7 DRUG INTERACTIONS
7.1 Drugs Affecting Cytochrome P-450 Enzymes
Ondansetron does not appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver. Because ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of ondansetron [see Clinical Pharmacology (12.3)]. On the basis of limited available data, no dosage adjustment is recommended for patients on these drugs.
Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with ondansetron is contraindicated [see Contraindications (4)].
7.3 Phenytoin, Carbamazepine, and Rifampin
In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), 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 [see Clinical Pharmacology (12.3)].
Although there are no data on pharmacokinetic drug interactions between ondansetron and tramadol, data from two small trials indicate that concomitant use of ondansetron may result in reduced analgesic activity of tramadol. Patients on concomitant ondansetron self-administered tramadol more frequently in these trials, leading to an increased cumulative dose in patient-controlled administration of tramadol.
7.5 Serotonergic Drugs
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including SSRIs and SNRIs [see Warnings and Precautions (5.3)].
In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.
In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase blood levels of high-dose methotrexate.
The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.