Schedule H

Oral

• Oral capsules: 250 mg, 500 mg

• Oral powder for suspension: 250 mg per 5 mL (after reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Dravet Syndrome (Adjunctive Therapy) — Specialist Use Only

Stiripentol is indicated as add-on treatment for convulsive seizures in Dravet syndrome in patients aged ≥2 years who remain inadequately controlled despite concurrent clobazam and valproate therapy.

Parameter Recommendation

Starting dose 10 mg/kg/day in 2–3 divided doses

Titration Increase by 10 mg/kg/day every 3–7 days

Usual maintenance dose 50 mg/kg/day in 2–3 divided doses

Maximum dose 75 mg/kg/day (absolute ceiling ~4 g/day in larger patients)

Clinical Notes:

• Mandatory combination therapy with clobazam and valproate; monotherapy is not effective

• Stiripentol significantly elevates clobazam and its active metabolite (desmethylclobazam) plasma concentrations; anticipatory clobazam dose reduction (typically 25–50%) may be required

• Administer with food to enhance absorption and reduce gastrointestinal upset

• Monitor closely for excessive sedation, appetite suppression, and haematological abnormalities

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

NOT ESTABLISHED

No off-label adult indications are supported by Indian expert guidance or routine clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indication: Dravet Syndrome (Adjunct to Clobazam + Valproate)

Minimum age: 2 years

Weight Category Starting Dose Titration Maintenance Dose Maximum Dose

All weights (≥2 years) 10 mg/kg/day in 2–3 divided doses Increase by 10 mg/kg/day every 3–7 days 50 mg/kg/day 75 mg/kg/day (max ~4 g/day)

Safety Monitoring:

• Baseline and periodic complete blood count (neutropenia risk)

• Liver function tests every 2 weeks during titration, then every 3 months

• Weight and nutritional assessment at each visit (anorexia is frequent)

• Growth monitoring in long-term therapy

Clinical Notes:

• Powder formulation preferred in younger children unable to swallow capsules

• Avoid concurrent strong CYP enzyme inducers (carbamazepine, phenytoin, phenobarbital) — these significantly reduce stiripentol efficacy

• Use strictly under paediatric neurologist supervision

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

NOT RECOMMENDED

No off-label paediatric indications exist outside Dravet syndrome in Indian protocols.

Mild to moderate impairment No dose adjustment required

• Known hypersensitivity to stiripentol or any formulation excipients

• Concurrent administration of narrow therapeutic index drugs primarily metabolised by CYP1A2 or CYP2C19 (e.g., theophylline, cisapride)

• Severe hepatic impairment

• Pre-existing hepatic dysfunction — heightened hepatotoxicity risk

• History of haematological abnormalities — neutropenia and thrombocytopenia may occur

• Patients prone to anorexia or underweight — appetite suppression is common

• Concurrent use of CNS depressants — additive sedation

• Strong CYP enzyme inducers reduce stiripentol plasma levels and efficacy

• Patients with history of behavioural or psychiatric disturbances (relative caution)

Aspect Information

Overall safety Limited human data; animal studies show potential developmental risks

Recommendation Not recommended unless benefit clearly outweighs risk; use only under specialist supervision

Preferred alternatives For general epilepsy: levetiracetam (selected cases); valproate carries teratogenic risks but may be continued in Dravet syndrome after risk-benefit discussion

Monitoring If used: fetal growth surveillance, detailed anomaly scan, maternal drug levels

Aspect Information

Compatibility Not recommended; breastfeeding should be avoided if possible

Excretion in milk Limited human data; likely present in low concentrations

Preferred alternatives Consider formula feeding if maternal stiripentol is essential

Infant monitoring If breastfeeding continues: observe for sedation, poor feeding, inadequate weight gain

• No established indication in elderly population

• If used for any reason:

• Initiate at lowest effective dose

• Titrate slowly with careful monitoring

• Increased susceptibility to sedation, hepatic adverse effects, and polypharmacy interactions

• Assess renal and hepatic function before and during therapy

Drug Interaction Clinical Action

Clobazam Stiripentol inhibits CYP2C19 → marked increase in clobazam and desmethylclobazam levels Reduce clobazam dose by 25–50% when initiating stiripentol

Phenytoin CYP2C9/2C19 inhibition → toxic phenytoin accumulation Avoid combination or monitor levels intensively

Carbamazepine Strong CYP inducer → reduces stiripentol efficacy Avoid combination

Phenobarbital CYP inducer → lowers stiripentol levels Avoid combination

Theophylline CYP1A2 substrate → metabolism inhibited → toxicity Contraindicated

Cisapride QT prolongation risk compounded Contraindicated

Mechanism: Stiripentol is a potent inhibitor of CYP1A2, CYP2C19, and CYP3A4 enzymes.

Drug Interaction Clinical Action

Valproate Additive sedation; potential for increased hepatotoxicity Monitor LFTs and sedation levels

Omeprazole CYP2C19 inhibition → increased stiripentol exposure Use lowest effective omeprazole dose

Warfarin Hepatic metabolism potentially affected Monitor INR frequently

Other benzodiazepines Additive CNS depression Use cautiously; monitor for excessive sedation

Rifampicin CYP inducer → may reduce stiripentol levels Avoid if possible; monitor efficacy

• Drowsiness, somnolence

• Anorexia, weight loss

• Ataxia, gait disturbance

• Nausea, vomiting

• Irritability, behavioural changes

• Mild transaminase elevation

Adverse Effect Action Required

Neutropenia, thrombocytopenia Discontinue if severe; haematology consultation

Significant hepatitis or marked LFT elevation (>3× ULN) Discontinue immediately; hepatology input

Severe sedation or coma (especially with clobazam) Hospitalisation; reduce/stop clobazam; supportive care

Psychotic reactions (rare) Discontinue; psychiatric evaluation

Phase Parameters Frequency

Baseline CBC with differential, LFTs, weight, nutritional status, medication review for CYP interactions Before initiation

During titration CBC, LFTs, sedation assessment, appetite/GI symptoms Every 2 weeks

Stable maintenance CBC, LFTs, weight, growth parameters (children), behavioural assessment Every 3–6 months

Long-term Nutritional status, developmental milestones (children), seizure frequency documentation Ongoing at each visit

Brand Name Manufacturer

STROPTOL Torrent Pharmaceuticals

STIRIPEN Cipla

STOGAM Sun Pharma

STIRISURE Lupin

Note: Available in both capsule and powder for suspension formulations across brands

• Not included in NLEM — private purchase only

• No government supply programme; significant financial burden on families

1. Stiripentol is not a standalone antiepileptic — efficacy in Dravet syndrome is established only as adjunct to clobazam plus valproate; do not use as monotherapy.

1. Pre-emptive clobazam dose reduction — anticipate and reduce clobazam dose by 25–50% when initiating stiripentol to prevent excessive sedation and behavioural adverse effects.

1. Appetite suppression is nearly universal — counsel caregivers, provide dietary support, and consider nutritional supplements, particularly in young children.

1. Avoid enzyme-inducing antiepileptics — carbamazepine, phenytoin, and phenobarbital substantially reduce stiripentol plasma concentrations and therapeutic effect.

1. Regular haematological surveillance — neutropenia can develop insidiously; ensure periodic CBC monitoring, especially during first 6 months.

1. Not indicated for common epilepsies — reserve use exclusively for Dravet syndrome under specialist paediatric neurology supervision.

Stiripentol; antiepileptic; Dravet syndrome; paediatric epilepsy; CYP inhibitor; GABAergic; CNS depressant; hepatic monitoring; specialist-only; orphan drug

RxIndia v1.0 — 28 May 2025

• CDSCO (India-approved product labelling)

• AIIMS Paediatric Neurology Formulary 2023

• IAP Textbook of Paediatrics, 2021

• National Formulary of India (NFI) 2021

• Indian Pharmacopoeia 2018

• Indian expert consensus: Dravet syndrome management in children — Indian Journal of Paediatrics 2020

• Manufacturer product inserts (Cipla, Torrent, Sun Pharma)