Introduction
Granisetron is a 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). First approved by the FDA in 1993, it has become a cornerstone medication in supportive oncology care and perioperative management.
Mechanism of Action
Granisetron exerts its antiemetic effects by selectively blocking serotonin 5-HT3 receptors located both peripherally on vagal nerve terminals in the gastrointestinal tract and centrally in the chemoreceptor trigger zone of the area postrema. By antagonizing these receptors, granisetron prevents serotonin binding and subsequent activation of the vomiting reflex pathway.
Indications
- Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy
- Prevention and treatment of postoperative nausea and vomiting
- Prevention of radiation-induced nausea and vomiting (off-label)
Dosage and Administration
Oral tablets:- Chemotherapy-induced: 2 mg once daily or 1 mg twice daily
- Postoperative: 1 mg within 1 hour before anesthesia
- Chemotherapy-induced: 10 mcg/kg (maximum 1 mg) administered 30 minutes before chemotherapy
- Postoperative: 1 mg administered before induction of anesthesia or immediately before reversal
- Apply one patch (3.1 mg/24 hours) to upper outer arm 24-48 hours before chemotherapy
- Remove patch a minimum of 24 hours after completion of chemotherapy
- Hepatic impairment: No dosage adjustment required
- Renal impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Pediatrics: Safety and efficacy not established for transdermal formulation
Pharmacokinetics
Absorption: Oral bioavailability approximately 60%; IV administration provides immediate systemic availability; transdermal delivery provides sustained release over 7 days Distribution: Volume of distribution ~3 L/kg; 65% protein bound Metabolism: Extensive hepatic metabolism primarily via CYP3A4 Elimination: Half-life approximately 9 hours (adults); excreted in urine (48%) and feces (38%) as metabolitesContraindications
- Hypersensitivity to granisetron or any component of the formulation
- Concomitant use with apomorphine due to risk of profound hypotension and loss of consciousness
Warnings and Precautions
- Serotonin syndrome: May occur with concomitant use of other serotonergic drugs
- QT prolongation: Dose-dependent effect; use with caution in patients with cardiac conduction abnormalities
- Gastrointestinal effects: May mask progressive ileus or gastric distention following abdominal surgery
- Hypersensitivity reactions: Including anaphylaxis, has been reported
- Extravasation risk: With IV administration; ensure proper intravenous access
Drug Interactions
- Apomorphine: Contraindicated due to risk of profound hypotension
- Drugs that prolong QT interval: Increased risk of torsades de pointes (e.g., antiarrhythmics, antipsychotics, antibiotics)
- CYP3A4 inducers: May decrease granisetron concentrations (e.g., rifampin, carbamazepine)
- CYP3A4 inhibitors: May increase granisetron concentrations (e.g., ketoconazole, clarithromycin)
- Other serotonergic drugs: Increased risk of serotonin syndrome (e.g., SSRIs, SNRIs, tramadol)
Adverse Effects
Common (≥1%):- Headache (14-21%)
- Constipation (3-18%)
- Asthenia (5%)
- Diarrhea (4%)
- Abdominal pain (2%)
- QT prolongation and torsades de pointes
- Serotonin syndrome
- Hypersensitivity reactions including anaphylaxis
- Extrapyramidal symptoms (rare)
Monitoring Parameters
- Efficacy: Control of nausea and vomiting
- ECG monitoring in patients with cardiac risk factors or receiving high doses
- Signs of serotonin syndrome: hyperthermia, rigidity, myoclonus, autonomic instability
- Signs of hypersensitivity reactions
- Bowel function in postoperative patients
Patient Education
- Take oral medication as prescribed, with or without food
- For transdermal patch: Apply to clean, dry, intact skin on upper outer arm; avoid areas with irritation; protect from sunlight
- Report severe headache, constipation lasting more than 3 days, or signs of allergic reaction
- Inform healthcare providers of all medications being taken
- Do not remove patch before completion of chemotherapy
- Patch may contain conducting metal parts; remove before MRI
References
1. Granisetron [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2021. 2. Navari RM. Management of chemotherapy-induced nausea and vomiting. Drugs. 2013;73(3):249-262. 3. Gan TJ, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118(1):85-113. 4. Roila F, et al. MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting. Ann Oncol. 2016;27(suppl 5):v119-v133. 5. FDA-approved labeling for granisetron. Accessdata.fda.gov. Accessed [current date].