Schedule H

Oral, Intravenous, Intramuscular

• Tablets: 4 mg, 8 mg

• Orally Disintegrating Tablets (ODT): 4 mg, 8 mg

• Oral Solution/Syrup: 2 mg/5 mL

• Injection: 2 mg/mL (2 mL ampoule = 4 mg; 4 mL ampoule = 8 mg)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

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

A. Moderately Emetogenic Chemotherapy:

Parameter Recommendation

Starting dose 8 mg orally or IV 30 minutes before chemotherapy

Titration Not applicable

Usual maintenance dose 8 mg orally every 8–12 hours for 1–2 days post-chemotherapy

Maximum dose 24 mg/day orally; single IV dose not to exceed 16 mg

B. Highly Emetogenic Chemotherapy (with dexamethasone):

Parameter Recommendation

Starting dose 8 mg IV 30 minutes before chemotherapy (with dexamethasone 12–20 mg IV)

Titration Not applicable

Usual maintenance dose 8 mg orally twice daily for 1–2 days

Maximum dose Single IV dose 16 mg; total daily dose 24 mg

Clinical Notes:

• Always combine with dexamethasone for highly emetogenic regimens

• For multi-day chemotherapy, continue ondansetron for each treatment day plus 1–2 days after

• NK1 receptor antagonist (aprepitant) may be added for highly emetogenic regimens if available

1. Postoperative Nausea and Vomiting (PONV) — Adults

Parameter Recommendation

Starting dose (Prophylaxis) 4 mg IV at induction of anaesthesia OR at end of surgery

Titration Not applicable

Usual maintenance dose Single dose usually sufficient; may repeat 4 mg if vomiting recurs

Maximum dose 16 mg/day

Treatment of Established PONV:

Parameter Recommendation

Dose 4 mg IV as single dose

Repeat dosing May repeat after 4–6 hours if needed

Maximum dose 16 mg/day

Clinical Notes:

• More effective for preventing vomiting than nausea

• Consider combination with dexamethasone 4–8 mg IV for high-risk patients

1. Radiotherapy-Induced Nausea and Vomiting — Adults

Parameter Recommendation

Starting dose 8 mg orally 1–2 hours before each radiotherapy fraction

Titration Not applicable

Usual maintenance dose 8 mg orally twice daily on radiotherapy days

Maximum dose 24 mg/day

Clinical Notes:

• Higher doses may be required for total body irradiation or upper abdominal radiation

• Continue for 1–2 days after completion of radiation if nausea persists

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Supervision Evidence Basis

Hyperemesis Gravidarum — OFF-LABEL 4–8 mg orally TDS or 4 mg IV BD Until symptoms controlled; short-term use preferred Specialist only (Obstetrics) Indian obstetric practice; use when first-line agents (doxylamine-pyridoxine, promethazine) fail

Opioid-Induced Nausea/Vomiting — OFF-LABEL 4–8 mg orally or IV TDS Duration of opioid therapy General use acceptable Palliative care protocols; clinical experience

Pruritus in Cholestasis — OFF-LABEL 4–8 mg orally TDS As required Specialist only (Gastroenterology) Limited evidence; Indian hepatology practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Chemotherapy-Induced Nausea and Vomiting

Age Restriction: Not recommended below 6 months of age except under specialist oncology supervision.

Intravenous Dosing:

Body Weight IV Dose (Single) Timing Maximum Single Dose

<10 kg 0.1 mg/kg 30 minutes before chemotherapy —

10–40 kg 0.15 mg/kg OR 4 mg 30 minutes before chemotherapy 8 mg

40 kg 8 mg (adult dose) 30 minutes before chemotherapy 8 mg per dose

Oral Dosing:

Body Surface Area Oral Dose Frequency Maximum Daily Dose

<0.6 m² 2 mg Every 12 hours for 1–2 days 4 mg/day

0.6–1.2 m² 4 mg Every 12 hours for 1–2 days 8 mg/day

1.2 m² 8 mg Every 12 hours for 1–2 days 16 mg/day

1. Postoperative Nausea and Vomiting

Parameter Recommendation

Starting dose 0.1 mg/kg IV (maximum 4 mg)

Timing At end of anaesthesia or when nausea occurs

Titration Not applicable

Maximum dose 4 mg per dose

Clinical Notes:

• Single dose usually sufficient

• Slow IV administration over 2–5 minutes preferred

• ECG monitoring if QT prolongation risk factors present

Secondary Indications – Paediatric (Off-label)

Indication Age Dose Duration Notes Evidence Basis

Acute Gastroenteritis with Vomiting — OFF-LABEL ≥6 months 0.15 mg/kg orally (max 4 mg) Single dose; may repeat once after 8 hours Use only in moderate-severe vomiting preventing oral rehydration IAP guidelines; WHO supportive; multiple RCTs

Important Restrictions:

• Not for routine use in mild viral gastroenteritis

• Should not replace oral rehydration therapy

• Assess for red flags (bilious vomiting, dehydration, altered sensorium) before prescribing

Age Restriction Statement:

Not recommended below 6 months of age except under specialist supervision (paediatric oncology/critical care).

Safety Monitoring:

• Monitor for QT prolongation in children with electrolyte disturbances

• Observe for constipation, especially with repeated dosing

• Watch for extrapyramidal symptoms (rare)

Dialysis:

• Haemodialysis: No supplemental dose required; ondansetron not significantly dialysed

• Peritoneal dialysis: No adjustment required

Note: Use with standard monitoring; metabolites may accumulate in severe renal impairment but clinical significance is unclear.

Note: Clearance reduced by approximately 50% in severe hepatic impairment.

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

• Concomitant use with apomorphine — risk of profound hypotension and loss of consciousness

• Congenital long QT syndrome

• Pre-existing QT interval prolongation or risk factors for QT prolongation

• Electrolyte abnormalities — hypokalaemia, hypomagnesaemia (correct before use)

• Concomitant use of other QT-prolonging drugs

• Bradyarrhythmias or heart failure

• Hepatic impairment (reduced clearance)

• Subacute intestinal obstruction — may mask symptoms

• Recent abdominal surgery — may reduce lower GI motility

• Patients receiving other serotonergic drugs — risk of serotonin syndrome

Parameter Details

Risk category Limited human data; some studies suggest possible increased risk of orofacial clefts with first-trimester use — not definitively established

Preferred alternatives First-line: Doxylamine + Pyridoxine combination; Second-line: Promethazine, Metoclopramide

When may be used May be used when first-line agents fail; hyperemesis gravidarum refractory to other treatment; benefit must outweigh potential risk

Monitoring Monitor maternal QT interval if used with other drugs; fetal growth monitoring as per standard antenatal care

Parameter Details

Compatibility Compatible with breastfeeding

Drug levels in milk Low (estimated infant dose <5% of maternal weight-adjusted dose)

Preferred alternatives Single-dose or short-term use preferred; domperidone or metoclopramide also options

Infant monitoring Observe for drowsiness, constipation, feeding difficulties (rare)

Parameter Recommendation

Starting dose 4 mg orally or IV; start at lower end of dosing range

Titration Not typically required; assess response before increasing

Maximum dose 16 mg/day preferred; avoid doses >16 mg/day

Special risks Increased risk of QT prolongation; higher prevalence of electrolyte abnormalities; increased constipation risk; assess baseline ECG in cardiac patients

Note: No specific pharmacokinetic changes in elderly with normal organ function, but increased sensitivity to adverse effects.

Drug/Class Mechanism/Effect Recommendation

Apomorphine Profound hypotension and loss of consciousness Contraindicated — avoid combination

Class IA antiarrhythmics (quinidine, procainamide) Additive QT prolongation Avoid combination; if unavoidable, ECG monitoring mandatory

Class III antiarrhythmics (amiodarone, sotalol) Additive QT prolongation → risk of torsades de pointes Avoid if possible; ECG monitoring if used together

Haloperidol, droperidol QT prolongation risk Use with caution; monitor ECG

High-dose methadone Additive QT prolongation Monitor ECG; correct electrolytes

Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) Reduced ondansetron plasma levels → decreased efficacy May need higher ondansetron dose or alternative antiemetic

Drug/Class Effect Recommendation

CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin) Increased ondansetron levels → increased QT risk Monitor for adverse effects; consider dose reduction in hepatic impairment

SSRIs (fluoxetine, sertraline, paroxetine) Possible serotonin syndrome; minor QT effect Monitor for serotonin syndrome symptoms; usually safe in short-term use

SNRIs (venlafaxine, duloxetine) Possible serotonin syndrome Monitor as above

Tramadol Ondansetron may reduce tramadol analgesic efficacy; serotonin syndrome risk Monitor pain control; may need alternative analgesic

Dexamethasone Used therapeutically together; no pharmacokinetic interaction Standard combination for CINV prophylaxis

Loop/Thiazide diuretics Hypokalaemia may increase QT prolongation risk Monitor potassium levels

Fluoroquinolones (levofloxacin, moxifloxacin) Additive QT prolongation Use with caution; ECG if risk factors present

• Headache (most common)

• Constipation

• Fatigue / asthenia

• Dizziness

• Flushing / warmth sensation

• Injection site reactions (pain, erythema with IV/IM)

• Diarrhoea (paradoxical)

• Transient visual disturbances

Adverse Effect Clinical Action

QT prolongation / Torsades de pointes Discontinue immediately; ECG monitoring; correct electrolytes; manage arrhythmia

Serotonin syndrome Discontinue ondansetron and other serotonergic drugs; supportive care; may require hospitalisation

Anaphylaxis / Severe hypersensitivity Immediate discontinuation; emergency management

Stevens-Johnson Syndrome / TEN Very rare; discontinue immediately; dermatology referral; hospitalisation

Transient blindness Rare; typically resolves within 48 hours; reported mainly with IV use

Hepatotoxicity Rare; usually mild transaminase elevation; discontinue if significant

Baseline:

• ECG in high-risk patients (elderly, cardiac disease, QT-prolonging drugs, electrolyte disturbances)

• Serum electrolytes (potassium, magnesium) in patients with risk factors

• Liver function tests if hepatic impairment suspected

After Initiation:

• Clinical response — vomiting control, ability to tolerate oral intake

• Assess hydration status

• Monitor for constipation, especially with repeated dosing

• ECG if QT-prolonging drugs added or electrolyte abnormalities develop

Long-term (if used repeatedly):

• Periodic electrolyte monitoring

• Liver function tests if prolonged use

• Bowel function assessment

Single-Ingredient Formulations:

• Emeset (Cipla)

• Ondem (Alkem)

• Vomikind (Mankind)

• Zofran (GSK) — originator brand

• Zondan (Dr. Reddy's)

• Onset (Sun Pharma)

• Emigo (Torrent)

• Emitron (FDC)

• Osetron (Cadila)

ODT Formulations:

• Emeset MD (Cipla)

• Ondem MD (Alkem)

Note: Fixed-dose combinations not commonly used; single-agent preferred for flexibility in dosing.

• Included in NLEM 2022

• NPPA price ceiling applicable

• Available through government supply for oncology programmes

1. Combine with dexamethasone for CINV — ondansetron alone is less effective for highly emetogenic chemotherapy; combination significantly improves control

1. IV dose ceiling of 16 mg — single IV doses exceeding 16 mg associated with QT prolongation; older recommendations of 32 mg IV no longer supported

1. Severe hepatic impairment — maximum 8 mg/day due to reduced clearance and increased QT risk

1. Paediatric gastroenteritis use is off-label but evidence-supported — single oral dose can facilitate oral rehydration in children with persistent vomiting; not a substitute for ORS

1. ODT formulation advantage — dissolves on tongue without water; useful in patients with active vomiting or difficulty swallowing

1. Constipation is common — especially with repeated dosing; counsel patients and consider prophylactic laxatives in cancer patients on opioids

1. No benefit over metoclopramide for simple nausea — reserve for chemotherapy/radiotherapy/PONV; avoid routine use for non-specific nausea

antiemetic; 5-HT3 antagonist; CINV; PONV; chemotherapy; QT-prolongation; paediatric-use; pregnancy-caution; lactation-compatible; NLEM India; Schedule H

RxIndia v1.0 — 05 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• IAP Drug Formulary

• AIIMS Antiemetic Protocols

• WHO Model List of Essential Medicines (paediatric supportive)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)

• Published RCTs and meta-analyses for off-label paediatric gastroenteritis use