ONDANSETRON HYDROCHLORIDE (Page 4 of 4)

DRUG ABUSE AND DEPENDENCE

Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

OVERDOSAGE

There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. Individual doses as large as 150 mg and total daily dosages (three doses) as large as 252 mg have been administered intravenously without significant adverse events. These doses are more than 10 times the recommended daily dose.

In addition to the adverse events listed above, the following events have been described in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes’ duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose. Hypotension (and faintness) occurred in another patient that took 48 mg of oral ondansetron. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed. In all instances, the events resolved completely.

DOSAGE AND ADMINISTRATION

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

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

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

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

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

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

Prevention of Postoperative Nausea and Vomiting: Adult Dosing: The recommended I.V. dosage of ondansetron for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, 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 for pediatric surgical patients (1 month to 12 years of age) is a single 0.1-mg/kg dose for patients weighing 40 kg or less, or a single 4-mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ondansetron.

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

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

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

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

Stability: Ondansetron injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following 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 odansetron injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative. After dilution, do not use beyond 24 hours.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration 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, 2 mg/mL, is supplied as follows:

NDC 64679-726-01 2-mL single-dose vials (Carton of 5)

NDC 64679-727-01 20-mL multidose vials (Singles)

Store at 20°-25°C (68°-77°F) (See USP Controlled Room Temperature). Protect from light.

Retain in carton until time of use.

REFERENCES

1. Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228.
2. 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.
3. 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.
4. De Witte JL, Schoenmaekers B, Sessler DI, et al. Anesth Analg. 2001;92:1319-1321.
5. Arcioni R, della Rocca M, Romanò R, et al. Anesth Analg. 2002;94:1553-1557.

Manufactured by:

Wockhardt Limited

Mumbai, India.

Distributed by:

Wockhardt USA LLC.

20 Waterview Blvd.

Parsippany, NJ 07054

USA.

ONDANSETRON HYDROCHLORIDE ondansetron hydrochloride injection

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:55648-726 Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ONDANSETRON HYDROCHLORIDE (ONDANSETRON) ONDANSETRON 2 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE CITRIC ACID MONOHYDRATE TRISODIUM CITRATE DIHYDRATE WATER

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:55648-726-01 5 VIAL, SINGLE-DOSE (VIAL) in 1 CARTON contains a VIAL, SINGLE-DOSE 1 2 mL in 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (55648-726-01)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077716 12/27/2006

ONDANSETRON HYDROCHLORIDE ondansetron hydrochloride injection

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:55648-727 Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ONDANSETRON HYDROCHLORIDE (ONDANSETRON) ONDANSETRON 2 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE CITRIC ACID MONOHYDRATE TRISODIUM CITRATE DIHYDRATE METHYLPARABEN PROPYLPARABEN WATER

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:55648-727-01 1 VIAL, MULTI-DOSE (VIAL) in 1 CARTON contains a VIAL, MULTI-DOSE 1 20 mL in 1 VIAL, MULTI-DOSE This package is contained within the CARTON (55648-727-01)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077577 12/27/2006

Labeler — WOCKHARDT LIMITED (650069115)

Establishment
Name	Address	ID/FEI	Operations
WOCKHARDT LIMITED		676257570	manufacture

Revised: 11/2011 WOCKHARDT LIMITED