Section 01 · Monograph

Clobazam

Reviewed Nov 2026FDA label

OnfiBenzodiazepine

Black Box Warning

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death
The use of benzodiazepines, including clobazam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death
Abrupt discontinuation or rapid dosage reduction of clobazam after continued use may precipitate acute withdrawal reactions, which can be life-threatening (this is a class-wide boxed warning applied to all benzodiazepines)

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age and olderFDA-labeled

A 1,5-benzodiazepine (differs in ring structure from the more common 1,4-benzodiazepines such as diazepam and clonazepam), though it still acts at the benzodiazepine binding site on the GABA-A receptor
Potentiates GABAergic inhibitory neurotransmission by enhancing GABA-A receptor chloride channel opening
Exact mechanism underlying anticonvulsant effect not fully established

Weight ≤30kg: initiate 5mg once daily; titrate to a target/maximum of 20mg/day (divided doses)
Weight >30kg: initiate 10mg once daily; titrate to a target/maximum of 40mg/day (divided doses)
Total daily doses above 5mg are given in two divided doses
CYP2C19 poor metabolizers: start at 5mg/day and titrate more slowly, generally to about half the standard weight-based target dose, due to elevated levels of the active metabolite N-desmethylclobazam
Taper gradually when discontinuing — do not stop abruptly
Schedule IV controlled substance (CIV)

Opioids: risk of profound sedation, respiratory depression, coma, and death — avoid or use minimum effective doses with close monitoring
Clobazam is metabolized primarily by CYP3A4 to its active metabolite N-desmethylclobazam, which is then metabolized by CYP2C19 — CYP2C19 inhibitors (e.g., fluconazole, omeprazole) can increase active metabolite exposure
Clobazam is a weak-to-moderate inhibitor of CYP2D6 — may increase levels of CYP2D6 substrates
Alcohol increases clobazam exposure by roughly 50% and adds to CNS depression
May reduce effectiveness of hormonal contraceptives — recommend additional/alternative non-hormonal contraception
Additive CNS/respiratory depression with other benzodiazepines, sedative-hypnotics, and CNS depressants

Common (≥10% and greater than placebo): somnolence/sedation, constipation, pyrexia, lethargy, drooling
Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported; risk appears greatest in the first 8 weeks — discontinue at first sign of rash unless clearly unrelated to drug
Withdrawal symptoms with abrupt discontinuation: seizures, psychosis, hallucinations, behavioral disturbance, tremor, anxiety
Suicidal ideation/behavior (class effect of ASMs)
Paradoxical reactions (agitation, aggression) possible

Monitor for excessive sedation/CNS and respiratory depression, particularly if combined with opioids or other CNS depressants
Watch closely for rash/skin reactions, especially during the first 8 weeks of treatment
Assess for signs of misuse, abuse, or dependence throughout treatment
Monitor for suicidal thoughts/behavior
Consider CYP2C19 genotype/phenotype status when dosing is not proceeding as expected
Do not discontinue abruptly — monitor during dose taper

Animal studies showed developmental toxicity at subtherapeutic maternal exposures; human data limited
Use during pregnancy only if potential benefit justifies potential fetal risk
Encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334)
Clobazam is excreted in human milk; weigh clinical importance of the drug to the mother against risk to the nursing infant