and release drip chamber to establish proper fluid level in chamber during

      infusion of Ondansetron in 5 % Dextrose Injection.

6.       Open flow control clamp to expel air from set. Close clamp.

7.       Attach set to venipuncture device. If device is not indwelling, prime and make

      venipuncture.

8.       Perform venipuncture.

9.       Regulate rate of administration with flow control clamp.

Caution: Ondansetron in 5 % Dextrose Injection in flexible plastic containers is to be administered by I.V. drip infusion only. Ondansetron in 5 % Dextrose Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form. If used with a primary I.V. fluid system, the primary solution should be discontinued during ondansetron in 5 % Dextrose Injection. Do not administer unless solution is clear and container is undamaged.

Warning:  Do not use flexible plastic container in series connections.

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

Trihexyphenidyl Hydrochloride

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether trihexyphenidyl HCl may best be given before or after meals should be determined by the way the patient reacts. Postencephalitic patients, who are usually more prone to excessive salivation, may prefer to take it after meals and may, in addition, require small amounts of atropine which, under such circumstances, is sometimes an effective adjuvant. If trihexyphenidyl HCl tends to dry the mouth excessively, it may be better to take it before meals, unless it causes nausea. If taken after meals, the thirst sometimes induced can be allayed by mint candies, chewing gum or water.

Trihexyphenidyl HCl in Idiopathic Parkinsonism

As initial therapy for parkinsonism, 1 mg of trihexyphenidyl HCl may be administered the first day. The dose may then be increased by 2 mg increments at intervals of three to five days, until a total of 6 to 10 mg is given daily. The total daily dose will depend upon what is found to be the optimal level. Many patients derive maximum benefit from this daily total of 6 to 10 mg, but some patients, chiefly those in the postencephalitic group, may require a total daily dose of 12 to 15 mg.

Trihexyphenidyl HCl in Drug-Induced Parkinsonism

The size and frequency of dose of trihexyphenidyl HCl needed to control extrapyramidal reactions to commonly employed tranquilizers, notably the phenothiazines, thioxanthenes, and butyrophenones, must be determined empirically. The total daily dosage usually ranges between 5 and 15 mg, although, in some cases, these reactions have been satisfactorily controlled on as little as 1 mg daily. It may be advisable to commence therapy with a single 1 mg dose. If the extrapyramidal manifestations are not controlled in a few hours, the subsequent doses may be progressively increased until satisfactory control is achieved. Satisfactory control may sometimes be more rapidly achieved by temporarily reducing the dosage of the tranquilizer on instituting trihexyphenidyl HCl therapy and then adjusting dosage of both drugs until the desired ataractic effect is retained without onset of extrapyramidal reactions.

It is sometimes possible to maintain the patient on a reduced trihexyphenidyl HCl dosage after the reactions have remained under control for several days. Instances have been reported in which these reactions have remained in remission for long periods after trihexyphenidyl HCl therapy was discontinued.

Concomitant Use of Trihexyphenidyl HCl with Levodopa

When trihexyphenidyl HCl is used concomitantly with levodopa, the usual dose of each may need to be reduced. Careful adjustment is necessary, depending on side effects and degree of symptom control. Trihexyphenidyl HCl dosage of 3 to 6 mg daily, in divided doses, is usually adequate.

Concomitant Use of Trihexyphenidyl HCl with Other Parasympathetic Inhibitors

Trihexyphenidyl HCl may be substituted, in whole or in part, for other parasympathetic inhibitors. The usual technique is partial substitution initially, with progressive reduction in the other medication as the dose of trihexyphenidyl HCl is increased.

The total daily intake of trihexyphenidyl HCl tablets is tolerated best if divided into 3 doses and taken at mealtimes. High doses (>10 mg daily) may be divided into 4 parts, with 3 doses administered at mealtimes and the fourth at bedtime.

Trihexyphenidyl HCl in Idiopathic Parkinsonism

As initial therapy for parkinsonism, 1 mg of trihexyphenidyl HCl may be administered the first day. The dose may then be increased by 2 mg increments at intervals of three to five days, until a total of 6 to 10 mg is given daily. The total daily dose will depend upon what is found to be the optimal level. Many patients derive maximum benefit from this daily total of 6 to 10 mg, but some patients, chiefly those in the postencephalitic group, may require a total daily dose of 12 to 15 mg.

Trihexyphenidyl HCl in Drug-Induced Parkinsonism

The size and frequency of dose of trihexyphenidyl HCl needed to control extrapyramidal reactions to commonly employed tranquilizers, notably the phenothiazines, thioxanthenes, and butyrophenones, must be determined empirically. The total daily dosage usually ranges between 5 and 15 mg, although, in some cases, these reactions have been satisfactorily controlled on as little as 1 mg daily. It may be advisable to commence therapy with a single 1 mg dose. If the extrapyramidal manifestations are not controlled in a few hours, the subsequent doses may be progressively increased until satisfactory control is achieved. Satisfactory control may sometimes be more rapidly achieved by temporarily reducing the dosage of the tranquilizer on instituting trihexyphenidyl HCl therapy and then adjusting dosage of both drugs until the desired ataractic effect is retained without onset of extrapyramidal reactions.

It is sometimes possible to maintain the patient on a reduced trihexyphenidyl HCl dosage after the reactions have remained under control for several days. Instances have been reported in which these reactions have remained in remission for long periods after trihexyphenidyl HCl therapy was discontinued.

Concomitant Use of Trihexyphenidyl HCl with Levodopa

When trihexyphenidyl HCl is used concomitantly with levodopa, the usual dose of each may need to be reduced. Careful adjustment is necessary, depending on side effects and degree of symptom control. Trihexyphenidyl HCl dosage of 3 to 6 mg daily, in divided doses, is usually adequate.

Concomitant Use of Trihexyphenidyl HCl with Other Parasympathetic Inhibitors

Trihexyphenidyl HCl may be substituted, in whole or in part, for other parasympathetic inhibitors. The usual technique is partial substitution initially, with progressive reduction in the other medication as the dose of trihexyphenidyl HCl is increased.

The total daily intake of trihexyphenidyl HCl tablets is tolerated best if divided into 3 doses and taken at mealtimes. High doses (>10 mg daily) may be divided into 4 parts, with 3 doses administered at mealtimes and the fourth at bedtime.
Amoxicillin

Amoxicillin

2.1 Dosing for Adult and Pediatric Patients > 3Months of Age

Except for gonorrhea, treatment 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. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some 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.

2.2 Dosing in Neonates and Infants Aged 12 Weeks ( 3 Months)

Treatment 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. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple therapy: The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days.

Dual therapy: The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.

Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min. should not receive a 875-mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
Butorphanol Tartrate

Butorphanol Tartrate

Factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and surgical procedure involved. Use in the elderly, in patients with hepatic or renal disease, or in labor requires extra caution (see PRECAUTIONS section and CLINICAL PHARMACOLOGY: Individualization of Dosage section). The following doses are for patients who do not have impaired hepatic or renal function and who are not on CNS active agents.

Use for Pain

Butorphanol Tartrate Injection

Intravenous: The usual recommended single dose for IV administration is 1 mg repeated every 3 to 4 hours as necessary. The effective dosage range, depending on the severity of pain, is 0.5 to 2 mg repeated every 3 to 4 hours.

Intramuscular: The usual recommended single dose for IM administration is 2 mg in patients who will be able to remain recumbent, in the event drowsiness or dizziness occurs. This may be repeated every 3 to 4 hours, as necessary. The effective dosage range depending on the severity of pain is 1 to 4 mg repeated every 3 to 4 hours. There are insufficient clinical data to recommend single doses above 4 mg.

Use as Preoperative/Preanesthetic Medication

The preoperative medication dosage of butorphanol tartrate injection should be individualized (see CLINICAL PHARMACOLOGY: Individualization of Dosage section). The usual adult dose is 2 mg IM, administered 60 to 90 minutes before surgery. This is approximately equivalent in sedative effect to 10 mg morphine or 80 mg meperidine.

Use in Balanced Anesthesia

The usual dose of butorphanol tartrate injection is 2 mg IV shortly before induction and/or 0.5 to 1.0 mg IV in increments during anesthesia. The increment may be higher, up to 0.06 mg/kg (4 mg/70 kg), depending on previous sedative, analgesic, and hypnotic drugs administered. The total dose of butorphanol tartrate injection will vary; however, patients seldom require less than 4 mg or more than 12.5 mg (approximately 0.06 to 0.18 mg/kg).

Labor

In patients at full term in early labor a 1 to 2 mg dose of butorphanol tartrate injection IV or IM may be administered and repeated after 4 hours. Alternative analgesia should be used for pain associated with delivery or if delivery is expected to occur within 4 hours.

If concomitant use of butorphanol tartrate injection with drugs that may potentiate its effects is deemed necessary (see PRECAUTIONS: Drug Interactions), the lowest effective dose should be employed.

Safety and Handling

Butorphanol tartrate injection is supplied in sealed delivery systems that have a low risk of accidental exposure to health care workers. Ordinary care should be taken to avoid aerosol generation while preparing a syringe for use. Following skin contact, rinsing with cool water is recommended.

The disposal of Schedule IV controlled substances must be consistent with State and Federal Regulations.
Cefoxitin

Cefoxitin

The intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only.

TREATMENT

Adults

The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 1 for dosage guidelines).

If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.

Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:

In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 2) may be used as a guide.

When only the serum creatinine level 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 (mg/100 mL)

Females         =             0.85 x male value

In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 2.

Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients

The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.

At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).

In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 2).

PREVENTION

Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.

For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:

Adults:

2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.

Pediatric Patients (3 months and older):

30 to 40 mg/kg doses may be given at the times designated above.

Cesarean section patients:

For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3-dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 1: Guidelines for Dosage of Cefoxitin for Injection   Type of Infection   Daily Dosage   Frequency and Route * Including patients in whom bacteremia is absent or unlikely.   Uncomplicated forms* of infections such as pneumonia, urinary tract infection, cutaneous infection   3-4 grams   1 gram every 6-8 hours IV   Moderately severe or severe infections   6-8 grams   1 gram every 4 hoursor 2 grams every 6-8 hours IV   Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)   12 grams   2 grams every 4 hoursor 3 grams every 6 hours IV Table 2: Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function   Renal Function   Creatinine Clearance(mL/min)   Dose(grams)   Frequency   Mild impairment   50-30   1-2   every 8-12 hours   Moderate impairment   29-10   1-2   every 12-24 hours   Severe impairment   9-5   0.5-1   every 12-24 hours   Essentially no function   <5   0.5-1   every 24-48 hours Table 3: Preparation of Solution for Intravenous Administration   Strength   Amount of Diluent to be Added (mL)*   Approximate Withdrawable Volume (mL)   Approximate Average Concentration (mg/mL) * Shake to dissolve and let stand until clear. 10 grams Pharmacy Bulk Package 43 or 93 49 or 98.5   200 or 100
DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE BOTTLE - NOT FOR DIRECT INFUSION

For Bulk Packages

The Pharmacy Bulk Package bottle is for use in a pharmacy admixture service under a laminar flow hood. Penetration into the Pharmacy Bulk Package bottle should be made only one time after reconstitution with a sterile transfer set or other sterile dispensing device, which allows measured distribution of the contents. Dispense the contents in aliquots using aseptic technique. The use of a syringe with a needle is not recommended as it may cause leakage.

AFTER INITIAL ENTRY USE ENTIRE CONTENTS OF THE PHARMACY BULK PACKAGE PROMPTLY. A maximum time of 4 HOURS from initial entry is permitted to complete fluid transfer operations. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 4 HOURS. This time limit should begin with the introducing of solvent or diluent into the Pharmacy Bulk Package bottle. RECONSTITUTED BULK SOLUTION SHOULD NOT BE USED FOR DIRECT INFUSION.

Preparation of Solution

The directions for preparing cefoxitin for injection Pharmacy Bulk Package are summarized in Table 3.

For Intravenous Use

The 10 grams bulk packages should be constituted with 43 or 93 mL of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection.

RECONSTITUTED STOCK SOLUTION MUST BE TRANSFERRED AND FURTHER DILUTED FOR I.V. INFUSION.

These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Bulk Packages portion of the COMPATIBILITY AND STABILITY section.

ADMINISTRATION

Cefoxitin for injection may be administered intravenously after constitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The intent of this pharmacy bulk package is for the preparation of solutions for intravenous infusion only.

Intravenous Administration

The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent intravenous administration. Using an infusion system, a solution containing 1 gram or 2 grams may be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusions of the solution containing cefoxitin for injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin for injection may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®3 or scalp vein-type needles are preferred for this type of infusion.

Solutions of cefoxitin for injection, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin for injection and aminoglycosides may be administered separately to the same patient.
3 Registered trademark of Abbott Laboratories, Inc.
COMPATIBILITY AND STABILITY

Pharmacy Bulk Packages

Cefoxitin for injection supplied in pharmacy bulk package bottles and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, should be DISCARDED 4 HOURS AFTER INITIAL ENTRY, FURTHER DILUTION IS REQUIRED BEFORE USE. RECONSTITUTED BULK SOLUTION SHOULD NOT BE USED FOR DIRECT INFUSION.

These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:

   0.9 percent Sodium Chloride Injection   5 percent or 10 percent Dextrose Injection   5 percent Dextrose and 0.9 percent Sodium Chloride Injection   5 percent Dextrose Injection with 0.2 percent or 0.45 percent saline solution   Lactated Ringer's Injection   5 percent Dextrose in Lactated Ringer's Injection   5 percent Sodium Bicarbonate Injection   M/6 sodium lactate solution   Mannitol 5% and 10%

After the periods mentioned above, any unused solutions should be discarded.
Cefoxitin

Cefoxitin

TREATMENT

Adults

The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 1 for dosage guidelines).

If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.

Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:

In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 2) may be used as a guide.

When only the serum creatinine level 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 (mg/100 mL)

Females         =             0.85 x male value

In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 2.

Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients

The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.

At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).

In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 2).

PREVENTION

Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.

For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:

Adults:

2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.

Pediatric Patients (3 months and older):

30 to 40 mg/kg doses may be given at the times designated above.

Adults

2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.

Pediatric Patients

(3 months and older):

30 to 40 mg/kg doses may be given at the times designated above.

Cesarean section patients:

For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3-dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 1: Guidelines for Dosage of Cefoxitin for Injection    Type of Infection    Daily Dosage    Frequency and Route * Including patients in whom bacteremia is absent or unlikely.    Uncomplicated forms* of infections such as pneumonia, urinary tract infection, cutaneous infection    3-4 grams    1 gram every 6-8 hours IV    Moderately severe or severe infections    6-8 grams    1 gram every 4 hoursor 2 grams every 6-8 hours IV    Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)    12 grams    2 grams every 4 hoursor 3 grams every 6 hours IV Table 2: Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function    Renal Function    Creatinine Clearance(mL/min)    Dose(grams)    Frequency    Mild impairment    50-30    1-2    every 8-12 hours    Moderate impairment    29-10    1-2    every 12-24 hours    Severe impairment    9-5    0.5-1    every 12-24 hours    Essentially no function    <5    0.5-1    every 24-48 hours Table 3: Preparation of Solution for Intravenous Administration    Strength    Amount of Diluent to be Added (mL)*    Approximate Withdrawable Volume (mL)    Approximate Average Concentration (mg/mL) * Shake to dissolve and let stand until clear. 1 gram vial 10 10.5    95 2 gram vial   10 or 20 11.1 or 21   180 or 95
Preparation of Solution

Table 3 is provided for convenience in constituting cefoxitin for injection for intravenous administration.

For Vials

One gram should be constituted with at least 10 mL, and 2 grams with 10 or 20 mL, of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the vials portion of the COMPATIBILITY AND STABILITYsection.

Benzyl Alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, in whom use of cefoxitin for injection may be indicated, small pediatric patients in this range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when cefoxitin for injection is constituted for administration to pediatric patients in this age range.

ADMINISTRATION

Cefoxitin for injection may be administered intravenously after constitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent intravenous administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Using an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusion of the solution containing cefoxitin for injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin for injection may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®3 or scalp vein-type needles are preferred for this type of infusion.

Solutions of cefoxitin for injection, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin for injection and aminoglycosides may be administered separately to the same patient.
3 Registered trademark of Abbott Laboratories, Inc.
COMPATIBILITY AND STABILITY

Vials

Cefoxitin for injection, as supplied in vials package and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 6 hours at room temperatue or for one week under refrigeration (below 5ºC).

These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:

   0.9 percent Sodium Chloride Injection   5 percent or 10 percent Dextrose Injection   5 percent Dextrose and 0.9 percent Sodium Chloride Injection   5 percent Dextrose Injection with 0.2 percent or 0.45 percent saline solution   Lactated Ringer's Injection   5 percent Dextrose in Lactated Ringer's Injection   5 percent Sodium Bicarbonate Injection   M/6 sodium lactate solution   Mannitol 5% and 10%

After the periods mentioned above, any unused solutions should be discarded.
Cortisone Acetate

Cortisone Acetate

For Oral Administration

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.

The initial dosage varies from 25 to 300 mg a day depending on the disease being treated. In less severe diseases doses lower than 25 mg may suffice, while in severe diseases doses higher than 300 mg may be required. The initial dosage should be maintained or adjusted until the patient's response is satisfactory. If satisfactory clinical response does not occur after a reasonable period of time, discontinue cortisone acetate tablets and transfer the patient to other therapy.

After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response.

Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.

If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.
Chloroquine

Chloroquine

The dosage of chloroquine phosphate is often expressed in terms of equivalent chloroquine base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base and each 500 mg tablet of chloroquine phosphate is equivalent to 300 mg base. In infants and children the dosage is preferably calculated by body weight.

Malaria: Suppression – Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week.

Pediatric Dose: The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 600 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.

For Treatment of Acute Attack

Adults: An initial dose of 1 g (= 600 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate of 1.5 g base in three days.

The dosage for adults of low body weight and for infants and children should be determined as follows:

First dose: 10 mg base per kg (but not exceeding a single dose of 600 mg base).

Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base).

Third dose: (24 hours after first dose) 5 mg base per kg.

Fourth dose: (36 hours after first dose) 5 mg base per kg.

For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary.

Extraintestinal Amebiasis: Adults: 1 g (600 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.

Geriatric Use: See PRECAUTIONS, Geriatric Use.
Hydroxychloroquine Sulf...

Hydroxychloroquine Sulfate

There is currently no dosage information available for this product. We apologize for any inconvenience.
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium Suspension

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of amoxicillin and clavulanate potassium. Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/28.5 mg per 5 mL suspension of amoxicillin and clavulanate potassium contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/57 mg per 5 mL suspension contains 57 mg of clavulanic acid per 5 mL. Therefore, the 200 mg/28.5 mg per 5 mL and 400 mg/57 mg per 5 mL suspensions of amoxicillin and clavulanate potassium should not be substituted for amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, as they are not interchangeable.

Dosage

Pediatric patients 3 months and older: Based on the amoxicillin component (600 mg/5 mL), the recommended dose of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is 90 mg/kg/day divided every 12 hours, administered for 10 days (see chart below).
Body Weight (kg) Volume of Amoxicillin and Clavulanate Potassium for oral suspension, 600 mg/42.9 mg per 5 mL providing 90 mg/kg/day 8 3.0 mL twice daily 12 4.5 mL twice daily 16 6.0 mL twice daily 20 7.5 mL twice daily 24 9.0 mL twice daily 28 10.5 mL twice daily 32 12.0 mL twice daily 36 13.5 mL twice daily
Pediatric patients weighing 40 kg and more: Experience with amoxicillin and clavulanate potassium for oral suspension,600 mg/42.9 mg per 5 mL in this group is not available.

Adults: Experience with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL in adults is not available and adults who have difficulty swallowing should not be given amoxicillin and clavulanate potassium for oral suspension 600 mg/42.9 mg per 5 mL in place of the amoxicillin and clavulanate potassium 500-mg/125 mg or 875-mg/125 mg tablet.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS.)

Directions for Mixing Oral Suspension

Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Amoxicillin and Clavulanate Potassium for oral suspension, 600 mg/42.9 mg per 5 mL Bottle Size Amount of WaterRequired for Reconstitution 75 mL 66 mL 125 mL 110 mL 200 mL 176 mL
Each teaspoonful (5 mL) will contain 600 mg amoxicillin as the trihydrate and 42.9 mg of clavulanic acid as the potassium salt.

NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.

Administration

To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium 600 mg/42.9 mg per 5 mL should be taken at the start of a meal. Absorption of clavulanate potassium may be enhanced when amoxicillin and clavulanate potassium is administered at the start of a meal.
Carisoprodol

Carisoprodol

The recommended dose of Carisoprodol Tablets is 350 mg three times a day and at bedtime. The recommended maximum duration of Carisoprodol Tablets use is up to two or three weeks.
Ephedrine Sulfate

Ephedrine Sulfate

Adults and children 12 years of age and over:

Oral dosage is 12.5 to 25 milligrams every 4 hours, not to exceed 150 milligrams in 24 hours, or as directed by a doctor. Do not exceed recommended dose unless directed by a doctor.
Children under 12 years of age: Consult a doctor.
Gemfibrozil

Gemfibrozil

The recommended dose for adults is 1200 mg administered in two divided doses 30 minutes before the morning and evening meals (see CLINICAL PHARMACOLOGY).
Flurazepam

Flurazepam

Dosage should be individualized for maximal beneficial effects. The usual adult dosage is 30 mg before retiring. In some patients, 15 mg may suffice. In elderly and/or debilitated patients, 15 mg is usually sufficient for a therapeutic response and it is therefore recommended that therapy be initiated with this dosage.
Calcitriol

Calcitriol

The optimal dose of Calcitriol Injection must be carefully determined for each patient.

The effectiveness of Calcitriol Injection therapy is predicated on the assumption that each patient is receiving an adequate and appropriate daily intake of calcium. The RDA for calcium in adults is 800 mg. To ensure that each patient receives an adequate daily intake of calcium, the physician should either prescribe a calcium supplement or instruct the patient in proper dietary measures.

The recommended initial dose of Calcitriol Injection, depending on the severity of the hypocalcemia and/or secondary hyperparathyroidism, is 1 mcg (0.02 mcg/kg) to 2 mcg administered three times weekly, approximately every other day. Doses as small as 0.5 mcg and as large as 4 mcg three times weekly have been used as an initial dose. If a satisfactory response is not observed, the dose may be increased by 0.5 to 1 mcg at two to four week intervals. During this titration period, serum calcium and phosphorus levels should be obtained at least twice weekly. If hypercalcemia or a serum calcium times phosphate product greater than 70 is noted, the drug should be immediately discontinued until these parameters are appropriate. Then, the Calcitriol Injection dose should be reinitiated at a lower dose. Doses may need to be reduced as the PTH levels decrease in response to the therapy. Thus, incremental dosing must be individualized and commensurate with PTH, serum calcium and phosphorus levels. The following is a suggested approach in dose titration:
PTH Levels Calcitriol Injection Dose The same or increasing increase Decreasing by <30% increase Decreasing by >30%, <60% maintain Decreasing by >60% decrease One and one-half to three times the upper limit of normal maintain
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard unused portion.
Milrinone Lactate

Milrinone Lactate

Milrinone Lactate in 5% Dextrose Injection should not be used for administering a loading dose. The information regarding loading doses for milrinone is for informational purposes only. A loading dose of milrinone lactate injection (1 mg [base]/mL) should be administered followed by a continuous infusion (maintenance dose) according to the following guidelines:

Loading Dose

50 mcg/kg: Administer slowly over 10 minutes.

The table below shows the loading dose in milliliters (mL) of milrinone (1mg/mL) by patient body weight (kg).
Loading Dose (mL) Using 1 mg/mL Concentration Patient Body Weight (kg) kg 30 40 50 60 70 80 90 100 110 120 mL 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0
The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see Maintenance Dose for diluents) may simplify the visualization of the injection rate.

Maintenance Dose
Infusion Rate Total Daily Dose (24 Hours) Minimum 0.375 mcg/kg/min 0.59 mg/kg Administer as a Standard 0.50 mcg/kg/min 0.77 mg/kg continuous Maximum 0.75 mcg/kg/min 1.13 mg/kg intravenous infusion
The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

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

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.

Note: Milrinone Lactate in 5% Dextrose Injection supplied in 100 mL and 200 mL Flexible Containers (200 mcg/mL in 5% Dextrose Injection) need not be diluted prior to use.
Milrinone Infusion Rate (mL/hr) Using 200 mcg/mL Concentration Maintenance Dose Patient Body Weight (kg) (mcg/kg/min) 30 40 50 60 70 80 90 100 110 120 0.375 3.4 4.5 5.6 6.8 7.9 9.0 10.1 11.3 12.4 13.5 0.400 3.6 4.8 6.0 7.2 8.4 9.6 10.8 12.0 13.2 14.4 0.500 4.5 6.0 7.5 9.0 10.5 12.0 13.5 15.0 16.5 18.0 0.600 5.4 7.2 9.0 10.8 12.6 14.4 16.2 18.0 19.8 21.6 0.700 6.3 8.4 10.5 12.6 14.7 16.8 18.9 21.0 23.1 25.2 0.750 6.8 9.0 11.3 13.5 15.8 18.0 20.3 22.5 24.8 27.0
When administering milrinone by continuous infusion, it is advisable to use a calibrated electronic infusion device.

The Flexible Container has a concentration of milrinone equivalent to 200 mcg/mL in 5% Dextrose Injection and is more convenient to use than dilutions prepared from the vials. To use the Flexible Container, tear the overwrap at the notch and remove the Pre-Mix solution container. Squeeze the container firmly to check for leaks. Discard the container if leaks are found since the sterility of the product could be affected. Do not add supplementary medication.

To prepare the container for administration of milrinone intravenously, use aseptic techniques.
1)The flow control clamp of the administration set is closed. 2)The cover of the outlet port at the bottom of the container is removed. 3)Noting the full directions on the administration set carton, the piercing pin of the set is inserted into the port with a twisting motion until it is firmly seated. 4)The container is suspended on the hanger. 5)The drip chamber is squeezed and released to establish the fill level. 6)The flow control clamp is opened to expel air from the set, and then closed. 7)The set is attached to the venipuncture device, primed, and if not indwelling, the venipuncture is performed. 8)The rate of administration is controlled with the flow control clamp. WARNING- DO NOT USE IN SERIES CONNECTIONS. Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Intravenous drug products should be inspected visually and should not be used if particulate matter or discoloration is present.

Dosage Adjustment in Renally Impaired Patients

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

Naproxen

Carefully consider the potential benefits and risks of naproxen and other treatment options before deciding to use naproxen. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with naproxen, the dose and frequency should be adjusted to suit an individual patient's needs.

Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although naproxen circulates in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 1 hour in patients taking naproxen (see CLINICAL PHARMACOLOGY).

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients with Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatine clearance <30 mL/min) (see WARNINGS: Renal Effects).
Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis Naproxen 250 mg twice daily or 375 mg twice daily or 500 mg twice daily
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice the daily doses do not generally make a difference in response (See CLINICAL PHARMACOLOGY).

Acute Gout

The recommended starting dose is 750 mg of naproxen followed by 250 mg every 8 hours until the attack has subsided.
Flumazenil

Flumazenil

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

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

Reversal of Conscious Sedation

Adult Patients

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

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

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

Pediatric Patients

For the reversal of the sedative effects of benzodiazepines administered for conscious sedation in pediatric patients greater than 1 year of age, the recommended initial dose is 0.01 mg/kg (up to 0.2 mg) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, further injections of 0.01 mg/kg (up to 0.2 mg) can be administered and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 0.05 mg/kg or 1 mg, whichever is lower. The dose should be individualized based on the patient’s response. The mean total dose administered in the pediatric clinical trial of flumazenil was 0.65 mg (range: 0.08 mg to 1.00 mg). Approximately one-half of patients required the maximum of five injections.

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

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

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

Reversal of General Anesthesia in Adult Patients

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

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

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

Management of Suspected Benzodiazepine Overdose in Adult Patients

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

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

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

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

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

Safety and Handling

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

Zolpidem

The dose of zolpidem tartrate tablets should be individualized.

2.1 Dosage in adults

The recommended dose for adults is 10 mg once daily immediately before bedtime. The total zolpidem tartrate tablets dose should not exceed 10 mg per day.

2.2 Special Populations

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate tablets. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of zolpidem tartrate tablets in both of these patient poulations is 5 mg once daily immediately before bedtime. [see Warnings and Precautions (5)].

2.3 Use with CNS depressants

Dosage adjustment may be necessary when zolpidem tartrate tablets are combined with other CNS depressant drugs because of the potentially additive effects [see Warnings and Precautions (5)].

2.4 Administration

The effect of zolpidem tartrate tablets may be slowed by ingestion with or immediately after a meal.
Amlodipine Besylate

Amlodipine Besylate

2.1 Adults

The usual initial antihypertensive oral dose of amlodipine is 5 mg once daily with a maximum dose of 10 mg once daily.

Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding amlodipine to other antihypertensive therapy.

Adjust dosage according to each patient's need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient's response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.

The recommended dose for chronic stable or vasospastic angina is 5 to 10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect [see Adverse Reactions (6)].

The recommended dose range for patients with coronary artery disease is 5 to 10 mg once daily. In clinical studies, the majority of patients required 10 mg [see Clinical Studies (14.4)].

2.2 Children

The effective antihypertensive oral dose in pediatric patients ages 6–17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients [see Clinical Pharmacology (12.4), Clinical Studies (14.1)].
Severe Allergy And Sinu...

Severe Allergy And Sinus Headache

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

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

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See DIRECTION FOR USE-Preparation for Intramuscular Injection section.)

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/SulbactamHalf-Life (Hours)
Recommended Ampicillin and Sulbactamfor Injection Dosage ≥ 30 1 1.5 to 3 g q 6 h-q 8 h 15 to 29 5 1.5 to 3 g q 12 h 5 to 14 9 1.5 to 3 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males
weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value
Clonidine Hydrochloride...

Clonidine Hydrochloride

The recommended starting dose of clonidine hydrochloride injection for continuous epidural infusion is 30 mcg/hr. Although dosage may be titrated up or down depending on pain relief and occurrence of adverse events, experience with dosage rates above 40 mcg/hr is limited.

Familiarization with the continuous epidural infusion device is essential. Patients receiving epidural clonidine from a continuous infusion device should be closely monitored for the first few days to assess their response.

The 500 mcg/mL (0.5mg/mL) strength product must be diluted prior to use in 0.9% Sodium Chloride for Injection, USP, to a final concentration of 100 mcg/mL:
Volume of Clonidine Hydrochloride Injection 500 mcg/mL Volume of 0.9% Sodium Chloride for Injection, USP Resulting Final Clonidine Hydrochloride Injection Concentration (100 mcg/mL) 1 mL 4 mL 500 mcg/5 mL 2 mL 8 mL 1000 mcg/10 mL 3 mL 12 mL 1500 mcg/15 mL 4 mL 16 mL 2000 mcg/20 mL 5 mL 20 mL 2500 mcg/25 mL 6 mL 24 mL 3000 mcg/ 30 mL 7 mL 28 mL 3500 mcg/ 35 mL 8 mL 32 mL 4000 mcg/40 mL 9 mL 36 mL 4500 mcg/45 mL 10 mL 40 mL 5000 mcg/50 mL
Renal Impairment: Dosage should be adjusted according to the degree of renal impairment, and patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.

Clonidine hydrochloride injection must not be used with a preservative.

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

Hydrochlorothiazide

For Control of Hypertension

The adult initial dose of hydrochlorothiazide is one capsule given once daily whether given alone or in combination with other antihypertensives. Total daily doses greater than 50 mg are not recommended.
Diphenhydramine Hydroch...

Diphenhydramine Hydrochloride

THIS PRODUCT IS FOR INTRAVENOUS OR INTRAMUSCULAR ADMINISTRATION ONLY.

Diphenhydramine Hydrochloride Injection is indicated when the oral form is impractical.

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT.

Pediatric Patients, Other Than Premature Infants and Neonates

5 mg/kg/24 hours or 150 mg/m2/24 hours. Maximum daily dosage is 300 mg. Divide into four doses, administered intravenously at a rate generally not exceeding 25 mg/min, or deep intramuscularly.

Adults

10 to 50 mg intravenously at a rate generally not exceeding 25 mg/min, or deep intramuscularly; 100 mg if required; maximum daily dosage is 400 mg.

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

Fludrocortisone Acetate

Dosage depends on the severity of the disease and the response of the patient. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma) (see WARNINGS and PRECAUTIONS, General).

Addison’s Disease

In Addison’s disease, the combination of Fludrocortisone Acetate Tablets with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity with minimal risks of unwanted effects.

The usual dose is 0.1 mg of Fludrocortisone Acetate Tablets daily, although dosage ranging from 0.1 mg three times a week to 0.2 mg daily has been employed. In the event transient hypertension develops as a consequence of therapy, the dose should be reduced to 0.05 mg daily. Fludrocortisone Acetate Tablets are preferably administered in conjunction with cortisone (10 mg to 37.5 mg daily in divided doses) or hydrocortisone (10 mg to 30 mg daily in divided doses).

Salt-Losing Adrenogenital Syndrome

The recommended dosage for treating the salt-losing adrenogenital syndrome is 0.1 mg to 0.2 mg of Fludrocortisone Acetate Tablets daily.
Cephalexin Suspension

Cephalexin Suspension

Cephalexin for Oral Suspension USP is administered orally. Adults—The adult dosage ranges from 1 to 4 g daily in divided doses.The usual adult dose is 250 mg every 6 hours. For the following infections, a dosage of 500 mg may be administered every 12 hours: streptococcal pharyngitis, skin and skin structure infections, and uncomplicated cystitis in patients over 15 years of age. Cystitis therapy should be continued for 7 to 14 days. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of Cephalexin for Oral Suspension greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered.Pediatric Patients—The usual recommended daily dosage for pediatric patients is 25 to 50 mg/kg in divided doses. For streptococcal pharyngitis in patients over 1 year of age and for skin and skin structure infections, the total daily dose may be divided and administered every 12 hours. Cephalexin for Oral Suspension Weight 125 mg/5 mL 10 kg (22 lb) 1/2 to 1 tsp q.i.d. 20 kg (44 lb) 1 to 2 tsp q.i.d. 40 kg (88 lb) 2 to 4 tsp q.i.d. Weight 250 mg/5 mL 10 kg (22 lb) 1/4 to 1/2 tsp q.i.d. 20 kg (44 lb) 1/2 to 1 tsp q.i.d. 40 kg (88 lb) 1 to 2 tsp q.i.d. or Weight 125 mg/5 mL 10 kg (22 lb) 1 to 2 tsp b.i.d. 20 kg (44 lb) 2 to 4 tsp b.i.d. 40 kg (88 lb) 4 to 8 tsp b.i.d. Weight 250 mg/5 mL 10 kg (22 lb) 1/2 to 1 tsp b.i.d. 20 kg (44 lb) 1 to 2 tsp b.i.d. 40 kg (88 lb) 2 to 4 tsp b.i.d. In severe infections, the dosage may be doubled. In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required. In the treatment of ß-hemolytic streptococcal infections, a therapeutic dosage of cephalexin should be administered for at least 10 days.
Mefloquine Hydrochlorid...

Mefloquine Hydrochloride

(see INDICATIONS AND USAGE)

Adult Patients

Treatment of mild to moderate malaria in adults caused by P. vivax or mefloquine-susceptible strains of P. falciparum

Five tablets (1250 mg) mefloquine hydrochloride to be given as a single oral dose. The drug should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water.

If a full-treatment course with Mefloquine Hydrochloride Tablets does not lead to improvement within 48 to 72 hours, Mefloquine Hydrochloride Tablets should not be used for retreatment. An alternative therapy should be used. Similarly, if previous prophylaxis with mefloquine has failed, Mefloquine Hydrochloride Tablets should not be used for curative treatment.
Note: Patients with acute P. vivax malaria, treated with Mefloquine Hydrochloride Tablets, are at high risk of relapse because Mefloquine Hydrochloride Tablets do not eliminate exoerythrocytic (hepatic phase) parasites. To avoid relapse after initial treatment of the acute infection with Mefloquine Hydrochloride Tablets, patients should subsequently be treated with an 8-aminoquinoline derivative (e.g., primaquine).
Malaria Prophylaxis

One 250 mg Mefloquine Hydrochloride Tablet once weekly.

Prophylactic drug administration should begin 1 week before arrival in an endemic area. Subsequent weekly doses should be taken regularly, always on the same day of each week, preferably after the main meal. To reduce the risk of malaria after leaving an endemic area, prophylaxis must be continued for 4 additional weeks to ensure suppressive blood levels of the drug when merozoites emerge from the liver. Tablets should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water.

In certain cases, e.g., when a traveler is taking other medication, it may be desirable to start prophylaxis 2 to 3 weeks prior to departure, in order to ensure that the combination of drugs is well tolerated (see PRECAUTIONS: Drug Interactions).

When prophylaxis with Mefloquine Hydrochloride Tablets fails, physicians should carefully evaluate which antimalarial to use for therapy.

Pediatric Patients

Treatment of mild to moderate malaria in pediatric patients caused by mefloquine-susceptible strains of P. falciparum

Twenty (20) to 25 mg/kg body weight. Splitting the total therapeutic dose into 2 doses taken 6 to 8 hours apart may reduce the occurrence or severity of adverse effects. Experience with Mefloquine Hydrochloride Tablets in pediatric patients weighing less than 20 kg is limited. The drug should not be taken on an empty stomach and should be administered with ample water. The tablets may be crushed and suspended in a small amount of water, milk or other beverage for administration to small children and other persons unable to swallow them whole.

If a full-treatment course with Mefloquine Hydrochloride Tablets does not lead to improvement within 48 to 72 hours, Mefloquine Hydrochloride Tablets should not be used for retreatment. An alternative therapy should be used. Similarly, if previous prophylaxis with mefloquine has failed, Mefloquine Hydrochloride Tablets should not be used for curative treatment.

In pediatric patients, the administration of Mefloquine Hydrochloride Tablets for the treatment of malaria has been associated with early vomiting. In some cases, early vomiting has been cited as a possible cause of treatment failure (see PRECAUTIONS). If a significant loss of drug product is observed or suspected because of vomiting, a second full dose of Mefloquine Hydrochloride Tablets should be administered to patients who vomit less than 30 minutes after receiving the drug. If vomiting occurs 30 to 60 minutes after a dose, an additional half-dose should be given. If vomiting recurs, the patient should be monitored closely and alternative malaria treatment considered if improvement is not observed within a reasonable period of time.

The safety and effectiveness of Mefloquine Hydrochloride Tablets to treat malaria in pediatric patients below the age of 6 months have not been established.

Malaria Prophylaxis

The recommended prophylactic dose of Mefloquine Hydrochloride Tablets is approximately 5 mg/kg body weight once weekly. One 250 mg Mefloquine Hydrochloride Tablet should be taken once weekly in pediatric patients weighing over 45 kg. In pediatric patients weighing less than 45 kg, the weekly dose decreases in proportion to body weight:

30 to 45 kg: 3/4 tablet20 to 30 kg: 1/2 tablet

Experience with Mefloquine Hydrochloride Tablets in pediatric patients weighing less than 20 kg is limited.
Hydromorphone Hydrochlo...

Hydromorphone Hydrochloride

The usual starting dose is 1-2 mg subcutaneously orintramuscularly every 4 to 6 hours as necessary for pain control. The dose should be adjusted according to severity of pain, as well as the patient’s underlying disease, age and size. Severe pain can usually be controlled by 3-4 mg every 4 to 6 hours as required. Patients with terminal cancer may become tolerant to narcotic analgesics and may, therefore, require higher doses for adequate pain relief. Should intravenous administration be necessary, the injection should be given very slowly (over at least 3 to 5 minutes, depending on the dose) [see WARNINGS, INTRAVENOUS USE]. A gradual increase in dosage may be required if analgesia is inadequate, tolerance occurs or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

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

Meperidine Hydrochloride

For Relief of Pain

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

Adults

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

Children

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

For Preoperative Medication

Adults

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

Children

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

For Support of Anesthesia

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

For Obstetrical Analgesia

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

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

Phenylephrine Hydrochloride

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

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

SUBCUTANEOUSLY OR INTRAMUSCULARLY: Usual dose, from 2 mg to 5 mg. Range, from 1 mg to 10 mg. Initial dose should not exceed 5 mg.INTRAVENOUSLY: Usual dose, 0.2 mg. Range, from 0.1 mg to 0.5 mg. Initial dose should not exceed 0.5 mg.Injections should not be repeated more often than every 10 to 15 minutes. A 5 mg intramuscular dose should raise blood pressure for one to two hours. A 0.5 mg intravenous dose should elevate the blood pressure for about 15 minutes.

Severe Hypotension and Shock - Including Drug-Related Hypotension

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

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

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

Continuous Infusion:

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

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

Spinal Anesthesia-Hypotension

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

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

Prolongation of Spinal Anesthesia

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

Vasoconstrictor for Regional Analgesia

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

Paroxysmal Supraventricular Tachycardia

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

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

Milrinone Lactate

Milrinone Lactate in 5% Dextrose Injection should not be used for administering a loading dose. The information regarding loading dose for milrinone is for 1 mg/mL vial only. A loading dose of milrinone lactate injection (1 mg [base]/mL) should be administered followed by a continuous infusion (maintenance dose) according to the following guidelines:
  LOADING DOSE — 50 mcg/kg: Administer slowly over 10 minutes   The table below shows the loading dose in milliliters (mL) of milrinone (1 mg/mL) by patient body weight (kg).   Loading Dose (mL) Using 1 mg/mL Concentration   Patient Body Weight kg)   kg   30   40   50   60   70   80   90   100   110   120   mL   1.5   2.0   2.5   3.0   3.5   4.0   4.5   5.0   5.5   6.0
The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see Maintenance Dose for diluents) may simplify the visualization of the injection rate.
  MAINTENANCE DOSE      Infusion Rate   Total Daily Dose (24 hours)      Minimum   0.375 mcg/kg/min   0.59 mg/kg   Administer as a continuous intravenous infusion   Standard   0.50 mcg/kg/min   0.77 mg/kg   Maximum   0.75 mcg/kg/min   1.13 mg/kg
Milrinone drawn from vials should be diluted prior to maintenance dose administration. The diluents that may be used are 0.45% Sodium Chloride Injection, USP; 0.9% Sodium Chloride Injection, USP; or 5% Dextrose Injection, USP. The table below shows the volume of diluent in milliliters (mL) that must be used to achieve 200 mcg/mL concentration for infusion, and the resultant total volumes.
  Desired Infusion Concentration mcg/mL   Milrinone 1 mg/mL(mL)   Diluent (mL)   Total Volume (mL)   200   10   40   50   200   20   80   100
The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

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

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.

Note: Milrinone Lactate in 5% Dextrose Injection supplied in 100 mL and 200 mL Flexible Containers (200 mcg/mL in 5% Dextrose Injection) need not be diluted prior to use.
  Milrinone Infusion Rate(mL/hr) Using 200 mcg/mL Concentration   Maintenance Dose (mcg/kg/min)   Patient Body Weight (kg)      30   40   50   60   70   80   90   100   110   120   0.375   3.4   4.5   5.6   6.8   7.9   9.0   10.1   11.3   12.4   13.5   0.400   3.6   4.8   6.0   7.2   8.4   9.6   10.8   12.0   13.2   14.4   0.500   4.5   6.0   7.5   9.0   10.5   12.0   13.5   15.0   16.5   18.0   0.600   5.4   7.2   9.0   10.8   12.6   14.4   16.2   18.0   19.8   21.6   0.700   6.3   8.4   10.5   12.6   14.7   16.8   18.9   21.0   23.1   25.2   0.750   6.8   9.0   11.3   13.5   15.8   18.0   20.3   22.5   24.8   27.0
When administering milrinone lactate by continuous infusion, it is advisable to use a calibrated electronic infusion device.

The Flexible Container has a concentration of milrinone equivalent to 200 mcg/mL in 5% Dextrose Injection and is more convenient to use than dilutions prepared from the vials. To use the Flexible Container, tear the overwrap at the notch and remove the Pre-Mix solution container. Squeeze the container firmly to check for leaks. Discard the container if leaks are found since the sterility of the product could be affected. Do not add supplementary medication.

To prepare the container for administration of milrinone intravenously, use aseptic techniques.1. The flow control clamp of the administration set is closed.2. The cover of the outlet port at the bottom of the container is removed.3. Noting the full directions on the administration set carton, the piercing pin of the set is inserted into the port with a twisting motion until it is firmly sealed.4. The container is suspended on the hanger.5. The drop chamber is squeezed and released to establish the fill level.6. The flow control clamp is opened to expel air from the set and then closed.7. The set is attached to the venipuncture device, primed, and if not indwelling, the venipuncture is performed.8. The rate of administration is controlled with the flow control clamp. WARNING - DO NOT USE IN SERIES CONNECTIONS. Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Intravenous drug products should be inspected visually and should not be used if particulate matter or discoloration is present.

Dosage Adjustment in Renally Impaired Patients

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

Phenobarbital Sodium

Dosages of barbiturates must be individualized with full knowledge of their particular characteristics and recommended rates of administration. Factors to consider are the patient’s age, weight and condition.

Suggested doses of phenobarbital sodium for specific indications follow:

Pediatric Dosage

Recommended by the American Academy of Pediatrics (intended as a guide)

    Preoperative Sedation: 1 to 3 mg/kg IM or IV

    Anticonvulsion: 4 to 6 mg/kg/day for 7 to 10 days to blood level of 10 to 15 mcg/mL or 10 to 15 mg/kg/day IM or IV

    Status Epilepticus: 15 to 20 mg/kg over 10 to 15 minutes IV

Adult Dosage

(intended as a guide)

    Daytime Sedation: 30 to 120 mg daily in 2 to 3 divided doses IM or IV

    Bedtime Hypnosis: 100 to 320 mg IM or IV

    Preoperative Sedation: IM only — 100 to 200 mg 60 to 90 minutes before surgery

    Acute Convulsions: 20 to 320 mg IM or IV, repeated in 6 hours as necessary

Parenteral routes should be used only when oral administration is impossible or impractical.

Intramuscular injection of the sodium salts of barbiturates should be made deeply into a large muscle and a volume of 5 mL should not be exceeded at any one site because of possible tissue irritation. Injection into or near peripheral nerves may result in permanent neurological deficit. After intramuscular injection of a hypnotic dose, the patient’s vital signs should be monitored.

Subcutaneous administration is not recommended (see CONTRAINDICATIONS).

Intravenous Administration

Intravenous injection is restricted to conditions in which other routes are not feasible, either because the patient is unconscious (as in cerebral hemorrhage, eclampsia or status epilepticus), or because the patient resists (as in delirium) or because prompt action is imperative. Slow IV injection is essential, and patients should be carefully observed during administration. This requires that blood pressure, respiration and cardiac function be maintained, vital signs be recorded and equipment for resuscitation and artificial ventilation be available. The rate of intravenous injection for adults should not exceed 60 mg/min for phenobarbital sodium.

When given intravenously, do not use small veins, such as those on the dorsum of the hand or wrist. Preference should be given to a larger vein to minimize the risk of irritation with the possibility of resultant thrombosis. Avoid administration into varicose veins because circulation there is retarded. Inadvertent injection into or adjacent to an artery has resulted in gangrene requiring amputation of an extremity or a portion thereof. Careful technique, including aspiration, is necessary to avoid inadvertent intraarterial injection. (See below.)

Treatment of Adverse Effects Due to Inadvertent Error in Administration

Extravasation into subcutaneous tissues causes tissue irritation. This may vary from slight tenderness and redness to necrosis. Recommended treatment includes the application of moist heat and the injection of 0.5% procaine solution into the affected area.

Intraarterial injection of any barbiturate must be avoided. The accidental intraarterial injection of a small amount of the solution may cause spasm and severe pain along the course of the artery. The injection should be terminated if the patient complains of pain or if other indications of accidental intraarterial injection occur, such as a white hand with cyanosed skin or patches of discolored skin and delayed onset of hypnosis.

The consequences of intraarterial injection of phenobarbital can vary from transient pain to gangrene. It is not possible to formulate strict rules for management of such accidents. The following procedures have been suggested: 1) release of the tourniquet or restrictive garments to permit dilution of injected drug, 2) relief of arterial spasm by injecting 10 mL of a 1% procaine solution into the artery and, if considered necessary, brachial plexus block, 3) prevention of thrombosis by early anticoagulant therapy and 4) supportive treatment.

Anticonvulsant Use

A therapeutic anticonvulsant level of phenobarbital in the serum is 10 to 25 µg/mL. To achieve the blood levels considered therapeutic in children, higher per-kilogram dosages are generally necessary for phenobarbital and most other anticonvulsants. In children and infants, phenobarbital at loading doses of 15 to 20 mg/kg produces blood levels of about 20 µg/mL shortly after administration.

In status epilepticus, it is imperative to achieve therapeutic blood levels of a barbiturate (or other anticonvulsants) as rapidly as possible. When administered intravenously, phenobarbital sodium may require 15 minutes or more to attain peak concentrations in the brain. If phenobarbital sodium is injected continuously until the convulsions stop, the brain concentration will continue to rise and can eventually exceed that required to control the seizures. Because a barbiturate-induced depression may occur along with a postictal depression once the seizures are controlled, it is important, therefore, to use the minimal amount required and to wait for the anticonvulsant effect to develop before administering a second dose.

Phenobarbital has been used in the treatment and prophylaxis of febrile seizures. However, it has not been established that prevention of febrile seizures influences the subsequent development of epilepsy.

Special Patient Population

Dosage should be reduced in the elderly or debilitated because these patients may be more sensitive to barbiturates. Dosage should be reduced for patients with impaired renal function or hepatic disease.

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

Ondansetron

Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of Ondansetron Hydrochloride Tablets is 24 mg given as three 8-mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Multiday, single-dose administration of a 24 mg dosage has not been studied.

Pediatric Use

There is no experience with the use of a 24 mg dosage in pediatric patients.

Geriatric Use

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

Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Cancer Chemotherapy

The recommended adult oral dosage is one 8 mg Ondansetron Hydrochloride Tablet given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg ondansetron tablet should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Pediatric Use

For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg Ondansetron Hydrochloride Tablet given three times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg Ondansetron Hydrochloride Tablet should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

Geriatric Use

The dosage is the same as for the general population.

Prevention of Nausea and Vomiting Associated with Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen

The recommended oral dosage is one 8 mg Ondansetron Hydrochloride Tablet given 3 times a day.

For total body irradiation, one 8 mg Ondansetron Hydrochloride Tablet should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen, one 8 mg Ondansetron Hydrochloride Tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen, one 8 mg Ondansetron Hydrochloride Tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Pediatric Use

There is no experience with the use of Ondansetron Hydrochloride Tablets in the prevention of radiation-induced nausea and vomiting in pediatric patients.

Geriatric Use

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

Postoperative Nausea and Vomiting

The recommended dosage is 16 mg given as two 8 mg Ondansetron Hydrochloride Tablets 1 hour before induction of anesthesia.

Pediatric Use

There is no experience with the use of Ondansetron Hydrochloride Tablets in the prevention of postoperative nausea and vomiting in pediatric patients.

Geriatric Use

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

Dosage Adjustment for Patients With Impaired Renal Function

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

Dosage Adjustment for Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh2 score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.
Promethazine Hydrochlor...

Promethazine Hydrochloride

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Enalaprilat

FOR INTRAVENOUS ADMINISTRATION ONLY

The dose in hypertension is 1.25 mg every six hours administered intravenously over a five minute period. A clinical response is usually seen within 15 minutes. Peak effects after the first dose may not occur for up to four hours after dosing. The peak effects of the second and subsequent doses may exceed those of the first.

No dosage regimen for enalaprilat injection, USP has been clearly demonstrated to be more effective in treating hypertension than 1.25 mg every six hours. However, in controlled clinical studies in hypertension, doses as high as 5 mg every six hours were well tolerated for up to 36 hours. There has been inadequate experience with doses greater than 20 mg per day.

In studies of patients with hypertension, enalaprilat injection, USP has not been administered for periods longer than 48 hours. In other studies, patients have received enalaprilat injection, USP for as long as seven days.

The dose for patients being converted to enalaprilat injection, USP from oral therapy for hypertension with enalapril maleate is 1.25 mg every six hours. For conversion from intravenous to oral therapy, the recommended initial dose of Tablets VASOTEC (Enalapril Maleate) is 5 mg once a day with subsequent dosage adjustments as necessary.

Patients On Diuretic Therapy

For patients on diuretic therapy the recommended starting dose for hypertension is 0.625 mg administered intravenously over a five minute period; also see below, Patients at Risk of Excessive Hypotension. A clinical response is usually seen within 15 minutes. Peak effects after the first dose may not occur for up to four hours after dosing, although most of the effect is usually apparent within the first hour. If after one hour there is an inadequate clinical response, the 0.625 mg dose may be repeated. Additional doses of 1.25 mg may be administered at six hour intervals.

For conversion from intravenous to oral therapy, the recommended initial dose of Tablets VASOTEC (Enalapril Maleate) for patients who have responded to 0.625 mg of enalaprilat every six hours is 2.5 mg once a day with subsequent dosage adjustment as necessary.

Dosage Adjustment In Renal Impairment

The usual dose of 1.25 mg of enalaprilat every six hours is recommended for patients with a creatinine clearance >30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≤30 mL/min (serum creatinine ≥3 mg/dL), the initial dose is 0.625 mg (see WARNINGS).

If after one hour there is an inadequate clinical response, the 0.625 mg dose may be repeated. Additional doses of 1.25 mg may be administered at six hour intervals.

For dialysis patients, see below, Patients At Risk of Excessive Hypotension.

For conversion from intravenous to oral therapy, the recommended initial dose of Tablets VASOTEC (Enalapril Maleate) is 5 mg once a day for patients with creatinine clearance >30 mL/min and 2.5 mg once daily for patients with creatinine clearance ≤30 mL/min. Dosage should then be adjusted according to blood pressure response.

Patients At Risk of Excessive Hypotension

Hypertensive patients at risk of excessive hypotension include those with the following concurrent conditions or characteristics: heart failure, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis, or severe volume and/or salt depletion of any etiology (see WARNINGS). Single doses of enalaprilat as low as 0.2 mg have produced excessive hypotension in normotensive patients with these diagnoses. Because of the potential for an extreme hypotensive response in these patients, therapy should be started under very close medical supervision. The starting dose should be no greater than 0.625 mg administered intravenously over a period of no less than five minutes and preferably longer (up to one hour).

Patients should be followed closely whenever the dose of enalaprilat is adjusted and/or diuretic is increased.

Administration

Enalaprilat injection, USP should be administered as a slow intravenous infusion, as indicated above. It may be administered as provided or diluted with up to 50 mL of a compatible diluent.

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

Compatibility and Stability

Enalaprilat injection, USP as supplied and mixed with the following intravenous diluents has been found to maintain full activity for 24 hours at room temperature:

5 percent Dextrose Injection0.9 percent Sodium Chloride Injection0.9 percent Sodium Chloride Injection in 5 percent Dextrose5 percent Dextrose in Lactated Ringer’s InjectionMcGaw ISOLYTE*** E. (*** Registered trademark of American Hospital Supply Corporation)
Progesterone

Progesterone

Progesterone injection is administered by intramuscular injection. It differs from other commonly used steroids in that it is irritating at the place of injection.

Amenorrhea: Five to 10 mg are given for six to eight consecutive days. If there has been sufficient ovarian activity to produce a proliferative endometrium, one can expect withdrawal bleeding forty-eight to seventy-two hours after the last injection. This may be followed by spontaneous normal cycles.

Functional Uterine Bleeding: Five to 10 mg are given daily for six doses. Bleeding may be expected to cease within six days. When estrogen is given as well, the administration of progesterone is begun after two weeks of estrogen therapy. If menstrual flow begins during the course of injections of progesterone, they are discontinued.

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

Sertraline Hydrochloride

Initial Treatment

Dosage for Adults

Major Depressive Disorder

Sertraline hydrochloride treatment should be administered at a dose of 50 mg once daily.

While a relationship between dose and effect has not been established for major depressive disorder, patients were dosed in a range of 50-200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride for the treatment of this indication. Consequently, a dose of 50 mg, administered once daily, is recommended as the initial therapeutic dose. Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week.

Premenstrual Dysphoric Disorder

Sertraline hydrochloride treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment.

While a relationship between dose and effect has not been established for PMDD, patients were dosed in the range of 50-150 mg/day with dose increases at the onset of each new menstrual cycle (see Clinical Trials under CLINICAL PHARMACOLOGY). Patients not responding to a 50 mg/day dose may benefit from dose increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dose has been established with luteal phase dosing, a 50 mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period.

Sertraline hydrochloride should be administered once daily, either in the morning or evening.

Maintenance/Continuation/Extended Treatment

Major Depressive Disorder

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy beyond response to the acute episode. Systematic evaluation of sertraline hydrochloride has demonstrated that its antidepressant efficacy is maintained for periods of up to 44 weeks following 8 weeks of initial treatment at a dose of 50-200 mg/day (mean dose of 70 mg/day) (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Premenstrual Dysphoric Disorder

The effectiveness of sertraline hydrochloride in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. However, as women commonly report that symptoms worsen with age until relieved by the onset of menopause, it is reasonable to consider continuation of a responding patient. Dosage adjustments, which may include changes between dosage regimens (e.g., daily throughout the menstrual cycle versus during the luteal phase of the menstrual cycle), may be needed to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

Switching Patients to or from a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with sertraline hydrochloride. In addition, at least 14 days should be allowed after stopping sertraline hydrochloride before starting an MAOI (see CONTRAINDICATIONS and WARNINGS).

Special Populations

Dosage for Hepatically Impaired Patients

The use of sertraline in patients with liver disease should be approached with caution. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to sertraline hydrochloride and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline hydrochloride during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering sertraline hydrochloride in the third trimester.

Discontinuation of Treatment with Sertraline

Symptoms associated with discontinuation of sertraline hydrochloride and other SSRIs and SNRIs, have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
Amoxicillin

Amoxicillin

Amoxicillin capsules may be given without regard to meals. However, food effect studies have not been performed with the 500 mg formulation.

Neonates and infants aged ≤ 12 weeks (≤ 3 months):

Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin is 30 mg/kg/day divided q12h.
Adults and pediatric patients >3 months:
* Dosing for infections caused by less susceptible organisms should follow the recommendations for severe infections.
† The children's dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations. Infection Severity* Usual Usual Dose Adult Dose for Children >3 months† Ear/nose/throat Mild/Moderate 500 mg 25 mg/kg/day every 12 hours in divided doses or every 12 hours 250 mg or every 8 hours 20 mg/kg/day in divided doses every 8 hours Severe 875 mg 45 mg/kg/day every 12 hours in divided doses or every 12 hours 500 mg or every 8 hours 40 mg/kg/day in divided doses every 8 hours Lower respiratory Mild/Moderate 875 mg 45 mg/kg/day Tract or Severe every 12 hours in divided doses or every 12 hours 500 mg every or 8 hours 40 mg/kg/day in divided doses every 8 hours Skin/Skin Mild/Moderate 500 mg 25 mg/kg/day Structure every 12 hours in divided doses or every 12 hours 250 mg every or 8 hours 20 mg/kg/day in divided doses every 8 hours Severe 875 mg 45 mg/kg/day every 12 hours in divided doses or every 12 hours 500 mg every or 8 hours 40 mg/kg/day in divided doses every 8 hours Genitourinary Mild/Moderate 500 mg 25 mg/kg/day Tract every 12 hours in divided doses or every 12 hours 250 mg every or 8 hours 20 mg/kg/day in divided doses every 8 hours Severe 875 mg 45 mg/kg/day every 12 hours in divided doses or every 12 hours 500 mg or every 8 hours 40 mg/kg/day in divided doses every 8 hours Gonorrhea 3 grams Prepubertal children: Acute, as 50 mg/kg amoxicillin combined with uncomplicated single oral dose 25 mg/kg probenecid as a single dose. ano-genital and
NOTE: SINCE PROBENECID IS CONTRA-
urethral infections in males and females INDICATED IN CHILDREN UNDER 2 YEARS. DO NOT USE THIS REGIMEN IN THESE CASES.
All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS - Laboratory Tests.)

Larger doses may be required for stubborn or severe infections.

General:

It should be recognized that in the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisals are necessary. Smaller doses than those recommended above should not be used. Even higher doses may be needed at times. 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. Except for gonorrhea, treatment 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. It is recommended that there be at least 10 days' treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever.

H. pylori eradication to reduce the risk of duodenal ulcer recurrence:

Triple therapy:

Amoxicillin/clarithromycin/lansoprazole

The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (q12h) for 14 days. (See INDICATIONS AND USAGE.)

Dual therapy:

Amoxicillin/lansoprazole

The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (q8h) for 14 days. (See INDICATIONS AND USAGE.)

Please refer to clarithromycin and lansoprazole full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally impaired patients.

Dosing recommendations for adults with impaired renal function:

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of <30 mL/min. should not receive the 875-mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/minute glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

There are currently no dosing recommendations for pediatric patients with impaired renal function.
Lamotrigine

Lamotrigine

2.1 General Dosing Considerations

Rash: There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by (1) coadministration of lamotrigine with valproate, (2) exceeding the recommended initial dose of lamotrigine, or (3) exceeding the recommended dose escalation for lamotrigine. However, cases have occurred in the absence of these factors [see Boxed Warning]. Therefore, it is important that the dosing recommendations be followed closely.

The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation of lamotrigine is exceeded and in patients with a history of allergy or rash to other AEDs.

It is recommended that lamotrigine not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine, unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine, the need to restart with the initial dosing recommendations should be assessed. The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. The half-life of lamotrigine is affected by other concomitant medications [see Clinical Pharmacology (12.3)].

Lamotrigine Added to Drugs Known to Induce or Inhibit Glucuronidation: Drugs other than those listed in the Clinical Pharmacology section [see Clinical Pharmacology (12.3)] have not been systematically evaluated in combination with lamotrigine. Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine and doses of lamotrigine may require adjustment based on clinical response.

Target Plasma Levels for Patients With Epilepsy or Bipolar Disorder: A therapeutic plasma concentration range has not been established for lamotrigine. Dosing of lamotrigine should be based on therapeutic response [see Clinical Pharmacology (12.3)].

Women Taking Estrogen-Containing Oral Contraceptives:Starting lamotrigine in Women Taking Estrogen-Containing Oral Contraceptives: Although estrogen-containing oral contraceptives have been shown to increase the clearance of lamotrigine [see Clinical Pharmacology (12.3)], no adjustments to the recommended dose-escalation guidelines for lamotrigine should be necessary solely based on the use of estrogen-containing oral contraceptives. Therefore, dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine based on the concomitant AED or other concomitant medications (see Table 1 or Table 5). See below for adjustments to maintenance doses of lamotrigine in women taking estrogen-containing oral contraceptives.

Adjustments to the Maintenance Dose of lamotrigine in Women Taking Estrogen-Containing Oral Contraceptives:(1) Taking Estrogen-Containing Oral Contraceptives: For women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine will in most cases need to be increased, by as much as 2-fold over the recommended target maintenance dose, in order to maintain a consistent lamotrigine plasma level [see Clinical Pharmacology (12.3)].

(2) Starting Estrogen-Containing Oral Contraceptives: In women taking a stable dose of lamotrigine and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose will in most cases need to be increased by as much as 2-fold in order to maintain a consistent lamotrigine plasma level. The dose increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week. Dose increases should not exceed the recommended rate (see Table 1 or Table 5) unless lamotrigine plasma levels or clinical response support larger increases. Gradual transient increases in lamotrigine plasma levels may occur during the week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation. Increased lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and diplopia. If adverse reactions attributable to lamotrigine consistently occur during the pill-free week, dose adjustments to the overall maintenance dose may be necessary. Dose adjustments limited to the pill-free week are not recommended. For women taking lamotrigine in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine should be necessary.

(3) Stopping Estrogen-Containing Oral Contraceptives: For women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine will in most cases need to be decreased by as much as 50% in order to maintain a consistent lamotrigine plasma level. The decrease in dose of lamotrigine should not exceed 25% of the total daily dose per week over a 2-week period, unless clinical response or lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology (12.3)]. For women taking lamotrigine in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine should be necessary.

Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy: The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the progestin-only pills had no effect on lamotrigine plasma levels. Therefore, adjustments to the dosage of lamotrigine in the presence of progestogens alone will likely not be needed.

Patients With Hepatic Impairment: Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24 patients with mild, moderate, and severe liver impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)], the following general recommendations can be made. No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response.

Patients With Renal Impairment: Initial doses of lamotrigine should be based on patients' concomitant medications (see Tables 1-3 or Table 5); reduced maintenance doses may be effective for patients with significant renal impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. Because there is inadequate experience in this population, lamotrigine should be used with caution in these patients.

Discontinuation Strategy:Epilepsy: For patients receiving lamotrigine in combination with other AEDs, a reevaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse reactions is observed.

If a decision is made to discontinue therapy with lamotrigine, a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.9)].

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation should prolong the half-life of lamotrigine; discontinuing valproate should shorten the half-life of lamotrigine.

Bipolar Disorder: In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of lamotrigine. In clinical trials in patients with Bipolar Disorder, 2 patients experienced seizures shortly after abrupt withdrawal of lamotrigine. However, there were confounding factors that may have contributed to the occurrence of seizures in these bipolar patients. Discontinuation of lamotrigine should involve a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.9)].

2.2 Epilepsy – Adjunctive Therapy

This section provides specific dosing recommendations for patients greater than 12 years of age and patients aged 2 to 12 years. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AED or other concomitant medications (Table 1 for patients greater than 12 years of age and Table 2 for patients aged 2 to 12 years). A weight-based dosing guide for patients aged 2 to 12 years on concomitant valproate is provided in Table 3.

Patients Greater Than 12 Years of Age: Recommended dosing guidelines are summarized in Table 1.
Table 1. Escalation Regimen for Lamotrigine in Patients Greater Than 12 Years of Age With Epilepsy For Patients TAKING Valproatea For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 25 mg every other day 25 mg every day 50 mg/day Weeks 3 and 4 25 mg every day 50 mg/day
100 mg/day
(in 2 divided doses) Week 5 onwards to maintenance Increase by 25 to 50 mg/day every 1 to 2 weeks Increase by 50 mg/day every 1 to 2 weeks Increase by 100 mg/day every 1 to 2 weeks. Usual maintenance dose
100 to 200 mg/day with valproate alone

100 to 400 mg/day with valproate and other drugs that induce glucuronidation
(in 1 or 2 divided doses)
225 to 375 mg/day
(in 2 divided doses)
300 to 500 mg/day
(in 2 divided doses)
aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bThese drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.

Patients Aged 2 to 12 Years: Recommended dosing guidelines are summarized in Table 2.

Smaller starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by smaller starting doses and slower dose escalations. Therefore, maintenance doses will take longer to reach in clinical practice than in clinical trials. It may take several weeks to months to achieve an individualized maintenance dose. Maintenance doses in patients weighing less than 30 kg, regardless of age or concomitant AED, may need to be increased as much as 50%, based on clinical response.
Table 2. Escalation Regimen for Lamotrigine in Patients Aged 2 to 12 Years With Epilepsy For Patients TAKING Valproatea For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproate a Weeks 1 and 2
0.15 mg/kg/day
in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide)
0.3 mg/kg/day

in 1 or 2 divided doses, rounded down to the nearest whole tablet

0.6 mg/kg/day

in 2 divided doses, rounded down to the nearest whole tablet
Weeks 3 and 4
0.3 mg/kg/day
in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide)
0.6 mg/kg/day

in 2 divided doses, rounded down to the nearest whole tablet

1.2 mg/kg/day

in 2 divided doses, rounded down to the nearest whole tablet
Week 5 onwards to maintenance The dose should be increased every 1 to 2 weeks as follows: calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose The dose should be increased every 1 to 2 weeks as follows: calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose The dose should be increased every 1 to 2 weeks as follows: calculate 1.2 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose Usual maintenance dose
1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses)
1 to 3 mg/kg/day with valproate alone
4.5 to 7.5 mg/kg/day
(maximum 300 mg/day in 2 divided doses) 5 to 15 mg/kg/day (maximum 400 mg/day in 2 divided doses) Maintenance dose in patients less than 30 kg May need to be increased by as much as 50%, based on clinical response May need to be increased by as much as 50%, based on clinical response May need to be increased by as much as 50%, based on clinical response
Note: Only whole tablets should be used for dosing.

aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bThese drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.
Table 3. The Initial Weight-Based Dosing Guide for Patients Aged 2 to 12 Years Taking Valproate (Weeks 1 to 4) With Epilepsy If the patient’s weight is Give this daily dose, using the most appropriate combination of lamotrigine 2-mg and 5-mg tablets Greater than And less than Weeks 1 and 2 Weeks 3 and 4 6.7 kg 14 kg 2 mg every other day 2 mg every day 14.1 kg 27 kg 2 mg every day 4 mg every day 27.1 kg 34 kg 4 mg every day 8 mg every day 34.1 kg 40 kg 5 mg every day 10 mg every day
Usual Adjunctive Maintenance Dose for Epilepsy: The usual maintenance doses identified in Tables 1 and 2 are derived from dosing regimens employed in the placebo-controlled adjunctive studies in which the efficacy of lamotrigine was established. In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone without valproate, maintenance doses of adjunctive lamotrigine as high as 700 mg/day have been used. In patients receiving valproate alone, maintenance doses of adjunctive lamotrigine as high as 200 mg/day have been used. The advantage of using doses above those recommended in Tables 1 through 4 has not been established in controlled trials.

2.3 Epilepsy – Conversion From Adjunctive Therapy to Monotherapy

The goal of the transition regimen is to effect the conversion to monotherapy with lamotrigine under conditions that ensure adequate seizure control while mitigating the risk of serious rash associated with the rapid titration of lamotrigine.

The recommended maintenance dose of lamotrigine as monotherapy is 500 mg/day given in 2 divided doses.

To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of lamotrigine should not be exceeded [see Boxed Warning].

Conversion From Adjunctive Therapy With Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy With Lamotrigine: After achieving a dose of 500 mg/day of lamotrigine according to the guidelines in Table 1, the concomitant AED should be withdrawn by 20% decrements each week over a 4-week period. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial.

Conversion From Adjunctive Therapy With Valproate to Monotherapy With Lamotrigine: The conversion regimen involves 4 steps outlined in Table 4.
Table 4. Conversion From Adjunctive Therapy With Valproate to Monotherapy With Lamotrigine in Patients ≥16 Years of Age With Epilepsy Lamotrigine Valproate Step 1 Achieve a dose of 200 mg/day according to guidelines in Table 1 (if not already on 200 mg/day).
Maintain previous stable dose.
Step 2 Maintain at 200 mg/day. Decrease to 500 mg/day by decrements no greater than 500 mg/day/week and then maintain the dose of 500 mg/day for 1 week. Step 3 Increase to 300 mg/day and maintain for 1 week. Simultaneously decrease to 250 mg/day and maintain for 1 week. Step 4 Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day. Discontinue.
Conversion From Adjunctive Therapy With Antiepileptic Drugs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy With Lamotrigine: No specific dosing guidelines can be provided for conversion to monotherapy with LAMICTAL with AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate.

2.4 Bipolar Disorder

The goal of maintenance treatment with lamotrigine is to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The target dose of lamotrigine is 200 mg/day (100 mg/day in patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that increase the apparent clearance of lamotrigine). In the clinical trials, doses up to 400 mg/day as monotherapy were evaluated; however, no additional benefit was seen at 400 mg/day compared with 200 mg/day [see Clinical Studies (14.2)]. Accordingly, doses above 200 mg/day are not recommended. Treatment with lamotrigine is introduced, based on concurrent medications, according to the regimen outlined in Table 5. If other psychotropic medications are withdrawn following stabilization, the dose of lamotrigine should be adjusted. For patients discontinuing valproate, the dose of lamotrigine should be doubled over a 2-week period in equal weekly increments (see Table 6). For patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation, the dose of lamotrigine should remain constant for the first week and then should be decreased by half over a 2-week period in equal weekly decrements (see Table 6). The dose of lamotrigine may then be further adjusted to the target dose (200 mg) as clinically indicated.

If other drugs are subsequently introduced, the dose of lamotrigine may need to be adjusted. In particular, the introduction of valproate requires reduction in the dose of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of lamotrigine should not be exceeded [see Boxed Warning].
Table 5. Escalation Regimen for Lamotrigine for Patients With Bipolar Disorder For Patients TAKING Valproatea For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 25 mg every other day 25 mg daily 50 mg daily Weeks 3 and 4 25 mg daily 50 mg daily 100 mg daily, in divided doses Week 5 50 mg daily 100 mg daily 200 mg daily, in divided doses Week 6 100 mg daily 200 mg daily 300 mg daily, in divided doses Week 7 100 mg daily 200 mg daily up to 400 mg daily, in divided doses
aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bThese drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.
Table 6. Dosage Adjustments to Lamotrigine for Patients With Bipolar Disorder Following Discontinuation of Psychotropic Medications Discontinuation of Psychotropic Drugs (excluding Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea) After Discontinuation of Valproatea After Discontinuation of Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb
Current dose of LAMICTAL (mg/day)
100
Current dose of LAMICTAL (mg/day)
400 Week 1 Maintain current dose of lamotrigine 150 400 Week 2 Maintain current dose of lamotrigine 200 300 Week 3 onward Maintain current dose of lamotrigine 200 200
aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bThese drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.

The benefit of continuing treatment in patients who had been stabilized in an 8- to 16-week open-label phase with lamotrigine was established in 2 randomized, placebo-controlled clinical maintenance trials [see Clinical Studies (14.2)]. However, the optimal duration of treatment with lamotrigine has not been established. Thus, patients should be periodically reassessed to determine the need for maintenance treatment.
Dipyridamole

Dipyridamole

The dose of intravenous Dipyridamole Injection as an adjunct to thallium myocardial perfusion imaging should be adjusted according to the weight of the patient. The recommended dose is 0.142 mg/kg/min (0.57 mg/kg total) infused over 4 minutes. Although the maximum tolerated dose has not been determined, clinical experience suggests that a total dose beyond 60 mg is not needed for any patient.Prior to intravenous administration, Dipyridamole Injection should be diluted in at least a 1:2 ratio with sodium chloride injection 0.45%, sodium chloride injection 0.9% or dextrose injection 5% for a total volume of approximately 20 to 50 mL. Infusion of undiluted dipyridamole may cause local irritation.

Thallium-201 should be injected within 5 minutes following the 4-minute infusion of dipyridamole.

Do not mix Dipyridamole Injection with other drugs in the same syringe or infusion container.

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

Gabapentin

Gabapentin capsules are given orally with or without food.

If gabapentin dose is reduced, discontinued or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

Postherpetic Neuralgia

In adults with postherpetic neuralgia, gabapentin therapy may be initiated as a single 300 mg dose on Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID). The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range. Additional benefit of using doses greater than 1800 mg/day was not demonstrated.

Epilepsy

Gabapentin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.

Patients > 12 Years of Age

The effective dose of gabapentin is 900 to 1800 mg/day and given in divided doses (three times a day) using 300 or 400 mg capsules. The starting dose is 300 mg three times a day. If necessary, the dose may be increased using 300 or 400 mg capsules three times a day up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the TID schedule should not exceed 12 hours.

Pediatric Patients Age 3-12 Years

The starting dose should range from 10 to 15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of gabapentin in patients 5 years of age and older is 25-35 mg/kg/day and given in divided doses (three times a day). The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three times a day) (see CLINICAL PHARMACOLOGY, Pediatrics). Dosages up to 50 mg/kg/day have been well-tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, because there are no significant pharmacokinetic interactions among gabapentin and other commonly used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably.

If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

Dosage in Renal Impairment

Creatinine clearance is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance (CCr) can be reasonably well estimated using the equation of Cockcroft and Gault:

    for females CCr=(0.85)(140-age)(weight)/[(72)(SCr)]

    for males CCr=(140-age)(weight)/[(72)(SCr)]

Where age is in years, weight is in kilograms and SCr is serum creatinine in mg/dL.

Dosage adjustment in patients ≥ 12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).
TABLE 6. Gabapentin Dosage Based on Renal Function
a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.
   Renal Function Creatinine Clearance (mL/min)    Total Daily Dose Range (mg/day)    Dose Regimen (mg)   ≥ 60    900 to 3600    200 TID    400 TID    600 TID    800 TID    1200 TID    > 30 to 59    400 to 1400    200 BID    300 BID    400 BID    500 BID    700 BID    > 15 to 29    200 to 700    200 QD    300 QD    400 QD    500 QD    700 QD    15a    100 to 300    100 QD    125 QD    150 QD    200 QD    300 QD            Post-Hemodialysis Supplemental Dose (mg)b    Hemodialysis    125b    150b    200b    250b    350b
The use of gabapentin in patients <12 years of age with compromised renal function has not been studied.

Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.
Milrinone Lactate

Milrinone Lactate

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

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

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

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

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

Dosage Adjustment in Renally Impaired Patients

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

Morphine Sulfate

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

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

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

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

Adults

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

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

Infants and Children

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

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

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

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

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

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

Gabapentin

Gabapentin Capsules are given orally with or without food.

If Gabapentin Capsules dose is reduced, discontinued or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

Postherpetic Neuralgia

In adults with postherpetic neuralgia, Gabapentin Capsules therapy may be initiated as a single 300 mg dose on Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID). The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range. Additional benefit of using doses greater than 1800 mg/day was not demonstrated.

Epilepsy

Gabapentin Capsules are recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.

Patients > 12 Years of Age

The effective dose of Gabapentin Capsules is 900 to 1800 mg/day and given in divided doses (three times a day) using 300 or 400 mg capsules. The starting dose is 300 mg three times a day. If necessary, the dose may be increased using 300 or 400 mg capsules three times a day up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the TID schedule should not exceed 12 hours.

Pediatric Patients Age 3 - 12 years

The starting dose should range from 10 to 15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of Gabapentin Capsules in patients 5 years of age and older is 25 35 mg/kg/day and given in divided doses (three times a day). The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three times a day) (see CLINICAL PHARMACOLOGY, Pediatrics ). Dosages up to 50 mg/kg/day have been well-tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize Gabapentin Capsules therapy. Further, because there are no significant pharmacokinetic interactions among Gabapentin Capsules and other commonly used antiepileptic drugs, the addition of Gabapentin Capsules does not alter the plasma levels of these drugs appreciably.

If Gabapentin Capsules are discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

Dosage in Renal Impairment

Creatinine clearance is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance (CCr) can be reasonably well estimated using the equation of Cockcroft and Gault:

for females CCr = (0.85)(140 - age)(weight)/[(72)(SCr)]

for males CCr = (140 - age)(weight)/[(72)(SCr)]

Where age is in years, weight is in kilograms and SCr is serum creatinine in mg/dL.

Dosage adjustment in patients ≥ 12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).
TABLE 6. Gabapentin Capsules Dosage Based on Renal Function
a For patients with creatinine clearance < 15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.
Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg) ≥ 60 900 to 3600 200 TID 400 TID 600 TID 800 TID 1200 TID > 30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID > 15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15a 100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)b Hemodialysis 125b 150b 200b 250b 350b
The use of Gabapentin Capsules in patients < 12 years of age with compromised renal function has not been studied.

Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Direct Intravenous Single Injections (Bolus)

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

Continuous Intravenous Infusion

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

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

DILUTION

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

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

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

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

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

Transition to Further Antiarrhythmic Therapy

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

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

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

Midazolam

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

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

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

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

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

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

Monitoring:

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

Adults and Pediatrics:

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

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

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

Pediatrics:

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

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

Usual Adult Dose

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

When initiating an infusion with midazolam in hemodynamically compromised patients, the usual loading dose of midazolam should be titrated in small increments and the patient monitored for hemodynamic instability, e.g., hypotension. These patients are also vulnerable to the respiratory depressant effects of midazolam and require careful monitoring of respiratory rate and oxygen saturation.

CONTINUOUS INTRAVENOUS INFUSIONFor sedation in critical care settings

USUAL NEONATAL DOSEBased on pharmacokinetic parameters and reported clinical experience in preterm and term neonates WHOSE TRACHEA WAS INTUBATED, continuous intravenous infusions of Midazolam Injection should be initiated at a rate of 0.03 mg/kg/hr (0.5 mcg/kg/min) in neonates <32 weeks and 0.06 mg/kg/hr (1 mcg/kg/min) in neonates >32 weeks. Intravenous loading doses should not be used in neonates, rather the infusion may be run more rapidly for the first several hours to establish therapeutic plasma levels. The rate of infusion should be carefully and frequently reassessed, particularly after the first 24 hours so as to administer the lowest possible effective dose and reduce the potential for drug accumulation. This is particularly important because of the potential for adverse effects related to metabolism of the benzyl alcohol (see Usage in Preterm Infants and Neonates). Hypotension may be observed in patients who are critically ill and in preterm and term infants, particularly those receiving fentanyl and/or when midazolam is administered rapidly. Due to an increased risk of apnea, extreme caution is advised when sedating preterm and former preterm patients whose trachea is not intubated.

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

Primidone

Adult dosage

Patients 8 years of age and older who have received no previous treatment may be started on Primidone Tabletsaccording to the following regimen using either 50 mg or 250 mg Primidone Tablets.

Days 1 to 3: 100 to 125 mg at bedtimeDays 4 to 6: 100 to 125 mg b.i.d.Days 7 to 9: 100 to 125 mg t.i.d.Day 10 to maintenance: 250 mg t.i.d.

For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg Primidone Tablets daily in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5-12 μg/mL.

In Patients Already Receiving Other Anticonvulsants

Primidone Tablets should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with Primidone Tablets alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.

Pediatric dosage

For children under 8 years of age, the following regimen may be used:

Days 1 to 3: 50 mg at bedtimeDays 4 to 6: 50 mg b.i.d.Days 7 to 9: 100 mg b.i.d.Day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d.

For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or, 10 to 25 mg/kg/day in divided doses.
Gemfibrozil

Gemfibrozil

The recommended dose for adults is 1200 mg administered in two divided doses 30 minutes before the morning and evening meals (see CLINICAL PHARMACOLOGY).
Hydrochlorothiazide

Hydrochlorothiazide

Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.

Adults

For Edema

The usual adult dosage is 25 to 100 mg daily as a single or divided dose. Many patients with edema respond to intermittent therapy, i.e., administration on alternate days or on three to five days each week. With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.

For Control Of Hypertension

The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium (see also PRECAUTIONS).

Patients usually do not require doses in excess of 50 mg of hydrochlorothiazide daily when used concomitantly with other antihypertensive agents.

Infants and Children

For Diuresis and For Control of Hypertension

The usual pediatric dosage is 0.5 to 1 mg per pound (1 to 2 mg/kg) per day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 1.5 mg per pound (3 mg/kg) per day in two divided doses may be required (see PRECAUTIONS, Pediatric Use).
Heparin Sodium

Heparin Sodium

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Slight discoloration does not alter potency.

Confirm the choice of the correct Heparin Sodium Injection vial prior to administration of the drug to a patient. (See WARNINGS, Fatal Medication Errors.) The 1 mL vial must not be confused with a “catheter lock flush” vial or other 1 mL vial of inappropriate strength. To lessen this risk, the 1 mL vial includes a red cautionary label that extends above the main label. Read the cautionary statement and confirm that you have selected the correct medication and strength. Then locate the “Tear Here” point on the label, and remove this red cautionary label prior to removing the flip-off cap.

When heparin is added to an infusion solution for continuous intravenous administration, the container should be inverted at least six times to ensure adequate mixing and prevent pooling of the heparin in the solution.

Heparin sodium is not effective by oral administration and should be given by intermittent intravenous injection, intravenous infusion, or deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal fat layer) injection. The intramuscular route of administration should be avoided because of the frequent occurrence of hematoma at the injection site.

The dosage of heparin sodium should be adjusted according to the patient’s coagulation test results. When heparin is given by continuous intravenous infusion, the coagulation time should be determined approximately every 4 hours in the early stages of treatment. When the drug is administered intermittently by intravenous injection, coagulation tests should be performed before each injection during the early stages of treatment and at appropriate intervals thereafter. Dosage is considered adequate when the activated partial thromboplastin time (APTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. After deep subcutaneous (intrafat) injections, tests for adequacy of dosage are best performed on samples drawn 4 to 6 hours after the injection.

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

Converting to Oral Anticoagulant

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

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

Therapeutic Anticoagulant Effect With Full-Dose Heparin

Although dosage must be adjusted for the individual patient according to the results of suitable laboratory tests, the following dosage schedules may be used as guidelines:

METHOD OFADMINISTRATION
FREQUENCY RECOMMENDED DOSE[based on 150 lb (68 kg) patient] Deep Subcutaneous (Intrafat) Injection Initial dose
5,000 units by IV injection, followed by 10,000 to 20,000 units of a concentrated solution, subcutaneously
A different site should be used for each injection to prevent the development of massive hematoma
Every 8 hoursor
8,000 to 10,000 units of a concentrated solution Every 12 hours
15,000 to 20,000 units of a concentrated solution
Intermittent Intravenous Injection Initial dose
10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
Every 4 to 6 hours
5,000 to 10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
Intravenous Infusion Initial dose 5,000 units by IV injection Continuous
20,000 to 40,000 units/24 hours in 1000 mL of 0.9% Sodium Chloride Injection, USP (or in any compatible solution) for infusion

Pediatric Use

Use preservative-free Heparin Sodium Injection in neonates and infants (see WARNINGS, Benzyl Alcohol Toxicity and PRECAUTIONS, Pediatric Use).

There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. In general, the following dosage schedule may be used as a guideline in pediatric patients:

Initial Dose

75 to 100 units/kg (IV bolus over 10 minutes)

Maintenance Dose

Infants: 25 to 30 units/kg/hour; Infants < 2 months have the highest requirments (average 28 units/kg/hour)

Children > 1 year of age: 18 to 20 units/kg/hour; Older children may require less heparin, similar to weight-adjusted adult dosage

Monitoring

Adjust heparin to maintain APTT of 60 to 85 seconds, assuming this reflects an anti-Factor Xa level of 0.35 to 0.70

Geriatric Use

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

Surgery of the Heart and Blood Vessels

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

Low-Dose Prophylaxis of Postoperative Thromboembolism

A number of well-controlled clinical trials have demonstrated that low-dose heparin prophylaxis, given just prior to and after surgery, will reduce the incidence of postoperative deep vein thrombosis in the legs (as measured by the I-125 fibrinogen technique and venography) and of clinical pulmonary embolism. The most widely used dosage has been 5,000 units 2 hours before surgery and 5,000 units every 8 to 12 hours thereafter for 7 days or until the patient is fully ambulatory, whichever is longer. The heparin is given by deep subcutaneous injection in the arm or abdomen with a fine needle (25- to 26-gauge) to minimize tissue trauma. A concentrated solution of heparin sodium is recommended. Such prophylaxis should be reserved for patients over the age of 40 who are undergoing major surgery. Patients with bleeding disorders and those having neurosurgery, spinal anesthesia, eye surgery or potentially sanguineous operations should be excluded, as should patients receiving oral anticoagulants or platelet-active drugs (see WARNINGS). The value of such prophylaxis in hip surgery has not been established. The possibility of increased bleeding during surgery or postoperatively should be borne in mind. If such bleeding occurs, discontinuance of heparin and neutralization with protamine sulfate are advisable. If clinical evidence of thromboembolism develops despite low-dose prophylaxis, full therapeutic doses of anticoagulants should be given unless contraindicated. All patients should be screened prior to heparinization to rule out bleeding disorders, and monitoring should be performed with appropriate coagulation tests just prior to surgery. Coagulation test values should be normal or only slightly elevated. There is usually no need for daily monitoring of the effect of low-dose heparin in patients with normal coagulation parameters.

Extracorporeal Dialysis

Follow equipment manufacturers’ operating directions carefully.

Blood Transfusion

Addition of 400 to 600 USP units per 100 mL of whole blood is usually employed to prevent coagulation. Usually, 7,500 USP units of heparin sodium are added to 100 mL of 0.9% Sodium Chloride Injection, USP (or 75,000 USP units per 1000 mL of 0.9% Sodium Chloride Injection, USP) and mixed; from this sterile solution, 6 to 8 mL are added per 100 mL of whole blood.

Laboratory Samples

Addition of 70 to 150 units of heparin sodium per 10 to 20 mL sample of whole blood is usually employed to prevent coagulation of the sample. Leukocyte counts should be performed on heparinized blood within 2 hours after addition of the heparin. Heparinized blood should not be used for isoagglutinin, complement, or erythrocyte fragility tests or platelet counts.
Butalbital

Butalbital

One or two tablets every 4 hours. Total daily dose should not exceed 6 tablets.
Isoniazid

Isoniazid

(See also INDICATIONS): NOTE: For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: (1) the recommendations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42; RR-4, 1993 and (2) Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149; 1359-1374, 1994.

For Treatment of Tuberculosis - Isoniazid is used in conjunction with other effective anti-tuberculosis agents. Drug susceptibility testing should be performed on the organisms initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli become resistant, therapy must be changed to agents to which the bacilli are susceptible.

Usual Oral Dosage (depending on the regimen used):
Adults: 5 mg/kg up to 300 mg daily in a single dose; or 15 mg/kg up to 900 mg day, two or three times/week Children: 10-15 mg/kg up to 300 mg daily in a single dose; or 20-40 mg/kg up to 900 mg/day, two or three time/week
Patients with Pulmonary Tuberculosis Without HIV Infection

There are 3 regimen options for the initial treatment of tuberculosis in children and adults:

Option 1: Daily isoniazid, rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of isoniazid and rifampin daily or 2-3 times weekly. Ethambutol or streptomycin should be added to the initial regimen until sensitivity to isoniazid and rifampin is demonstrated. The addition of a fourth drug is optional if the relative prevalence of isoniazid-resistant Mycobacterium tuberculosis isolates in the community is less than or equal to four percent.

Option 2: Daily isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol for 2 weeks followed by twice weekly administration of the same drugs for 6 weeks, subsequently twice weekly isoniazid and rifampin for 16 weeks.

Option 3: Three times weekly with isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin for 6 months.

*All regimens given twice weekly or 3 times weekly should be administered by directly observed therapy (see also Directly Observed Therapy).

The above treatment guidelines apply only when the disease is caused by organisms that are susceptible to the standard antituberculous agents. Because of the impact of resistance to isoniazid and rifampin on the response to therapy, it is essential that physicians initiating therapy for tuberculosis be familiar with the prevalence of drug resistance in their communities. It is suggested that ethambutol not be used in children whose visual acuity cannot be monitored.

Patients with Pulmonary Tuberculosis and HIV Infection

The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness. For this reason, therapeutic decisions for the impaired host must be individualized. Since patients co-infected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of MDRTB.

Patients with Extra pulmonary Tuberculosis

The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease. Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective. Because of the insufficient data, miliary tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 months therapy.

Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative inaccessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings.

The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Pott's Disease. Corticosteriods have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.

Pregnant Women with Tuberculosis

The options listed above must be adjusted for the pregnant patient. Streptomycin interferes with in utero development of the ear and may cause congenital deafness. Routine use of pyrazinamide is also not recommended in pregnancy because of inadequate teratogenicity data. The initial treatment regimen should consist of isoniazid and rifampin. Ethambutol should be included unless primary isoniazid resistance is unlikely (isoniazid resistance rate documented to be less than 4%).

Treatment of Patients with Multi-Drug Resistant Tuberculosis (MDRTB)

Multiple-drug resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended.

Directly Observed Therapy (DOT)

A major cause of drug-resistant tuberculosis is patient non-compliance with treatment. The use of DOT can help assure patient compliance with drug therapy. DOT is the observation of the patient by a health care provider or other responsible person as the patient ingests anti-tuberculosis medications. DOT can be achieved with daily, twice weekly or thrice weekly regimens, and is recommended for all patients.

For Preventative Therapy of Tuberculosis

Before isoniazid preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Appropriate evaluations should be performed if Extra pulmonary tuberculosis is suspected.

Adults over 30 Kg: 300 mg per day in a single dose.

Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose. In situations where adherence with daily preventative therapy cannot be assured, 20-30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of administration8.

Continuous administration of isoniazid for a sufficient period is an essential part of the regimen because relapse rates are higher if chemotherapy is stopped prematurely. In the treatment of tuberculosis, resistant organisms may multiply and the emergence of resistant organisms during the treatment may necessitate a change in the regimen.

For following patient compliance: the Potts-Cozart test9, a simple colorimetric6 method of checking for isoniazid in the urine, is a useful tool for assuring patient compliance, which is essential for effective tuberculosis control. Additionally, isoniazid test strips are also available to check patient compliance.

Concomitant administration of pyridoxine (B6) is recommended in the malnourished and in those predisposed to neuropathy (e.g., alcoholics and diabetics).
Lorazepam

Lorazepam

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

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

Status Epilepticus

GENERAL ADVICE

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

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

INTRAVENOUS INJECTION

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

INTRAMUSCULAR INJECTION

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

PEDIATRIC

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

Preanesthetic

INTRAMUSCULAR INJECTION

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

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

INTRAVENOUS INJECTION

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

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

Dose Administration in Special Populations

ELDERLY PATIENTS AND PATIENTS WITH HEPATIC DISEASE

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

PATIENTS WITH RENAL DISEASE

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

DOSE ADJUSTMENT DUE TO DRUG INTERACTIONS

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

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

Administration

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

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

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

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

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

Ciprofloxacin

ADULTS

Ciprofloxacin tablets should be administered orally to adults as described in the Dosage Guidelines table.

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defense mechanisms, and the status of renal function and hepatic function.

The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder for oral solution, other highly buffered drugs, or other products containing calcium, iron or zinc.
ADULT DOSAGE GUIDELINES Infection Severity Dose Frequency Usual Durations†         Urinary Tract      Acute Uncomplicated      250 mg       q 12 h      3 Days      Mild/Moderate      250 mg       q 12 h      7 to 14 Days      Severe/Complicated      500 mg       q 12 h      7 to 14 Days      Chronic Bacterial Prostatitis          Mild/Moderate      500 mg       q 12 h      28 Days      Lower Respiratory Tract      Mild/Moderate      500 mg       q 12 h      7 to 14 days      Severe/Complicated      750 mg       q 12 h      7 to 14 days      Acute Sinusitis      Mild/Moderate      500 mg       q 12 h      10 days      Skin and Skin Structure      Mild/Moderate      500 mg       q 12 h      7 to 14 Days      Severe/Complicated      750 mg       q 12 h      7 to 14 Days      Bone and Joint      Mild/Moderate      500 mg       q 12 h      ≥4 to 6 weeks      Severe/Complicated      750 mg       q 12 h      ≥4 to 6 weeks      Intra-Abdominal*      Complicated         500 mg       q 12 h      7 to 14 Days      Infectious Diarrhea      Mild/Moderate/Severe          500 mg       q 12 h      5 to 7 Days      Typhoid Fever      Mild/Moderate      500 mg       q 12 h      10 Days      Urethral and Cervical    Gonococcal Infections      Uncomplicated      250 mg       single dose      single dose      Inhalational anthrax(post-exposure)**          500 mg       q 12 h      60 Days
  *  used in conjunction with metronidazole † Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection     have disappeared, except for inhalational anthrax (post-exposure). **  Drug administration should begin as soon as possible after suspected or confirmed exposure.

This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.4 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION.Conversion of IV to Oral Dosing in Adults Patients whose therapy is started with Ciprofloxacin I.V. may be switched to Ciprofloxacin Tablets when clinically indicated at the discretion of the physician (See CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens).
Equivalent AUC Dosing Regimens Ciprofloxacin Oral Dosage Equivalent Ciprofloxacin IV Dosage   250 mg Tablet q 12 h   200 mg IV q 12 h   500 mg Tablet q 12 h   400 mg IV q 12 h   750 mg Tablet q 12 h   400 mg IV q 8 h
Adults with Impaired Renal Function Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:
RECOMMENDED STARTING AND MAINTENANCE DOSES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION Creatinine Clearance (mL/min) Dose   > 50      See Usual Dosage.   30 – 50      250 – 500 mg q 12 h   5 – 29      250 – 500 mg q 18 h      Patients on hemodialysis      or Peritoneal dialysis          250 – 500 mg q 24 h      (after dialysis) When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance.                                                                       Weight (kg) x (140 - age) Men: Creatinine clearance (mL/min) =         72 x serum creatinine (mg/dL) Women: 0.85 x the value calculated for men. The serum creatinine should represent a steady state of renal function. In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals noted above. Patients should be carefully monitored.
PEDIATRICS
Ciprofloxacin Tablets should be administered orally as described in the Dosage Guidelines table. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See ADVERSE REACTIONS and CLINICAL STUDIES.) Dosing and initial route of therapy (i.e., I.V. or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg I.V. every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician. PEDIATRIC DOSAGE GUIDELINES Infection RouteofAdministration Dose (mg/kg) Frequency TotalDuration     Complicated Urinary Tract or Pyelonephritis   Intravenous   6 to 10 mg/kg(maximum 400 mgper dose; not to be exceeded  even in patients weighing > 51 kg)   Every 8 hours    10-21 days*     (Patients from 1 to 17 years of age)   Oral   10 mg/kg to 20 mg/kg   (maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg)   Every 12 hours     Inhalational Anthrax (Post-Exposure)**   Intravenous   10 mg/kg(maximum 400 mg per  dose)   Every 12 hours    60 days   Oral   15 mg/kg(maximum 500 mg per dose)   Every 12 hours * The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). ** Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit. 5 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION. Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of complicated urinary tract infection and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (i.e., creatinine clearance of < 50 mL/min/1.73m 2).
Atropine Sulfate

Atropine Sulfate

The usual dose of atropine sulfate is 0.4 to 0.6 mg. Suggested dosages for pediatric patients are as follows:7 - 16 lbs. – 0.1 mg 40 - 65 lbs. – 0.3 mg17 - 24 lbs. – 0.15 mg 65 - 90 lbs. – 0.4 mg24 - 40 lbs. – 0.2 mg Over 90 lbs. – 0.4 to 0.6 mg
Table of Dosage Equivalents Atropine Sulfate Solution (mL required) mg required 1 mg per mL 0.4 mg per mL 1 1 0.80 0.80 0.60 0.60 0.50 0.50 0.40 0.40 1 0.30 0.30 0.75 0.25 0.25 0.63 0.20 0.20 0.50 0.18 0.18 0.45 0.15 0.15 0.38 0.12 0.12 0.30 0.10 0.10 0.25
These doses may be exceeded in certain cases.For hypotonic radiography of the gastrointestinal tract, the usual adult dose is 1 mg intramuscularly.Adults suspected of contact with organic phosporous insecticides of the parathion type should be given atropine sulfate 0.8 mg intramuscularly. If an atropine effect is not apparent within 30 minutes or if definite symptoms of the poisoning occur (nausea, vomiting, diarrhea, pupillary constriction, pulmonary edema, fasciculations of eyelids and tongue, jerky ocular movements and excessive sweating, salivation and bronchial secretion), atropine sulfate 2 mg should be given intramuscularly at hourly intervals until signs of atropinization are observed. Up to 2 or 3 times of this dose (4 to 6 mg) may be required in severe cases.

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

Folic Acid

Oral administration is preferred. Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid given orally. Parenteral administration is not advocated but may be necessary in some individuals (e.g., patients receiving parenteral or enteral alimentation). Doses greater than 0.1 mg should not be used unless anemia due to vitamin B12 deficiency has been ruled out or is being adequately treated with cobalamin. Daily doses greater than 1 mg do not enhance the hematologic effect, and most of the excess is excreted unchanged in the urine.

The usual therapeutic dosage in adults and children (regardless of age) is up to 1 mg daily. Resistant cases may require larger doses.

When clinical symptoms have subsided and the blood picture has become normal, a daily maintenance level should be used, i.e., 0.1 mg for infants and up to 0.3 mg for children under 4 years of age, 0.4 mg for adults and children 4 or more years of age, and 0.8 mg for pregnant and lactating women, but never less than 0.1 mg/day. Patients should be kept under close supervision and adjustment of the maintenance level made if relapse appears imminent.

In the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection, the maintenance level may need to be increased.
Isosorbide

Isosorbide

The recommended starting dose of Isosorbide Mononitrate Tablets is 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily. After several days, the dosage may be increased to 120 mg (given as a single 120 mg tablet or as two 60 mg tablets) once daily. Rarely, 240 mg may be required. The daily dose of Isosorbide Mononitrate Tablets should be taken in the morning on arising. Isosorbide Mononitrate Extended-Release Tablets should not be chewed or crushed and should be swallowed together with a half-glassful of fluid. Do not break the 30 mg tablet.
Glycopyrrolate

Glycopyrrolate

The dosage of Glycopyrrolate Tablets should be adjusted to the needs of the individual patient to assure symptomatic control with a minimum of adverse reactions. The presently recommended maximum daily dosage of glycopyrrolate is 8 mg. Glycopyrrolate 1 mg Tablets. The recommended initial dosage of Glycopyrrolate Tablets 1 mg for adults is one tablet three times daily (in the morning, early afternoon, and at bedtime). Some patients may require two tablets at bedtime to assure overnight control of symptoms. For maintenance, a dosage of one tablet twice a day is frequently adequate. Glycopyrrolate 2 mg Tablets. The recommended dosage of Glycopyrrolate Tablets 2 mg for adults is one tablet two or three times daily at equally spaced intervals. Glycopyrrolate Tablets are not recommended for use in pediatric patients under the age of 12 years.
Bumetanide

Bumetanide

Dosage should be individualized with careful monitoring of patient response.

Parenteral Administration

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

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

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

Miscibility and Parenteral Solutions

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

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

Aminophylline

General Considerations:

The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a peak serum theophylline concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance (e.g., 400-1600 mg/day in adults <60 years old and 10-36 mg/kg/day in children 1-9 years old). For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either sub-therapeutic or potentially toxic serum theophylline concentrations in individual patients. For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1-9 years, the steady-state peak serum theophylline concentration will be <10 mcg/mL in about 30% of patients, 10-20 mcg/mL in about 50% and 20-30 mcg/mL in about 20% of patients. The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.

Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated, in small increments (See Table V). Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum theophylline concentrations to reach the new steady state. Dosage adjustment should be guided by serum theophylline concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI). Health care providers should instruct patients and care givers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (see WARNINGS).

If the patient's symptoms are well controlled, there are no apparent adverse effects, and no intervening factors that might alter dosage requirements (see WARNINGS and PRECAUTIONS), serum theophylline concentrations should be monitored at 6 month intervals for rapidly growing children and at yearly intervals for all others. In acutely ill patients, serum theophylline concentrations should be monitored at frequent intervals, e.g., every 24 hours.

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

Table V contains theophylline dosing titration schema recommended for patients in various age groups and clinical circumstances. Table VI contains recommendations for theophylline dosage adjustment based upon serum theophylline concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient. In general, these recommendations should serve as the upper limit for dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum theophylline concentration.
Table V. Dosing initiation and titration ╖ [*Aminophylline equivalent in (*)]
╖ Patients with more rapid metabolism, clinically identified by higher than average dose requirements, should receive a smaller dose more frequently to prevent breakthrough symptoms resulting from low trough concentrations before the next dose. A reliably absorbed slow-release formulation will decrease fluctuations and permit longer dosing intervals.
A. Children (1-15 years) and adults (16-60 years) without risk factors for impaired clearance. Titration Step Children < 45 kg Children > 45 kg and adults 1. Starting Dosage 12-14 (*15.2-17.7) mg/kg/day up to a maximum of 300 (*380)mg/day divided Q4-6 hrs ╖ 300 (*380) divided Q6-8 hrs ╖ 2. After 3 days, if tolerated,, increase dose to: 16 (*20.3) mg/kg/day up to a maximum of 400 (*507) mg/day divided Q4-6 hrs ╖ 400 (*507) mg/day divided Q6-8 hrs ╖ 3. After 3 more days, if tolerated.increase dose to: 20 (*25.3) mg/kg/day up to a maximum of 600 mg (*760) mg/day divided Q4-6 hrs ╖ 600 (*760) mg/day divided Q6-8 hrs ╖
B.Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations: In children 1-15 years of age, the final theophylline dose should not exceed 16 (*20.3) mg/kg/day up to a maximum of 400 (*507) mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations.

In adolescents ≥16 years and adults, including the elderly, the final theophylline dose should not exceed 400 (*507) mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations.

C.Loading Dose for Acute Bronchodilatation: An inhaled beta-2 selective agonist, alone or in combination with a systemically administered corticosteroid, is the most effective treatment for acute exacerbations of reversible airways obstruction. Theophylline is a relatively weak bronchodilator, is less effective than an inhaled beta-2 selective agonist and provides no added benefit in the treatment of acute bronchospasm. If an inhaled or parenteral beta agonist is not available, a loading dose of an oral immediate release theophylline can be used as a temporary measure. A single 5 mg/kg dose of theophylline, in a patient who has not received any theophylline in the previous 24 hours, will produce an average peak serum theophylline concentration of 10 mcg/mL (range 5-15 mcg/mL). If dosing with theophylline is to be continued beyond the loading dose, the guidelines in Sections A.3, or B., above, should be utilized and serum theophylline concentration monitored at 24 hour intervals to adjust final dosage.
Table VI. Dosage adjustment guided by serum theophylline concentration.
¶ Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS).
Peak Serum Concentration Dosage Adjustment <9.9 mcg/mL If symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Recheck serum concentration after three days for further dosage adjustment 10 to 14.9 mcg/mL If symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6-12 month intervals.¶ If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. 15-19.9 mcg/mL Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated.¶ 20-24.9 mcg/mL Decrease dose by 25% eyen if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. 25-30 mcg/mL Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated (see recommendations for chronic overdosage). >30 mcg/mL Treat overdose as indicated (see recommendations for chronic overdosage). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.
Cephalexin

Cephalexin

Cephalexin capsules, USP are administered orally.

Adults

The adult dosage ranges from 1 to 4 g daily in divided doses. The 333 mg and 750 mg strengths should be administered such that the daily dose is within 1 to 4 grams per day. The usual adult dose is 250 mg every 6 hours. For the following infections, a dosage of 500 mg may be administered every 12 hours: streptococcal pharyngitis, skin and skin structure infections, and uncomplicated cystitis in patients over 15 years of age. Cystitis therapy should be continued for 7 to 14 days. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of Cephalexin capsules, USP greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered.

Pediatric Patients

Cephalexin Oral Suspension may be better suited for certain dosages in the pediatric population.

The usual recommended daily dosage for pediatric patients is 25 to 50 mg/kg in divided doses. For streptococcal pharyngitis in patients over 1 year of age and for skin and skin structure infections, the total daily dose may be divided and administered every 12 hours.

In severe infections, the dosage may be doubled.

In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required.

In the treatment of β-hemolytic streptococcal infections, a therapeutic dosage of Cephalexin capsules, USP should be administered for at least 10 days.
Ativan

Ativan

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

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

Status Epilepticus

GENERAL ADVICE

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

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

INTRAVENOUS INJECTION

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

INTRAMUSCULAR INJECTION

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

PEDIATRIC

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

Preanesthetic

INTRAMUSCULAR INJECTION

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

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

INTRAVENOUS INJECTION

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

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

Dose Administration in Special Populations

ELDERLY PATIENTS AND PATIENTS WITH HEPATIC DISEASE

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

PATIENTS WITH RENAL DISEASE

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

DOSE ADJUSTMENT DUE TO DRUG INTERACTIONS

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

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

Administration

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

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

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

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

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

Lorazepam

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

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

Status Epilepticus

GENERAL ADVICE

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

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

INTRAVENOUS INJECTION

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

INTRAMUSCULAR INJECTION

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

PEDIATRIC

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

Preanesthetic

INTRAMUSCULAR INJECTION

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

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

INTRAVENOUS INJECTION

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

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

Dose Administration in Special Populations

ELDERLY PATIENTS AND PATIENTS WITH HEPATIC DISEASE

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

PATIENTS WITH RENAL DISEASE

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

DOSE ADJUSTMENT DUE TO DRUG INTERACTIONS

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

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

Administration

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

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

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

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

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

Famotidine

In some hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, Famotidine Injection may be administered until oral therapy can be instituted.The recommended dosage for Famotidine Injection in adult patients is 20 mg intravenously q 12 h.The doses and regimen for parenteral administration in patients with GERD have not been established.

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

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

Dosage for Pediatric Patients 1-16 Years of Age

See PRECAUTIONS, Pediatric Patients 1-16 Years of Age.The studies described in PRECAUTIONS, Pediatric Patients 1-16 Years of Age suggest that the starting dose in pediatric patients 1-16 years of age is 0.25 mg/kg intravenously (injected over a period of not less than two minutes or as a 15-minute infusion) q 12 h up to 40 mg/day.While published uncontrolled clinical studies suggest effectiveness of famotidine in the treatment of peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or gastric pH determination and endoscopy. Published uncontrolled studies in pediatric patients 1-16 years of age have demonstrated gastric acid suppression with doses up to 0.5 mg/kg intravenously q 12 h.

Dosage Adjustments for Patients with Moderate or Severe Renal Insufficiency

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

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

The dosage of famotidine in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult intravenous dose is 20 mg q 12 h. Doses should be adjusted to individual patient needs and should continue as long as clinically indicated. In some patients, a higher starting dose may be required. Oral doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.To prepare intravenous solutions, aseptically dilute 2 mL of Famotidine Injection (solution containing 10 mg/mL) with Sodium Chloride Injection 0.9% or other compatible intravenous solution (see Stability) to a total volume of either 5 mL or 10 mL and inject over a period of not less than 2 minutes.To prepare intravenous infusion solutions, aseptically dilute 2 mL of Famotidine Injection with 100 mL of Dextrose 5% or other compatible solution (see Stability), and infuse over a 15-30 minute period.

Concomitant Use of Antacids

Antacids may be given orally concomitantly if needed.

Stability

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.When added to or diluted with most commonly used intravenous solutions, e.g., Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5% and 10% or Lactated Ringer’s Injection, diluted Famotidine Injection is physically and chemically stable (i.e., maintains at least 90% of initial potency) for 7 days at room temperature–see HOW SUPPLIED, Storage.When added to or diluted with Sodium Bicarbonate Injection 5%, Famotidine Injection at a concentration of 0.2 mg/mL (the recommended concentration of famotidine intravenous infusion solutions) is physically and chemically stable (i.e., maintains at least 90% of initial potency) for 7 days at room temperature–see HOW SUPPLIED, Storage. However, a precipitate may form at higher concentrations of Famotidine Injection (>0.2 mg/mL) in Sodium Bicarbonate Injection 5%.
Dopram

Dopram

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS)

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

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

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

BY INFUSION

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

In the Management of Drug-Induced CNS Depression

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

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

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

Diluent Compatibility

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

Incompatibility

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

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

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

Adenosine

For rapid bolus intravenous use only.

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

Adult Patients

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

The recommended intravenous doses for adults are as follows:

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

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

Pediatric Patients

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

Pediatric Patients with a Body Weight < 50 kg:

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

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

Pediatric Patients with a Body Weight > 50 kg:

Administer the adult dose.

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

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

Ampicillin And Sulbactam

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

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

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

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

Pediatric Patients 1 Year of Age or Older:

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

Impaired Renal Function

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

Sufentanil Citrate

The dosage of sufentanil should be individualized in each case according to body weight, physical status, underlying pathological condition, use of other drugs, and type of surgical procedure and anesthesia. In obese patients (more than 20% above ideal total body weight), the dosage of sufentanil should be determined on the basis of lean body weight. Dosage should be reduced in elderly and debilitated patients (see PRECAUTIONS).

Vital signs should be monitored routinely.

Because the clearance of sufentanil is reduced in neonates, especially those with cardiovascular disease, the dose of sufentanil should be reduced accordingly (see PRECAUTIONS).

Intravenous Use

Sufentanil citrate may be administered intravenously by slow injection or infusion 1) in doses up to 8 mcg/kg as an analgesic adjunct to general anesthesia and 2) in doses ≥ 8 mcg/kg as a primary anesthetic agent for induction and maintenance of anesthesia (see Dosage Range Chart). If benzodiazepines, barbiturates, inhalation agents, other opioids or other central nervous system depressants are used concomitantly, the dose of sufentanil and/or these agents should be reduced (see PRECAUTIONS). In all cases, dosage should be titrated to individual patient response.

Usage In Children

For induction and maintenance of anesthesia in pediatric patients less than 12 years of age undergoing cardiovascular surgery, an anesthetic dose of 10-25 mcg/kg administered with 100% oxygen is generally recommended. Supplemental dosages of up to 25-50 mcg are recommended for maintenance, based on response to initial dose and as determined by changes in vital signs indicating surgical stress or lightening of anesthesia.

Premedication

The selection of preanesthetic medications should be based upon the needs of the individual patient.

Neuromuscular Blocking Agents

The neuromuscular blocking agent selected should be compatible with the patient’s condition, taking into account the hemodynamic effects of a particular muscle relaxant and the degree of skeletal muscle relaxation required (see CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS).
ADULT DOSAGE RANGE CHART for Intravenous use (expressed as sufentanil) ANALGESIC COMPONENT TO GENERAL ANESTHESIA TOTAL DOSAGE REQUIREMENTS OF 1 MCG/KG/HR OR LESS ARE RECOMMENDED TOTAL DOSAGE MAINTENANCE DOSAGE ANALGESIC DOSAGES Incremental or Infusion 1–2 mcg/kg (expected duration of anesthesia 1–2 hours). Approximately 75% or more of the total sufentanil dosage may be administered prior to intubation by either slow injection or infusion titrated to individual patient response. Dosages in this range are generally administered with nitrous oxide/oxygen in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required. Incremental 10–25 mcg (0.2–0.5 mL) may be administered in increments as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. Supplemental dosages should be individualized and adjusted to the remaining operative time anticipated. Infusion Sufentanil citrate may be administered as an intermittent or continuous infusion as needed in response to signs of lightening of analgesia. In absence of signs of lightening of analgesia, infusion rates should always be adjusted downward until there is some response to surgical stimulation. Maintenance infusion rates should be adjusted based upon the induction dose of sufentanil so that the total dose does not exceed 1 mcg/kg/hr of expected surgical time. Dosage should be individualized and adjusted to the remaining operative time anticipated. ANALGESIC DOSAGES Incremental or Infusion 2-8 mcg/kg (expected duration of anesthesia 2–8 hours). Approximately 75% or less of the total calculated sufentanil dosage may be administered by slow injection or infusion prior to intubation, titrated to individual patient response. Dosages in this range are generally administered with nitrous oxide/oxygen in patients undergoing more complicated major surgical procedures in which endotracheal intubation and mechanical ventilation are required. At dosages in this range, sufentanil has been shown to provide some attenuation of sympathetic reflex activity in response to surgical stimuli, provide hemodynamic stability and provide relatively rapid recovery. Incremental 10–50 mcg (0.2–1 mL) may be administered in increments as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. Supplemental dosages should be individualized and adjusted to the remaining operative time anticipated. Infusion Sufentanil citrate may be administered as an intermittent or continuous infusion as needed in response to signs of lightening of analgesia. In absence of signs of lightening of analgesia, infusion rates should always be adjusted downward until there is some response to surgical stimulation. Maintenance infusion rates should be adjusted based upon the induction dose of sufentanil so that the total dose does not exceed 1 mcg/kg/hr of expected surgical time. Dosage should be individualized and adjusted to the remaining operative time anticipated. ANESTHETIC DOSAGES Incremental or Infusion 8–30 mcg/kg (anesthetic doses). At this anesthetic dosage range, sufentanil is generally administered as a slow injection, as an infusion or as an injection followed by an infusion. Sufentanil with 100% oxygen and a muscle relaxant has been found to produce sleep at dosages ≥ 8 mcg/kg and to maintain a deep level of anesthesia without the use of additional anesthetic agents. The addition of N2O to these dosages will reduce systolic blood pressure. At dosages in this range of up to 25 mcg/kg, catecholamine release is attenuated. Dosages of 25–30 mcg/kg have been shown to block sympathetic response including catecholamine release. High doses are indicated in patients undergoing major surgical procedures in which endotracheal intubation and mechanical ventilation are required, such as cardiovascular surgery and neurosurgery in the sitting position with maintenance of favorable myocardial and cerebral oxygen balance. Postoperative observation is essential and postoperative mechanical ventilation may be required at the higher dosage range due to extended postoperative respiratory depression. Dosage should be titrated to individual patient response. Incremental Depending on the initial dose, maintenance doses of 0.5–10 mcg/kg may be administered by slow injection in anticipation of surgical stress such as incision, sternotomy or cardiopulmonary bypass. Infusion Sufentanil citrate may be administered by continuous or intermittent infusion as needed in response to signs of lightening of anesthesia. In the absence of lightening of anesthesia, infusion rates should always be adjusted downward until there is some response to surgical stimulation. The maintenance infusion rate for sufentanil should be based upon the induction dose so that the total dose for the procedure does not exceed 30 mcg/kg.
In patients administered high doses of sufentanil, it is essential that qualiﬁed personnel and adequate facilities are available for the management of postoperative respiratory depression.

Also see WARNINGS and PRECAUTIONS sections.

For purposes of administering small volumes of Sufentanil Citrate Injection accurately, the use of a tuberculin syringe or equivalent is recommended.
EPIDURAL USE IN LABOR AND DELIVERY Proper placement of the needle or catheter in the epidural space should be veriﬁed before sufentanil citrate is injected to assure that unintentional intravascular or intrathecal administration does not occur. Unintentional intravascular injection of sufentanil could result in a potentially serious overdose, including acute truncal muscular rigidity and apnea. Unintentional intrathecal injection of the full sufentanil-bupivacaine epidural doses and volume could produce effects of high spinal anesthesia, including prolonged paralysis and delayed recovery. If analgesia is inadequate, the placement and integrity of the catheter should be veriﬁed prior to the administration of any additional epidural medications. Sufentanil should be administered by slow injection. Respiration should be closely monitored following each administration of an epidural injection of sufentanil. DOSAGE FOR LABOR AND DELIVERY The recommended dosage is sufentanil 10–15 mcg administered with 10 mL bupivacaine 0.125% with or without epinephrine. Sufentanil and bupivacaine should be mixed together before administration. Doses can be repeated twice (for a total of three doses) at not less than one hour intervals until delivery.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Infumorph 200

Infumorph 200

INFUMORPH 200 AND 500 (10 AND 25 MG/ML, RESPECTIVELY) SHOULD NOT BE USED FOR SINGLE-DOSE NEURAXIAL INJECTION BECAUSE LOWER DOSES CAN BE MORE RELIABLY ADMINISTERED WITH THE STANDARD PREPARATION OF DURAMORPH (0.5 AND 1 MG/ML).

CANDIDATES FOR NEURAXIAL ADMINISTRATION OF INFUMORPH IN A CONTINUOUS MICROINFUSION DEVICE SHOULD BE HOSPITALIZED TO PROVIDE FOR ADEQUATE PATIENT MONITORING DURING ASSESSMENT OF RESPONSE TO SINGLE DOSES OF INTRATHECAL OR EPIDURAL MORPHINE. HOSPITALIZATION SHOULD BE MAINTAINED FOR SEVERAL DAYS AFTER SURGERY INVOLVING THE INFUSION DEVICE FOR ADDITIONAL MONITORING AND ADJUSTMENT OF DAILY DOSAGE. THE FACILITY MUST BE EQUIPPED WITH RESUSCITATIVE EQUIPMENT, OXYGEN, NALOXONE INJECTION AND OTHER RESUSCITATIVE DRUGS. BECAUSE OF THE RISK OF DELAYED RESPIRATORY DEPRESSION, PATIENTS SHOULD BE OBSERVED IN A FULLY EQUIPPED AND STAFFED ENVIRONMENT FOR AT LEAST 24 HOURS AFTER EACH TEST DOSE AND, AS INDICATED, FOR THE FIRST SEVERAL DAYS AFTER SURGERY.

Familiarization with the continuous microinfusion device is essential. The desired amount of morphine should be withdrawn from the ampul through a microfilter. To minimize risk from glass or other particles, the product must be filtered through a 5 µ (or smaller) microfilter before injecting into the microinfusion device. If dilution is required, 0.9% Sodium Chloride Injection is recommended.

Intrathecal Dosage:

The starting dose must be individualized, based upon in‑hospital evaluation of the response to serial single-dose intrathecal bolus injections of regular DURAMORPH (Morphine Sulfate Injection, USP) 0.5 mg/mL or 1 mg/mL, with close observation of the analgesic efficacy and adverse effects prior to surgery involving the continuous microinfusion device.

The recommended initial lumbar intrathecal dose range in patients with no tolerance to opioids is 0.2 to 1 mg/day. The published range of doses for individuals who have some degree of opioid tolerance varies from 1 to 10 mg/day. The upper daily dosage limit for each patient must be individualized.

Limited experience with continuous intrathecal infusion of morphine has shown that the daily doses have to be increased over time. Although the rate of increase, over time, in the dose required to sustain analgesia is highly variable, an estimate of the expected rate of increase is shown in the following Figure.

Doses above 20 mg/day should be employed with caution since they may be associated with a higher likelihood of serious side effects (see WARNINGS concerning potential neurological hazards and ADVERSE REACTIONS).

GERIATRIC:

Administer with extreme caution. (See PRECAUTIONS.)

Epidural Dosage:

The starting dose must be individualized, based upon in-hospital evaluation of the response to serial single-dose epidural bolus injections of regular DURAMORPH (Morphine Sulfate Injection, USP) 0.5 mg/mL or 1 mg/mL, with dose observation for analgesic efficacy and adverse effects prior to surgery involving the continuous microinfusion device.

The recommended initial epidural dose in patients who are not tolerant to opioids ranges from 3.5 to 7.5 mg/day. The usual starting dose for continuous epidural infusion, based upon limited data in patients who have some degree of opioid tolerance, is 4.5 to 10 mg/day. The dose requirements may increase significantly during treatment, frequently to 20-30 mg/day. The upper daily limit for each patient must be individualized.

GERIATRIC USE:

Administer with extreme caution. (See PRECAUTIONS.)
Fentanyl Citrate

Fentanyl Citrate

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

Single Dose - Destroy unused contents. 50 mcg = 0.05 mg = 1 mL

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

Vital signs should be monitored routinely.

I. Premedication

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

II. Adjunct to General Anesthesia

See Dosage Range Charts.

III. Adjunct to Regional Anesthesia

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

IV. Postoperatively (recovery room)

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

Usage in Children

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

Dosage Range Chart
Total Dosage (expressed as fentanyl base) Low dose—2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). Fentanyl in small doses is most useful for minor, but painful, surgical procedures. In addition to the analgesia during surgery, fentanyl may also provide some pain relief in the immediate postoperative period. Moderate dose—2 to 20 mcg/kg (0.002 to 0.02 mg/kg) (0.04 to 0.4 mL/kg). Where surgery becomes more major, a larger dose is required. With this dose, in addition to adequate analgesia, one would expect to see some abolition of the stress response. However, respiratory depression will be such that artificial ventilation during anesthesia is necessary, and careful observation of ventilation postoperatively is essential. High dose—20 to 50 mcg/kg (0.02 to 0.05 mg/kg) (0.4 to 1 mL/kg). During open heart surgery and certain more complicated neurosurgical and orthopedic procedures where surgery is more prolonged, and in the opinion of the anesthesiologist, the stress response to surgery would be detrimental to the well being of the patient, dosages of 20 to 50 mcg/kg (0.02 to 0.05 mg/kg) (0.4 to 1 mL/kg) of fentanyl with nitrous oxide/oxygen have been shown to attenuate the stress response as defined by increased levels of circulating growth hormone, catecholamine, ADH and prolactin. When dosages in this range have been used during surgery, postoperative ventilation and observation are essential due to extended post-operative respiratory depression. The main objective of this technique would be to produce “stress free” anesthesia.
Dosage Range Chart
Maintenance Dose (expressed as fentanyl base) Low dose—2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). Additional dosages of fentanyl are infrequently needed in these minor procedures. Moderate dose—2 to 20 mcg/kg (0.002 to 0.02 mg/kg) (0.04 to 0.4 mL/kg). 25 to 100 mcg (0.025 to 0.1 mg) (0.5 to 2 mL) may be administered intravenously or intramuscularly when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. High dose—20 to 50 mcg/kg (0.02 to 0.05 mg/kg) (0.4 to 1 mL/kg). Maintenance dosage (ranging from 25 mcg [0.025 mg] [0.5 mL] to one half the initial loading dose) will be dictated by the changes in vital signs which indicate stress and lightening of analgesia. However, the additional dosage selected must be individualized especially if the anticipated remaining operative time is short.
As a General Anesthetic

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

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

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

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

Robinul

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS)

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

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

Adults

PREANESTHETIC MEDICATION

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

INTRAOPERATIVE MEDICATION

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

REVERSAL OF NEUROMUSCULAR BLOCKADE

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

PEPTIC ULCER

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

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

Pediatric Patients

(see PRECAUTIONS - Pediatric Use)

PREANESTHETIC MEDICATION

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

INFANTS

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

INTRAOPERATIVE MEDICATION

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

REVERSAL OF NEUROMUSCULAR BLOCKADE

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

PEPTIC ULCER

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

Diluent Compatibilities

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

Diluent Incompatibilities

Lactated Ringer’s solution

Admixture Compatibilities

PHYSICAL COMPATIBILITY

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

Admixture Incompatibilities

PHYSICAL IMCOMPATIBILITY

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

Flumazenil

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

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

Reversal of Conscious Sedation

ADULT PATIENTS

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

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

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

PEDIATRIC PATIENTS

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

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

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

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

Reversal of General Anesthesia in Adult Patients

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

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

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

Management of Suspected Benzodiazepine Overdose in Adult Patients

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

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

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

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

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

Safety and Handling

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

Glycopyrrolate

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS)

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

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

Adults

PREANESTHETIC MEDICATION

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

INTRAOPERATIVE MEDICATION

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

REVERSAL OF NEUROMUSCULAR BLOCKADE

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

PEPTIC ULCER

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

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

Pediatric Patients

(see PRECAUTIONS - Pediatric Use)

PREANESTHETIC MEDICATION

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

INFANTS

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

INTRAOPERATIVE MEDICATION

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

REVERSAL OF NEUROMUSCULAR BLOCKADE

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

PEPTIC ULCER

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

Diluent Compatibilities

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

Diluent Incompatibilities

Lactated Ringer’s solution

Admixture Compatibilities

PHYSICAL COMPATIBILITY

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

Admixture Incompatibilities

PHYSICAL INCOMPATIBILITY

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

Sodium Chloride

The volume of the preparation to be used for diluting or dissolving any drug for injection is dependent on the vehicle concentration, dose and route of administration as recommended by the manufacturer.

Use aseptic technique for entry and withdrawal from container.

This parenteral should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
Sodium Chloride

Sodium Chloride

Before Sodium Chloride Injection, USP, 0.9% is used as a vehicle for the administration of a drug, specific references should be checked for any possible incompatibility with sodium chloride.

The volume of the preparation to be used for diluting or dissolving any drug for injection is dependent on the vehicle concentration, dose and route of administration as recommended by the manufacturer.

Sodium Chloride Injection, USP, 0.9% is also indicated for use in flushing intravenous catheters. Prior to and after administration of the medication, the intravenous catheter should be flushed in its entirety with Sodium Chloride Injection, USP, 0.9%. Use in accord with any warnings or precautions appropriate to the medication being administered.

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

Isosorbide Dinitrate

As noted under CLINICAL PHARMACOLOGY, multiple studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for ISDN must provide a daily dose-free interval to minimize the development of this tolerance. In the case of sublingual tablets, it is probably true that one of the daily dose-free intervals must be somewhat longer than 14 hours.

As also noted under CLINICAL PHARMACOLOGY, the efficacy of daily doses after the first has never been demonstrated.

Large controlled studies with other nitrates suggest that no dosing regimen with Isosorbide Dinitrate Sublingual Tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.

A patient anticipating activity likely to cause angina should take one isosorbide dinitrate sublingual tablet (2.5 to 5 mg) about 15 minutes before the activity is expected to begin. Isosorbide dinitrate sublingual tablets may be used to abort an acute anginal episode, but its use is recommended only in patients who fail to respond to sublingual nitroglycerin.
Robaxin

Robaxin

For Intravenous and Intramuscular Use Only. Total adult dosage should not exceed 30 mL (3 vials) a day for more than 3 consecutive days except in the treatment of tetanus. If the condition persists, a like course may be repeated after a drug-free interval of 48 hours. Dosage and frequency of injection should be based on the severity of the condition being treated and therapeutic response noted.

For the relief of symptoms of moderate degree, one dose of 1 gram (one 10 mL vial) may be adequate. Ordinarily this injection need not be repeated, as the administration of the oral form will usually sustain the relief initiated by the injection. For the severest cases or in postoperative conditions in which oral administration is not feasible, additional doses of 1 gram may be repeated every 8 hours up to a maximum of 3 g/day for no more than 3 consecutive days.

Directions for Intravenous Use

ROBAXIN Injectable may be administered undiluted directly into the vein at a maximum rate of three mL per minute. It may also be added to an intravenous drip of Sodium Chloride Injection (Sterile Isotonic Sodium Chloride Solution for Parenteral Use) or five percent Dextrose Injection (Sterile 5 percent Dextrose Solution); one vial given as a single dose should not be diluted to more than 250 mL for I.V. infusion. AFTER MIXING WITH I.V. INFUSION FLUIDS, DO NOT REFRIGERATE. Care should be exercised to avoid vascular extravasation of this hypertonic solution, which may result in thrombophlebitis. It is preferable that the patient be in a recumbent position during and for at least 10 to 15 minutes following the injection.

Directions for Intramuscular Use

When the intramuscular route is indicated, not more than five mL (one-half vial) should be injected into each gluteal region. The injections may be repeated at eight hour intervals, if necessary. When satisfactory relief of symptoms is achieved, it can usually be maintained with tablets.

Not Recommended for Subcutaneous Administration.

Special Directions for Use in Tetanus

There is clinical evidence which suggests that methocarbamol may have a beneficial effect in the control of the neuromuscular manifestations of tetanus. It does not, however, replace the usual procedure of debridement, tetanus antitoxin, penicillin, tracheotomy, attention to fluid balance, and supportive care. ROBAXIN Injectable should be added to the regimen as soon as possible.

For adults: Inject one or two vials directly into the tubing of the previously inserted indwelling needle. An additional 10 mL or 20 mL may be added to the infusion bottle so that a total of up to 30 mL (three vials) is given as the initial dose (see PRECAUTIONS). This procedure should be repeated every six hours until conditions allow for the insertion of a nasogastric tube. Crushed methocarbamol tablets suspended in water or saline may then be given through this tube. Total daily oral doses up to 24 grams may be required as judged by patient response.For pediatric patients: A minimum initial dose of 15 mg/kg or 500 mg/m2 is recommended. This dosage may be repeated every six hours, if required. The total dose should not exceed 1.8 g/m2 for 3 consecutive days. The maintenance dosage may be given by injection into tubing or by I.V. infusion with an appropriate quantity of fluid. See directions for I.V. use.
Fosphenytoin Sodium

Fosphenytoin Sodium

The dose, concentration, and infusion rate of fosphenytoin should always be expressed as phenytoin sodium equivalents (PE). There is no need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). 1.5 mg of fosphenytoin sodium is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg PE. The amount and concentration of fosphenytoin is always expressed in terms of mg of phenytoin sodium equivalents (mg PE).

Do not confuse the concentration of fosphenytoin with the total amount of drug in the vial.

Caution must be used when administering fosphenytoin due to the risk of dosing errors (see WARNINGS). Medication errors associated with fosphenytoin have resulted in patients receiving the wrong dose of fosphenytoin. Fosphenytoin is marketed in 2 mL vials containing a total of 100 mg PE and 10 mL vials containing a total of 500 mg PE. Both vials contain a concentration of 50 mg PE/mL. Errors have occurred when the concentration of the vial (50 mg PE/mL) was misinterpreted to mean that the total content of the vial was 50 mg PE. These errors have resulted in two- or ten-fold overdoses of fosphenytoin since each of the vials actually contains a total of 100 mg PE or 500 mg PE. In some cases, ten-fold overdoses were associated with fatal outcomes. To help minimize confusion, the prescribed dose of fosphenytoin should always be expressed in milligrams of phenytoin equivalents (mg PE). Additionally, when ordering and storing fosphenytoin, consider displaying the total drug content (i.e., 100 mg PE/2 mL or 500 mg PE/10 mL) instead of concentration in computer systems, pre-printed orders, and automated dispensing cabinet databases to help ensure that total drug content can be clearly identified. Care should be taken to ensure the appropriate volume of fosphenytoin is withdrawn from the vial when preparing the dose for administration. Attention to these details may prevent some fosphenytoin medication errors from occurring.

Prior to IV infusion, dilute fosphenytoin in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL. The maximum concentration of fosphenytoin in any solution should be 25 mg PE/mL. When fosphenytoin is given as an intravenous infusion, fosphenytoin needs to be diluted and should only be administered at a rate not exceeding 150 mg PE/min.

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

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

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

Nonemergent Loading and Maintenance Dosing

Because of the risks of cardiac and local toxicity associated with intravenous fosphenytoin, oral phenytoin should be used whenever possible. The loading dose of fosphenytoin is 10 – 20 mg PE/kg given IV or IM. The rate of administration for IV fosphenytoin should be no greater than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur (approximately 20 minutes after the end of fosphenytoin infusion).

The initial daily maintenance dose of fosphenytoin is 4 – 6 mg PE/kg/day in divided doses.

IM or IV Substitution For Oral Phenytoin Therapy

When treatment with oral phenytoin is not possible, fosphenytoin can be substituted for oral phenytoin at the same total daily dose. Dilantin capsules are approximately 90% bioavailable by the oral route. Phenytoin, supplied as fosphenytoin, is 100% bioavailable by both the IM and IV routes. For this reason, plasma phenytoin concentrations may increase modestly when IM or IV fosphenytoin is substituted for oral phenytoin sodium therapy. The rate of administration for IV fosphenytoin should be no greater than 150 mg PE/min. In controlled trials, IM fosphenytoin was administered as a single daily dose utilizing either 1 or 2 injection sites. Some patients may require more frequent dosing.

Dosing in Special Populations

Patients with Renal or Hepatic Disease:

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

Elderly Patients:

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

Pediatric:

The safety and efficacy of fosphenytoin in pediatric patients have not been established.
Neostigmine Methylsulfa...

Neostigmine Methylsulfate

Symptomatic control of myasthenia gravis: One mL of the 1:2000 solution (0.5 mg) subcutaneously or intramuscularly. Subsequent doses should be based on the individual patient's response. In most patients, however, oral treatment with neostigmine bromide tablets, 15 mg each, is adequate for control of symtoms.Prevention of postoperative distention and urinary retention: 0.25 mg subcutaneously or intramuscularly as soon as possible after operation; repeat every 4 to 6 hours for two or three days.Treatment of postoperative distention: One mL of 1:2000 solution (0.5 mg) subcutaneously or intramuscularly, as required.Treatment of urinary retention: One mL of the 1:2000 solution (0.5 mg) subcutaneously or intramuscularly. If urination does not occur within an hour, the patient should be catheterized. After the patient has voided, or the bladder has been emptied, continue the 0.5 mg injections every three hours for at least 5 injections.Reversal of Effects on Nondepolarizing Neuromuscular Blocking Agents: When Neostigmine Methylsulfate Injection is administered intravenously, it is recommended that atropine sulfate (0.6 to 1.2 mg) also be given intravenously using separate syringes. Some authorities have recommended that the atropine be injected several minutes before the neostigmine rather than concomitantly. The usual dose is 0.5 to 2 mg Neostigmine Methylsulfate Injection given by slow intravenous injection, repeated as required. Only in exceptional cases should the total dose neostigmine exceed 5 mg. It is recommended that the patient be well ventilated and a patent airway maintained until complete recovery of normal respiration is assured. The optimum time for administration of the drug is during hyperventilation when the carbon dioxide level of the blood is low. It should never be administered in the presence of high concentrations of halothane or cyclopropane. In cardiac cases and severely ill patients, it is advisable to titrate the exact dose of neostigmine required, using a peripheral nerve stimulator device. In the presence of bradycardia, the pulse rate should be increased to about 80/minute with atropine before administering neostigmine.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Isosorrbide Dinitrate

Isosorrbide Dinitrate

As noted under CLINICAL PHARMACOLOGY , multiple-dose studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for isosorbide dinitrate tablets must provide a daily dose-free interval to minimize the development of this tolerance. With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hours long.

As also noted under CLINICAL PHARMACOLOGY , the effects of the second and later doses have been smaller and shorter-lasting than the effects of the first.

Large controlled studies with other nitrates suggest that no dosing regimen with isosorbide dinitrate oral tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.

As with all titratable drugs, it is important to administer minimum dose which produces the desired clinical effect. The usual starting dose of isosorbide dinitrate tablets is 5 mg to 40 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen.
Ketorolac Tromethamine

Ketorolac Tromethamine

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

Ketorolac Tromethamine Injection

ADULT PATIENTS

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

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

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

ADULT PATIENTS

IM Dosing:
Patients < 65 years of age: One dose of 60 mg. Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 30 mg.
IV Dosing:
Patients < 65 years of age: One dose of 30 mg. Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 15 mg.
PEDIATRIC PATIENTS (2 TO 16 YEARS OF AGE):

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

IM Dosing:
One dose of 1 mg/kg up to a maximum of 30 mg.
IV Dosing:
One dose of 0.5 mg/kg up to a maximum of 15 mg.
Multiple-Dose Treatment (IV or IM) in Adults
Patients < 65 years of age: The recommended dose is 30 mg Ketorolac Tromethamine Injection every 6 hours. The maximum daily dose should not exceed 120 mg. For patients ≥ 65 years of age, renally impaired patients (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

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

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

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

Donepezil Hydrochloride

Donepezil hydrochloride tablets should be taken in the evening, just prior to retiring.

Donepezil hydrochloride tablets can be taken with or without food.

2.1. Mild to Moderate Alzheimer’s Disease

The dosages of donepezil hydrochloride tablets shown to be effective in controlled clinical trials are 5 mg and 10 mg administered once per day.

The higher dose of 10 mg did not provide a statistically significantly greater clinical benefit than 5 mg. There is a suggestion, however, based upon order of group mean scores and dose trend analyses of data from these clinical trials, that a daily dose of 10 mg of donepezil hydrochloride tablets might provide additional benefit for some patients. Accordingly, whether or not to employ a dose of 10 mg is a matter of prescriber and patient preference.

2.2. Severe Alzheimer’s Disease

Donepezil hydrochloride tablets have been shown to be effective in controlled clinical trials at a dose of 10 mg administered once daily.

2.3. Titration

The recommended starting dose of donepezil hydrochloride tablets are 5 mg once daily. Evidence from the controlled trials in mild to moderate Alzheimer’s disease indicates that the 10 mg dose, with a one week titration, is likely to be associated with a higher incidence of cholinergic adverse events compared to the 5 mg dose. In open-label trials using a 6 week titration, the type and frequency of these same adverse events were similar between the 5 mg and 10 mg dose groups. Therefore, because donepezil hydrochloride tablets steady state is achieved about 15 days after it is started and because the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks.

2.1. Mild to Moderate Alzheimer’s Disease

The dosages of donepezil hydrochloride tablets shown to be effective in controlled clinical trials are 5 mg and 10 mg administered once per day.

The higher dose of 10 mg did not provide a statistically significantly greater clinical benefit than 5 mg. There is a suggestion, however, based upon order of group mean scores and dose trend analyses of data from these clinical trials, that a daily dose of 10 mg of donepezil hydrochloride tablets might provide additional benefit for some patients. Accordingly, whether or not to employ a dose of 10 mg is a matter of prescriber and patient preference.

2.2. Severe Alzheimer’s Disease

Donepezil hydrochloride tablets have been shown to be effective in controlled clinical trials at a dose of 10 mg administered once daily.

2.3. Titration

The recommended starting dose of donepezil hydrochloride tablets are 5 mg once daily. Evidence from the controlled trials in mild to moderate Alzheimer’s disease indicates that the 10 mg dose, with a one week titration, is likely to be associated with a higher incidence of cholinergic adverse events compared to the 5 mg dose. In open-label trials using a 6 week titration, the type and frequency of these same adverse events were similar between the 5 mg and 10 mg dose groups. Therefore, because donepezil hydrochloride tablets steady state is achieved about 15 days after it is started and because the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks.
Promethazine Hydrochlor...

Promethazine Hydrochloride

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Chlorpromazine Hydrochloride

Adults

Adjust dosage to individual and the severity of his condition, recognizing that the milligram for milligram potency relationship among all dosage forms has not been precisely established clinically. It is important to increase dosage until symptoms are controlled. Dosage should be increased more gradually in debilitated or emaciated patients. In continued therapy, gradually reduce dosage to the lowest effective maintenance level, after symptoms have been controlled for a reasonable period.

Increase parenteral dosage only if hypotension has not occurred. Before using IM, see Important Notes On Injection.

ELDERLY PATIENTS

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

PSYCHOTIC DISORDERS

Increase dosage gradually until symptoms are controlled. Maximum improvement may not be seen for weeks or even months. Continue optimum dosage for 2 weeks; then gradually reduce dosage to the lowest effective maintenance level. Daily dosage of 200 mg is not unusual. Some patients require higher dosages (e.g., 800 mg daily is not uncommon in discharged mental patients).

Hospitalized Patients: Acute Schizophrenic or Manic States

IM: 25 mg (1 mL). If necessary, give additional 25 to 50 mg injection in 1 hour. Increase subsequent IM doses gradually over several days–up to 400 mg q4-6h in exceptionally severe cases–until patient is controlled. Usually the patient becomes quiet and cooperative within 24 to 48 hours and oral doses may be substituted.

Prompt Control of Severe Symptoms

IM: 25 mg (1 mL). If necessary, repeat in 1 hour. Subsequent doses should be oral, 25-50 mg tid.

NAUSEA AND VOMITING

IM: 25 mg (1 mL). If no hypotension occurs, give 25 to 50 mg q3-4h prn, until vomiting stops. Then switch to oral dosage.

During Surgery

IM: 12.5 mg (0.5 mL). Repeat in 1/2 hour if necessary and if no hypotension occurs. IV: 2 mg per fractional injection, at 2-minute intervals. Do not exceed 25 mg. Dilute to 1 mg/mL, i.e., 1 mL (25 mg) mixed with 24 mL of saline.

PRESURGICAL APPREHENSION

IM: 12.5 to 25 mg (0.5-1 mL), 1 to 2 hours before operation.

INTRACTABLE HICCUPS

If symptoms persist for 2-3 days after trial with oral therapy, give 25 to 50 mg (1-2 mL) IM. Should symptoms persist, use slow IV infusion with patient flat in bed: 25 to 50 mg (1-2 mL) in 500 to 1000 mL of saline. Follow blood pressure closely.

ACUTE INTERMITTENT PORPHYRIA

IM: 25 mg (1 mL) tid or qid until patient can take oral therapy.

TETANUS

IM:25 to 50 mg (1-2 mL) given 3 or 4 times daily, usually in conjunction with barbiturates. Total doses and frequency of administration must be determined by the patient’s response, starting with low doses and increasing gradually. IV: 25 to 50 mg (1-2 mL). Dilute to at least 1 mg per mL and administer at a rate of 1 mg per minute.

Pediatric Patients (6 months to 12 years of age)

Chlorpromazine should generally not be used in pediatric patients under 6 months of age except where potentially lifesaving. It should not be used in conditions for which specific pediatric dosages have not been established.

SEVERE BEHAVIORAL PROBLEMS

Outpatients

Select route of administration according to severity of patient’s condition and increase dosage gradually as required. IM: 1/4 mg/lb body weight q6-8h, prn.

Hospitalized Patients

As with outpatients, start with low doses and increase dosage gradually. In severe behavior disorders, higher dosages (50-100 mg daily, and in older children, 200 mg daily or more) may be necessary. There is little evidence that behavior improvement in severely disturbed mentally retarded patients is further enhanced by doses beyond 500 mg per day. Maximum IM Dosage: Patients up to 5 years (or 50 lbs.), not over 40 mg/day;5-12 years (or 50-100 lbs.), not over 75 mg/day except in unmanageable cases.

NAUSEA AND VOMITING

Dosage and frequency of administration should be adjusted according to the severity of the symptoms and response of the patient. The duration of activity following intramuscular administration may last up to 12 hours. Subsequent doses may be given by the same route if necessary. IM: 1/4 mg/lb body weight q6-8h, prn. Maximum IM Dosage: Pediatric patients 6 months to 5 years (or 50 lbs.), not over 40 mg/day; 5-12 years (or 50-100 lbs.), not over 75 mg/day except in severe cases.

During Surgery

IM: 1/8 mg/lb body weight. Repeat in 1/2 hour if necessary and if no hypotension occurs. IV: 1 mg per fractional injection at 2-minute intervals and not exceeding recommended IM dosage. Always dilute to 1 mg/mL, i.e., 1 mL (25 mg) mixed with 24 mL of saline.

PRESURGICAL APPREHENSION

1/4 mg/lb body weight IM 1 to 2 hours before operation.

TETANUS

IM or IV: 1/4 mg/lb body weight q6-8h. When given IV, dilute to at least 1 mg/mL and administer at a rate of 1 mg per 2 minutes. In patients up to 50 lbs., do not exceed 40 mg daily; 50 to 100 lbs., do not exceed 75 mg except in severe cases.

Important Notes on Injection

Inject slowly, deep into upper outer quadrant of buttock.

Because of possible hypotensive effects, reserve parenteral administration for bedfast patients or for acute ambulatory cases, and keep patient lying down for at least 1/2 hour after injection. If irritation is a problem, dilute injection with saline or 2% procaine; mixing with other agents in the syringe is not recommended. Subcutaneous injection is not advised. AVOID INJECTING UNDILUTED CHLORPROMAZINE HYDROCHLORIDE INJECTION INTO VEIN. IV ROUTE IS ONLY FOR SEVERE HICCUPS, SURGERY AND TETANUS.

Because of the possibility of contact dermatitis, avoid getting solution on hands or clothing.

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

Promethazine Hydrochloride

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Promethazine Hydrochloride

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Promethazine Hydrochloride

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Phenergan

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Phenergan

Important Notes on Administration

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

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

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

Allergic Conditions

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

Sedation

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

Nausea and Vomiting

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

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

Preoperative and Postoperative Use

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

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

Obstetrics

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

Pediatric Patients

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

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

Dicyclomine Hydrochloride

Dosage must be adjusted to individual patient needs.

2.1 Oral Dosage and Administration in Adults

The recommended initial dose is 20 mg four times a day. After one week treatment with the initial dose, the dose may be increased to 40 mg four times a day unless side effects limit dosage escalation.

If efficacy is not achieved within 2 weeks or side effects require doses below 80 mg per day, the drug should be discontinued. Documented safety data are not available for doses above 80 mg daily for periods longer than 2 weeks.
Escitalopram

Escitalopram

Escitalopram tablets should be administered once daily, in the morning or evening, with or without food.

2.1 Major Depressive Disorder

Initial Treatment

Adolescents

The recommended dose of escitalopram tablets is 10 mg once daily. A flexible-dose trial of escitalopram tablets (10 to 20 mg/day) demonstrated the effectiveness of escitalopram tablets [see Clinical Studies (14.1)].  If the dose is increased to 20 mg, this should occur after a minimum of three weeks.

Adults

The recommended dose of escitalopram tablets is 10 mg once daily. A fixed-dose trial of escitalopram tablets demonstrated the effectiveness of both 10 mg and 20 mg of escitalopram tablets, but failed to demonstrate a greater benefit of 20 mg over 10 mg [see Clinical Studies (14.1)].  If the dose is increased to 20 mg, this should occur after a minimum of one week.

Maintenance Treatment

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of continuing escitalopram tablets 10 or 20 mg/day in adults patients with major depressive disorder who responded while taking escitalopram tablets during an 8-week, acute-treatment phase demonstrated a benefit of such maintenance treatment[see Clinical Studies (14.1)]. Nevertheless, the physician who elects to use escitalopram tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Generalized Anxiety Disorder

Initial Treatment

Adults

The recommended starting dose of escitalopram tablets is 10 mg once daily. If the dose is increased to 20 mg, this should occur after a minimum of one week.

Maintenance Treatment

Generalized anxiety disorder is recognized as a chronic condition. The efficacy of escitalopram tablets in the treatment of GAD beyond 8 weeks has not been systematically studied. The physician who elects to use escitalopram tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.3 Special Populations

10 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment.

No dosage adjustment is necessary for patients with mild or moderate renal impairment. Escitalopram tablets should be used with caution in patients with severe renal impairment.

2.4 Discontinuation of Treatment with Escitalopram Tablets

Symptoms associated with discontinuation of escitalopram tablets and other SSRIs and SNRIs have been reported [see Warnings and Precautions (5.3)].  Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

2.5 Switching Patients To or From a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of escitalopram tablets therapy. Similarly, at least 14 days should be allowed after stopping escitalopram tablets before starting an MAOI [see Contraindications (4.1 ) and Warnings and Precautions (5.10)].
Terbutaline Sulfate

Terbutaline Sulfate

Vials should be used only for subcutaneous administration and not intravenous infusion.

Sterility and accurate dosing cannot be assured if the vials are not used in accordance with DOSAGE AND ADMINISTRATION.

Discard unused portion after single patient use.

The usual subcutaneous dose of terbutaline sulfate injection is 0.25 mg injected into the lateral deltoid area. If significant clinical improvement does not occur within 15 to 30 minutes, a second dose of 0.25 mg may be administered. If the patient then fails to respond within another 15 to 30 minutes, other therapeutic measures should be considered. The total dose within 4 hours should not exceed 0.5 mg.

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

Neostigmine Methylsulfate

Symptomatic control of myasthenia gravis: One mL of the 1:2000 solution (0.5 mg) subcutaneously or intramuscularly. Subsequent doses should be based on the individual patient's response. In most patients, however, oral treatment with neostigmine bromide tablets, 15 mg each, is adequate for control of symtoms.Prevention of postoperative distention and urinary retention: 0.25 mg subcutaneously or intramuscularly as soon as possible after operation; repeat every 4 to 6 hours for two or three days.Treatment of postoperative distention: One mL of 1:2000 solution (0.5 mg) subcutaneously or intramuscularly, as required.Treatment of urinary retention: One mL of the 1:2000 solution (0.5 mg) subcutaneously or intramuscularly. If urination does not occur within an hour, the patient should be catheterized. After the patient has voided, or the bladder has been emptied, continue the 0.5 mg injections every three hours for at least 5 injections.Reversal of Effects on Nondepolarizing Neuromuscular Blocking Agents: When Neostigmine Methylsulfate Injection is administered intravenously, it is recommended that atropine sulfate (0.6 to 1.2 mg) also be given intravenously using separate syringes. Some authorities have recommended that the atropine be injected several minutes before the neostigmine rather than concomitantly. The usual dose is 0.5 to 2 mg Neostigmine Methylsulfate Injection given by slow intravenous injection, repeated as required. Only in exceptional cases should the total dose neostigmine exceed 5 mg. It is recommended that the patient be well ventilated and a patent airway maintained until complete recovery of normal respiration is assured. The optimum time for administration of the drug is during hyperventilation when the carbon dioxide level of the blood is low. It should never be administered in the presence of high concentrations of halothane or cyclopropane. In cardiac cases and severely ill patients, it is advisable to titrate the exact dose of neostigmine required, using a peripheral nerve stimulator device. In the presence of bradycardia, the pulse rate should be increased to about 80/minute with atropine before administering neostigmine.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Amiodarone Hydrochlorid...

Amiodarone Hydrochloride

Amiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:
Table 1: AMIODARONE DOSE RECOMMENDATIONS: FIRST 24 HOURS Loading infusions First Rapid: 150 mg over the FIRST 10 minutes (15 mg/min). Add 3 mL of amiodarone (150 mg) to 100 mLD5W (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes. Followed by Slow: 360 mg over the NEXT 6 hours (1 mg/min). Add 18 mL of amiodarone (900 mg) to 500 mL D5W (concentration = 1.8 mg/mL) Maintenance infusion 540 mg over the REMAINING 18 hours (0.5 mg/min). Decrease the rate of the slow loading infusion to 0.5 mg/min.
After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for amiodarone concentrations greater than 2 mg/mL). The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.

In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of amiodarone (mixed in 100 mL of D5W and infused over 10 minutes to minimize the potential for hypotension).

The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Do not exceed an initial infusion rate of 30 mg/min.

Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks.

The surface properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone must be delivered by a volumetric infusion pump.

Administer amiodarone, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration.

Intravenous amiodarone loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death [see Warnings and Precautions (5.3)].

Intravenous amiodarone concentrations greater than 3 mg/mL in D5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, do not exceed amiodarone concentrations of 2 mg/mL, unless a central venous catheter is used [see Adverse Reactions (6.2)].

Amiodarone infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.

Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, but all of the clinical experience has been with PVC tubing and the concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect dosing in these studies.

Amiodarone has been found to leach out plasticizers, including DEHP [di-(2-ethylhexyl)phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing amiodarone at higher concentrations and lower flow rates than provided in DOSAGE AND ADMINISTRATION. Polysorbate 80, a component of amiodarone injection, is also known to leach DEHP from PVC [see Description (11)].

Amiodarone does not need to be protected from light during administration.

NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.
Table 2: AMIODARONE HCl SOLUTION STABILITY Solution Concentration(mg/mL) Container Comments 5% Dextrose in Water (D5W) 1 to 6 PVC Physically compatible, with amiodarone loss <10% at 2 hours at room temperature. 5% Dextrose in Water (D5W) 1 to 6 Polyolefin, Glass Physically compatible, with no amiodarone loss at 24 hours at room temperature.
Admixture Incompatibility

Amiodarone in D5W is incompatible with the drugs shown in Table 3.
Table 3: Y-SITE INJECTION INCOMPATIBILITY Drug Vehicle Amiodarone Concentration Comments Aminophylline D5W 4 mg/mL Precipitate Cefamandole Nafate D5W 4 mg/mL Precipitate Cefazolin Sodium D5W 4 mg/mL Precipitate Mezlocillin Sodium D5W 4 mg/mL Precipitate Heparin Sodium D5W -- Precipitate Sodium Bicarbonate D5W 3 mg/mL Precipitate
Intravenous to Oral Transition

Patients whose arrhythmias have been suppressed by amiodarone may be switched to oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone.

Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone [see Drug Interactions (7)].

Table 4 provides suggested doses of oral amiodarone to be initiated after varying durations of amiodarone administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone.
Table 4: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION Duration of Amiodarone Infusion* Initial Daily Dose of Oral Amiodarone * Assuming a 720 mg/day infusion (0.5 mg/min). † Intravenous amiodarone is not intended for maintenance treatment. < 1 week 800 to 1600 mg 1-3 weeks 600 to 800 mg > 3 weeks† 400 mg
Target Antifungal

Target Antifungal

Cefadroxil for oral suspension is acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Adults

Urinary Tract Infections

For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).

For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.).

Skin and Skin Structure Infections

For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.).

Pharyngitis and Tonsillitis

Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis— 1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of cefadroxil for oral suspension should be administered for at least 10 days.

See chart for total daily dosage for children.

DAILY DOSAGE OF CEFADROXIL FOR ORAL SUSPENSION
Child's Weight
lbs

kg

250 mg/5 mL

500 mg/5 mL

10

4.5

½ tsp

-

20

9.1

1 tsp

-

30

13.6

1½ tsp

-

40

18.2

2 tsp

1 tsp

50

22.7

2½ tsp

1¼ tsp

60

27.3

3 tsp

1½ tsp

70 & Above

31.8+

--

2 tsp

Renal Impairment

In patients with renal impairment, the dosage of cefadroxil monohydrate should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil monohydrate and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 m2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0 to 10 mL/min 36 hours 10 to 25 mL/min 24 hours 25 to 50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.
Reconstitution Directions for Oral Suspension Bottle Size Reconstitution Directions 100 mL Suspend in a total of 67 mL of water. Method: Tap bottle lightly to loosen powder. Add 67 mL of water in two portions. Shake well after each addition. 75 mL Suspend in a total of 51 mL of water Method: Tap bottle lightly to loosen powder. Add 51 mL of water in two portions. Shake well after each addition. 50 mL Suspend in a total of 34 mL of water Method: Tap bottle lightly to loosen powder. Add 34 mL of water in two portions. Shake well after each addition. After reconstitution, store in refrigerator. Shake well before using. Keep container tightly closed. Discard unused portion after 14 days.
Tetanus And Diphtheria ...

Tetanus And Diphtheria Toxoids Adsorbed

2.1 Epilepsy

Valproate sodium injection is for intravenous use only.

Use of valproate sodium injection for periods of more than 14 days has not been studied. Patients should be switched to oral valproate products as soon as it is clinically feasible.

Valproate sodium injection should be administered as a 60 minute infusion (but not more than 20 mg/min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary.

In one clinical safety study, approximately 90 patients with epilepsy and with no measurable plasma levels of valproate were given single infusions of valproate sodium injection (up to 15 mg/kg and mean dose of 1184 mg) over 5-10 minutes (1.5-3.0 mg/kg/min). Patients generally tolerated the more rapid infusions well [see ADVERSE REACTIONS (6.1)]. This study was not designed to assess the effectiveness of these regimens. For pharmacokinetics with rapid infusions, see CLINICAL PHARMACOLOGY (12.3).

Initial Exposure to Valproate The following dosage recommendations were obtained from studies utilizing oral divalproex sodium products.

Complex Partial Seizures For adults and children 10 years of age or older.

Monotherapy (Initial Therapy)Valproate sodium injection has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

Conversion to MonotherapyPatients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50-100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of valproate sodium injection therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.

Adjunctive TherapyValproate sodium injection may be added to the patient’s regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in divided doses. In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see CLINICAL STUDIES (14)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see DRUG INTERACTIONS (7)].

Simple and Complex Absence Seizures The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. If the total daily dose exceeds 250 mg, it should be given in divided doses. A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentration for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see CLINICAL PHARMACOLOGY (12.3)]. As the valproate sodium injection dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see DRUG INTERACTIONS (7.2)]. Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

Replacement TherapyWhen switching from oral valproate products, the total daily dose of valproate sodium injection should be equivalent to the total daily dose of the oral valproate product [see CLINICAL PHARMACOLOGY (12)], and should be administered as a 60 minute infusion (but not more than 20 mg/min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary. Patients receiving doses near the maximum recommended daily dose of 60 mg/kg/day, particularly those not receiving enzyme-inducing drugs, should be monitored more closely. If the total daily dose exceeds 250 mg, it should be given in a divided regimen. There is no experience with more rapid infusions in patients receiving valproate sodium injection as replacement therapy. However, the equivalence shown between valproate sodium injection and oral valproate products (divalproex sodium) at steady state was only evaluated in an every 6 hour regimen. Whether, when valproate sodium injection is given less frequently (i.e., twice or three times a day), trough levels fall below those that result from an oral dosage form given via the same regimen, is unknown. For this reason, when valproate sodium injection is given twice or three times a day, close monitoring of trough plasma levels may be needed.

2.2 General Dosing Advice

Dosing in Elderly PatientsDue to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see WARNINGS AND PRECAUTIONS (5.13), USE IN SPECIFIC POPULATIONS (8.5) and CLINICAL PHARMACOLOGY (12.3)].

Dose-Related Adverse ReactionsThe frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see WARNINGS AND PRECAUTIONS (5.7)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

AdministrationRapid infusion of valproate sodium injection has been associated with an increase in adverse reactions. There is limited experience with infusion times of less than 60 minutes or rates of infusion > 20 mg/min in patients with epilepsy [see ADVERSE REACTIONS (6)]. Valproate sodium injection should be administered intravenously as a 60 minute infusion, as noted above. It should be diluted with at least 50 mL of a compatible diluent. Any unused portion of the vial contents should be discarded. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Compatibility and StabilityValproate sodium injection was found to be physically compatible and chemically stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinyl chloride (PVC) bags at controlled room temperature 15º to 30°C (59º to 86°F).
dextrose (5%) injection, USP sodium chloride (0.9%) injection, USP lactated ringer’s injection, USP
Glycopyrrolate

Glycopyrrolate

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS).

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

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

Adults

Preanesthetic Medication

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

Intraoperative Medication

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

Reversal of Neuromuscular Blockade

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

Peptic Ulcer

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

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

Pediatric Patients

(see PRECAUTIONS, Pediatric Use)

Preanesthetic Medication

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

Infants

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

Intraoperative Medication

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

Reversal of Neuromuscular Blockade

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

Peptic Ulcer

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

Diluent Compatibilities

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

Diluent Incompatibilities

Lactated Ringer’s solution.

Admixture Compatibilities

Physical Compatibility

This list does not constitute an endorsement of the clinical utility or safety of co‑administration of glycopyrrolate with these drugs. Glycopyrrolate injection is compatible for mixing and injection with the following injectable dosage forms: atropine sulfate, USP; physostigmine salicylate; diphenhydramine HCl; codeine phosphate, USP; benz-quinamide HCl; hydromorphone HCl, USP; droperidol; levorphanol tartrate; lidocaine, USP; meperidine HCl, USP; pyridostigmine bromide; morphine sulfate, USP; nalbuphine HCl; oxymorphone HCl; procaine HCl, USP; promethazine HCl, USP; neostigmine methylsulfate, USP; scopolamine HBr, USP; butorphanol tartrate; fentanyl citrate; trimethobenzamide HCl; and hydroxyzine HCl. Glycopyrrolate injection may be administered via the tubing of a running infusion of normal saline.

Admixture Incompatibilities

Physical Incompatibility

Since the stability of glycopyrrolate is questionable above a pH of 6.0 do not combine glycopyrrolate injection in the same syringe with methohexital Na; chloramphenicol Na succinate; dimenhydrinate; pentobarbital Na; thiopental Na; secobarbital Na; sodium bicarbonate; diazepam; dexamethasone Na phosphate; or pentazocine lactate. These mixtures will result in a pH higher than 6.0 and may result in gas production or precipitation.
Naproxen

Naproxen

Carefully consider the potential benefits and risks of naproxen sodium and other treatment options before deciding to use naproxen sodium. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with naproxen sodium, the dose and frequency should be adjusted to suit an individual patient's needs.

Although naproxen sodium circulates in the plasma as naproxen, it has pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium and within 1 hour in patients taking naproxen.

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hapatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients:

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients With Moderate to Severe Renal Impairment:

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects).

Rheumatoid Arthritis, Osteoarthritis, and Ankylosing Spondylitis:

The recommended dose of naproxen sodium is 275 mg (equivalent to 250 mg naproxen with 25 mg sodium) or 550 mg (equivalent to 500 mg of naproxen with 50 mg sodium) twice daily. During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to naproxen sodium 1650 mg per day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen sodium 1650 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis:

The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (i.e., 5 mg/kg given twice a day). Naproxen sodium tablets are not well suited to this dosage so use of naproxen oral suspension is recommended for this indication.

Management of Pain, Primary Dysmenorrhea and Acute Tendinitis and Bursitis:

The recommended starting dose is 550 mg of naproxen sodium, followed by 550 mg every 12 hours or 275 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg of naproxen sodium. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more rapidly absorbed, naproxen sodium is recommended for the management of acute painful conditions when prompt onset of pain relief is desired (see CLINICAL PHARMACOLOGY. INDICATIONS AND USAGE).

Acute Gout: The recommended starting dose is 825 mg of naproxen sodium, followed by 275 mg every 8 hours until the attack has subsided.
Ergotamine

Ergotamine

Procedure: For the best results, dosage should start at the first sign of an attack.

Adults: Take 2 tablets at the start of attack; 1 additional tablet every ½ hour, if needed for full relief (maximum 6 tablets per attack, 10 per week).

Early Administration Gives Maximum Effectiveness.

Maximum Adult Dosage: Six tablets is the maximum dose for an individual attack.

Total weekly dosage should not exceed 10 tablets. Ergotamine tartrate and caffeine-tablets should not be used for chronic daily administration.

In carefully selected patients, with due consideration of maximum dosage recommendations, administration of the drug at bedtime may be an appropriate short-term preventive measure.
Lithium Carbonate

Lithium Carbonate

Doses of extended-release tablets are usually given b.i.d. (approximately 12-hour intervals). When initiating therapy with extended-release lithium, dosage must be individualized according to serum levels and clinical response.

When switching a patient from immediate-release capsules to the lithium carbonate extended-release tablets, give the same total daily dose when possible. Most patients on maintenance therapy are stabilized on 900 mg daily, e.g., 450 mg lithium carbonate extended-release b.i.d. When the previous dosage of immediate-release lithium is not a multiple of 450 mg, for example, 1500 mg, initiate lithium extended-release tablet at the multiple of 450 mg nearest to, but below, the original daily dosage, i.e., 1350 mg. When the two doses are unequal, give the larger dose in the evening. In the above example, with a total daily dosage of 1350 mg, generally 450 mg lithium carbonate extended-release should be given in the morning and 900 mg lithium carbonate extended-release in the evening. If desired, the total daily dosage of 1350 mg can be given in three equal 450 mg lithium carbonate extended-release doses. These patients should be monitored at 1 to 2 week intervals, and dosage adjusted if necessary, until stable and satisfactory serum levels and clinical state are achieved.

When patients require closer titration than that available with doses of lithium carbonate extended-release in increments of 450 mg, immediate-release capsules should be used.

Acute Mania

Optimal patient response to lithium carbonate can usually be established and maintained with 1800 mg per day in divided doses. Such doses will normally produce the desired serum lithium level ranging between 1 and 1.5 mEq/L.

Dosage must be individualized according to serum levels and clinical response. Regular monitoring of the patient’s clinical state and serum lithium levels is necessary. Serum levels should be determined twice per week during the acute phase, and until the serum level and clinical condition of the patient have been stabilized.

Long Term Control

The desirable serum lithium levels are 0.6 to 1.2 mEq/L. Dosage will vary from one individual to another, but usually 900 mg to 1200 mg per day in divided doses will maintain this level. Serum lithium levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months.

Patients unusually sensitive to lithium may exhibit toxic signs at serum levels below 1 mEq/L.

N B

Blood samples for serum lithium determinations should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8 to 12 hours after the previous dose). Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis.

Elderly patients often respond to reduced dosage, and may exhibit signs of toxicity at serum levels ordinarily tolerated by younger patients.
Cefazolin

Cefazolin

Usual Adult Dosage

Type of infection

Dose

Frequency

Moderate to severe infections

500 mg to 1 gram

every 6 to 8 hours

Mild infections caused by susceptible gram-positive cocci

250 mg to 500 mg

every 8 hours

Acute, uncomplicated urinary tract infections

1 gram

every 12 hours

Pneumococcal pneumonia

500 mg

every 12 hours

Severe, life-threatening infections (e.g., endocarditis, septicemia)*

1 gram to 1.5 grams

every 6 hours

* In rare instances, doses of up to 12 grams of cefazolin for injection per day have been used.

Perioperative Prophylactic Use

To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are: a. 1 gram IV administered ½ hour to 1 hour prior to the start of surgery. b. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV during surgery (administration modified depending on the duration of the operative procedure). c. 500 mg to 1 gram IV every 6 to 8 hours for 24 hours postoperatively.

It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision and (2) cefazolin for injection be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms.

In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin for injection may be continued for 3 to 5 days following the completion of surgery.

Dosage Adjustment for Patients with Reduced Renal Function

Cefazolin for injection may be used in patients with reduced renal function with the following dosage adjustments. Patients with a creatinine clearance of 55 mL/min or greater or a serum creatinine of 1.5 mg % or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min or serum creatinine of 1.6 to 3 mg % can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min or serum creatinine of 3.1 to 4.5 mg % should be given 1/2 the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min or less or serum creatinine of 4.6 mg % or greater should be given 1/2 the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Patients undergoing peritoneal dialysis, see CLINICAL PHARMACOLOGY.

Pediatric Dosage

In pediatric patients, a total daily dosage of 25 to 50 mg/kg (approximately 10 to 20 mg/lb) of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg/kg (45 mg/lb) of body weight for severe infections. Since safety for use in premature infants and in neonates has not been established, the use of cefazolin for injection in these patients is not recommended.

In pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 mL/min), 60% of the normal daily dose given in equally divided doses every 12 hours should be sufficient. In patients with moderate impairment (creatinine clearance of 40 to 20 mL/min), 25% of the normal daily dose given in equally divided doses every 12 hours should be adequate. Pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 mL/min) may be given 10% of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.

RECONSTITUTION

Preparation of Parenteral Solution

Parenteral drug products should be SHAKEN WELL when reconstituted, and inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solutions should be discarded.

Reconstituted solutions may range in color from pale yellow to yellow without a change in potency.

Directions for Proper Use of Pharmacy Bulk Package

Not for direct infusion. This Pharmacy Bulk Package is for use in a hospital pharmacy admixture service only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time after reconstitution using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial closure entry is permitted to complete fluid transfer operations. This time limit should begin with the introduction of the solvent or diluent into the Pharmacy Bulk Package. DISCARD ANY UNUSED PORTION AFTER 4 HOURS.

Pharmacy Bulk Package Add Sterile Water for Injection, Bacteriostatic Water for Injection or Sodium Chloride Injection according to the table below. SHAKE WELL. Use promptly. (Discard vial within 4 hours after initial entry.)

Pharmacy Bulk Package Size

Amount of Diluent

Appropriate Concentration

Approximate Available Volume

10 grams

45 mL

1 gram/5 mL

51 mL

96 mL

1 gram/10 mL

102 mL

20 grams

87 mL

1 gram/5 mL

99 mL

ADMINISTRATION

Intravenous Administration

Intermittent or continuous infusion: Dilute reconstituted Cefazolin for Injection, USP in 50 to 100 mL of one of the following solutions:

Sodium Chloride Injection, USP5% or 10% Dextrose Injection, USP5% Dextrose in Lactated Ringer’s Injection, USP5% Dextrose and 0.9% Sodium Chloride Injection, USP5% Dextrose and 0.45% Sodium Chloride Injection, USP5% Dextrose and 0.2% Sodium Chloride Injection, USPLactated Ringer’s Injection, USPInvert Sugar 5% or 10% in Sterile Water for InjectionRinger’s Injection, USP5% Sodium Bicarbonate Injection, USP

When diluted according to the instructions above, cefazolin is stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5ºC or 41ºF).

Prior to administration parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.
Minocycline Hydrochlori...

Minocycline Hydrochloride

Oral Sedative Dose, Adults - 30 to 120 mg daily in 2 or 3 divided doses. Children - 6 mg/kg of body weight daily in 3 divided doses.

Oral Hypnotic Dose, Adults - 100 to 320 mg.

Oral Anticonvulsant Dose, Adults - 50 to 100 mg 2 or 3 times daily.

Children - 15 to 50 mg 2 or 3 times daily.
Oxytocin

Oxytocin

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

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

A. Induction or Stimulation of Labor

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

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

C. Treatment of Incomplete or Inevitable Abortion

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

Ampicillin And Sulbactam

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

Ampicillin and sulbactam for injection should be administered by slow intravenous injection over at least 10-15 minutes or can also be delivered in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

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

Pediatric Patients 1 Year of Age or Older:

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

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

Impaired Renal Function

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

Ampicillin And Sulbactam

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

Ampicillin and sulbactam for injection should be administered by slow intravenous injection over at least 10-15 minutes or can also be delivered in greater dilutions with 50-100 mL of a compatible diluent as an intravenous infusion over 15-30 minutes.

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

Pediatric Patients 1 Year of Age or Older:

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

Impaired Renal Function

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

Ampicillin And Sulbactam

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

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

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See DIRECTION FOR USE-Preparation for Intramuscular Injection section.)

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/SulbactamHalf-Life (Hours) Recommended Ampicillin and Sulbactamfor Injection Dosage ≥30 1 1.5 to 3 g q 6 h-q 8 h 15 to 29 5 1.5 to 3 g q 12 h 5 to 14 9 1.5 to 3 g q 24 h
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males weight (kg) × (140 - age)72 × serum creatinine Females 0.85 × above value
Sertraline

Sertraline

Initial Treatment

Dosage for Adults

Major Depressive Disorder and Obsessive-Compulsive Disorder

Sertraline treatment should be administered at a dose of 50 mg once daily.

Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder

Sertraline treatment should be initiated with a dose of 25 mg once daily. After one week, the dose should be increased to 50 mg once daily.

While a relationship between dose and effect has not been established for major depressive disorder, OCD, panic disorder, PTSD or social anxiety disorder, patients were dosed in a range of 50 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline for the treatment of these indications. Consequently, a dose of 50 mg, administered once daily, is recommended as the initial therapeutic dose. Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day. Given the 24 hour elimination half-life of sertraline, dose changes should not occur at intervals of less than 1 week.

Premenstrual Dysphoric Disorder

Sertraline treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment.

While a relationship between dose and effect has not been established for PMDD, patients were dosed in the range of 50 to 150 mg/day with dose increases at the onset of each new menstrual cycle (see Clinical Trials under CLINICAL PHARMACOLOGY). Patients not responding to a 50 mg/day dose may benefit from dose increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dose has been established with luteal phase dosing, a 50 mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period.

Sertraline tablets should be administered once daily, either in the morning or evening.

Maintenance/Continuation/Extended Treatment

Major Depressive Disorder

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy beyond response to the acute episode. Systematic evaluation of sertraline has demonstrated that its antidepressant efficacy is maintained for periods of up to 44 weeks following 8 weeks of initial treatment at a dose of 50 to 200 mg/day (mean dose of 70 mg/day) (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Posttraumatic Stress Disorder

It is generally agreed that PTSD requires several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline has demonstrated that its efficacy in PTSD is maintained for periods of up to 28 weeks following 24 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Social Anxiety Disorder

Social anxiety disorder is a chronic condition that may require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline has demonstrated that its efficacy in social anxiety disorder is maintained for periods of up to 24 weeks following 20 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). Dosage adjustments should be made to maintain patients on the lowest effective dose and patients should be periodically reassessed to determine the need for long-term treatment.

Obsessive-Compulsive Disorder and Panic Disorder

It is generally agreed that OCD and Panic Disorder require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of continuing sertraline for periods of up to 28 weeks in patients with OCD and Panic Disorder who have responded while taking sertraline during initial treatment phases of 24 to 52 weeks of treatment at a dose range of 50 to 200 mg/day has demonstrated a benefit of such maintenance treatment (see Clinical Trials under CLINICALPHARMACOLOGY). It is not known whether the dose of sertraline needed for maintenance treatment is identical to the dose needed to achieve an initial response. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.

Premenstrual Dysphoric Disorder

The effectiveness of sertraline in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. However, as women commonly report that symptoms worsen with age until relieved by the onset of menopause, it is reasonable to consider continuation of a responding patient. Dosage adjustments, which may include changes between dosage regimens (e.g., daily throughout the menstrual cycle versus during the luteal phase of the menstrual cycle), may be needed to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

Switching Patients to or from a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with sertraline. In addition, at least 14 days should be allowed after stopping sertraline before starting an MAOI (see CONTRAINDICATIONS and WARNINGS).

Special Populations

Dosage for Hepatically Impaired Patients

The use of sertraline in patients with liver disease should be approached with caution. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY andPRECAUTIONS).

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to sertraline and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering sertraline in the third trimester.

Discontinuation of Treatment with Sertraline

Symptoms associated with discontinuation of sertraline and other SSRIs and SNRIs, have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
Levofloxacin

Levofloxacin

2.1 Dosage in Adult Patients with Normal Renal Function

The usual dose of levofloxacin injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance < 50 mL/min, adjustments to the dosing regimen are required [see DOSAGE AND ADMINISTRATION (2.3)].

Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)

Type of Infection1

Dosed Every 24 hours

Duration(days)2

Nosocomial Pneumonia

750 mg

7–14

Community Acquired Pneumonia3

500 mg

7–14

Community Acquired Pneumonia4

750 mg

5

Acute Bacterial Sinusitis

750 mg

5

500 mg

10–14

Acute Bacterial Exacerbation of Chronic Bronchitis

500 mg

7

Complicated Skin and Skin Structure Infections (SSSI)

750 mg

7–14

Uncomplicated SSSI

500 mg

7–10

Chronic Bacterial Prostatitis

500 mg

28

Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)5

750 mg

5

Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)6

250 mg

10

Uncomplicated Urinary Tract Infection

250 mg

3

Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg 7,8 Pediatric patients < 50 kg and ≥ 6 months of age 7,8

500 mgsee Table 2 below (2.2)

60 8 60 8

Plague, adult and pediatric patients > 50 kg 9 Pediatric patients < 50 kg and ≥ 6 months of age

500 mgsee Table 2 below (2.2)
10 to 1410 to 14
1 Due to the designated pathogens [see INDICATIONS AND USAGE (1)]. 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see INDICATIONS AND USAGE (1.2)].4 Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see INDICATIONS AND USAGE (1.3)]. 5 This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia. 6 This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli.7 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see CLINICAL STUDIES (14.9)]. 8 The safety of levofloxacin in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see WARNINGS AND PRECAUTIONS (5.10); USE IN SPECIFIC POPULATIONS (8.4); and CLINICAL STUDIES (14.9)] Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.9 Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of levofloxacin typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated.

2.2 Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.

Table 2: Dosage in Pediatric Patients ≥ 6 months of age

Type of Infection 1

Dose

Freq. Once Every

Duration2
Inhalational Anthrax (post-exposure)3,4
Pediatric patients > 50 kg

500 mg

24 hr

60 days4

Pediatric patients < 50 kg and ≥ 6 months of age

8 mg/kg (not to exceed 250 mg per dose)

12 hr

60 days4
Plague5 Pediatric patients > 50 kg 500 mg 24 hr 10 to 14 days Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg (not to exceed 250 mg per dose) 12 hr 10 to 14 days
1 Due to Bacillus anthracis [see INDICATIONS AND USAGE (1.13) and Yersinia pestis (see INDICATIONS AND USAGE (1.14)] 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see CLINICAL STUDIES (14.9)] 4 The safety of levofloxacin in pediatric patients for durations of therapy beyond 14 has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see WARNINGS AND PRECAUTIONS (5.10); USE IN SPECIFIC POPULATIONS (8.4); CLINICAL STUDIES (14.9).] Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.5 Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.

2.3 Dosage Adjustment in Adults with Renal Impairment

Administer levofloxacin with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance < 50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see USE IN SPECIFIC POPULATIONS (8.6)].

Table 3 shows how to adjust dose based on creatinine clearance.

Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance < 50 mL/min)

Dosage in Normal Renal FunctionEvery 24 hours

Creatinine Clearance20 to 49 mL/min

Creatinine Clearance10 to 19 mL/min

Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD)

750 mg

750 mg every 48 hours

750 mg initial dose, then 500 mg every 48 hours

750 mg initial dose, then 500 mg every 48 hours

500 mg

500 mg initial dose, then 250 mg every 24 hours

500 mg initial dose, then 250 mg every 48 hours

500 mg initial dose, then 250 mg every 48 hours

250 mg

No dosage adjustment required

250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required

No information on dosing adjustment is available

2.4 Drug Interaction with Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

Levofloxacin InjectionLevofloxacin Injection should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see DOSAGE AND ADMINISTRATION (2.6)].

2.5 Administration Instructions

Levofloxacin Injection Caution: Rapid or bolus intravenous infusion of levofloxacin has been associated with hypotension and must be avoided. Levofloxacin injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. Levofloxacin injection should be administered only by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Hydration for Patients Receiving Levofloxacin Injection Adequate hydration of patients receiving intravenous levofloxacin should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see ADVERSE REACTIONS (6.1); PATIENT COUNSELING INFORMATION (17.2)].

2.6 Preparation of Intravenous Product

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

Because only limited data are available on the compatibility of levofloxacin injection with other intravenous substances, additives or other medications should not be added to Levofloxacin Injection Premix in Single Dose Flexible Containers, or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of levofloxacin injection with an infusion solution compatible with levofloxacin injection and with any other drug(s) administered via this common line.

Levofloxacin Injection Premix in Single Dose Flexible Containers (5 mg/mL)Levofloxacin injection is supplied in flexible containers within a foil overwrap. These contain a premixed, ready to use levofloxacin solution in 5% dextrose (D5W) for single dose. The 50 mL premixed flexible containers contain 250 mg/50 mL, the 100 mL premixed flexible containers contain 500 mg/100 mL, and the 200 mL premixed flexible containers contain 750 mg/150 mL of levofloxacin solution. The concentration of each container is 5 mg/mL. No further dilution of these preparations is necessary. Because the premix flexible containers are for single dose only, any unused portion should be discarded.

Instructions for the Use of Levofloxacin Injection Premix in Flexible Containers:
Tear outer wrap at the notch and remove solution container. Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised. Do not use if the solution is cloudy or a precipitate is present. Use sterile equipment. WARNING: Do not use flexible containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Preparation for Administration:
Close flow control clamp of administration set. Remove cover from port at bottom of container. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton. Suspend container from hanger. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of Levofloxacin Injection Premix in Flexible Containers. Open flow control clamp to expel air from set. Close clamp. Regulate rate of administration with flow control clamp.
Flumazenil

Flumazenil

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

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

Reversal of Conscious Sedation

Adult Patients

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

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

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

Pediatric Patients

For the reversal of the sedative effects of benzodiazepines administered for conscious sedation in pediatric patients greater than 1 year of age, the recommended initial dose is 0.01 mg/kg (up to 0.2 mg) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, further injections of 0.01 mg/kg (up to 0.2 mg) can be administered and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 0.05 mg/kg or 1 mg, whichever is lower. The dose should be individualized based on the patient’s response. The mean total dose administered in the pediatric clinical trial of flumazenil was 0.65 mg (range: 0.08 mg to 1.00 mg). Approximately one-half of patients required the maximum of five injections.

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

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

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

Reversal of General Anesthesia in Adult Patients

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

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

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

Management of Suspected Benzodiazepine Overdose in Adult Patients

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

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

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

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

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

Safety and Handling

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

Doxycyclate Hyclate

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day.

In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For children above eight years of age: The recommended dosage schedule for children weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration (See ADVERSE REACTIONS).

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of doxycycline in patients with renal impairment.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage, as required.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg by mouth twice a day for 7 days.

Nongonococcal urethritis (NGU) caused by C. trachomatis or U. urealyticum: 100 mg, by mouth, twice a day for 7 days.

Syphilis - early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks.

Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice a day for 4 weeks.

Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1 to 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

Inhalational anthrax (post-exposure):

ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days.

CHILDREN: weighing less than 100 lb (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 lb or more should receive the adult dose.
Cortisone Acetate

Cortisone Acetate

For Oral AdministrationDOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.

The initial dosage varies from 25 to 300 mg a day depending on the disease being treated. In less severe diseases doses lower than 25 mg may suffice, while in severe diseases doses higher than 300 mg may be required. The initial dosage should be maintained or adjusted until the patient’s response is satisfactory. If satisfactory clinical response does not occur after a reasonable period of time, discontinue cortisone acetate tablets and transfer the patient to other therapy.

After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response.

Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.

If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.
Duramorph

Duramorph

DURAMORPH is intended for intravenous, epidural or intrathecal administration.

Not For Use in Continuous Microinfusion Devices

Intravenous Administration

DOSAGE:

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

Geriatric Use -

Administer with extreme caution. (See PRECAUTIONS.)

Epidural Administration

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

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

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

EPIDURAL ADULT DOSAGE:

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

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

Geriatric Use -

Administer with extreme caution. (See PRECAUTIONS.)

EPIDURAL PEDIATRIC USE:

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

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

INTRATHECAL ADULT DOSAGE:

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

Geriatric Use -

Administer with extreme caution. (See PRECAUTIONS.)

REPEAT DOSAGE:

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

INTRATHECAL PEDIATRIC USE:

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

Oxytocin

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

Induction or Stimulation of Labor

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

Accurate control of the rate of infusion flow is essential. An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane.

An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances.

To prepare the usual solution for intravenous infusion - one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent.

The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL. Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion.

The initial dose should be no more than 1 to 2 mU/min. The dose may be gradually increased in increments of no more than 1 to 2 mU/min, until a contraction pattern has been established which is similar to normal labor.

The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored.

The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress. Oxygen should be administered to the mother. The mother and fetus must be evaluated by the responsible physician.

Control of Postpartum Uterine Bleeding

Intravenous Infusion (Drip Method) – To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony.

Intramuscular Administration – 1 mL (10 units) of oxytocin can be given after delivery of the placenta.

Treatment of Incomplete or Inevitable Abortion

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

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

Up And Up Nicotine Polacrilex

2.1 Epilepsy

Valproate sodium injection is for intravenous use only.

Use of valproate sodium injection for periods of more than 14 days has not been studied. Patients should be switched to oral valproate products as soon as it is clinically feasible.

Valproate sodium injection should be administered as a 60 minute infusion (but not more than 20 mg/‌min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary.

In one clinical safety study, approximately 90 patients with epilepsy and with no measurable plasma levels of valproate were given single infusions of valproate sodium injection (up to 15 mg/‌kg and mean dose of 1184 mg) over 5-10 minutes (1.5-3.0 mg/kg/min). Patients generally tolerated the more rapid infusions well [see ADVERSE REACTIONS (6.1)]. This study was not designed to assess the effectiveness of these regimens. For pharmacokinetics with rapid infusions, see CLINICAL PHARMACOLOGY (12.3).

Initial Exposure to ValproateThe following dosage recommendations were obtained from studies utilizing oral divalproex sodium products.

Complex Partial SeizuresFor adults and children 10 years of age or older.

Monotherapy (Initial Therapy)Valproate sodium injection has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.

The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

Conversion to MonotherapyPatients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50-100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of valproate sodium injection therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.

Adjunctive TherapyValproate sodium injection may be added to the patient’s regimen at a dosage of 10 to 15 mg/‌kg/‌day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in divided doses.

In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see CLINICAL STUDIES (14)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see DRUG INTERACTIONS (7)].

Simple and Complex Absence SeizuresThe recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/‌kg/‌day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. If the total daily dose exceeds 250 mg, it should be given in divided doses.

A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentration for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see CLINICAL PHARMACOLOGY (12.3)].

As the valproate sodium injection dosage is titrated upward, blood concentrations of phenobarbital and/‌or phenytoin may be affected [see DRUG INTERACTIONS (7.2)].

Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

Replacement TherapyWhen switching from oral valproate products, the total daily dose of valproate sodium injection should be equivalent to the total daily dose of the oral valproate product [see CLINICAL PHARMACOLOGY (12)], and should be administered as a 60 minute infusion (but not more than 20 mg/min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary. Patients receiving doses near the maximum recommended daily dose of 60 mg/kg/day, particularly those not receiving enzyme-inducing drugs, should be monitored more closely. If the total daily dose exceeds 250 mg, it should be given in a divided regimen. There is no experience with more rapid infusions in patients receiving valproate sodium injection as replacement therapy. However, the equivalence shown between valproate sodium injection and oral valproate products (divalproex sodium) at steady state was only evaluated in an every 6 hour regimen. Whether, when valproate sodium injection is given less frequently (i.e., twice or three times a day), trough levels fall below those that result from an oral dosage form given via the same regimen, is unknown. For this reason, when valproate sodium injection is given twice or three times a day, close monitoring of trough plasma levels may be needed.

2.2 General Dosing Advice

Dosing in Elderly PatientsDue to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see WARNINGS AND PRECAUTIONS (5.13), USE IN SPECIFIC POPULATIONS (8.5) and CLINICAL PHARMACOLOGY (12.3)].

Dose-Related Adverse ReactionsThe frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see WARNINGS AND PRECAUTIONS (5.7)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

AdministrationRapid infusion of valproate sodium injection has been associated with an increase in adverse reactions. There is limited experience with infusion times of less than 60 minutes or rates of infusion > 20 mg/min in patients with epilepsy [see ADVERSE REACTIONS (6)].

Valproate sodium injection should be administered intravenously as a 60 minute infusion, as noted above. It should be diluted with at least 50 mL of a compatible diluent. Any unused portion of the vial contents should be discarded.

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

Compatibility and StabilityValproate sodium injection was found to be physically compatible and chemically stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinyl chloride (PVC) bags at controlled room temperature 15º to 30°C (59º to 86°F).
dextrose (5%) injection, USP sodium chloride (0.9%) injection, USP lactated ringer’s injection, USP
Butalbital

Butalbital

Oral: one tablet every four hours. Total daily dosage should not exceed 6 tablets.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Butalbital

Butalbital

Oral: one capsule every four hours. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium suspension may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium suspension is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium suspension should be taken at the start of a meal.

2.1 Adults

The usual adult dose is one 500-mg tablet of amoxicillin and clavulanate potassium every 12 hours or one 250-mg tablet of amoxicillin and clavulanate potassium every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875-mg tablet of amoxicillin and clavulanate potassium every 12 hours or one 500-mg tablet of amoxicillin and clavulanate potassium every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/5 mL or 250 mg/5 mL suspension in place of the 500-mg tablet. The 200 mg/5 mL suspension or the 400 mg/5 mL suspension may be used in place of the 875-mg tablet.

Two 250-mg tablets of amoxicillin and clavulanate potassium should not be substituted for one 500-mg tablet of amoxicillin and clavulanate potassium. Since both the 250-mg and 500-mg tablets of amoxicillin and clavulanate potassium contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250-mg tablets are not equivalent to one 500-mg tablet of amoxicillin and clavulanate potassium.

The 250-mg tablet of amoxicillin and clavulanate potassium and the 250-mg chewable tablet should not be substituted for each other, as they are not interchangeable. The 250-mg tablet of amoxicillin and clavulanate potassium and the 250-mg chewable tablet do not contain the same amount of clavulanic acid (as the potassium salt). The 250-mg tablet of amoxicillin and clavulanate potassium contains 125 mg of clavulanic acid, whereas the 250-mg chewable tablet contains 62.5 mg of clavulanic acid.

2.2 Pediatric Patients

Based on the amoxicillin component, amoxicillin and clavulanate potassium suspension should be dosed as follows:

      Neonates and Infants Aged <12 weeks (<3 months): The recommended dose of amoxicillin and clavulanate potassium suspension 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Experience with the 200 mg/5 mL formulation in this age group is limited, and thus, use of the 125 mg/5 mL oral suspension is recommended.

      Patients Aged 12 weeks (3 months) and Older: See dosing regimens provided in Table 1. The every 12 hours regimen is recommended as it is associated with significantly less diarrhea [see Clinical Studies (14.2)]. However, the every 12 hours suspension (200 mg/5 mL and 400 mg/5 mL) and chewable tablets (200 mg and 400 mg) contain aspartame and should not be used by phenylketonurics. [see Warnings and Precautions (5.6)]
Table 1: Dosing in Patients Aged 12 weeks (3 months) and Older INFECTION DOSING REGIMEN Every 12 hours Every 8 hours 200 mg/5 mL or 400 mg/5 mL oral suspensiona 125 mg/5 mL or 250 mg/5 mL oral suspensiona Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections 45 mg/kg/day every 12 hours 40 mg/kg/day every 8 hours Less severe infections 25 mg/kg/day every 12 hours 20 mg/kg/day every 8 hours
a Each strength of suspension of amoxicillin and clavulanate potassium is available as a chewable tablet for use by older children. b Duration of therapy studied and recommended for acute otitis media is 10 days.

      Patients Weighing 40 kg or More: Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.

The 250-mg tablet of amoxicillin and clavulanate potassium should not be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250-mg tablet of amoxicillin and clavulanate potassium (250/125) versus the 250-mg chewable tablet of amoxicillin and clavulanate potassium (250/62.5).

2.3 Patients with Renal Impairment

      Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive the 875-mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

2.4 Directions for Mixing Oral Suspension

      Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see Table 2 below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Table 2: Amount of Water for Mixing Oral Suspension Strength Bottle Size Amount of Water for Reconstitution Contents of Each Teaspoonful (5 mL) 200 mg/5 mL 50 mL75 mL100 mL 48 mL71 mL95 mL 200 mg amoxicillin and 28.5 mg of clavulanic acid as the potassium salt 400 mg/5 mL 50 mL 75 mL 100 mL 45 mL 68 mL 90 mL 400 mg amoxicillin and 57.0 mg of clavulanic acid as the potassium salt
Note: Shake oral suspension well before using. Reconstituted suspension must be stored under refrigeration and discarded after 10 days.
Topiramate

Topiramate

2.1    Epilepsy

It is not necessary to monitor topiramate plasma concentrations to optimize topiramate tablets therapy.

On occasion, the addition of topiramate to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with topiramate may require adjustment of the dose of topiramate.

Because of the bitter taste, tablets should not be broken.

Topiramate can be taken without regard to meals.Monotherapy Use Adults and Pediatric Patients 10 Years and Older

The recommended dose for topiramate monotherapy in adults and pediatric patients 10 years of age and older is 400 mg/day in two divided doses. Approximately 58% of patients randomized to 400 mg/day achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/day. The dose should be achieved by titration according to the following schedule (Table 1):
Table 1:      Monotherapy Titration Schedule for Adults and Pediatric Patients 10 years and older Morning Dose Evening Dose Week 1 25 mg 25 mg Week 2 50 mg 50 mg Week 3 75 mg 75 mg Week 4 100 mg 100 mg Week 5 150 mg 150 mg Week 6 200 mg 200 mg
Adjunctive Therapy Use Adults 17 Years of Age and Over - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome The recommended total daily dose of topiramate tablets as adjunctive therapy in adults with partial onset seizures is 200 to 400 mg/day in two divided doses, and 400 mg/day in two divided doses as adjunctive treatment in adults with primary generalized tonic-clonic seizures. It is recommended that therapy be initiated at 25 to 50 mg/day followed by titration to an effective dose in increments of 25 to 50 mg/day every week. Titrating in increments of 25 mg/day every week may delay the time to reach an effective dose. Doses above 400 mg/day (600, 800 or 1,000 mg/day) have not been shown to improve responses in dose-response studies in adults with partial onset seizures. Daily doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose was reached at the end of 8 weeks [See Clinical Studies (14.1)].

Pediatric Patients Ages 10 - 16 Years – Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of Topiramate as adjunctive therapy for pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose of 6 mg/kg/day was reached at the end of 8 weeks [See Clinical Studies (14.1)].

2.4    Patients with Renal Impairment

In renally impaired subjects (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

2.5    Geriatric Patients (Ages 65 Years and Over)

Dosage adjustment may be indicated in the elderly patient when impaired renal function (creatinine clearance rate <70 mL/min/1.73 m2) is evident [See Clinical Pharmacology (12.3)].

2.6    Patients Undergoing Hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.

2.7    Patients with Hepatic Disease

In hepatically impaired patients, topiramate plasma concentrations may be increased. The mechanism is not well understood.
Glipizide Xl

Glipizide Xl

The initial dosage of Hydrocortisone Tablets, USP may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, Hydrocortisone Tablets should be discontinued and the patient transferred to other appropriate therapy.

IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT.

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of Hydrocortisone Tablets for a period of time consistent with the patient's condition.

If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually, rather than abruptly.

Multiple Sclerosis:

In treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective (20 mg of hydrocortisone is equivalent to 5 mg of prednisolone).
Azacitidine

Azacitidine

2.1 Prevention of Nausea and Vomiting Associated with Initial and Repeat Courses of Emetogenic Chemotherapy

Ondansetron injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

AdultsThe recommended adult intravenous dosage of ondansetron is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Pharmacology (12.2)]. The first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of ondansetron.

PediatricsFor pediatric patients 6 months through 18 years of age, the intravenous dosage of ondansetron is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Studies (14.1) and Clinical Pharmacology (12.2, 12.3)]. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of ondansetron. The drug should be infused intravenously over 15 minutes.

2.2 Prevention of Postoperative Nausea and Vomiting

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

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

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

2.3 Stability and Handling

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

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

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

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

2.4 Dosage Adjustment for Patients with Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), a single maximal daily dose of 8 mg infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron in these patients [see Clinical Pharmacology (12.3)].
Doxercalciferol

Doxercalciferol

Adult Administration

For intravenous use only. The optimal dose of doxercalciferol injection must be carefully determined for each patient.

The recommended initial dose of doxercalciferol injection is 4 mcg administered intravenously as a bolus dose 3 times weekly at the end of dialysis (approximately every other day). The initial dose should be adjusted, as needed, in order to lower blood iPTH into the range of 150 to 300 pg/mL. The dose may be increased at 8-week intervals by 1 mcg to 2 mcg if iPTH is not lowered by 50% and fails to reach the target range. Dosages higher than 18 mcg weekly have not been studied. Drug administration should be suspended if iPTH falls below 100 pg/mL and restarted one week later at a dose that is at least 1 mcg lower than the last administered dose. During titration, iPTH, serum calcium, and serum phosphorus levels should be obtained weekly. If hypercalcemia, hyperphosphatemia, or a serum calcium times phosphorus product greater than 55 mg2/dL2 is noted, the dose of doxercalciferol injection should be decreased or suspended and/or the dose of phosphate binders should be appropriately adjusted. If suspended, the drug should be restarted at a dose that is 1 mcg lower.

Dosing must be individualized and based on iPTH levels with monitoring of serum calcium and serum phosphorus levels. Table 5 presents a suggested approach in dose titration:
Table 5: Initial Dosing iPTH Level Doxercalciferol Injection Dose > 400 pg/mL 4 mcg 3 times per week at the end of dialysis, or approximately every other day Dose Titration iPTH Level Doxercalciferol Injection Dose Decrease by < 50% and above 300 pg/mL Increase by 1 mcg to 2 mcg at 8-week intervals as necessary Decrease by > 50% and above 300 pg/mL Maintain 150 to 300 pg/mL Maintain < 100 pg/mL Suspend for one week, then resume at a dose that is at least 1 mcg lower
Discard unused portion.
Penicillin V Potassium

Penicillin V Potassium

The dosage of penicillin V potassium tablets should be determined according to the sensitivity of the causative microorganisms and the severity of infection, and adjusted to the clinical response of the patient.

The usual dosage recommendations for adults and children 12 years and over are as follows:

Streptococcal Infections Mild to moderately severe - of the upper respiratory tract and including scarlet fever and erysipelas: 125 to 250 mg (200,000 to 400,000 units) every 6 to 8 hours for 10 days.

Pneumococcal InfectionsMild to moderately severe - of the respiratory tract, including otitis media: 250 to 500 mg (400,000 to 800,000 units) every 6 hours until the patient has been afebrile for at least 2 days.

Staphylococcal Infections Mild infections of skin and soft tissue (culture and sensitive tests should be performed): 250 to 500 mg (400,000 to 800,000 units) every 6 to 8 hours.

Fusospirochetosis (Vincent "s infection) of the oropharynx. Mild to moderately severe infections: 250 to 500 mg (400,000 to 800,000 units) every 6 to 8 hours.

For the prevention of recurrence following rheumatic fever and/or chorea: 125 to 250 mg (200,000 to 400,000 units) twice daily on a continuing basis.

For prophylaxis against bacterial endocarditis1 in patients with congenital heart disease or rheumatic or other acquired valvular heart disease when undergoing dental procedures or surgical procedures of the upper respiratory tract: 2 gram of penicillin V (1 gram for children under 60 lbs.) 1 hour before the procedure, and then, 1 gram (500 mg for children under 60 lbs.) 6 hours later.
Prednisone

Prednisone

Gastric irritation may be reduced if taken before, during, or immediately after meals or with food or milk.

The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity (am) for single dose administration. Therefore, it is recommended that prednisone be administered in the morning prior to 9 am and when large doses are given, administration of antacids between meals to help prevent peptic ulcers. Multiple dose therapy should be evenly distributed in evenly spaced intervals throughout the day.

Dietary salt restriction may be advisable in patients.

Do not stop taking this medicine without first talking to your doctor. Avoid abrupt withdraw of therapy.

The initial dosage of prednisone may vary from 5 mg to 60 mg per day, depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice, while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, prednisone should be discontinued and the patient transferred to other appropriate therapy. IT SHOULD BEEMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BEINDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THERESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small increments at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation, it may be necessary to increase the dosage of prednisone for a period of time consistent with the patient’s condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

Multiple Sclerosis

In the treatment of acute exacerbations of multiple sclerosis daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective. (Dosage range is the same for prednisone and prednisolone.)

Alternate Day Therapy

Alternate day therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every other morning. The purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the cushingoid state, corticoid withdrawal symptoms, and growth suppression in children.

The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or therapeutic effect of corticoids persists longer than their physical presence and metabolic effects and (b) administration of the corticosteroid every other morning allows for re-establishment of more nearly normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day.

A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from a low point about 10 pm to a peak level about 6 am. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 am and 8 am. This rise in cortisol dampens ACTH production and in turn adrenocortical activity. There is a gradual fall in plasma corticoids during the day with lowest levels occurring about midnight.

The diurnal rhythm of the HPA axis is lost in Cushing’s disease, a syndrome of adrenocortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy administered in conventional daily divided doses. It would appear, then, that a disturbance in the diurnal cycle with maintenance of elevated corticoid values during the night may play a significant role in the development of undesirable corticoid effects. Escape from these constantly elevated plasma levels for even short periods of time may be instrumental in protecting against undesirable pharmacologic effects.

During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every 6 hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenocortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenocortical suppression for 1 1/4 to 1 1/2 days following a single dose) and thus are recommended for alternate day therapy.

The following should be kept in mind when considering alternate day therapy:
Basic principles and indications for corticosteroid therapy should apply. The benefits ofalternate day therapy should not encourage the indiscriminate use of steroids. Alternate day therapy is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid therapy is anticipated. In less severe disease processes in which corticoid therapy is indicated, it may be possible to initiate treatment with alternate day therapy. More severe disease states usually will require daily divided high dose therapy for initial control of the disease process. The initial suppressive dose level should be continued until satisfactory clinical response is obtained, usually four to ten days in the case of many allergic and collagen diseases. It is important to keep the period of initial suppressive dose as brief as possible particularly when subsequent use of alternate day therapy is intended. Once control has been established, two courses are available: (a) change to alternate day therapy and then gradually reduce the amount of corticoid given every other day or (b) following control of the disease process reduce the daily dose of corticoid to the lowest effective level as rapidly as possible and then change over to an alternate day schedule. Theoretically, course (a) may be preferable. Because of the advantages of alternate day therapy, it may be desirable to try patients on this form of therapy who have been on daily corticoids for long periods of time (e.g., patients with rheumatoid arthritis). Since these patients may already have a suppressed HPA axis, establishing them on alternate day therapy may be difficult and not always successful. However, it is recommended that regular attempts be made to change them over. It may be helpful to triple or even quadruple the daily maintenance dose and administer this every other day rather than just doubling the daily dose if difficulty is encountered. Once the patient is again controlled, an attempt should be made to reduce this dose to a minimum. As indicated above, certain corticosteroids, because of their prolonged suppressive effect on adrenal activity, are not recommended for alternate day therapy (e.g., dexamethasone and betamethasone). The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocortical activity the least, when given at the time of maximal activity (am). In using alternate day therapy it is important, as in all therapeutic situations to individualize and tailor the therapy to each patient. Complete control of symptoms will not be possible in all patients. An explanation of the benefits of alternate day therapy will help the patient to understand and tolerate the possible flare-up in symptoms which may occur in the latter part of the off-steroid day. Other symptomatic therapy may be added or increased at this time if needed. In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily divided corticoid dose for control. Once control is again established alternate day therapy may be re-instituted. Although many of the undesirable features of corticosteroid therapy can be minimized by alternate day therapy, as in any therapeutic situation, the physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid therapy is being considered.
Meijer Enema

Meijer Enema

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

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

Transfer to oral therapy as soon as possible.
Benztropine Mesylate

Benztropine Mesylate

Since there is no significant difference in onset of effect after intravenous or intramuscular injection, usually there is no need to use the intravenous route. The drug is quickly effective after either route, with improvement sometimes noticeable a few minutes after injection. In emergency situations, when the condition of the patient is alarming, 1 to 2 mL of the injection normally will provide quick relief. If the parkinsonian effect begins to return, the dose can be repeated.

Because of cumulative action, therapy should be initiated with a low dose which is increased gradually at five or six-day intervals to the smallest amount necessary for optimal relief. Increases should be made in increments of 0.5 mg, to a maximum of 6 mg, or until optimal results are obtained without excessive adverse reactions.

Postencephalitic and Idiopathic Parkinsonism

The following dosing guidelines were written in reference to both benztropine mesylate tablets and benztropine mesylate injection. Benztropine mesylate tablets should be used when patients are able to take oral medication.

The usual daily dose is 1 to 2 mg, with a range of 0.5 to 6 mg parenterally.

As with any agent used in parkinsonism, dosage must be individualized according to age and weight, and the type of parkinsonism being treated. Generally, older patients, and thin patients cannot tolerate large doses. Most patients with postencephalitic parkinsonism need fairly large doses and tolerate them well. Patients with a poor mental outlook are usually poor candidates for therapy.

In idiopathic parkinsonism, therapy may be initiated with a single daily dose of 0.5 to 1 mg at bedtime. In some patients, this will be adequate; in others 4 to 6 mg a day may be required.

In postencephalitic parkinsonism, therapy may be initiated in most patients with 2 mg a day in one or more doses. In highly sensitive patients, therapy may be initiated with 0.5 mg at bedtime, and increased as necessary.

Some patients experience greatest relief by taking the entire dose at bedtime; others react more favorably to divided doses, two to four times a day. Frequently, one dose a day is sufficient, and divided doses may be unnecessary or undesirable.

The long duration of action of this drug makes it particularly suitable for bedtime medication when its effects may last throughout the night, enabling patients to turn in bed during the night more easily, and to rise in the morning.

When benztropine mesylate is started, do not terminate therapy with other antiparkinsonian agents abruptly. If the other agents are to be reduced or discontinued, it must be done gradually. Many patients obtain greatest relief with combination therapy.

Benztropine mesylate may be used concomitantly with carbidopa-levodopa, or with levodopa, in which case dosage adjustment may be required in order to maintain optimum response.

Drug-Induced Extrapyramidal Disorders

In treating extrapyramidal disorders due to neuroleptic drugs (e.g., phenothiazines), the recommended dosage is 1 to 4 mg once or twice a day parenterally. Dosage must be individualized according to the need of the patient. Some patients require more than recommended; others do not need as much.

In acute dystonic reactions, 1 to 2 mL of the injection usually relieves the condition quickly.

When extrapyramidal disorders develop soon after initiation of treatment with neuroleptic drugs (e.g., phenothiazines), they are likely to be transient. One to 2 mg of benztropine mesylate two or three times a day usually provides relief within one or two days. After one or two weeks, the drug should be withdrawn to determine the continued need for it. If such disorders recur, benztropine mesylate can be reinstituted.

Certain drug-induced extrapyramidal disorders that develop slowly may not respond to benztropine mesylate.

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

Cefadroxil

Cefadroxil capsules are acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Adults

Urinary Tract Infections:

For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).

For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.).

Skin and Skin Structure Infections:

For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.).

Pharyngitis and Tonsillitis:

Treatment of group A beta hemolytic streptococcal pharyngitis and tonsillitis - 1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta hemolytic streptococcal infections, a therapeutic dosage of cefadroxil capsules should be administered for at least 10 days.

Renal Impairment:

In patients with renal impairment, the dosage of cefadroxil monohydrate should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil capsules and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 m2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0-10 mL/min 36 hours 10-25 mL/min 24 hours 25-50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.
Zithromax

Zithromax

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

Except for gonorrhea, treatment 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. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some 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.
Table 1. Dosing Recommendations for Adult and Pediatric Patients > 3 Months of Age Infection Severity a Usual Adult Dose Usual Dose for Children > 3 Monthsb Ear/Nose/ThroatSkin/ Skin StructureGenitourinary Tract Mild/Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/Moderate or Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours GonorrheaAcute, uncomplicated ano-genital and urethral infections in males and females 3 grams as single oral dose Prepubertal children:50 mg/kg Amoxicillin, combined with 25 mg/kg probenecid as a single dose.Note: since probenecid is contraindicated in children under 2 years, do not use this regimen in children under 2 years of age.
a Dosing for infections caused by bacteria that are intermediate in their susceptibility to Amoxicillin should follow the recommendations for severe infections.b The children’s dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations.

2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

Treatment 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. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. Due to incompletely developed renal function affecting elimination of Amoxicillin in this age group, the recommended upper dose of Amoxicillin 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple therapy: The recommended adult oral dose is 1 gram Amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days.

Dual therapy: The recommended adult oral dose is 1 gram Amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.

Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min. should not receive a 875-mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
2.5 Directions for Mixing Oral Suspension

Tap bottle until all powder flows freely. Add approximately 1/3 of the total amount of water for reconstitution (see Table 2) and shake vigorously to wet powder. Add remainder of the water and again shake vigorously.
Table 2. Amount of Water for Mixing Oral Suspension Strength Bottle Size Amount of Water Required for Reconstitution Oral Suspension 125 mg /5 mL 80 mL 66 mL 100 mL 83 mL 150 mL 125 mL Oral Suspension 200 mg /5 mL 50 mL 39 mL 75 mL 59 mL 100 mL 78 mL Oral Suspension 250 mg /5 mL 80 mL 59 mL 100 mL 73 ml 150 mL 110 mL Oral Suspension 400 mg /5 mL 50 mL 34 mL 75 mL 51 mL 100 mL 68 mL
After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing. Alternate means of administration are to add the required amount of suspension to formula, milk, fruit juice, water, ginger ale, or cold drinks. These preparations should then be taken immediately.

NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable, but not required.
Ondansetron

Ondansetron

2.1 Prevention of Nausea and Vomiting Associated with Initial and Repeat Courses of Emetogenic Chemotherapy

Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.Adults: The recommended adult intravenous dosage of Ondansetron Injection is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Pharmacology (12.2)]. The first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of Ondansetron Injection.Pediatrics: For pediatric patients 6 months through 18 years of age, the intravenous dosage of Ondansetron Injection, is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Studies (14.1), Clinical Pharmacology (12.2, 12.3)]. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of Ondansetron Injection. The drug should be infused intravenously over 15 minutes.

2.2 Prevention of Postoperative Nausea and Vomiting

Ondansetron Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.Adults: The recommended adult intravenous dosage of Ondansetron Injection is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring within 2 hours after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, intravenous dose of ondansetron 4 mg, administration of a second intravenous dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.Pediatrics: For pediatric patients 1 month through 12 years of age, the dosage is a single 0.1-mg/kg dose for patients weighing 40 kg or less, or a single 4-mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic Ondansetron Injection.

2.3 Stability and Handling

After dilution, do not use beyond 24 hours. Although Ondansetron Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative.Ondansetron Injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following intravenous fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.Precaution: Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.

2.4 Dosage Adjustment for Patients with Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), a single maximal daily dose of 8 mg infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron in these patients [see Clinical Pharmacology (12.3)].
Ondansetron

Ondansetron

2.1 Prevention of Nausea and Vomiting Associated with Initial and Repeat Courses of Emetogenic Chemotherapy

Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Adults: The recommended adult intravenous dosage of Ondansetron Injection is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Pharmacology (12.2)]. The first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of Ondansetron Injection.

Pediatrics: For pediatric patients 6 months through 18 years of age, the intravenous dosage of Ondansetron Injection, is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Studies (14.1), Clinical Pharmacology (12.2, 12.3)]. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of Ondansetron Injection. The drug should be infused intravenously over 15 minutes.

2.2 Prevention of Postoperative Nausea and Vomiting

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

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

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

2.3 Stability and Handling

After dilution, do not use beyond 24 hours. Although Ondansetron Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative.Ondansetron Injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following intravenous fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.Precaution: Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.

2.4 Dosage Adjustment for Patients with Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), a single maximal daily dose of 8 mg infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron in these patients [see Clinical Pharmacology (12.3)].
Cefazolin

Cefazolin

Usual Adult Dosage
*
ln rare instances, doses of up to 12 grams of cefazolin per day have been used
Type of Infection Dose Frequency Moderate to severe infections 500 mg to 1 gram every 6 to 8 hours Mild infections caused by susceptible gram–positive cocci 250 mg to 500 mg every 8 hours Acute, uncomplicated urinary tract infections 1 gram every 12 hours Pneumococcal pneumonia 500 mg every 12 hours Severe, life-threatening infections (e.g., endocarditis, septicemia)* 1 gram to 1.5 grams every 6 hours
Perioperative Prophylactic Use

To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are:

a. 1 gram IV or IM administered 1/2 hour to 1 hour prior to the start of surgery.

b. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV or IM during surgery (administration modified depending on the duration of the operative procedure).

c. 500 mg to 1 gram IV or IM every 6 to 8 hours for 24 hours postoperatively.

It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms.

In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin for injection may be continued for 3 to 5 days following the completion of surgery.

Dosage Adjustment for Patients with Reduced Renal Function

Cefazolin may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg % or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3 mg % can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg % should be given 1/2 the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg % or greater should be given 1/2 the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Patients undergoing peritoneal dialysis: see CLINICAL PHARMACOLOGY.

Pediatric Dosage

In pediatric patients, a total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight for severe infections. Since safety for use in premature infants and in neonates has not been established, the use of cefazolin in these patients is not recommended.
Pediatric Dosage Guide Weight 25 mg/kg/day Divided into 3 Doses 25 mg/kg/day Divided into 4 Doses Lbs Kg Approximate Single Dose mg/q8h Vol. (mL) needed with dilution of 125 mg/mL Approximate Single Dose mg/q6h Vol. (mL) needed with dilution of 125 mg/mL 10 4.5 40 mg 0.35 mL 30 mg 0.25 mL 20 9 75 mg 0.6 mL 55 mg 0.45 mL 30 13.6 115 mg 0.9 mL 85 mg 0.7 mL 40 18.1 150 mg 1.2 mL 115 mg 0.9 mL 50 22.7 190 mg 1.5 mL 140 mg 1.1 mL Weight 50 mg/kg/day Divided into 3 Doses 50 mg/kg/day Divided into 4 Doses Lbs Kg Approximate Single Dose mg/q8h Vol. (mL) needed with dilution of 225 mg/mL Approximate Single Dose mg/q6h Vol. (mL) needed with dilution of 225 mg/mL 10 4.5 75 mg 0.35 mL 55 mg 0.25 mL 20 9 150 mg 0.7 mL 110 mg 0.5 mL 30 13.6 225 mg 1 mL 170 mg 0.75 mL 40 18.1 300 mg 1.35 mL 225 mg 1 mL 50 22.7 375 mg 1.7 mL 285 mg 1.25 mL
In pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 mL/min.), 60 percent of the normal daily dose given in equally divided doses every 12 hours should be sufficient. In patients with moderate impairment (creatinine clearance of 40 to 20 mL/min.), 25 percent of the normal daily dose given in equally divided doses every 12 hours should be adequate. Pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 mL/min.) may be given 10 percent of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.

RECONSTITUTION

Preparation of Parenteral Solution

Parenteral drug products should be SHAKEN WELL when reconstituted, and inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solutions should be discarded.

When reconstituted or diluted according to the instructions below, cefazolin for injection is stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5°C or 41°F). Reconstituted solutions may range in color from pale yellow to yellow without a change in potency.

Single-Dose Vials

For IM injection, IV direct (bolus) injection or IV infusion, reconstitute with Sterile Water for Injection according to the following table. SHAKE WELL.
Vial size Amount of Diluent ApproximateConcentration Approximate Available Volume 500 mg 2 mL 225 mg/mL 2.2 mL 1 gram 2.5 mL 330 mg/mL 3 mL
ADMINISTRATION

Intramuscular Administration

Reconstitute vials with Sterile Water for Injection according to the dilution table above. Shake well until dissolved. Cefazolin should be injected into a large muscle mass. Pain on injection is infrequent with cefazolin.

Intravenous Administration

Direct (bolus) injection: Following reconstitution according to the above table, further dilute vials with approximately 5 mL Sterile Water for Injection. Inject the solution slowly over 3 to 5 minutes, directly or through tubing for patients receiving parenteral fluids (see list below).

Intermittent or continuous infusion: Dilute reconstituted cefazolin in 50 to 100 mL of 1 of the following solutions:
Sodium Chloride Injection, USP 5% or 10% Dextrose Injection, USP 5% Dextrose in Lactated Ringer's Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP 5% Dextrose and 0.45% Sodium Chloride Injection, USP 5% Dextrose and 0.2% Sodium Chloride Injection, USP Lactated Ringer's Injection, USP Invert Sugar 5% or 10% in Sterile Water for Injection Ringer's Injection, USP 5% Sodium Bicarbonate Injection, USP
Argatroban

Argatroban

Argatroban Injection must be diluted 100-fold prior to infusion. Argatroban should not be mixed with other drugs prior to dilution.

2.1 Preparation for Intraveneous Administration:

Argatroban should be diluted in 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer’s Injection to a final concentration of 1 mg/mL. The contents of each 2.5-mL vial should be diluted 100-fold by mixing with 250 mL of diluent. Use 250 mg (2.5 mL) per 250 mL of diluent or 500 mg (5 mL) per 500 mL of diluent.

The constituted solution must be mixed by repeated inversion of the diluent bag for 1 minute. Upon preparation, the solution may show slight but brief haziness due to the formation of microprecipitates that rapidly dissolve upon mixing. Use of diluent at room temperature is recommended. The final solution must be clear before use. The pH of the intravenous solution prepared as recommended is 3.2 to 7.5. Solutions prepared as recommended are stable at controlled room temperature, 20º to 25ºC (68º to 77ºF) (see USP) in ambient indoor light for 24 hours; therefore, light-resistant measure such as foil protection for intravenous lines are unnecessary. Solutions are physically and chemically stable for up to 96 hours when protected from light and stored at controlled room temperature, 20º to 25ºC (68º to 77ºF) (see USP) or at refrigerated conditions, 5º±3ºC (41º±5ºF). Prepared solutions should not be exposed to direct sunlight. No significant potency losses have been noted following simulated delivery of the solution through intravenous tubing.

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

2.2 Dosing in Patients with Heparin- Induced Thrombocytopenia

Initial Dosage:

Before administering argatroban, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion (see Table 1).

Table 1.Recommended Doses and Infusion Rates for 2 mcg/kg/min Dose of Argatroban for Patients With HIT* and Without Hepatic Impairment (1 mg/mL Final Concentration)

Body Weight (kg)

Dose (mcg/min)

Infusion Rate (mL/hr)

50

100

6

60

120

7

70

140

8

80

160

10

90

180

11

100

200

12

110

220

13

120

240

14

130

260

16

140

280

17

*with or without thrombosis

Monitoring Therapy:For use in HIT, therapy with Argatroban Injection is monitored using the aPTT with a target range of 1.5 to 3 times the initial baseline value (not to exceed 100 seconds). Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within 1 to 3 hours following initiation of Argatroban Injection.

Check the aPTT 2 hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.

Dosage Adjustment:After the initiation of Argatroban Injection, adjust the dose (not to exceed 10 mcg/kg/min) as necessary to obtain a steady-state aPTT in the target range [see Clinical Studies (14.1)].

2.3 Dosing in Patients Undergoing Percutaneous Coronary Intervention

Initial Dosage:Initiate an infusion of Argatroban Injection at 25 mcg/kg/min and administer a bolus of 350 mcg/kg via a large bore intravenous line over 3 to 5 minutes (see Table 2). Check an activated clotting time (ACT) 5 to 10 minutes after the bolus dose is completed. The PCI procedure may proceed if the ACT is greater than 300 seconds.

Dosage Adjustment:If the ACT is less than 300 seconds, an additional intravenous bolus dose of 150 mcg/kg should be administered, the infusion dose increased to 30 mcg/kg/min, and the ACT checked 5 to 10 minutes later (see Table 2).

If the ACT is greater than 450 seconds, decrease the infusion rate to 15 mcg/kg/min, and check the ACT 5 to 10 minutes later (Table 3).

Continue titrating the dose until a therapeutic ACT (between 300 and 450 seconds) has been achieved; continue the same infusion rate for the duration of the PCI procedure.

In case of dissection, impending abrupt closure, thrombus formation during the procedure, or inability to achieve or maintain an ACT over 300 seconds, additional bolus doses of 150 mcg/kg may be administered and the infusion dose increased to 40 mcg/kg/min. Check the ACT after each additional bolus or change in the rate of infusion.

Table 2.Recommended Starting and Maintenance Doses (Within the Target ACT Range) Argatroban Injection in Patients Undergoing PCI Without Hepatic Impairment   (1 mg/mL Final Concentration)

Body Weight (kg)

Starting Bolus Dose

(350 mcg/kg)

Starting and Maintenance Continuous Infusion DosingFor ACT 300-450 seconds25 mcg/kg/min
Bolus Dose(mcg)
Bolus Volume(mL)
Continuous Infusion Dose (mg/min)
Continuous Infusion Rate (mL/hr)

50

17500

18

1250

75

60

21000

21

1500

90

70

24500

25

1750

105

80

28000

28

2000

120

90

31500

32

2250

135

100

35000

35

2500

150

110

38500

39

2750

165

120

42000

42

3000

180

130

45500

46

3250

195

140

49000

49

3500

210

NOTE: 1 mg = 1000mcg; 1 kg = 2.2 lbs

Table 3 Recommended Dose Adjustments of Argatroban Injection for Patients Outside of ACT Target Range Undergoing PCI Without Hepatic Impairment (1 mg/mL Final Concentration)

Body Weight (kg)

If ACT Less than 300 secondsDosage Adjustment† 30 mcg/kg/min

If ACT Greater than 450 seconds Dosage Adjustment* 15 mcg/kg/min

Additional Bolus Dose (mcg)

Bolus Volume (mL)

Continuous Infusion Dose (mcg/min)

Continuous Infusion Rate (mL/hr)

Continuous Infusion Dose (mcg/min)

Continuous Infusion Rate (mL/hr)

50

7500

8

1500

90

750

45

60

9000

9

1800

108

900

54

70

10500

11

2100

126

1050

63

80

12000

12

2400

144

1200

72

90

13500

14

2700

162

1350

81

100

15000

15

3000

180

1500

90

110

16500

17

3300

198

1650

99

120

18000

18

3600

216

1800

108

130

19500

20

3900

234

1950

117

140

21000

21

4200

252

2100

126

NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 lbs†Additional intravenous bolus dose of 150 mcg/kg should be administered if ACT less than 300 seconds.* No bolus dose is given if ACT greater than 450 seconds

Monitoring Therapy:For use in PCI, therapy with Argatroban Injection is monitored using ACT. Obtain ACTs before dosing, 5 to 10 minutes after bolus dosing, following adjustments in the infusion rate, and at the end of the PCI procedure. Obtain additional ACTs every 20 to 30 minutes during prolonged procedure.

Continued Anticoagulation after PCI:If a patient requires anticoagulation after the procedure, Argatroban Injection may be continued, but at a rate of 2 mcg/kg/min and adjusted as needed to maintain the aPTT in the desired range [see Dosage and Administration (2.1)].

2.4 Dosing in Patients With Hepatic Impairment

Initial Dosage:

For adult patients with HIT and moderate or severe hepatic impairment (based on Child-Pugh classification), an initial dose of 0.5 mcg/kg/min is recommended, based on the approximately 4-fold decrease in argatroban clearance relative to those with normal hepatic function. Monitor the aPTT closely, and adjust the dosage as clinically indicated.

Monitoring Therapy:Achievement of steady state aPTT levels may take longer and require more dose adjustments in patients with hepatic impairment compared to patients with normal hepatic function.

For patients with hepatic impairment undergoing PCI and who have HIT or are at risk for HIT, carefully titrate argatroban until the desired level of anticoagulation is achieved. Use of Argatroban in PCI patients with clinically significant hepatic disease or AST/ALT levels ≥3 times the upper limit of normal should be avoided [see Warnings and Precautions (5.2)].

2.5 Dosing in Pediatric Patients With Heparin-Induced Thrombocytopenia/Heparin-Induced Thrombocytopenia and Thrombosis Syndrome

Initial Dosage:Initial argatroban infusion doses are lower for seriously ill pediatric patients compared to adults with normal hepatic function [see Use in Specific Populations (8.4)].

Monitoring Therapy:In general, therapy with argatroban is monitored using the aPTT. Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within one to three hours following initiation of argatroban in patients without hepatic impairment [see Warnings and Precautions (5.2)]. Dose adjustment may be required to attain the target aPTT. Check the aPTT two hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.

Dosage Adjustment: [see Use in Specific Populations (8.4)]

2.6 Conversion to Oral Anticoagulant Therapy

Initiating Oral Anticoagulant Therapy:When converting patients from Argatroban to oral anticoagulant therapy, consider the potential for combined effects on INR with co-administration of Argatroban and warfarin. A loading dose of warfarin should not be used. Initiate therapy using the expected daily dose of warfarin. To avoid prothrombotic effects and to ensure continuous anticoagulation when initiating warfarin, it is suggested that Argatroban and warfarin therapy be overlapped. There are insufficient data available to recommend the duration of the overlap.

Co-Administration of Warfarin and Argatroban Injection at Doses Up to 2 mcg/kg/min: Measure INR daily while Argatroban Injection and warfarin are co-administered. In general, with doses of Argatroban Injection up to 2 mcg/kg/min, Argatroban Injection can be discontinued when the INR is >4 on combined therapy. After Argatroban Inection is discontinued, repeat the INR measurement in 4 to 6 hours. If the repeat INR is below the desired therapeutic range, resume the infusion of Argatroban Injection and repeat the procedure daily until the desired therapeutic range on warfarin alone is reached.

Co-Administration of Warfarin and Argatroban Injection at Doses Greater than 2 mcg/kg/min: For doses greater than 2 mcg/kg/min, the relationship of INR between warfarin alone to the INR on warfarin plus argatroban is less predictable. In this case, in order to predict the INR on warfarin alone, temporarily reduce the dose of Argatroban Injection to a dose of 2 mcg/kg/min. Repeat the INR on Argatroban Injection and warfarin 4 to 6 hours after reduction of the Argatroban Injection dose and follow the process outlined above for administering Argatroban Injection at doses up to 2 mcg/kg/min.
Doxycycline

Doxycycline

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day.

In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For children above eight years of age: The recommended dosage schedule for children weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration (See ADVERSE REACTIONS).

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of doxycycline in patients with renal impairment.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage as required.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg, by mouth, twice a day for 7 days.

Nongonococcal urethritis (NGU) caused by C. trachomatis or U. urealyticum: 100 mg, by mouth, twice a day for 7 days.

Syphilis – early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks.

Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.

Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1 to 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

Inhalational anthrax (post-exposure):

ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days.

CHILDREN: weighing less than 100 lb (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 lb or more should receive the adult dose.
Dexamethasone Sodium Ph...

Dexamethasone Sodium Phosphate

Dexamethasone Sodium Phosphate Injection, 4 mg/mL-For intravenous, intramuscular, intra-articular, intralesional and soft tissue injection.

Dexamethasone Sodium Phosphate Injection, 10 mg/mL-For intravenous and intramuscular injection only.

Dexamethasone Sodium Phosphate Injection can be given directly from the vial or it can be added to Sodium Chloride Injection or Dextrose Injection and administered by intravenous drip.

Solutions used for intravenous administration or further dilution of this product should be preservative-free when used in the neonate, especially the premature infant.

When it is mixed with an infusion solution, sterile precautions should be observed. Since infusion solutions generally do not contain preservatives, mixtures should be used within 24 hours.

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.

Intravenous and Intramuscular Injection

The initial dosage of Dexamethasone Sodium Phosphate Injection varies from 0.5 to 9 mg a day depending on the disease being treated. In less severe diseases doses lower than 0.5 mg may suffice, while in severe diseases doses higher than 9 mg may be required.

The initial dosage should be maintained or adjusted until the patient's response is satisfactory. If a satisfactory clinical response does not occur after a reasonable period of time, discontinue Dexamethasone Sodium Phosphate Injection and transfer the patient to other therapy.

After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response.

Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.

If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.

When the intravenous route of administration is used, dosage usually should be the same as the oral dosage. In certain overwhelming, acute, life-threatening situations, however, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages. The slower rate of absorption by intramuscular administration should be recognized.

SHOCK

There is a tendency in current medical practice to use high (pharmacologic) doses of corticosteroids for the treatment of unresponsive shock. The following dosages of Dexamethasone Sodium Phosphate Injection have been suggested by various authors:
Author* Dosage Cavanagh1
3 mg/kg of body weight per 24 hours by constant intravenous infusion after an initial intravenous injection of 20 mg
Dietzman2
2 to 6 mg/kg of body weight as a single intravenous injection
Frank3
40 mg initially followed by repeat intravenous injection every 4 to 6 hours while shock persists
Oaks4
40 mg initially followed by repeat intravenous injection every 2 to 6 hours while shock persists
Schumer5
1 mg/kg of body weight as a single intravenous injection

Administration of high dose corticosteroid therapy should be continued only until the patient's condition has stabilized and usually not longer than 48 to 72 hours.

Although adverse reactions associated with high dose, short term corticosteroid therapy are uncommon, peptic ulceration may occur.

CEREBRAL EDEMA

Dexamethasone Sodium Phosphate Injection is generally administered initially in a dosage of 10 mg intravenously followed by four mg every six hours intramuscularly until the symptoms of cerebral edema subside. Response is usually noted within 12 to 24 hours and dosage may be reduced after two to four days and gradually discontinued over a period of five to seven days. For palliative management of patients with recurrent or inoperable brain tumors, maintenance therapy with two mg two or three times a day may be effective.

ACUTE ALLERGIC DISORDERS

In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders the following dosage schedule combining parenteral and oral therapy is suggested:

Dexamethasone Sodium Phosphate Injection, 4 mg/mL -First day, 1 or 2 mL (4 or 8 mg) intramuscularly.

Dexamethasone tablets, 0.75 mg - Second and third days, 4 tablets in two divided doses each day; fourth day 2 tablets in two divided doses; fifth and sixth days, 1 tablet each day; seventh day, no treatment; eighth day, follow-up visit.

This schedule is designed to ensure adequate therapy during acute episodes, while minimizing the risk of overdosage in chronic cases.

Intra-articular, Intralesional and Soft Tissue Injection

Intra-articular, intralesional and soft tissue injections are generally employed when the affected joints or areas are limited to one or two sites. Dosage and frequency of injection varies depending on the condition and the site of injection. The usual dose is from 0.2 to 6 mg. The frequency usually ranges from once every three to five days to once every two to three weeks. Frequent intra-articular injection may result in damage to joint tissues. Some of the usual single doses are:
Site of Injection Amount of Dexamethasone Phosphate (mg) Large Joints (e.g., knee) 2 to 4 Small Joints (e.g., Interphalangeal, Temporomandibular) 0.8 to 1 Bursae 2 to 3 Tendon Sheaths 0.4 to 1 Soft Tissue Infiltration 2 to 6 Ganglia 1 to 2
Dexamethasone Sodium Phosphate Injection is particularly recommended for use in conjunction with one of the less soluble, longer-acting steroids for intra-articular and soft tissue injection.

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

Lisinopril With Hydrochlorothiazide

Lisinopril monotherapy is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide monotherapy is effective in doses of 12.5 to 50 mg per day. In clinical trials of lisinopril/hydrochlorothiazide combination therapy using lisinopril doses of 10 to 80 mg and hydrochlorothiazide doses of 6.25 to 50 mg, the antihypertensive response rates generally increased with increasing dose of either component.

The side effects (see WARNINGS) of lisinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of lisinopril and hydrochlorothiazide may be associated with either or both dose-independent or dose-dependent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics.

To minimize dose-dependent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration Guided by Clinical Effect:

A patient whose blood pressure is not adequately controlled with either lisinopril or hydrochlorothiazide monotherapy may be switched to lisinopril and hydrochlorothiazide tablets 10/12.5 or lisinopril and hydrochlorothiazide tablets 20/12.5, depending on current monotherapy dose. Further increases of either or both components should depend on clinical response with blood pressure measured at the interdosing interval to ensure that there is an adequate antihypertensive effect at that time. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. After addition of the diuretic it may be possible to reduce the dose of lisinopril. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen may achieve similar or greater blood-pressure control without electrolyte disturbance if they are switched to lisinopril and hydrochlorothiazide tablets 10/12.5.

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of lisinopril. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with lisinopril to reduce the likelihood of hypotension (See WARNINGS). If the patient’s blood pressure is not controlled with lisinopril alone, diuretic therapy may be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour See WARNINGS and PRECAUTIONS, Drug Interactions).

Concomitant administration of lisinopril and hydrochlorothiazide tablets with potassium supplements, potassium salt substitutes or potassium-sparing diuretics may lead to increases of serum potassium (See PRECAUTIONS).

Replacement Therapy:

The combination may be substituted for the titrated individual components.

Use in Renal Impairment:

Regimens of therapy with lisinopril and hydrochlorothiazide need not take account of renal function as long as the patient's creatinine clearance is >30 mL/min/1.7 m2 (serum creatinine roughly ≤ 3 mg/dL or 265 μmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so lisinopril and hydrochlorothiazide is not recommended (See WARNINGS, Anaphylactoid Reactions During Membrane Exposure).
Lisinopril

Lisinopril

2.1 Hypertension

Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect.

Use with diuretics in adultsIf blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of lisinopril tablets.

The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.

Pediatric Patients 6 years of age and older with hypertension

For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m2, the recommended starting dose is 0.07 mg per kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology (12.3)].

Lisinopril tablets are not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2 [see Use in Specific Populations (8.4) and Clinical Studies (14.1)].

2.2 Heart Failure

The recommended starting dose for lisinopril tablets, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.

Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension [see Warnings and Precautions (5.4), and Drug Interactions (7.1)]. The appearance of hypotension after the initial dose of lisinopril tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

2.3 Reduction of Mortality in Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give lisinopril tablets 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least six weeks.

Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mmHg) during the first 3 days after the infarct [see Warnings and Precautions (5.4)]. If hypotension occurs (systolic blood pressure ≤ 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) lisinopril tablets should be withdrawn.

2.4 Dose in Patients with Renal Impairment

No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril tablets to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2.5 mg. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Phenytoin Sodium

Phenytoin Sodium

Because of the increased risk of adverse cardiovascular reactions associated with rapid administration, intravenous administration should not exceed 50 mg per minute in adults. In pediatric patients, the drug should be administered at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.

As non-emergency therapy, Phenytoin Sodium Injection should be administered more slowly as either a loading dose or by intermittent infusion. Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible.

Because adverse cardiovascular reactions have occurred during and after infusions, careful cardiac monitoring is needed during and after the administration of intravenous Phenytoin Sodium Injection. Reduction in rate of administration or discontinuation of dosing may be needed.

Because of the risk of local toxicity, intravenous Phenytoin Sodium Injection should be administered directly into a large peripheral or central vein through a large-gauge catheter. Prior to the administration, the patency of the IV catheter should be tested with a flush of sterile saline. Each injection of parenteral Phenytoin Sodium Injection should then be followed by a flush of sterile saline through the same catheter to avoid local venous irritation due to the alkalinity of the solution.

Phenytoin Sodium Injection can be given diluted with normal saline. The addition of parenteral Phenytoin Sodium Injection to dextrose and dextrose-containing solutions should be avoided due to lack of solubility and resultant precipitation.

Treatment with Phenytoin Sodium Injection can be initiated either with a loading dose or an infusion:

Loading Dose: A loading dose of parenteral Phenytoin Sodium Injection should be injected slowly, not exceeding 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Infusion: For infusion administration, parenteral Phenytoin Sodium Injection should be diluted in normal saline with the final concentration of phenytoin sodium in the solution no less than 5 mg/mL. Administration should commence immediately after the mixture has been prepared and must be completed within 1 to 4 hours (the infusion mixture should not be refrigerated). An in-line filter (0.22-0.55 microns) should be used.

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

The diluted infusion mixture (Phenytoin Sodium Injection plus normal saline) should not be refrigerated. If the undiluted parenteral Phenytoin Sodium Injection is refrigerated or frozen, a precipitate might form: this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. A faint yellow coloration may develop, however this has no effect on the potency of the solution.

Status Epilepticus

In adults, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg per minute (this will require approximately 20 minutes in a 70-kg patient).

The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6-8 hours.

In the pediatric population, a loading dose of 15-20 mg/kg of phenytoin sodium intravenously will usually produce plasma concentrations of phenytoin within the generally accepted therapeutic range (10-20 mcg/mL). The drug should be injected slowly intravenously at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.

Continuous monitoring of the electrocardiogram and blood pressure is essential. The patient should be observed for signs of respiratory depression.

Determination of phenytoin plasma levels is advised when using phenytoin in the management of status epilepticus and in the subsequent establishment of maintenance dosage.

Other measures, including concomitant administration of an intravenous benzodiazepine such as diazepam, or an intravenous short-acting barbiturate, will usually be necessary for rapid control of seizures because of the required slow rate of administration of phenytoin.

If administration of parenteral Phenytoin Sodium Injection does not terminate seizures, the use of other anticonvulsants, intravenous barbiturates, general anesthesia and other appropriate measures should be considered.

Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak plasma levels may require up to 24 hours.

Nonemergent Loading and Maintenance Dosing

Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible. In adults, a loading dose of 10 to 15 mg/kg should be administered slowly. The rate of intravenous administration should not exceed 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients. Slower administration rates are recommended to minimize the cardiovascular adverse reactions. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential.

The loading dose should be followed by maintenance doses of oral or intravenous phenytoin every 6-8 hours.

Ordinarily, Phenytoin Sodium Injection should not be given intramuscularly because of the risk of necrosis, abscess formation, and erratic absorption. If intramuscular administration is required, compensating dosage adjustments are necessary to maintain therapeutic plasma levels. An intramuscular dose 50% greater than the oral dose is necessary to maintain these levels. When returned to oral administration, the dose should be reduced by 50% of the original oral dose for one week to prevent excessive plasma levels due to sustained release from intramuscular tissue sites.

Monitoring plasma levels would help prevent a fall into the subtherapeutic range. Serum blood level determinations are especially helpful when possible drug interactions are suspected.

IV Substitution For Oral Phenytoin Therapy

When treatment with oral phenytoin is not possible, IV phenytoin can be substituted for oral phenytoin at the same total daily dose. Phenytoin capsules are approximately 90% bioavailable by the oral route. Phenytoin is 100% bioavailable by the IV route. For this reason, plasma phenytoin concentrations may increase modestly when IV phenytoin is substituted for oral phenytoin sodium therapy. The rate of administration for IV phenytoin should be no greater than 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form. Phenytoin Sodium Injection is formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.

Dosing in Special Populations

Patients with Renal or Hepatic Disease: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution.Unbound phenytoin concentrations may be more useful in these patient populations.

Elderly Patients: Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric: A loading dose of 15-20 mg/kg of Phenytoin Sodium Injection intravenously will usually produce plasma concentrations of phenytoin within the generally accepted therapeutic range (10-20 mcg/mL). The drug should be injected slowly intravenously at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.
Phenylephrine Hydrochlo...

Phenylephrine Hydrochloride

2.1 General Administration Instructions

Phenylephrine hydrochloride must be diluted before administration as bolus intravenous infusion or continuous intravenous infusion.

Inspect the solution for particulate matter and discoloration prior to administration. The diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions. Discard any unused portion.

During phenylephrine hydrochloride administration:
Correct intravascular volume depletion. Correct acidosis. Acidosis may reduce the effectiveness of phenylephrine.
2.2 Preparing a 100 mcg/mL Solution of Bolus Intravenous Administration

For bolus intravenous administration, withdraw 10 mg (1 mL of a 10 mg/mL concentration) of phenylephrine injection and dilute with 99 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. This will yield a final concentration of 100 mcg/mL. Withdraw an appropriate dose from the 100 mcg/mL solution prior to bolus intravenous administration.

2.3 Preparing a Solution for Continuous Intravenous Infusion

For continuous intravenous infusion, withdraw 10 mg (1 mL of 10 mg/mL concentration) of phenylephrine hydrochloride injection and add to 500 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (providing a final concentration of 20 mcg/mL).

2.4 Dosing for Perioperative Setting

In adult patients undergoing surgical procedures with either neuraxial anesthesia or general anesthesia:
50 mcg to 250 mcg by intravenous bolus administration. The most frequently reported initial bolus dose is 50 mcg or 100 mcg. 0.5 mcg/kg/min to 1.4 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal.
2.5 Dosing for Septic or Other Vasodilatory Shock

In adult patients with septic or other vasodilatory shock:
No bolus. 0.5 mcg/kg/min to 6 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal. Doses above 6 mcg/kg/min do not show significant incremental increase in blood pressure.
Phenytoin Sodium

Phenytoin Sodium

Because of the increased risk of adverse cardiovascular reactions associated with rapid administration, intravenous administration should not exceed 50 mg per minute in adults. In pediatric patients, the drug should be administered at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.

As non-emergency therapy, Phenytoin Sodium Injection should be administered more slowly as either a loading dose or by intermittent infusion. Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible.

Because adverse cardiovascular reactions have occurred during and after infusions, careful cardiac monitoring is needed during and after the administration of intravenous Phenytoin Sodium Injection. Reduction in rate of administration or discontinuation of dosing may be needed.

Because of the risk of local toxicity, intravenous Phenytoin Sodium Injection should be administered directly into a large peripheral or central vein through a large-gauge catheter. Prior to the administration, the patency of the IV catheter should be tested with a flush of sterile saline. Each injection of parenteral Phenytoin Sodium Injection should then be followed by a flush of sterile saline through the same catheter to avoid local venous irritation due to the alkalinity of the solution.

Phenytoin Sodium Injection can be given diluted with normal saline. The addition of parenteral Phenytoin Sodium Injection to dextrose and dextrose-containing solutions should be avoided due to lack of solubility and resultant precipitation.

Treatment with Phenytoin Sodium Injection can be initiated either with a loading dose or an infusion:

Loading Dose: A loading dose of parenteral Phenytoin Sodium Injection should be injected slowly, not exceeding 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Infusion: For infusion administration, parenteral Phenytoin Sodium Injection should be diluted in normal saline with the final concentration of phenytoin sodium in the solution no less than 5 mg/mL. Administration should commence immediately after the mixture has been prepared and must be completed within 1 to 4 hours (the infusion mixture should not be refrigerated). An in-line filter (0.22-0.55 microns) should be used.

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

The diluted infusion mixture (Phenytoin Sodium Injection plus normal saline) should not be refrigerated. If the undiluted parenteral Phenytoin Sodium Injection is refrigerated or frozen, a precipitate might form: this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. A faint yellow coloration may develop, however this has no effect on the potency of the solution.

Status Epilepticus

In adults, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg per minute (this will require approximately 20 minutes in a 70-kg patient).

The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6-8 hours.

In the pediatric population, a loading dose of 15-20 mg/kg of phenytoin sodium intravenously will usually produce plasma concentrations of phenytoin within the generally accepted therapeutic range (10-20 mcg/mL). The drug should be injected slowly intravenously at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.

Continuous monitoring of the electrocardiogram and blood pressure is essential. The patient should be observed for signs of respiratory depression.

Determination of phenytoin plasma levels is advised when using phenytoin in the management of status epilepticus and in the subsequent establishment of maintenance dosage.

Other measures, including concomitant administration of an intravenous benzodiazepine such as diazepam, or an intravenous short-acting barbiturate, will usually be necessary for rapid control of seizures because of the required slow rate of administration of phenytoin.

If administration of parenteral Phenytoin Sodium Injection does not terminate seizures, the use of other anticonvulsants, intravenous barbiturates, general anesthesia and other appropriate measures should be considered.

Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak plasma levels may require up to 24 hours.

Nonemergent Loading and Maintenance Dosing

Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible. In adults, a loading dose of 10 to 15 mg/kg should be administered slowly. The rate of intravenous administration should not exceed 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients. Slower administration rates are recommended to minimize the cardiovascular adverse reactions. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential.

The loading dose should be followed by maintenance doses of oral or intravenous phenytoin every 6-8 hours.

Ordinarily, Phenytoin Sodium Injection should not be given intramuscularly because of the risk of necrosis, abscess formation, and erratic absorption. If intramuscular administration is required, compensating dosage adjustments are necessary to maintain therapeutic plasma levels. An intramuscular dose 50% greater than the oral dose is necessary to maintain these levels. When returned to oral administration, the dose should be reduced by 50% of the original oral dose for one week to prevent excessive plasma levels due to sustained release from intramuscular tissue sites.

Monitoring plasma levels would help prevent a fall into the subtherapeutic range. Serum blood level determinations are especially helpful when possible drug interactions are suspected.

IV Substitution For Oral Phenytoin Therapy

When treatment with oral phenytoin is not possible, IV phenytoin can be substituted for oral phenytoin at the same total daily dose. Phenytoin capsules are approximately 90% bioavailable by the oral route. Phenytoin is 100% bioavailable by the IV route. For this reason, plasma phenytoin concentrations may increase modestly when IV phenytoin is substituted for oral phenytoin sodium therapy. The rate of administration for IV phenytoin should be no greater than 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form. Phenytoin Sodium Injection is formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.

Dosing in Special Populations

Patients with Renal or Hepatic Disease: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution.Unbound phenytoin concentrations may be more useful in these patient populations.

Elderly Patients: Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric: A loading dose of 15-20 mg/kg of Phenytoin Sodium Injection intravenously will usually produce plasma concentrations of phenytoin within the generally accepted therapeutic range (10-20 mcg/mL). The drug should be injected slowly intravenously at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.
The Body Shop Pomegrana...

The Body Shop Pomegranate Spf 15

Dosage and Administration in Adults

SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.

The daily dose of fluconazole for the treatment of infections should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.

Oropharyngeal candidiasis:

The recommended dosage of fluconazole for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis:

The recommended dosage of fluconazole for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.

Systemic Candida infections:

For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.

Urinary tract infections and peritonitis:

For the treatment of Candida urinary tract infections and peritonitis, daily doses of 50 to 200 mg have been used in open, noncomparative studies of small numbers of patients.

Cryptococcal meningitis:

The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of fluconazole for suppression of relapse of cryptoccocal meningitis in patients with AIDS is 200 mg once daily.

Prophylaxis in patients undergoing bone marrow transplantation:

The recommended fluconazole daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start fluconazole prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:
Pediatric Patients Adults * Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. 3 mg/kg 100 mg 6 mg/kg 200 mg 12* mg/kg 400 mg
Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY.) Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available.

Oropharyngeal candidiasis:

The recommended dosage of fluconazole for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis:

For the treatment of esophageal candidiasis, the recommended dosage of fluconazole in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms.

Systemic Candida infections:

For the treatment of candidemia and disseminated Candida infections, daily doses of 6 to 12 mg/kg/day have been used in an open, noncomparative study of a small number of children.

Cryptococcal meningitis:

For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole is 6 mg/kg once daily.

Dosage In Patients With Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:
Creatinine Clearance (mL/min) Percent of Recommended Dose > 50 100% ≤ 50 (no dialysis) 50% Regular dialysis 100% after each dialysis
These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.

When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults:

    Males:               Weight (kg) × (140 – age)                            72 × serum creatinine (mg/100 mL)

    Females:    0.85 × above value

Although the pharmacokinetics of fluconazole have not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children:

    K ×            linear length or height (cm)                        serum creatinine (mg/100 mL)

(Where K=0.55 for children older than 1 year and 0.45 for infants.)

Administration

Fluconazole may be administered either orally or by intravenous infusion. Fluconazole can be taken with or without food. Fluconazole injection has been used safely for up to fourteen days of intravenous therapy. The intravenous infusion of fluconazole should be administered at a maximum rate of approximately 200 mg/hour, given as a continuous infusion.

Fluconazole injection in glass and plastic containers is intended only for intravenous administration using sterile equipment.

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

Do not use if the solution is cloudy or precipitated or if the seal is not intact.

Directions for Intravenous Use of Fluconazole Injection in Plastic containers

Do not remove unit from overwrap until ready for use. The overwrap is a moisture barrier. The inner bag maintains the sterility of the product

CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.

To Open

Tear overwrap down side at slit and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. After removing overwrap, check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

DO NOT ADD SUPPLEMENTARY MEDICATION.

Preparation for Administration:
Suspend container from eyelet support. Remove plastic protector from outlet port at bottom of container. Attach administration set. Refer to complete directions accompanying set.
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 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 for Injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for Injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for Injection must not be administered simultaneously with calcium-containing IV solution, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients in other than neonates, Ceftriaxone for Injection 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 interaction 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 grams.

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

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

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

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

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

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

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

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

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

No dosage adjustment is necessary for patients with impairment of renal or hepatic function.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE:

The 10 gram vial 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. This closure may be penetrated only one time after reconstitution, using a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents.

The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial closure entry is permitted to complete fluid transfer operations. Unused portions of solution held longer than the recommended time periods should be discarded.
Reconstituted Bulk Solutions 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.

COMPATABILITY 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 compatability 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 vials or to further dilute a reconstituted vial 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 - 25°C (68 - 77°F) [See USP Controlled Room Temperature] and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.

Ceftriaxone for Injection 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 2 days 10 days 0.9% Sodium Chloride Solution 2 days 10 days 5% Dextrose Solution 2 days 10 days 10% Dextrose Solution 2 days 10 days 5% Dextrose + 0.9% Sodium Chloride Solution* 2 days Incompatible 5% Dextrose + 0.45% Sodium Chloride Solution 2 days Incompatible
The following intravenous Ceftriaxone for Injection solutions are stable at room temperature (25 °C) for 24 hours, at concentrations between 10 mg/mL and 40 mg/mL: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine III (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), Ionosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container).

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

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

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

Frozen solutions of Ceftriaxone for Injection should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.
Fosphenytoin Sodium

Fosphenytoin Sodium

The dose, concentration, and infusion rate of fosphenytoin sodium injection should always be expressed as phenytoin sodium equivalents (PE). There is no need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin sodium injection should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). 1.5 mg of fosphenytoin sodium is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg PE. The amount and concentration of fosphenytoin is always expressed in terms of mg of phenytoin sodium equivalents (mg PE).

Do not confuse the concentration of fosphenytoin sodium injection with the total amount of drug in the vial.

Caution must be used when administering fosphenytoin sodium injection due to the risk of dosing errors (see WARNINGS). Medication errors associated with fosphenytoin sodium injection have resulted in patients receiving the wrong dose of fosphenytoin. Fosphenytoin sodium injection is marketed in 2 mL vials containing a total of 100 mg PE and 10 mL vials containing a total of 500 mg PE. Both vials contain a concentration of 50 mg PE/mL. Errors have occurred when the concentration of the vial (50 mg PE/mL) was misinterpreted to mean that the total content of the vial was 50 mg PE. These errors have resulted in two- or ten-fold overdoses of fosphenytoin sodium injection since each of the vials actually contains a total of 100 mg PE or 500 mg PE. In some cases, ten-fold overdoses were associated with fatal outcomes. To help minimize confusion, the prescribed dose of fosphenytoin sodium injection should always be expressed in milligrams of phenytoin equivalents (mg PE). Additionally, when ordering and storing fosphenytoin sodium injection, consider displaying the total drug content (i.e., 100 mg PE/2 mL or 500 mg PE/10 mL) instead of concentration in computer systems, pre-printed orders, and automated dispensing cabinet databases to help ensure that total drug content can be clearly identified. Care should be taken to ensure the appropriate volume of fosphenytoin sodium injection is withdrawn from the vial when preparing the dose for administration. Attention to these details may prevent some fosphenytoin sodium injection medication errors from occurring.

Prior to IV infusion, dilute fosphenytoin sodium injection in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL. The maximum concentration of fosphenytoin sodium injection in any solution should be 25 mg PE/mL. When fosphenytoin sodium injection is given as an intravenous infusion, fosphenytoin sodium injection needs to be diluted and should only be administered at a rate not exceeding 150 mg PE/min.

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

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

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

Nonemergent Loading and Maintenance Dosing

Because of the risks of cardiac and local toxicity associated with intravenous fosphenytoin sodium injection, oral phenytoin should be used whenever possible.The loading dose of fosphenytoin sodium injection is 10 - 20 mg PE/kg given IV or IM. The rate of administration for IV fosphenytoin sodium injection should be no greater than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur (approximately 20 minutes after the end of fosphenytoin sodium injection infusion).

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

IM or IV Substitution for Oral Phenytoin Therapy

When treatment with oral phenytoin is not possible, fosphenytoin sodium injection can be substituted for oral phenytoin at the same total daily dose. Dilantin capsules are approximately 90% bioavailable by the oral route. Phenytoin, supplied as fosphenytoin sodium injection, is 100% bioavailable by both the IM and IV routes. For this reason, plasma phenytoin concentrations may increase modestly when IM or IV fosphenytoin sodium injection is substituted for oral phenytoin sodium therapy. The rate of administration for IV fosphenytoin sodium injection should be no greater than 150 mg PE/min. In controlled trials, IM fosphenytoin sodium injection was administered as a single daily dose utilizing either 1 or 2 injection sites. Some patients may require more frequent dosing.

Dosing in Special Populations

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

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

Pediatric: The safety and efficacy of fosphenytoin sodium injection in pediatric patients have not been established.
Oxycodone And Acetamino...

Oxycodone And Acetaminophen

Prior to initiating testosterone cypionate, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

Testosterone cypionate injection is for intramuscular use only.

It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle.

The suggested dosage for testosterone cypionate injection varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient's response and the appearance of adverse reactions.

Various dosage regimens have been used to induce pubertal changes in hypogonadal males; some experts have advocated lower dosages initially, gradually increasing the dose as puberty progresses, with or without a decrease to maintenance levels. Other experts emphasize that higher dosages are needed to induce pubertal changes and lower dosages can be used for maintenance after puberty. The chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose.

For replacement in the hypogonadal male, 50 to 400 mg should be administered every two to four weeks.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.
Ceftriaxone

Ceftriaxone

Ceftriaxone may be administered intravenously or intramuscularly.

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone vials or to further dilute a reconstituted vial 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 interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

NEONATES

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

Ceftriaxone is contraindicated in neonates if they require (or are expected to require) treatment with calcium‑containing IV solutions, including continuous calcium‑containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see CONTRAINDICATIONS).

PEDIATRIC PATIENTS

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

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

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

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

ADULTS

The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. For infections caused by Staphylococcus aureus (MSSA), the recommended daily dose is 2 to 4 grams, in order to achieve > 90% target attainment. The total daily dose should not exceed 4 grams.

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

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

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

Generally, ceftriaxone 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 USE

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

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

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

As with all intramuscular preparations, ceftriaxone should be injected well within the body of a relatively large muscle; aspiration helps to avoid unintentional injection into a blood vessel.
Vial Dosage Size Amount of Diluent to be Added 250 mg/mL 350 mg/mL
250 mg

0.9 mL

—

500 mg

1.8 mL

1.0 mL

1 gm

3.6 mL

2.1 mL

2 gm

7.2 mL

4.2 mL

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

Vial Dosage Size

Amount of Diluent to be Added

250 mg

2.4 mL

500 mg

4.8 mL

1 gm

9.6 mL

2 gm

19.2 mL

After reconstitution, each 1 mL of solution contains approximately 100 mg equivalent of ceftriaxone. Withdraw entire contents and dilute to the desired concentration with the appropriate IV diluent.
Mucus Relief Dm

Mucus Relief Dm

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS).

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

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

Adults

Preanesthetic Medication

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

Intraoperative Medication

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

Reversal of Neuromuscular Blockade

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

Peptic Ulcer

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

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

Pediatric Patients

(see PRECAUTIONS, Pediatric Use)

Preanesthetic Medication

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

Infants

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

Intraoperative Medication

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

Reversal of Neuromuscular Blockade

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

Peptic Ulcer

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

Diluent Compatibilities

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

Diluent Incompatibilities

Lactated Ringer’s solution.

Admixture Compatibilities

Physical Compatibility

This list does not constitute an endorsement of the clinical utility or safety of co‑administration of glycopyrrolate with these drugs. Glycopyrrolate injection is compatible for mixing and injection with the following injectable dosage forms: atropine sulfate, USP; physostigmine salicylate; diphenhydramine HCl; codeine phosphate, USP; benz-quinamide HCl; hydromorphone HCl, USP; droperidol; levorphanol tartrate; lidocaine, USP; meperidine HCl, USP; pyridostigmine bromide; morphine sulfate, USP; nalbuphine HCl; oxymorphone HCl; procaine HCl, USP; promethazine HCl, USP; neostigmine methylsulfate, USP; scopolamine HBr, USP; butorphanol tartrate; fentanyl citrate; trimethobenzamide HCl; and hydroxyzine HCl. Glycopyrrolate injection may be administered via the tubing of a running infusion of normal saline.

Admixture Incompatibilities

Physical Incompatibility

Since the stability of glycopyrrolate is questionable above a pH of 6.0 do not combine glycopyrrolate injection in the same syringe with methohexital Na; chloramphenicol Na succinate; dimenhydrinate; pentobarbital Na; thiopental Na; secobarbital Na; sodium bicarbonate; diazepam; dexamethasone Na phosphate; or pentazocine lactate. These mixtures will result in a pH higher than 6.0 and may result in gas production or precipitation.
Digoxin

Digoxin

2.1 Important Dosing and Administration Information

In selecting a Digoxin Tablets dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.

Consider interruption or reduction in Digoxin Tablets dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].

Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.

2.2 Loading Dosing Regimen in Adults and Pediatric Patients

For adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended Digoxin Tablets Oral Loading Dose mcg = microgram Age Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice
5 to 10 years 20 to 45 Adults and pediatric patients over 10 years      10 to 15
2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years Old

The maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology(12.3)].

The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Tablets Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgram Age Total Oral Maintenance Dose, mcg/kg/day      (given once daily) Adults and pediatric patients over 10 years      3.4 to 5.1
Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):

Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100(% Daily Loss = 14 + Creatinine clearance/5)

Reduce the dose of Digoxin Tablets in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Tablets in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona a Doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85. For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys. GFR (mL/min/1.73 m2) = (k x Height)/Scrc If no loading dose administered.d The doses listed assume average body composition. Corrected Creatinine Clearanceb Lean Body Weightd Number of Days Before Steady State Achievedc kg 40 50 60 70 80 90 100 10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7
2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years Old

The starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting Digoxin Tablets Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose, mcg/kg/dose 5 years to 10 years 3.2 to 6.4   Twice daily
Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of Digoxin Tablets in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b
a Recommended are doses to be given twice daily.b The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3. d If no loading dose administered.
CorrectedCreatinineClearancec Lean Body Weight Number of DaysBefore SteadyState Achievedd kg 20 30 40 50 60 10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 2.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7
2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood Levels

Monitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.

Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.

Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the Digoxin Tablets dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting Digoxin Tablets and correct post-treatment values by the reported baseline level.

Obtain serum digoxin concentrations just before the next scheduled Digoxin Tablets dose or at least

6 hours after the last dose. The digoxin concentration is likely to be 10 to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.

2.6 Switching from Intravenous Digoxin to Oral Digoxin

When switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous Digoxin Absolute   Bioavailability    Equivalent Doses (mcg)    Digoxin Tablets 60-80% 62.5    125 250 500 Digoxin Intravenous Injection    100% 50 100 200 400
Cefotaxime

Cefotaxime

The intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only. Dosing references to the intramuscular route of administration are for informational purposes only.

Adults

Dosage and route of administration should be determined by susceptibility of the causative organisms, severity of the infection, and the condition of the patient (see table for dosage guideline). Cefotaxime may be administered IM or IV after reconstitution. The maximum daily dosage should not exceed 12 grams.
GUIDELINES FOR DOSAGE OF CEFOTAXIME FOR INJECTION Type of Infection Daily Dose(grams) Frequency and Route Gonococcal urethritis/cervicitis in males and females 0.5 0.5 gram IM (single dose) Rectal gonorrhea in females 0.5 0.5 gram IM (single dose) Rectal gonorrhea in males 1 1 gram IM (single dose) Uncomplicated infections 2 1 gram every 12 hours IM or IV Moderate to severe infections 3-6 1-2 grams every 8 hours IM or IV Infections commonly needing antibiotics in higher dosage (e.g., septicemia) 6-8 2 grams every 6-8 hours IV Life-threatening infections up to 12 2 grams every 4 hours IV
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefotaxime sodium has no activity against this organism.

To prevent postoperative infection in contaminated or potentially contaminated surgery, the recommended dose is a single 1 gram IM or IV administered 30 to 90 minutes prior to start of surgery.

Cesarean Section Patients

The first dose of 1 gram is administered intravenously as soon as the umbilical cord is clamped. The second and third doses should be given as 1 gram intravenously or intramuscularly at 6 and 12 hours after the first dose.

Neonates, Infants, and Children

The following dosage schedule is recommended:

Neonates (birth to 1 month):

0-1 week of age 50 mg/kg per dose every 12 hours IV

1-4 weeks of age 50 mg/kg per dose every 8 hours IV

It is not necessary to differentiate between premature and normal-gestational age infants.

Infants and Children (1 month to 12 years):

For body weights less than 50 kg, the recommended daily dose is 50 to 180 mg/kg IM or IV body weight divided into four to six equal doses. The higher dosages should be used for more severe or serious infections, including meningitis. For body weights 50 kg or more, the usual adult dosage should be used; the maximum daily dosage should not exceed 12 grams.

Geriatric Use

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See PRECAUTIONS, General and PRECAUTIONS, Geriatric Use.)

Impaired Renal Function

See PRECAUTIONS, General.

NOTE: As with antibiotic therapy in general, administration of cefotaxime should be continued for a minimum of 48 to 72 hours after the patient defervesces or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended for infections caused by Group A beta-hemolytic streptococci in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment of several weeks and doses smaller than those indicated above should not be used.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE:

The 10 gram Pharmacy Bulk Package should be penetrated ONLY ONE TIME utilizing a suitable sterile transfer device or dispensing set and should be reconstituted with 47 mL of diluent for an approximate concentration of 200 mg/mL (withdrawable volume 52 mL) or 97 mL of diluent for an approximate concentration of 100 mg/mL withdrawable volume 102 mL), in a suitable work area such as a laminar flow hood, using aseptic technique. Shake to dissolve; inspect for particulate matter and discoloration prior to use. Stock solutions may be further diluted for IV infusion with diluents as listed in COMPATIBILITY AND STABILITY section. The reconstituted content of the 10 g Pharmacy Bulk Package should be withdrawn immediately, using a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. However, if it is not possible, aliquoting operations must be completed within four hours of reconstitution. Discard the reconstituted stock solution 4 hours after initial entry. Solutions of cefotaxime range from very pale yellow to light amber, depending on concentration, diluent used, and length and condition of storage.

Reconstituted Bulk Solutions Should Not Be Used For Direct Infusion

NOTE: Solutions of cefotaxime must not be admixed with aminoglycoside solutions. If cefotaxime and aminoglycosides are to be administered to the same patient, they must be administered separately and not as mixed injection.

A SOLUTION OF 1 G CEFOTAXIME IN 14 ML OF STERILE WATER FOR INJECTION IS ISOTONIC.

IM Administration: As with all IM preparations, cefotaxime should be injected well within the body of a relatively large muscle such as the upper outer quadrant of the buttock (i.e., gluteus maximus); aspiration is necessary to avoid inadvertent injection into a blood vessel. Individual IM doses of 2 grams may be given if the dose is divided and is administered in different intramuscular sites.

IV Administration: The IV route is preferable for patients with bacteremia, bacterial septicemia, peritonitis, meningitis, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent IV administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Cefotaxime should not be administered over a period of less than three minutes. (See WARNINGS). With an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing cefotaxime, it is advisable to discontinue temporarily the administration of other solutions at the same site.

For the administration of higher doses by continuous IV infusion, a solution of cefotaxime may be added to IV bottles containing the solutions discussed below.

COMPATIBILITY AND STABILITY

Solutions of cefotaxime reconstituted as described above (DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE) should be discarded 4 hours after initial entry.

Reconstituted solutions may be further diluted up to 1000 mL with the following solutions and maintain satisfactory potency for 24 hours at or below 22°C, and at least 5 days under refrigeration (at or below 5°C): 0.9% Sodium Chloride Injection; 5 or 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.2% Sodium Chloride Injection; Lactated Ringer’s Solution; Sodium Lactate Injection (M/6); 10% Invert Sugar Injection, 8.5% TRAVASOL® (Amino Acid) Injection without Electrolytes.

NOTE: Cefotaxime solutions exhibit maximum stability in the pH 5-7 range. Solutions of cefotaxime should not be prepared with diluents having a pH above 7.5, such as Sodium Bicarbonate Injection.

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

Cefotaxime

Adults

Dosage and route of administration should be determined by susceptibility of the causative organisms, severity of the infection, and the condition of the patient (see table for dosage guideline). Cefotaxime may be administered IM or IV after reconstitution. The maximum daily dosage should not exceed 12 grams.
GUIDELINES FOR DOSAGE OF CEFOTAXIME FOR INJECTION Type of Infection Daily Dose (grams) Frequency and Route Gonococcal urethritis/cervicitis in males and females 0.5 0.5 gram IM (single dose) Rectal gonorrhea in females 0.5 0.5 gram IM (single dose) Rectal gonorrhea in males 1 1 gram IM (single dose) Uncomplicated infections 2 1 gram every 12 hours IM or IV Moderate to severe infections 3-6 1-2 grams every 8 hours IM or IV Infections commonly needing antibiotics in higher dosage (e.g., septicemia) 6-8 2 grams every 6-8 hours IV Life-threatening infections up to 12 2 grams every 4 hours IV
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefotaxime sodium has no activity against this organism.

To prevent postoperative infection in contaminated or potentially contaminated surgery, the recommended dose is a single 1 gram IM or IV administered 30 to 90 minutes prior to start of surgery.

Cesarean Section Patients

The first dose of 1 gram is administered intravenously as soon as the umbilical cord is clamped. The second and third doses should be given as 1 gram intravenously or intramuscularly at 6 and 12 hours after the first dose.

Neonates, Infants, and Children

The following dosage schedule is recommended:

Neonates (birth to 1 month): 0-1 week of age 50 mg/kg per dose every 12 hours IV1-4 weeks of age 50 mg/kg per dose every 8 hours IV

It is not necessary to differentiate between premature and normal-gestational age infants.

Infants and Children (1 month to 12 years):For body weights less than 50 kg, the recommended daily dose is 50 to 180 mg/kg IM or IV body weight divided into four to six equal doses. The higher dosages should be used for more severe or serious infections, including meningitis. For body weights 50 kg or more, the usual adult dosage should be used; the maximum daily dosage should not exceed 12 grams.

Geriatric Use

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See PRECAUTIONS, General and PRECAUTIONS, Geriatric Use.)

Impaired Renal Function

See PRECAUTIONS, General.

NOTE: As with antibiotic therapy in general, administration of cefotaxime should be continued for a minimum of 48 to 72 hours after the patient defervesces or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended for infections caused by Group A beta-hemolytic streptococci in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment of several weeks and doses smaller than those indicated above should not be used.

Preparation of cefotaxime for injection sterile

Cefotaxime for IM or IV administration should be reconstituted as follows:
Strength
Diluent(mL)

Withdrawable Volume(mL)

Approximate Concentration(mg/mL)
500 mg vial* (IM) 2 2.2 230 1 g vial* (IM) 3 3.4 300 2 g vial* (IM) 5 6.0 330 500 mg vial* (IV) 10 10.2 50 1 g vial* (IV) 10 10.4 95 2 g vial* (IV) 10 11.0 180 1 g infusion 50-100 50-100 20-10 2 g infusion 50-100 50-100 40-20
(*) in conventional vials

Shake to dissolve; inspect for particulate matter and discoloration prior to use. Solutions of cefotaxime range from very pale yellow to light amber, depending on concentration, diluent used, and length and condition of storage.

For intramuscular use: Reconstitute VIALS with Sterile Water for Injection or Bacteriostatic Water for Injection as described above.

For intravenous use: Reconstitute VIALS with at least 10 mL of Sterile Water for Injection. Reconstitute INFUSION BOTTLES with 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection. For other diluents, see COMPATIBILITY AND STABILITY section.

NOTE: Solutions of cefotaxime must not be admixed with aminoglycoside solutions. If cefotaxime and aminoglycosides are to be administered to the same patient, they must be administered separately and not as mixed injection.

A SOLUTION OF 1 G CEFOTAXIME IN 14 ML OF STERILE WATER FOR INJECTION IS ISOTONIC.

IM Administration: As with all IM preparations, cefotaxime should be injected well within the body of a relatively large muscle such as the upper outer quadrant of the buttock (i.e., gluteus maximus); aspiration is necessary to avoid inadvertent injection into a blood vessel. Individual IM doses of 2 grams may be given if the dose is divided and is administered in different intramuscular sites.

IV Administration: The IV route is preferable for patients with bacteremia, bacterial septicemia, peritonitis, meningitis, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent IV administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Cefotaxime should not be administered over a period of less than three minutes. (See WARNINGS). With an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing cefotaxime, it is advisable to discontinue temporarily the administration of other solutions at the same site.

For the administration of higher doses by continuous IV infusion, a solution of cefotaxime may be added to IV bottles containing the solutions discussed below.

Compatibility and Stability

Solutions of cefotaxime reconstituted as described above (Preparation of cefotaxime for injection sterile) remain chemically stable (potency remains above 90%) as follows when stored in original containers and disposable plastic syringes:
Strength
ReconstitutedConcentrationmg/mL

Stability at orbelow 22ºC

Stability underRefrigeration(at or below 5ºC)
Original Containers Plastic Syringes 500 mg vial IM 230 12 hours 7 days 5 days 1 g vial IM 300 12 hours 7 days 5 days 2 g vial IM 330 12 hours 7 days 5 days 500 mg vial IV 50 24 hours 7 days 5 days 1 g vial IV 95 24 hours 7 days 5 days 2 g vial IV 180 12 hours 7 days 5 days 1 g infusion bottle 10-20 24 hours 10 days — 2 g infusion bottle 20-40 24 hours 10 days —
Reconstituted solutions stored in original containers and plastic syringes remain stable for 13 weeks frozen.

Reconstituted solutions may be further diluted up to 1000 mL with the following solutions and maintain satisfactory potency for 24 hours at or below 22°C, and at least 5 days under refrigeration (at or below 5°C): 0.9% Sodium Chloride Injection; 5 or 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.2% Sodium Chloride Injection; Lactated Ringer's Solution; Sodium Lactate Injection (M/6); 10% Invert Sugar Injection, 8.5% TRAVASOL® (Amino Acid) Injection without Electrolytes.

NOTE: Cefotaxime solutions exhibit maximum stability in the pH 5-7 range. Solutions of cefotaxime should not be prepared with diluents having a pH above 7.5, such as Sodium Bicarbonate Injection.

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

Acnefree Therapeutic Sulfur Mask

2.1 Asthma

Montelukast sodium should be taken once daily in the evening. The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.

There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion.

2.2 Exercise-Induced Bronchoconstriction (EIB)

For prevention of EIB, a single dose of montelukast sodium should be taken at least 2 hours before exercise.

The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

An additional dose of montelukast sodium should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting β-agonist. Safety and efficacy in patients younger than 6 years of age have not been established. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB.

2.3 Allergic Rhinitis

For allergic rhinitis, montelukast sodium should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs.

The following doses for the treatment of symptoms of seasonal allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.

The following doses for the treatment of symptoms of perennial allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established.

2.4 Asthma and Allergic Rhinitis

Patients with both asthma and allergic rhinitis should take only one montelukast sodium dose daily in the evening.
Butalbital

Butalbital

One or 2 tablets every 4 hours as needed. Total daily dosage should not exceed 6 tablets. Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Doxycycline Hyclate

Doxycycline Hyclate

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS. Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day.

In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For children above eight years of age: The recommended dosage schedule for children weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections, up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration (See ADVERSE REACTIONS).

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of doxycycline in patients with renal impairment.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage, as required.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg, by mouth, twice a day for 7 days.

Nongonococcal urethritis (NGU) caused by C. trachomatis or U. urealyticum: 100 mg, by mouth, twice a day for 7 days.

Syphilis - early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks.

Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.

Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1 to 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

Inhalational anthrax (post-exposure):ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days.CHILDREN: weighing less than 100 lb (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 lb or more should receive the adult dose.
Carisoprodol

Carisoprodol

The recommended dose of Carisoprodol Tablets is 350 mg three times a day and at bedtime. The recommended maximum duration of Carisoprodol Tablets use is up to two or three weeks.
Propylthiouracil

Propylthiouracil

Propylthiouracil is administered orally. The total daily dosage is usually given in 3 equal doses at approximately 8-hour intervals.

Adults

The initial dose is 300 mg daily. In patients with severe hyperthyroidism, very large goiters, or both, the initial dose may be increased to 400 mg daily; an occasional patient will require 600 to 900 mg daily initially. The usual maintenance dose is 100 to 150 mg daily. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pediatric Patients

Propylthiouracil is generally not recommended for use in the pediatric patient population except in rare instances in which other alternative therapies are not appropriate options. Studies evaluating appropriate dosing regimen have not been conducted in the pediatric population although general practice would suggest initiation of therapy in patients 6 years or older at a dosage of 50 mg daily with careful upward titration based on clinical response and evaluation of TSH and free T4 levels. Although cases of severe liver injury have been reported with doses as low as 50 mg/day, most cases were associated with doses of 300 mg/day and higher.

Geriatric Use

Clinical studies of propylthiouracil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Bethanechol Chloride

Bethanechol Chloride

2.1 Gout Prophylaxis

For prophylaxis of gout flares, the recommended dosage of colchicine capsules is 0.6 mg once or twice daily. The maximum dose is 1.2 mg per day.

Colchicine capsules are administered orally, without regard to meals.
Granisetron Hydrochlori...

Granisetron Hydrochloride

2.1 Prevention of Chemotherapy-Induced Nausea and Vomiting

Adult PatientsThe recommended dosage for Granisetron Hydrochloride Injection is 10 mcg/kg administered intravenously within 30 minutes before initiation of chemotherapy, and only on the day(s) chemotherapy is given.

Infusion PreparationGranisetron Hydrochloride Injection may be administered intravenously either undiluted over 30 seconds or diluted with 0.9% Sodium Chloride or 5% Dextrose and infused over 5 minutes.

StabilityIntravenous infusion of Granisetron Hydrochloride Injection should be prepared at the time of administration. However, Granisetron Hydrochloride Injection has been shown to be stable for at least 24 hours when diluted in 0.9% Sodium Chloride or 5% Dextrose and stored at room temperature under normal lighting conditions.

As a general precaution, Granisetron Hydrochloride Injection should not be mixed in solution with other drugs. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

Pediatric PatientsThe recommended dose in pediatric patients 2 to 16 years of age is 10 mcg/kg [see Clinical Studies (14)]. Pediatric patients under 2 years of age have not been studied.
Cefadroxil

Cefadroxil

Cefadroxil tablets are acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Adults

Urinary Tract Infections

For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).

For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.).

Skin and Skin Structure Infections

For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.).

Pharyngitis and Tonsillitis

Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis – 1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of cefadroxil tablets should be administered for at least 10 days.

Renal Impairment

In patients with renal impairment, the dosage of cefadroxil monohydrate should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil tablets and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 m2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0 to 10 mL/min 36 hours 10 to 25 mL/min 24 hours 25 to 50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.
Testosterone Enanthate

Testosterone Enanthate

Prior to initiating testosterone enanthate injection, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

Dosage and duration of therapy with testosterone enanthate injection will depend on age, sex, diagnosis, patient’s response to treatment, and appearance of adverse effects. When properly given, injections of testosterone enanthate, are well tolerated. Care should be taken to slowly inject the preparation deeply into the gluteal muscle, being sure to follow the usual precautions for intramuscular administration, such as the avoidance of intravascular injection (see PRECAUTIONS).

In general, total doses above 400 mg per month are not required because of the prolonged action of the preparation. Injections more frequently than every two weeks are rarely indicated. NOTE: Use of a wet needle or wet syringe may cause the solution to become cloudy; however this does not affect the potency of the material. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Testosterone enanthate injection is a clear, colorless to pale yellow solution.

Male hypogonadism: As replacement therapy, i.e., for eunuchism, the suggested dosage is 50 to 400 mg every 2 to 4 weeks.

In males with delayed puberty: Various dosage regimens have been used; some call for lower dosages initially with gradual increases as puberty progresses, with or without a decrease to maintenance levels. Other regimens call for higher dosage to induce pubertal changes and lower dosage for maintenance after puberty. The chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose. Dosage is within the range of 50 to 200 mg every 2 to 4 weeks for a limited duration, for example, 4 to 6 months. X-rays should be taken at appropriate intervals to determine the amount of bone maturation and skeletal development (see INDICATIONS AND USAGE and WARNINGS).

Palliation of inoperable mammary cancer in women: A dosage of 200 to 400 mg every 2 to 4 weeks is recommended. Women with metastatic breast carcinoma must be followed closely because androgen therapy occasionally appears to accelerate the disease.

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