EpilepsyRx

Clobazam

Onfi · Sympazan

DailyMed-verified antiseizure indications

Indication / use

Label / evidence summary
Clobazam, Onfi, and Sympazan: adjunctive treatment of Lennox-Gastaut syndrome-associated seizures from age 2 years.
Role
Maintenance
Class
1,5-benzodiazepine

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
For >30 kg: typically 10 mg/day initially, titrated weekly to 40 mg/day; divide doses above 5 mg/day.
Pediatric
Approved age 2 years and older for Lennox-Gastaut syndrome. ≤30 kg: start 5 mg/day; titrate weekly to 20 mg/day.
Titration / repeat dosing
≤30 kg: 5 mg/day, then 10 mg/day after 1 week and 20 mg/day after 2 weeks. >30 kg: 10 mg/day, then 20 mg/day after 1 week and 40 mg/day after 2 weeks. Divide doses above 5 mg/day.

Practical administration

Product instructions
The linked clobazam tablet label permits whole tablets, splitting along the score, or crushing into applesauce; food is optional. Do not transfer these instructions to a buccal film or another formulation.

Dose adjustment & concentrations

Renal impairment
No adjustment in mild–moderate impairment; limited data in severe impairment/ESRD.
Hepatic impairment
Start at 5 mg/day and titrate more slowly in mild–moderate impairment; insufficient severe-impairment data.
Serum reference information
Mayo trough intervals: clobazam 30–300 ng/mL; N-desmethylclobazam 300–3,000 ng/mL. Measure both when investigating sedation or interactions. Interpret with clinical response; these units are ng/mL.

Safety

Boxed warning
Boxed warnings—opioid co-use can cause profound sedation/respiratory depression; benzodiazepines carry abuse, dependence, and withdrawal risks. A single percentage is not estimable because risk depends strongly on opioids, dose, duration, and patient factors.
Contraindications
Hypersensitivity to clobazam or ingredients.
Serious precautions & monitoring
Sedation and respiratory depression, especially with opioids/CNS depressants. Serious rash (SJS/TEN), DRESS, dependence/withdrawal and neonatal sedation/withdrawal. Active metabolite exposure rises in CYP2C19 poor metabolizers; use the adjusted titration.

Common / selected adverse effects

  • Somnolence/sedation
  • Lethargy
  • Drooling
  • Constipation
  • Aggression
  • Ataxia

Drug interactions: toxicity & clinical action

Partner / combinationClinical effectClinical action
Cannabidiol, stiripentol, cenobamate, sulthiame or other CYP2C19 inhibitorsIncreased N-desmethylclobazam, sometimes with delayed/prolonged sedation or ataxia.Consider a clobazam reduction and clinical/level monitoring; metabolite effects may persist.
Opioids / alcohol / other sedativesAdditive profound sedation and respiratory depression.Avoid unnecessary combinations; limit doses and monitor breathing/alertness.
Hormonal contraceptivesWeak CYP3A4 induction may lower contraceptive effectiveness.Use additional nonhormonal contraception during treatment and for 28 days after stopping per label.

Pregnancy & contraception

Fetal / neonatal risk
Clobazam exposure late in pregnancy can cause neonatal sedation, respiratory depression or withdrawal. Animal studies found developmental toxicity below expected therapeutic exposure.
Contraception
Clobazam may reduce hormonal contraceptive effectiveness. Use an additional nonhormonal method during treatment and for 28 days after stopping.
Pregnancy / postpartum monitoring
Monitor exposed newborns for sedation, feeding difficulty and withdrawal.

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
Randomized, double-blind, placebo-controlled, parallel-group trial in 238 patients with Lennox-Gastaut syndrome; 4-week baseline, 3-week titration, and 12-week maintenance; primary endpoint was weekly drop-seizure reduction.
Primary endpoint
No single pivotal endpoint is identified in the cited source.
Results
In the pivotal randomized Lennox-Gastaut syndrome trial, mean weekly drop-seizure reductions were approximately 12%, 41%, 49%, and 68% for placebo, low-, medium-, and high-dose groups respectively; responder rates favored the medium and high doses.

Trial publications

Mechanism of action

  • A 1,5-benzodiazepine positive allosteric modulator at the GABA-A benzodiazepine site; it enhances GABA-mediated inhibition. Diazepam, clonazepam, lorazepam and midazolam are 1,4-benzodiazepines.
  • Active N-desmethylclobazam (norclobazam) contributes substantially. CYP2C19 clears this metabolite; inhibition or poor-metabolizer status can increase exposure and sedation.
  • Unlike stiripentol, its receptor action is benzodiazepine-site mediated; combining the two also changes clobazam/metabolite exposure.

Pharmacology

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

Pharmacokinetics

Bioavailability
Absolute oral bioavailability is not established in the cited U.S. label. Tablets are approximately 100% bioavailable relative to oral solution; tablet and suspension exposure is similar when fasting.
Elimination half-life
Clobazam 36–42 hours.
Volume of distribution
Apparent steady-state distribution volume approximately 100 L.
Active metabolite(s)
Yes: N-desmethylclobazam (norclobazam), the major circulating active metabolite.
Active-metabolite half-life
71–82 hours; accumulation can be much greater with CYP2C19 poor metabolism or CYP2C19 inhibitors.
Protein binding
Clobazam approximately 80–90%; N-desmethylclobazam approximately 70%.
Metabolism / elimination
CYP3A4 to active N-desmethylclobazam; CYP2C19 clears metabolite

Allow for delayed metabolite accumulation when adjusting treatment, particularly with cannabidiol, stiripentol or cenobamate.

Molecular structure

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

Product history

Initial U.S. approval
2011
Market / formulation history
2011 in the U.S.
Brands
Onfi · Sympazan
Manufacturer / marketer
Lundbeck (Onfi); Aquestive (Sympazan)
Generic availability
Yes (tablets/suspension)
Related drugs
A 1,5-benzodiazepine, structurally distinct from 1,4-benzodiazepines such as clonazepam and diazepam.

Sources & review status

Representative sources are selected product labels, not an exhaustive list of generic manufacturers. Consult the exact product and formulation prescribed. Brand-name package inserts are linked separately.

Brand reference: Onfi tablets / suspension ↗

Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 7/2024. This is a draft reference; final review is pending.

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