Schedule H

Oral, Intravenous (IV)

Formulation Strength

Tablets 1 mg, 2 mg

Injection (IV/IM) 1 mg/mL (1 mL ampoule), 3 mg/3 mL ampoule

Note: Transdermal patch formulation is NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Chemotherapy-Induced Nausea and Vomiting (CINV) — Prevention

(Moderate to highly emetogenic chemotherapy)

Oral Administration:

Parameter Recommendation

Starting dose 2 mg orally once, given 1 hour before chemotherapy OR 1 mg twice daily (first dose 1 hour before chemotherapy, second dose 12 hours later)

Titration Not applicable

Usual maintenance dose 2 mg/day (single dose or divided)

Maximum dose 2 mg/day

Intravenous Administration:

Parameter Recommendation

Starting dose 1 mg IV (or 10 mcg/kg) administered over 5 minutes, given within 30 minutes before chemotherapy

Titration Not applicable

Usual maintenance dose 1 mg IV once daily

Maximum dose 3 mg/day IV (as single dose or in divided doses)

Clinical Notes:

• Single daily dosing is as effective as divided dosing for most regimens

• Often combined with dexamethasone for highly emetogenic chemotherapy

• May be repeated for subsequent chemotherapy cycles

• Longer half-life (~9 hours) compared to ondansetron allows once-daily dosing

1. Postoperative Nausea and Vomiting (PONV) — Prevention and Treatment

Prevention:

Parameter Recommendation

Starting dose 1 mg IV given as slow injection over 30 seconds

Titration Not applicable

Usual maintenance dose 1 mg single dose

Maximum dose 1 mg (for prophylaxis)

Timing: Administer before induction of anaesthesia or at end of surgery before reversal

Treatment of Established PONV:

Parameter Recommendation

Starting dose 1 mg IV slow injection

Titration Not applicable

Usual maintenance dose 1 mg single dose

Maximum dose 1 mg

Clinical Notes:

• Single prophylactic dose is usually sufficient

• Oral route (1 mg) may be used 1 hour before surgery when IV access not yet established

Secondary Indications — Adults Only (Off-label, if any)

Indication Dose Duration Notes Evidence

Radiation-induced nausea and vomiting (RINV) 2 mg orally once daily, given 1 hour before radiation Duration of radiation course OFF-LABEL; Specialist only (radiation oncologist) Extrapolated from CINV studies; Indian oncology practice

Hyperemesis gravidarum (refractory cases) 1 mg IV or 1 mg oral twice daily Short-term only OFF-LABEL; Specialist only (obstetrician); Use only when ondansetron fails Limited evidence; case series

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Chemotherapy-Induced Nausea and Vomiting (CINV) — Children ≥2 years

Intravenous:

Parameter Recommendation

Starting dose 10–20 mcg/kg IV (maximum 1 mg) as single dose

Titration Not applicable

Usual maintenance dose 10–20 mcg/kg IV once daily

Maximum dose 1 mg per dose; 3 mg/day

Timing: Administer over 5 minutes, within 30 minutes before chemotherapy

Oral:

Parameter Recommendation

Starting dose 20–40 mcg/kg orally (maximum 2 mg)

Titration Not applicable

Usual maintenance dose 20–40 mcg/kg once daily

Maximum dose 2 mg/day

Timing: Administer 1 hour before chemotherapy

1. Postoperative Nausea and Vomiting (PONV) — Children ≥2 years

Parameter Recommendation

Starting dose 10–20 mcg/kg IV (maximum 1 mg)

Titration Not applicable

Usual maintenance dose Single dose

Maximum dose 1 mg

Timing: Before induction or at end of surgery

Secondary Indications — Paediatric Doses (Off-label, if any)

Not applicable.

No established off-label paediatric indications documented in Indian sources.

Safety Statement:

• Not recommended below 2 years of age due to limited safety and efficacy data

• Use in children should be under paediatric oncologist or anaesthesiologist supervision

• Monitor for QT prolongation if used with other medications

Note: Use with caution if concurrent nephrotoxic medications are administered

• Known hypersensitivity to granisetron or other 5-HT₃ receptor antagonists (ondansetron, palonosetron)

• Concurrent use with apomorphine (risk of profound hypotension and loss of consciousness)

• QT interval prolongation — avoid in patients with:

• Congenital long QT syndrome

• Concurrent QT-prolonging medications

• Electrolyte abnormalities (hypokalaemia, hypomagnesaemia)

• Severe hepatic impairment — risk of drug accumulation

• Post-abdominal surgery patients — may mask signs of progressive ileus or gastric distension

• Cardiac arrhythmias — baseline ECG in high-risk patients

• Elderly patients — increased susceptibility to QT effects

• Serotonin syndrome risk — when combined with serotonergic agents

Parameter Recommendation

Risk category Limited human data; no established teratogenicity in animal studies

Preferred alternatives Ondansetron (more extensive clinical experience in Indian obstetric practice)

When to use May be used if benefit outweighs risk; specialist supervision recommended

Monitoring Maternal QTc interval if co-administered with other QT-prolonging agents; fetal heart rate monitoring

Parameter Recommendation

Compatibility Likely compatible — low milk levels expected based on pharmacokinetics

Preferred alternatives Ondansetron (more clinical experience during lactation)

Drug levels in milk Low (expected; not directly measured)

Infant monitoring Feeding pattern, alertness, GI symptoms

Parameter Recommendation

Starting dose Same as adults (no specific dose reduction required)

Titration Not applicable

Special risks Increased susceptibility to QT prolongation; orthostatic hypotension; dizziness

Monitoring ECG in patients with cardiac risk factors; electrolytes

Interacting Drug/Class Effect Mechanism Management

Apomorphine Profound hypotension, loss of consciousness Synergistic hypotensive effect Contraindicated

QT-prolonging drugs (amiodarone, sotalol, haloperidol, moxifloxacin, azithromycin, fluoroquinolones) Additive QT prolongation; risk of torsades de pointes Pharmacodynamic interaction Avoid combination if possible; if essential, monitor ECG and electrolytes

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) Increased granisetron levels (theoretical) CYP3A4 inhibition Use with caution; monitor for adverse effects

Interacting Drug/Class Effect Management

Other 5-HT₃ antagonists (ondansetron, palonosetron) Additive side effects; no added efficacy Avoid combination

Serotonergic agents (SSRIs, SNRIs, tramadol, fentanyl) Potential serotonin syndrome Monitor for symptoms (agitation, hyperthermia, tremor, hyperreflexia)

Dexamethasone Enhanced antiemetic efficacy (synergistic) Commonly co-administered for CINV; no dose adjustment needed

CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) Reduced granisetron levels Monitor antiemetic efficacy

• Headache (most common; 10–20%)

• Constipation

• Dizziness

• Fatigue/asthenia

• Diarrhoea

• Abdominal pain

• Injection site reactions (IV administration)

Adverse Effect Action Required

QT prolongation / Torsades de pointes Discontinue; ECG monitoring; correct electrolytes; cardiology consultation

Serotonin syndrome (when combined with serotonergic drugs) Discontinue all serotonergic agents; supportive care; hospitalisation if severe

Severe hypersensitivity / Anaphylaxis Discontinue permanently; emergency management

Severe constipation / Ileus Assess for obstruction; supportive management

Phase Parameters

Baseline ECG in patients with cardiac risk factors, concomitant QT-prolonging drugs, or electrolyte abnormalities; LFTs in known hepatic disease

During therapy ECG if high-dose IV used or concurrent QT-prolonging medications; symptom response (nausea/vomiting control)

Long-term Not applicable — typically short-term use

Brand Name Manufacturer Formulations

Granisetron Generic Tablets 1 mg; Injection 1 mg/mL

Granicip Cipla Tablets 1 mg, 2 mg; Injection 1 mg/mL

Graniforce Mankind Tablets 1 mg; Injection 1 mg/mL

Granitero Hetero Tablets 1 mg; Injection 1 mg/mL

Emeset-Gran Cipla Injection 1 mg/mL, 3 mg/3mL

Kytril Roche (limited availability) Tablets; Injection

Notes:

• Not included in NLEM 2022

• Not under NPPA price control

• Available in cancer centres and tertiary hospitals; may not be in primary care government supply

1. Longer half-life advantage: Granisetron has a longer half-life (~9 hours) than ondansetron (~4 hours), allowing effective once-daily dosing and better coverage for delayed CINV

1. Single dose is sufficient: For most chemotherapy regimens, a single 1 mg IV dose is as effective as higher or divided doses — avoid unnecessary repeat dosing

1. Combination therapy for highly emetogenic chemotherapy: Combine with dexamethasone (and NK1 antagonist if available) for optimal CINV control with highly emetogenic agents (cisplatin, cyclophosphamide)

1. Not for motion sickness: 5-HT₃ antagonists including granisetron are ineffective for motion sickness — different pathophysiology

1. QT monitoring in high-risk patients: While granisetron has lower QT-prolongation risk than ondansetron, caution remains necessary in patients with cardiac risk factors or on multiple QT-prolonging drugs

1. Alternative when ondansetron causes headache: May be better tolerated than ondansetron in patients experiencing significant headache as side effect

granisetron; antiemetic; 5-HT3 antagonist; CINV; PONV; chemotherapy; radiation; oncology; QT prolongation; paediatric-approved; renal-safe; Schedule H

RxIndia v1.0 — 10 Jun 2025

• CDSCO (Central Drugs Standard Control Organisation)

• Indian Pharmacopoeia / National Formulary of India (IP/NFI)

• NLEM 2022 (for exclusion note)

• API Textbook of Medicine

• AIIMS Adult and Paediatric Drug Formularies

• IAP Guidelines for Paediatric Supportive Care

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian oncology practice protocols (CINV management)

• Product Inserts: Granicip (Cipla), Graniforce (Mankind)