Introduction
Kytril (granisetron hydrochloride) is a selective 5-HT3 receptor antagonist developed for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). As a second-generation serotonin receptor antagonist, it has become a cornerstone in supportive oncology care since its FDA approval in 1994.
Mechanism of Action
Kytril exerts its antiemetic effects through selective inhibition of serotonin (5-hydroxytryptamine [5-HT]) receptors in the central and peripheral nervous systems. The drug binds with high affinity to 5-HT3 receptors located in the chemoreceptor trigger zone (area postrema) and vagal nerve terminals in the gastrointestinal tract. By blocking serotonin binding at these sites, Kytril prevents the initiation of the vomiting reflex triggered by chemotherapeutic agents or surgical anesthesia.
Indications
- Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy
- Prevention and treatment of postoperative nausea and vomiting (PONV)
- Radiation-induced nausea and vomiting (off-label use)
Dosage and Administration
Intravenous formulation:- Chemotherapy-induced nausea/vomiting: 10 mcg/kg or 1 mg IV administered within 30 minutes before chemotherapy
- Postoperative nausea/vomiting: 1 mg IV administered before induction of anesthesia or immediately before reversal
- Chemotherapy-induced nausea/vomiting: 2 mg once daily or 1 mg twice daily
- Radiation-induced nausea/vomiting: 2 mg once daily 1 hour before radiation
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: No specific dosage adjustment recommended
- Pediatric: Safety and effectiveness established for children 2 years and older
Pharmacokinetics
Absorption: Oral bioavailability approximately 60%; IV administration provides immediate systemic availability Distribution: Volume of distribution ~3 L/kg; 65% protein binding Metabolism: Hepatic metabolism primarily via CYP3A4 with N-demethylation and oxidation Elimination: Half-life approximately 4-9 hours; 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: Potential risk, especially when used with other serotonergic drugs
- QT interval prolongation: Dose-dependent effect; use with caution in patients with cardiac conditions or those taking other QT-prolonging medications
- Gastrointestinal effects: May mask progressive ileus or gastric distention following abdominal surgery
- Hypersensitivity reactions: Including anaphylaxis, has been reported
- Phenylketonuria: Orally disintegrating tablets contain phenylalanine
Drug Interactions
- Serotonergic drugs: Increased risk of serotonin syndrome (SSRIs, SNRIs, MAOIs, tramadol)
- QT-prolonging agents: Additive effects on cardiac repolarization (antiarrhythmics, antipsychotics, antibiotics)
- CYP3A4 inducers: May decrease granisetron concentrations (rifampin, carbamazepine)
- CYP3A4 inhibitors: May increase granisetron concentrations (ketoconazole, clarithromycin)
Adverse Effects
Common (≥5%):- Headache (14-21%)
- Constipation (3-18%)
- Asthenia (5-18%)
- Diarrhea (4-9%)
- QT interval prolongation
- Hypersensitivity reactions
- Serotonin syndrome
- Extrapyramidal symptoms (rare)
Monitoring Parameters
- Efficacy of nausea/vomiting control
- Electrolyte balance (especially with prolonged vomiting)
- ECG monitoring in patients at risk for QT prolongation
- Signs of hypersensitivity reactions
- Neurological symptoms suggesting serotonin syndrome
- Bowel function in postoperative patients
Patient Education
- Take medication as prescribed, typically before chemotherapy or surgery
- Oral tablets may be taken with or without food
- Report any signs of allergic reaction (rash, itching, swelling)
- Inform healthcare providers of all medications being taken
- Be aware of potential for headache and constipation
- Seek immediate medical attention for rapid heart rate, dizziness, or fainting
- Do not drive or operate machinery if experiencing dizziness or drowsiness
References
1. Kytril [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2021. 2. American Society of Clinical Oncology. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020;38(24):2782-2797. 3. Gan TJ, et al. Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2020;131(2):411-448. 4. Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35(28):3240-3261. 5. Navari RM. Management of Chemotherapy-Induced Nausea and Vomiting. Drugs. 2013;73(3):249-262.