Ondansetron is a potent, highly selective competitive antagonist of serotonin 5-HT3 receptors. It is a cornerstone antiemetic agent, primarily used to prevent and treat nausea and vomiting induced by chemotherapy, radiotherapy, and post-operative recovery. Its mechanism provides a targeted approach with minimal effects on other receptor systems like dopamine, reducing the risk of extrapyramidal side effects common with older antiemetics.
Adult: Chemotherapy-induced: 8mg orally twice daily (first dose 30 min before chemo, second dose 8 hours later) OR a single 24mg dose 30 min before chemo. Radiotherapy-induced: 8mg orally three times daily. PONV: 16mg orally 1 hour before anesthesia OR 4-8mg IV just before induction.
Note: Tablets can be taken with or without food. Orally Disintegrating Tablets (ODTs): Place on tongue, allow to dissolve, then swallow with saliva. Do not chew. Can be taken without water. IV formulation is for hospital use only, administered as a slow injection or infusion over at least 15 minutes to minimize risk of QT prolongation.
Ondansetron selectively blocks serotonin (5-HT3) receptors both peripherally on vagal nerve terminals in the gastrointestinal tract and centrally in the chemoreceptor trigger zone (CTZ) of the area postrema in the medulla oblongata. Chemotherapy and radiotherapy cause the release of serotonin from enterochromaffin cells in the gut, which activates 5-HT3 receptors on vagal afferents, leading to vomiting. By antagonizing these receptors, ondansetron interrupts the vomiting reflex.
Pregnancy: Category B: Animal studies have shown no risk, but adequate and well-controlled studies in pregnant women are lacking. Use only if clearly needed, particularly in the first trimester. Commonly used for hyperemesis gravidarum when first-line treatments fail.
Driving: May cause dizziness or fatigue. Patients should not drive or operate machinery until they are sure they are not affected.
| Apomorphine | Profound hypotension and loss of consciousness. | Contraindicated |
| Drugs that prolong QT interval (e.g., Class Ia/III antiarrhythmics, macrolides, fluoroquinolones, antipsychotics) | Additive risk of QT prolongation and Torsades de Pointes. | Major |
| Serotonergic drugs (e.g., SSRIs, SNRIs, tramadol, fentanyl, lithium, MAOIs) | Increased risk of serotonin syndrome. | Major |
| Phenytoin, Carbamazepine, Rifampicin | Induce CYP3A4, reducing ondansetron plasma levels and efficacy. | Moderate |
| CYP3A4 inhibitors (e.g., Ketoconazole, Erythromycin, Clarithromycin) | May increase ondansetron plasma levels. | Moderate |