ONDANSETRON HYDROCHLORIDE (Page 5 of 6)

Observed During Clinical Practice

In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of ondansetron. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ondansetron.

Cardiovascular: Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.

General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported. Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable ondansetron.

Hepatobiliary: Liver enzyme abnormalities

Lower Respiratory: Hiccups

Neurology : Oculogyric crisis, appearing alone, as well as with other dystonic reactions

Skin: Urticaria

Special Senses: Eye Disorders : Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.

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 intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered 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 a patient that took 48 mg of ondansetron tablets. 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 Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy:

The recommended adult oral dosage of ondansetron 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 ondansetron 24 mg tablets has not been studied.

Pediatric Use: There is no experience with the use of 24 mg ondansetron tablets 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 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 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 tablet should be administered three 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 tablet given three times a day.

For total body irradiation , one 8 mg ondansetron 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 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 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 tablets, in the prevention of radiation-induced nausea and vomiting in pediatric patients.

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

Postoperative Nausea and Vomiting:

The recommended dosage is 16 mg given as two 8 mg ondansetron tablets 1 hour before induction of anesthesia.

Pediatric Use : There is no experience with the use of ondansetron tablets, in the prevention of postoperative nausea and vomiting in pediatric patients.

Geriatric Use : The dosage 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.

HOW SUPPLIED

Ondansetron tablets, 4 mg (ondansetron HCl dihydrate equivalent to 4 mg of ondansetron), are white, oval, film-coated tablets engraved with “130” on one side and plain on the other.

Ondansetron tablets, 8 mg (ondansetron HCl dihydrate equivalent to 8 mg of ondansetron), are yellow, oval, film-coated tablets engraved with “131” on one side and plain on the other.

Bottles: Store at 20° — 25°C (68° — 77°F). (See USP Controlled Room Temperature). Protect from light. Dispense in tight, light-resistant container as defined in the USP.

Unit dose packs: Store at 20° — 25°C (68° — 77°F). (See USP Controlled Room Temperature). Protect from light. Store blisters in cartons.

REFERENCE

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.

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PJPI0111
ISS. 09/2006

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