Section 01 · Monograph

Stiripentol

Reviewed Nov 2026FDA label

DiacomitGABA-A modulator

Indications

Adjunctive therapy for seizures associated with Dravet syndrome in patients ≥6 months of age (≥7kg) taking clobazamFDA-labeled

Enhances GABAergic transmission, thought to act as a positive allosteric modulator at the GABA-A receptor, increasing chloride currents
Also inhibits GABA reuptake and GABA transaminase to a lesser degree
Clinically significant pharmacokinetic mechanism: potent inhibitor of multiple hepatic CYP450 isoenzymes (notably CYP3A4, CYP2C19, and CYP1A2), which increases serum levels of co-administered clobazam (and its active metabolite N-desmethylclobazam) and valproate

Weight-based dosing, always used in combination with clobazam and valproate — not studied as monotherapy
Target dose approximately 50mg/kg/day given in 2-3 divided doses (with meals), up to a maximum of 3000mg/day
Typically initiated at a lower dose and titrated over 1 week to the target dose per weight-based tables in labeling
Capsules must be swallowed whole (not chewed/crushed); oral suspension powder mixed in a glass of water and taken immediately
Because stiripentol raises clobazam and valproate levels, concomitant clobazam and/or valproate doses are often reduced empirically at stiripentol initiation and titrated per clinical response/tolerability
Discontinue gradually rather than abruptly to minimize risk of withdrawal seizures/status epilepticus

No absolute contraindications listed in labeling beyond known hypersensitivity to stiripentol or excipients

Significantly increases clobazam and N-desmethylclobazam concentrations via CYP3A4/CYP2C19 inhibition — clobazam dose reduction (often ~25% or more) frequently required to avoid excess sedation
Increases valproate exposure — monitor for increased valproate-related adverse effects (e.g., GI upset, thrombocytopenia) and consider dose adjustment
As a CYP1A2, CYP2C19, and CYP3A4 inhibitor, has potential to increase levels of other drugs metabolized by these pathways (e.g., certain other AEDs)
Concomitant strong CYP450 inducers/inhibitors may alter stiripentol levels

Very common: somnolence/sedation (compounded by concomitant clobazam), decreased appetite and weight loss, ataxia, hypotonia
Common: nausea, vomiting, insomnia, aggression/irritability, dystonia, tremor
Neutropenia and thrombocytopenia have been reported
Suicidal ideation/behavior risk consistent with antiepileptic drug class labeling

CBC with differential (neutrophils, platelets) at baseline and approximately every 6 months during treatment
Liver function periodically given hepatic metabolism and interaction potential
Clinical monitoring for excess sedation/somnolence, especially at initiation and with clobazam co-therapy — reassess clobazam dose
Weight/growth and appetite in pediatric patients
Monitor for mood changes/suicidal ideation per AED class warning

Limited human pregnancy data; animal studies have not shown clear teratogenicity, but data are insufficient to define human risk
Encourage enrollment in an antiepileptic drug pregnancy registry if used during pregnancy
Unknown whether stiripentol is present in human milk; weigh benefits of treatment against potential infant exposure