Zofran (Ondansetron) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Phenytoin, Carbamazepine, and Rifampicin

In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.^1,3

Tramadol

Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small studies indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.^4,5

Chemotherapy

Tumor response to chemotherapy in the P-388 mouse leukemia model is not affected by ondansetron. In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.

In a crossover study in 76 pediatric patients, I.V. ondansetron did not increase blood levels of high-dose methotrexate.

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 1 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 ZOFRAN 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.

CONTRAINDICATIONS

ZOFRAN Tablets, ZOFRAN ODT Orally Disintegrating Tablets, and ZOFRAN Oral Solution are contraindicated for patients known to have hypersensitivity to the drug.

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.

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.

GlaxoSmithKline

Research Triangle Park, NC 27709

ZOFRAN Tablets and Oral Solution:

GlaxoSmithKline

Research Triangle Park, NC 27709

ZOFRAN ODT Orally Disintegrating Tablets:

Manufactured for GlaxoSmithKline

Research Triangle Park, NC 27709

by Cardinal Health

Blagrove, Swindon, Wiltshire, UK SN5 8RU

©2006, GlaxoSmithKline. All rights reserved.

February 2006 RL-2237