1. Clinical Overview
Granisetron is a potent and highly selective serotonin 5-HT3 receptor antagonist used primarily for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). It is a first-line antiemetic agent in modern oncology protocols. The 3mg tablet is a convenient, once-daily oral formulation, particularly used for delayed CINV.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30-60 minutes. IV: 1-3 minutes. | Oral: Up to 24 hours (sustained effect). IV: Up to 24 hours. | Approximately 60% (oral). |
2. Mechanism of Action
Granisetron selectively and competitively blocks serotonin (5-hydroxytryptamine or 5-HT) at the 5-HT3 receptors located 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, initiating the vomiting reflex. By blocking these receptors, granisetron interrupts the afferent signals to the vomiting center.
3. Indications & Uses
- Prevention & treatment of nausea and vomiting associated with emetogenic cancer chemotherapy (including high-dose cisplatin).
- Prevention & treatment of postoperative nausea and vomiting (PONV).
4. Dosage & Administration
Adult Dosage: Chemotherapy-induced: A single 2mg oral dose once daily OR two 1mg doses (the first given 1 hour before chemotherapy and the second 12 hours later). For delayed CINV, a single 3mg tablet is often used 1 hour before chemotherapy on day 1, and then once daily for up to 5 days post-chemotherapy as per protocol. Radiotherapy-induced: 2mg once daily within 1 hour of radiotherapy. Postoperative: 1-3mg single dose, usually 1 hour before induction of anesthesia.
Administration: Tablet can be taken with or without food, swallowed whole with a glass of water. For chemotherapy, the first dose is usually administered 1 hour before the start of chemotherapy. Do not crush or chew.
5. Side Effects
Common side effects may include:
- Headache (14-21%)
- Constipation (9-18%)
- Asthenia/Fatigue
- Diarrhea or abdominal pain
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Apomorphine | Granisetron may cause profound hypotension and loss of consciousness when used with apomorphine. Contraindicated. | Major |
| Drugs that prolong QT interval (e.g., Class Ia/III antiarrhythmics, macrolides, fluoroquinolones, antipsychotics) | Additive risk of QT prolongation and cardiac arrhythmias. Monitor ECG. | Major |
| Strong CYP3A4 inducers (e.g., Rifampicin, Phenytoin, Carbamazepine, St. John's Wort) | May decrease granisetron plasma concentrations, potentially reducing efficacy. | Moderate |
| Strong CYP3A4 inhibitors (e.g., Ketoconazole, Clarithromycin, Ritonavir) | May increase granisetron plasma concentrations. Clinical significance is likely low due to wide therapeutic index. | Minor |
| Other Serotonergic Drugs (e.g., SSRIs, SNRIs, TCAs, Tramadol, Fentanyl) | Theoretical increased risk of serotonin syndrome. Monitor for symptoms. | Moderate |
7. Patient Counselling
- DO take the tablet exactly as prescribed by your doctor, usually 1 hour before chemotherapy.
- DO inform your doctor if you are pregnant, planning pregnancy, or breastfeeding.
- DO inform your doctor about all other medicines you are taking, including herbal supplements.
- DONT take granisetron if you are allergic to it.
- DONT crush or chew the tablet.
8. Toxicology & Storage
Overdose: No specific antidote. Symptoms may include severe headache, severe constipation, and visual disturbances. In massive overdose, potential for QT prolongation and CNS effects (drowsiness, seizures) exists.
Storage: Store below 30°C. Protect from light and moisture. Keep out of reach of children.