Schedule H

Oral; Intravenous (as prodrug fosaprepitant)

• Capsules: 80 mg, 125 mg

• Capsule 40 mg: Limited availability in India (verify before prescribing for PONV)

• Oral Suspension: NOT AVAILABLE in India

• Injection (as fosaprepitant dimeglumine): 150 mg lyophilized powder for infusion

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) — Highly Emetogenic Chemotherapy (HEC)

3-Day Oral Regimen (Standard):

Day Dose Timing Co-administered Agents

Day 1 125 mg orally 1 hour before chemotherapy Dexamethasone 12 mg + 5-HT3 antagonist

Day 2 80 mg orally Once in morning Dexamethasone 8 mg

Day 3 80 mg orally Once in morning Dexamethasone 8 mg

Parameter Recommendation

Starting dose 125 mg orally on Day 1

Titration Not applicable

Usual maintenance dose 80 mg orally on Days 2–3

Maximum dose 125 mg per day

Single-Dose IV Alternative (Fosaprepitant):

Parameter Recommendation

Starting dose Fosaprepitant 150 mg IV over 20–30 minutes, 30 minutes before chemotherapy on Day 1

Titration Not applicable

Usual maintenance dose Not applicable (single-dose regimen replaces 3-day oral course)

Maximum dose 150 mg IV single dose

Clinical notes:

• Must be used as part of triplet antiemetic regimen (NK1 antagonist + 5-HT3 antagonist + dexamethasone)

• Reduce dexamethasone dose by approximately 50% when co-administered (Day 1: 12 mg instead of 20 mg; Days 2–4: 8 mg instead of 16 mg)

• Fosaprepitant 150 mg IV on Day 1 is bioequivalent to 3-day oral aprepitant regimen

1. Prevention of CINV — Moderately Emetogenic Chemotherapy (MEC)

Parameter Recommendation

Starting dose 125 mg orally on Day 1, 1 hour before chemotherapy

Titration Not applicable

Usual maintenance dose Days 2–3 dosing (80 mg daily) is optional for MEC; assess based on patient risk factors

Maximum dose 125 mg per day

Clinical notes:

• For MEC, Day 1 single-dose aprepitant with 5-HT3 antagonist and dexamethasone may suffice

• Extended 3-day regimen reserved for patients with additional risk factors or prior breakthrough CINV

1. Prevention of Postoperative Nausea and Vomiting (PONV) — High-Risk Patients

Parameter Recommendation

Starting dose 40 mg orally within 3 hours before induction of anaesthesia

Titration Not applicable

Usual maintenance dose Not applicable (single preoperative dose)

Maximum dose 40 mg single dose

Clinical notes:

• 40 mg capsule has limited availability in India — verify stock before prescribing

• Reserved for high-risk patients (female sex, non-smoker, history of PONV/motion sickness, opioid use postoperatively)

• Not for routine prophylaxis in all surgical patients

• Alternative: Use 80 mg capsule if 40 mg unavailable (higher than labelled PONV dose; specialist decision)

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

Indication Dose Duration Notes Evidence Basis

Radiotherapy-induced nausea and vomiting (high-risk sites: upper abdomen, craniospinal) 80 mg orally daily on radiation treatment days Throughout radiation course OFF-LABEL; Specialist only (radiation oncologist) Limited RCTs; Indian oncology centre protocols

Refractory nausea in advanced malignancy 80–125 mg orally on Day 1, then 80 mg on Days 2–3 as needed Short courses; reassess every cycle OFF-LABEL; Specialist only Palliative care practice; ESMO supportive care guidelines

PAEDIATRIC DOSING (Specialist Only)

Primary Indication: Prevention of CINV (Age ≥6 months to 17 years)

⚠️ Important: Oral suspension formulation is NOT AVAILABLE in India. Capsule-based dosing is feasible only for children who can swallow capsules whole (typically ≥6 years or ≥40 kg). For younger children or those unable to swallow capsules, fosaprepitant IV is preferred.

Oral Aprepitant (Capsule-based, for children who can swallow whole capsules)

Weight Category Day 1 Days 2–3 Formulation

≥40 kg 125 mg once 80 mg once daily Use adult capsules

30 to <40 kg 80 mg once 80 mg once daily Capsule

<30 kg Oral dosing not feasible in India (suspension unavailable) — Use IV fosaprepitant

Parameter Recommendation

Starting dose Weight-based as per table above

Titration Not applicable

Usual maintenance dose Days 2–3 dosing as above

Maximum dose 125 mg/day (Day 1); 80 mg/day (Days 2–3)

IV Fosaprepitant (Preferred for children <30 kg or unable to swallow capsules)

Age/Weight Dose Administration

6 months to <12 years 3 mg/kg IV (max 150 mg) on Day 1 Infuse over 60 minutes

≥12 years 150 mg IV on Day 1 Infuse over 20–30 minutes

Clinical notes:

• Always combine with 5-HT3 antagonist and weight-adjusted dexamethasone

• Minimum age: 6 months

• Monitor hepatic function (baseline and during treatment if repeated courses)

• Observe for infusion-site reactions with IV administration

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Notes Evidence Basis

Prevention of PONV in high-risk children (≥12 years or ≥40 kg) 40 mg orally preoperatively (if available) or 80 mg Single dose OFF-LABEL; Specialist only (paediatric anaesthesiologist) Limited paediatric anaesthesia data; extrapolated from adult trials

⚠️ Age Restriction Statement:

Not recommended in infants <6 months. Use in children <12 years requires specialist supervision (paediatric oncologist). Oral capsules not suitable for children unable to swallow whole; IV fosaprepitant preferred in such cases.

• Known hypersensitivity to aprepitant, fosaprepitant, or polysorbate 80 (excipient in IV formulation)

• Concurrent use with pimozide — risk of serious arrhythmias due to CYP3A4 inhibition and QT prolongation

• Severe hepatic impairment (Child-Pugh C)

• Hepatic impairment (moderate) — monitor LFTs

• Concurrent use with strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) — may significantly reduce aprepitant efficacy

• Concurrent use with strong CYP3A4 inhibitors (ketoconazole, itraconazole) — may increase aprepitant exposure

• Hormonal contraceptives — efficacy reduced for up to 28 days after last dose; advise alternative or additional contraception

• Warfarin therapy — may alter INR; close monitoring required

• Concurrent corticosteroid use — reduce dexamethasone and methylprednisolone doses appropriately

Aspect Recommendation

Overall safety Limited human data; animal studies show no teratogenicity at therapeutic doses

Risk category Use only if potential benefit justifies potential risk to fetus

Preferred alternatives For pregnancy-related nausea: doxylamine-pyridoxine, ondansetron (short-term), metoclopramide

When to use CINV prophylaxis in pregnant patient receiving chemotherapy for malignancy — oncologist and obstetrician joint decision

Monitoring Fetal growth monitoring if used; maternal LFTs

Aspect Recommendation

Compatible with breastfeeding Unknown — insufficient data on excretion in human milk

Preferred alternatives Ondansetron, metoclopramide (short-term) if antiemetic needed

Drug levels in milk Not established

Infant monitoring If used: monitor infant for feeding difficulties, gastrointestinal disturbance, irritability

Recommendation Avoid breastfeeding during treatment and for at least 1 week after last dose, or use alternatives

Aspect Recommendation

Starting dose Standard adult dosing if hepatic and renal function adequate

Titration Not applicable

Special considerations Higher likelihood of hepatic impairment — assess Child-Pugh status

Monitor for fatigue, dizziness

No dose adjustment solely based on age

Assess polypharmacy and potential CYP3A4 interactions carefully

Interacting Drug Effect Mechanism Recommendation

Pimozide Risk of serious ventricular arrhythmias, QT prolongation CYP3A4 inhibition increases pimozide levels AVOID — Contraindicated

Warfarin Decreased INR (aprepitant induces CYP2C9 after initial inhibition) Complex CYP2C9 interaction Monitor INR closely during aprepitant course and for 14 days after; adjust warfarin dose as needed

Hormonal contraceptives (oestrogen/progestogen) Reduced contraceptive efficacy CYP3A4 induction Advise alternative or additional non-hormonal contraception during treatment and for 28 days post last dose

Dexamethasone (oral) Increased dexamethasone exposure (~2-fold) CYP3A4 inhibition Reduce oral dexamethasone dose by ~50%

Methylprednisolone Increased methylprednisolone exposure CYP3A4 inhibition Reduce IV methylprednisolone by ~25%; oral by ~50%

Ergot alkaloids Risk of ergotism CYP3A4 inhibition Avoid concurrent use

Interacting Drug Effect Recommendation

Rifampicin Markedly decreased aprepitant levels (up to 90% reduction) Avoid concurrent use; if unavoidable, aprepitant efficacy may be significantly compromised

Phenytoin, Carbamazepine, Phenobarbital Decreased aprepitant levels Monitor for breakthrough CINV; consider dose adjustment or alternative antiemetic strategy

Ketoconazole, Itraconazole, Clarithromycin Increased aprepitant exposure Use with caution; no specific dose reduction established but monitor for adverse effects

Midazolam (oral) Increased sedation (midazolam AUC increased ~2.3-fold) Reduce midazolam dose or use with caution perioperatively

Docetaxel, Paclitaxel, Etoposide, Vinorelbine, Vincristine Possible increased chemotherapy exposure Monitor for chemotherapy toxicity; no routine dose adjustment but heightened vigilance

Diltiazem Increased levels of both drugs Monitor for bradycardia, hypotension

• Fatigue/asthenia

• Hiccups

• Constipation

• Diarrhoea

• Anorexia/decreased appetite

• Headache

• Dizziness

Adverse Effect Action Required

Anaphylaxis / severe hypersensitivity (rare) Discontinue immediately; do not rechallenge; emergency management

Stevens-Johnson syndrome / TEN (very rare) Discontinue immediately; dermatology and ICU referral

Severe hepatotoxicity / transaminase elevation Discontinue if ALT/AST >3× ULN with symptoms or >5× ULN

Infusion-site reactions (fosaprepitant) May include thrombophlebitis, erythema, pain; slow infusion rate, dilute adequately

Phase Parameters

Baseline LFTs (especially if hepatic disease history); assess concurrent medications for interactions

During treatment Clinical response to antiemetic therapy; GI symptoms; signs of hypersensitivity

Warfarin users INR monitoring during aprepitant course and for 2 weeks after

Repeated chemotherapy cycles Periodic LFTs if hepatic concerns; reassess drug interactions each cycle

Women on hormonal contraception Counsel regarding reduced efficacy; document in notes

Brand Name Manufacturer Formulation

Emend MSD (Merck) Capsules 80 mg, 125 mg; Fosaprepitant injection

Aprecap Glenmark Capsules 80 mg, 125 mg

Aprinat Natco Capsules 80 mg, 125 mg

Fosaprep Various Fosaprepitant 150 mg injection

Note: Brand availability varies by region. Verify current stock. 40 mg capsule availability is limited. Fixed-dose combinations are not standard for this drug.

NLEM Status: Not included in NLEM 2022; not under NPPA price control.

Note: Significant cost — assess patient affordability; generic options may offer lower pricing.

1. Triplet therapy is standard for HEC: Aprepitant must be combined with a 5-HT3 antagonist and dexamethasone — never use as monotherapy for CINV prevention.

1. Steroid dose adjustment is mandatory: Reduce oral dexamethasone by ~50% when co-administering aprepitant to avoid steroid-related adverse effects.

1. Contraceptive counselling is essential: Inform all women of reproductive age about reduced efficacy of hormonal contraceptives; document alternative contraception advice for 28 days post-treatment.

1. IV fosaprepitant offers convenience: Single 150 mg IV dose on Day 1 replaces 3-day oral regimen — improves compliance and is preferred if IV access is established.

1. Dilute IV formulation adequately: Fosaprepitant may cause infusion-site reactions including thrombophlebitis — infuse over 20–30 minutes in adequate volume; avoid bolus administration.

1. Not for established emesis: Aprepitant is prophylactic only — it is not effective for treating nausea/vomiting that has already occurred.

Aprepitant; NK1 antagonist; CINV; chemotherapy-induced nausea; antiemetic; fosaprepitant; highly emetogenic chemotherapy; oncology; hepatic-caution; CYP3A4 interactions; pregnancy-caution

RxIndia v1.0 — 19 May 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine

• ICMR — Supportive care in cancer chemotherapy guidelines

• AIIMS Oncology Department protocols

• IAP Guidelines for paediatric chemotherapy supportive care

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th edition

• Harrison's Principles of Internal Medicine

• MASCC/ESMO Antiemetic Guidelines (supportive reference for off-label indications)