Pharmacological Class
- Serotonin (5-HT3) receptor antagonists (antiemetics).
Mechanism of Action
- Chemotherapy and radiation trigger serotonin release from enterochromaffin cells in the GI tract.
- Serotonin binds to 5-HT3 receptors in the vagal nerve and chemoreceptor trigger zone (CTZ) in the brain.
- 5-HT3 antagonists block these receptors, preventing the vomiting reflex.
Oncology Indications
- Prevention of chemotherapy-induced nausea and vomiting (CINV):
- Effective for acute CINV (within 24 h).
- Less effective for delayed CINV → usually combined with NK1 antagonists (aprepitant) + dexamethasone.
- Radiation-induced nausea/vomiting (RINV).
- Postoperative nausea/vomiting (PONV) (perioperative use).
Common Agents & Brand Names
- Ondansetron → Zofran®, Zofran ODT®.
- Granisetron → Kytril®, Sancuso® (transdermal patch), Sustol® (ER injection).
- Dolasetron → Anzemet®.
- Palonosetron → Aloxi® (long half-life, effective for delayed CINV).
Formulations
- Oral tablets, ODT (orally disintegrating tablets), IV injection, transdermal patch (granisetron).
Toxicities & Adverse Effects
- Most common: Headache, constipation, dizziness, fatigue.
- Cardiac: QT prolongation, especially with IV high-dose ondansetron or dolasetron (avoid in patients with prolonged QT or concomitant QT-prolonging drugs).
- Rare: Hypersensitivity, serotonin syndrome (with other serotonergic drugs).
Monitoring & Clinical Considerations
- Monitor ECG in high-risk patients (QT prolongation risk).
- Adjust ondansetron dose in severe hepatic impairment.
- Palonosetron preferred in many oncology settings due to:
- Longer half-life (~40 h vs 4–9 h for others).
- Lower risk of QT prolongation.
- Effective for both acute and delayed CINV.
Key Oncology Point:
5-HT3 antagonists are cornerstone agents for acute CINV prophylaxis and must be used in combination regimens (with NK1 antagonists + corticosteroids) in highly and moderately emetogenic chemotherapy.