Section 01 · Monograph

Clonazepam

Reviewed Nov 2026FDA label

KlonopinBenzodiazepine

Black Box Warning

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death
The use of benzodiazepines, including clonazepam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death
Abrupt discontinuation or rapid dosage reduction of clonazepam after continued use may precipitate acute withdrawal reactions, which can be life-threatening

Seizure disorders: Lennox-Gastaut syndrome, akinetic seizures, and myoclonic seizures; also used for absence (petit mal) seizures unresponsive to succinimidesFDA-labeled
Panic disorder, with or without agoraphobia, in adultsFDA-labeled

REM sleep behavior disorder (RBD) — a parasomnia where patients act out dreams due to loss of normal REM-related muscle atonia, often an early marker of synucleinopathies (Parkinson's disease, dementia with Lewy bodies, multiple system atrophy). Typical off-label RBD dosing is low, 0.25-1 mg at bedtime, well below seizure/anxiety doses, aiming to suppress motor dyscontrol during REM via GABA-A enhancement. Melatonin (3-12 mg at bedtime) is often tried first or concurrently in RBD given a more favorable side-effect profile in the older, neurodegenerative-disease-prone population typically affected.Off-label

A 1,4-benzodiazepine that enhances GABA-A receptor-mediated chloride conductance, potentiating the inhibitory effects of GABA, the principal inhibitory neurotransmitter in the CNS
This broad enhancement of inhibitory tone raises seizure threshold and produces anxiolytic/sedative effects

Seizure disorders (adults): initial 1.5mg/day in 3 divided doses; increase by 0.5-1mg every 3 days until seizures are controlled; maximum 20mg/day
Panic disorder (adults): initial 0.25mg twice daily; increase to a target dose of 1mg/day after 3 days; some patients may require up to 4mg/day
Taper gradually when discontinuing to reduce risk of withdrawal seizures
Schedule IV controlled substance (CIV)

Opioids: additive respiratory depression — boxed warning; avoid unless no alternative, use lowest effective doses
CYP3A4 inducers (phenytoin, carbamazepine, phenobarbital) can decrease clonazepam levels by roughly a third
CYP3A4 inhibitors (e.g., fluconazole) may increase clonazepam concentrations
Additive CNS depression with alcohol, other benzodiazepines, barbiturates, antipsychotics, and other sedatives
Valproate combined with clonazepam has rarely been associated with absence status

Periodic blood counts and liver function tests with long-term therapy
Monitor for suicidal thoughts/behavior
Assess risk for abuse/misuse/dependence before and during treatment
Monitor respiratory status and sedation level, especially if combined with opioids or other CNS depressants
Watch for withdrawal symptoms when tapering or discontinuing

Human data on teratogenicity risk are inconclusive; animal studies have shown malformations at various doses
Encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334)
Use late in pregnancy may be associated with neonatal sedation and withdrawal symptoms
Effects on breastfed infants and milk production are unknown; monitor infant for sedation and poor feeding if used during lactation