EpilepsyRx

Stiripentol

Diacomit

DailyMed-verified antiseizure indications

Indication / use

Label / evidence summary
Diacomit: Dravet syndrome-associated seizures in patients taking clobazam, aged at least 6 months and weighing at least 7 kg. The label does not support monotherapy.
Role
Maintenance
Class
Non-benzodiazepine-site GABA-A potentiation plus inhibition of clobazam metabolism

Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.

Formulations & strengths

U.S. products unless another country is named. Strengths are per unit or stated volume.

Brand & formulation labels

Each link names the product and formulation it covers. Archived labels do not establish current availability.

Dosing & administration

Adult / product-specific schedule
50 mg/kg/day divided 2–3 times; max 3,000 mg/day.
Pediatric
Age 6 months–<1 year (≥7 kg), or age ≥1 year and 7–<10 kg: 25 mg/kg twice daily only. Age ≥1 year and ≥10 kg: 25 mg/kg twice daily or 16.67 mg/kg three times daily. Total 50 mg/kg/day; maximum 3,000 mg/day. Do not use three-times-daily dosing in the younger/lower-weight groups.
Titration / repeat dosing
Use the age/weight-specific frequency: twice daily only if <1 year or <10 kg. Total recommended dose 50 mg/kg/day, maximum 3,000 mg/day. Product-strength rounding and co-medication reductions require the full label.

Dose adjustment & concentrations

Renal impairment
Not recommended moderate/severe impairment.
Hepatic impairment
Not recommended moderate/severe impairment.
Serum reference information
No established therapeutic range

Safety

Boxed warning
No boxed warning.
Contraindications
None listed in the linked U.S. label.
Serious precautions & monitoring
Obtain hematologic testing before treatment and every 6 months for neutropenia/thrombocytopenia. Monitor appetite, growth/weight and sedation, particularly with clobazam. Suspension contains phenylalanine; check phenylketonuria precautions.

Common / selected adverse effects

  • Somnolence
  • Decreased appetite
  • Agitation
  • Ataxia
  • Weight decrease
  • Neutropenia

Drug interactions: toxicity & clinical action

Partner / combinationClinical effectClinical action
ClobazamRaises clobazam and active N-desmethylclobazam concentrations, often increasing somnolence.Label recommends an initial 25% clobazam reduction for somnolence; consider a further 25% if it persists.
Fenfluramine with clobazamRequires lower fenfluramine maximum.Use the fenfluramine stiripentol/clobazam regimen and its 17 mg/day ceiling.
CYP2C19/2C8, P-gp/BCRP and other susceptible substrates / strong inducersSubstrate toxicity can increase; inducers can reduce stiripentol.Check the exact partner and reduce/monitor as directed by label; avoid strong inducers when possible.

Pregnancy & contraception

Fetal / neonatal risk
Human stiripentol pregnancy data are inadequate. Animal studies found fetal malformations, developmental loss and impaired growth at maternal doses below the recommended clinical dose.

Clinical evidence

Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.

Direct pivotal trial

Trial summary

Study design / duration
Two multicenter, randomized, double-blind, placebo-controlled add-on trials in small pediatric Dravet syndrome cohorts already receiving clobazam and valproate; 2-month treatment followed 1-month baseline.
Primary endpoint
Sticlo France month 2: median change −91% vs +7.4% placebo; Italy −81% vs −27%. Ages 3–<18, Dravet syndrome on clobazam + valproate; 50 mg/kg/day.
Results
STICLO France and Italy used a >50% reduction in clonic/tonic-clonic seizures as the responder threshold: 71% and 67% with stiripentol versus 5% and 9% with placebo, added to clobazam and valproate.
Responder rate
Trial definition was >50% reduction (not ≥50%): France 15/21 (71%) vs 1/20 (5%); Italy 8/12 (67%) vs 1/11 (9.1%). Double-blind treatment 2 months.
Seizure freedom
43% (France) and 25% (Italy) reported no generalized clonic/tonic-clonic seizures during study; not freedom from all seizure types. Label §14.

Trial publications

Mechanism of action

  • Human antiseizure mechanism is incompletely established. Electrophysiology shows direct GABA-A positive allosteric modulation at a site distinct from the classical benzodiazepine site.
  • Neuronal experiments show longer channel openings (a barbiturate-like kinetic effect); this does not establish that stiripentol shares the phenobarbital binding site.
  • Recombinant studies show subunit dependence, with stronger α3 responses and activity at δ-containing receptors lacking the γ subunit required for classical benzodiazepine modulation. These are preclinical findings, not proven clinical selectivity.
  • Separately inhibits CYP3A4/CYP2C19, raising clobazam and active norclobazam concentrations. Direct receptor potentiation and this pharmacokinetic interaction can both contribute; monitor sedation and adjust clobazam per label.

Pharmacology

Adult values unless specified. Vd/F denotes apparent oral distribution volume.

Pharmacokinetics

Bioavailability
Absolute bioavailability is unknown. Oral absorption is substantial; capsule and powder AUCs were comparable in one study, but powder peak concentrations were higher.
Elimination half-life
Adult single-dose studies: 4.5–13 hours, increasing with dose. Pediatric Dravet syndrome population model: 8.5 hours at 10 kg to 23.5 hours at 60 kg during combination therapy.
Volume of distribution
Apparent volume in the pediatric Dravet syndrome model: 32.0 L at 10 kg to 191.8 L at 60 kg (approximately 3.2 L/kg), on valproate/clobazam combination therapy.
Active metabolite(s)
No clinically established active stiripentol metabolite. Increased active norclobazam results from inhibition of clobazam metabolism, not from conversion of stiripentol to norclobazam.
Active-metabolite half-life
Not applicable — no clinically established active metabolite.
Protein binding
~99%
Metabolism / elimination
CYP1A2, 2C19, and 3A4; strong inhibitor

Nonlinear, time-dependent clearance means a single adult half-life is an incomplete description of pediatric combination treatment.

Molecular structure

Molecular structure of Stiripentol
Principal compound; salt and product forms may differ.
NIH PubChem structure and record ↗

Product history

Initial U.S. approval
2018
Market / formulation history
2018 in the U.S.
Brands
Diacomit
Manufacturer / marketer
Biocodex (Diacomit)
Generic availability
No
Related drugs
Often used with clobazam; interaction is central to its clinical effect.

Sources & review status

Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 4/2026. This is a draft reference; final review is pending.