There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly co-administered with it. Specific studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental or propofol.
Ondansetron is metabolized by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolizing ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall ondansetron clearance or dose requirement.
Caution should be exercised when ondansetron is co-administered with drugs that prolong the QT interval and/or cause electrolyte abnormalities (see Precautions).
Use of ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of ondansetron with cardio toxic drugs (e.g. anthracyclines such as doxorubicin, daunorubicin or trastuzimab), antibiotics (such as erythromycin or ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias. (see Precautions).
Serotonergic Drugs (e.g. SSRIs and SNRIs): There have been post marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including SSRIs and SNRIs). (see Precautions).
Apomorphine: Based on reports of profound hypotension and loss of consciousness when ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.
Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.
Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.