Usage
Granisetron is prescribed for the prevention and treatment of nausea and vomiting associated with chemotherapy and radiotherapy in cancer patients, as well as for postoperative nausea and vomiting (PONV). It belongs to the pharmacological classification of 5-HT3 receptor antagonists, also known as serotonin-3 receptor antagonists. Granisetron works by blocking the action of serotonin, a neurotransmitter that can trigger nausea and vomiting, at the 5-HT3 receptors located in the central and peripheral nervous systems.
Alternate Names
Granisetron hydrochloride is the chemical name. Brand names include Kytril, Sustol, Sancuso, Granisol, and Granirex, among others. Generic versions are also widely available.
How It Works
Pharmacodynamics: Granisetron selectively antagonizes 5-HT3 receptors both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone. This action effectively blocks serotonin-induced nausea and vomiting.
Pharmacokinetics:
- Absorption: Granisetron is well absorbed after oral administration, with bioavailability around 60%. Peak plasma concentrations are reached within 1-2 hours. The subcutaneous route provides sustained release.
- Metabolism: Granisetron is primarily metabolized in the liver via oxidation and conjugation. The cytochrome P450 (CYP) enzymes involved include CYP3A4, CYP1A2, and CYP2D6.
- Elimination: The drug is eliminated through both renal and hepatic pathways. Approximately 12% of the administered dose is excreted unchanged in the urine within 48 hours, while the remaining portion is eliminated as metabolites in urine (49%) and feces (34%). The half-life is approximately 5 hours.
Mode of Action: Granisetron acts by competitively binding to 5-HT3 receptors, thereby inhibiting serotonin from binding and triggering the vomiting reflex. This mechanism is primarily at vagal nerve terminals in the gut and the chemoreceptor trigger zone in the brain.
Dosage
Standard Dosage
Adults:
- Oral: 2 mg once daily up to 1 hour before chemotherapy or 1 mg twice daily (1 hour before and 12 hours after chemotherapy).
- Intravenous (IV): 10 mcg/kg infused over 5 minutes or injected over 30 seconds, 30 minutes before chemotherapy.
- Subcutaneous (SC): 10 mg SC at least 30 minutes before moderately emetogenic chemotherapy (MEC) or anthracycline-cyclophosphamide (AC) chemotherapy, only on Day 1 and no more frequently than once every 7 days.
- Transdermal: One patch applied 24-48 hours before chemotherapy, can remain for up to 7 days.
Children (2-16 years):
- IV: 10-40 mcg/kg (max 3 mg) infused over 5 minutes, 30 minutes before chemotherapy. An additional dose may be given within 24 hours, but at least 10 minutes after the initial infusion. Maximum 2 doses/day. Safety and efficacy not established in children under 2 years of age.
Special Cases:
- Elderly Patients: No dose adjustment is usually required, but monitor for potential adverse effects.
- Patients with Renal Impairment: No dose adjustment necessary.
- Patients with Hepatic Dysfunction: No dose adjustment necessary.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiac conditions, especially those receiving cardiotoxic chemotherapy or drugs that prolong the QT interval.
Clinical Use Cases
Dosage guidelines are similar across various clinical settings involving chemotherapy-induced, radiotherapy-induced, and postoperative nausea and vomiting, following the recommendations provided above under “Standard Dosage”.
Dosage Adjustments
Dose modifications are generally not required for elderly patients or those with renal or hepatic impairment. However, individual patient response should be monitored.
Side Effects
Common Side Effects:
Headache, constipation, diarrhea, abdominal pain, asthenia, fever, dizziness, somnolence, insomnia, anxiety.
Rare but Serious Side Effects:
Hypersensitivity reactions (anaphylaxis, dyspnea, hypotension), QT interval prolongation, serotonin syndrome (altered mental status, autonomic instability, neuromuscular abnormalities). Injection site reactions (with SC formulation) can include infection, bruising, hematomas.
Long-Term Effects:
Limited data are available on the long-term effects of granisetron.
Adverse Drug Reactions (ADR):
Serious ADRs include severe hypersensitivity reactions, significant QT prolongation, and serotonin syndrome, requiring immediate discontinuation and medical intervention.
Contraindications
Hypersensitivity to granisetron, concomitant use with apomorphine.
Drug Interactions
Granisetron may interact with drugs that prolong the QT interval (e.g., apomorphine, dronedarone, thioridazine, certain antiarrhythmics), serotonergic drugs (e.g., SSRIs, SNRIs, TCAs, MAOIs, tramadol), inducers or inhibitors of CYP3A4, CYP1A2, and CYP2D6 enzymes.
Pregnancy and Breastfeeding
- Pregnancy: Limited human data. Animal studies have not shown teratogenic effects. Use only if clearly needed and the benefit outweighs the risk.
- Breastfeeding: It is unknown whether granisetron is excreted in human milk. Use with caution, considering potential risks to the infant.
Drug Profile Summary
See previous sections for detailed information on mechanism of action, side effects, contraindications, drug interactions, pregnancy & breastfeeding, dosage.
Monitoring Parameters: Monitor for adverse reactions, especially hypersensitivity, QT prolongation, and serotonin syndrome. Electrolyte levels and ECG in patients at risk for QT prolongation.
Popular Combinations
Granisetron is frequently combined with dexamethasone, particularly in the context of highly or moderately emetogenic chemotherapy regimens. This combination enhances antiemetic efficacy.
Precautions
See sections on “Side Effects,” “Contraindications,” and “Drug Interactions” for detailed precautions. Monitor patients post-abdominally surgery for potential masking of ileus or gastric distention.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Granisetron?
A: See section “Dosage” above for detailed standard and specific dosage guidelines.
Q2: What is the mechanism of action of Granisetron?
A: Granisetron selectively blocks 5-HT3 receptors, thereby inhibiting serotonin-mediated nausea and vomiting.
Q3: What are the most common side effects of Granisetron?
A: Headache, constipation, and diarrhea are among the most commonly reported side effects.
Q4: What are the serious side effects to watch out for with Granisetron?
A: QT prolongation, serotonin syndrome, and hypersensitivity reactions are rare but potentially serious side effects requiring urgent attention.
Q5: Can Granisetron be used in pregnant or breastfeeding women?
A: Limited human data. Animal studies have not shown teratogenic effects. Use with caution. Consult the “Pregnancy and Breastfeeding” section.
Q6: Are there any drug interactions I should be aware of when prescribing Granisetron?
A: Yes, see the dedicated “Drug Interactions” section for details on interacting drugs.
Q7: How should Granisetron be administered?
A: Granisetron can be administered orally, intravenously, subcutaneously, or transdermally, depending on the specific product and clinical indication.
Q8: Does Granisetron require any dosage adjustments in elderly patients or those with renal/hepatic impairment?
A: Generally, no dosage adjustments are needed, but close monitoring for adverse events is recommended.
Q9: What is Granisetron’s role in managing postoperative nausea and vomiting?
A: Granisetron is effective in preventing and treating PONV, typically administered IV prior to or after surgery.
Q10: Can Granisetron be used in pediatric patients?
A: Yes, for children 2 years and older. Refer to the “Dosage” section for pediatric dosage guidelines. Not recommended for children under 2 years old.
