Naurif

Approved Indications:

• Chemotherapy-Induced Nausea and Vomiting (CINV):
• Prevention of acute nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC).
• Prevention of delayed nausea and vomiting in moderate emetogenic chemotherapy (MEC).
• Radiotherapy-Induced Nausea and Vomiting (RINV):
• Prevention of nausea and vomiting in patients receiving fractionated radiotherapy to the abdomen, pelvis, or total body irradiation.
• Postoperative Nausea and Vomiting (PONV):
• Prevention and treatment of nausea and vomiting following surgery under general anesthesia.

Off-Label or Clinically Accepted Uses:

• Prevention of nausea in high-risk patients receiving combination chemotherapy regimens.
• Use in pediatric oncology patients for CINV prevention.

Adults:

• CINV (Intravenous): 1 mg IV over 5 minutes, 30 minutes prior to chemotherapy.
• CINV (Oral): 2 mg orally twice daily, starting 1 hour before chemotherapy, continued for up to 3–5 days based on emetogenic potential.
• PONV (IV): 1 mg IV immediately before induction of anesthesia.
• RINV: 2 mg orally twice daily during the period of radiation therapy.

Pediatrics (≥2 years):

• CINV (IV): 40 µg/kg IV 30 minutes before chemotherapy, may repeat every 24 hours as needed.
• Maximum dose: 3 mg per dose.

Elderly:

• No initial dose adjustment necessary. Monitor for renal impairment.

Special Populations:

• Renal impairment: No dose adjustment required for mild-to-moderate impairment; monitor closely in severe impairment.
• Hepatic impairment: Maximum recommended dose is 1 mg IV or 2 mg orally per day due to reduced clearance.

Administration Notes:

• IV infusion over at least 5 minutes to minimize injection-site reactions.
• Oral formulations should be swallowed whole; do not crush or chew.

Granisetron is a selective 5-HT3 receptor antagonist. It works by competitively inhibiting serotonin binding to 5-HT3 receptors located on vagal nerve terminals in the gastrointestinal tract and in the chemoreceptor trigger zone (CTZ) of the central nervous system. By blocking these receptors, granisetron prevents the initiation of the vomiting reflex triggered by chemotherapy, radiotherapy, or surgery, effectively reducing nausea and vomiting.

• Absorption: Rapid oral absorption; peak plasma concentration in 1–2 hours.
• Bioavailability: Approximately 60% after oral administration.
• Distribution: Widely distributed; volume of distribution ~3–5 L/kg; crosses the placenta.
• Protein Binding: ~65%.
• Metabolism: Extensively metabolized in the liver primarily via CYP3A4; minor contributions from CYP1A1 and CYP2D6.
• Active Metabolites: None clinically significant.
• Elimination: Excreted primarily as metabolites in urine (~50–60%) and feces (~30–40%).
• Half-Life: 9 hours (range 7–10 hours).

• Pregnancy: Category B — animal studies show no harm to the fetus; human data limited. Use only if clearly needed.
• Lactation: Granisetron is excreted in small amounts in breast milk; caution is advised. Breastfeeding is generally not recommended during treatment.
• Note: Data in pregnancy and lactation are limited; use only if benefits outweigh potential risks.

• Primary Class: Antiemetic
• Subclass: Selective 5-HT3 receptor antagonist

• Known hypersensitivity to granisetron or any component of the formulation.
• Severe hepatic impairment requiring dose adjustment beyond recommended limits.
• Concomitant use with other 5-HT3 antagonists (for the same indication) is generally contraindicated due to additive effects.

• High-risk groups:
• Patients with severe hepatic impairment.
• Patients with underlying cardiac conduction disorders (risk of QT prolongation).
• Serious risks:
• Rare risk of QT interval prolongation, especially with high doses or concomitant QT-prolonging drugs.
• Serotonin syndrome when used with other serotonergic drugs (rare).
• Monitoring:
• ECG monitoring recommended in patients with cardiac risk factors.
• Monitor for severe constipation, headache, or hypersensitivity reactions.

Common:

• Headache
• Constipation
• Fatigue
• Diarrhea
• Injection site reactions (for IV)

Serious/Rare:

• Hypersensitivity reactions: rash, urticaria, anaphylaxis (rare).
• Cardiac effects: QT prolongation, arrhythmias (dose-dependent).
• Extrapyramidal symptoms (very rare).

• Drug-Drug:
• Caution with other QT-prolonging drugs (e.g., antiarrhythmics, certain antibiotics).
• Potential additive serotonergic effects with SSRIs, SNRIs, or triptans (serotonin syndrome risk).
• CYP3A4 inhibitors (e.g., ketoconazole) may increase plasma granisetron levels; CYP3A4 inducers may reduce efficacy.
• Drug-Food: No significant food interactions reported.
• Drug-Alcohol: No significant interaction; alcohol may exacerbate nausea.

• FDA/EMA: Current guidelines emphasize granisetron as a first-line agent for prevention of acute CINV and PONV.
• Dosing updates: Oral extended-release granisetron available for single-dose CINV prevention.
• Safety: Increased awareness of QT prolongation in patients with risk factors; recommend ECG monitoring in high-risk populations.
• Guideline Recommendation: Granisetron is recommended in combination with dexamethasone for optimal CINV control.

• Store at 20°C–25°C (room temperature).
• Protect from moisture and light.
• Keep container tightly closed.
• Do not freeze.
• Oral tablets should be kept in their original packaging until use.