EpilepsyRx

Clonazepam

Klonopin

DailyMed-verified antiseizure indications

Indication / use

Label / evidence summary
Klonopin: alone or as adjunctive therapy for Lennox-Gastaut syndrome, akinetic seizures, and myoclonic seizures; it may help absence seizures after succinimides have failed.
Role
Maintenance
Class
1,4-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
Start ≤1.5 mg/day in 3 doses; individualized maintenance, maximum 20 mg/day.
Pediatric
≤10 years or ≤30 kg: start 0.01–0.03 mg/kg/day in 2–3 doses (initial ceiling 0.05 mg/kg/day); maintenance 0.1–0.2 mg/kg/day.
Titration / repeat dosing
Adults: add 0.5–1 mg/day every 3 days. Children: add ≤0.25–0.5 mg/day every 3 days; stop escalation for control or toxicity. Gradual individualized taper.

Dose adjustment & concentrations

Renal impairment
Caution: metabolites undergo renal elimination.
Hepatic impairment
Contraindicated in significant liver disease.
Serum reference information
Clinical response guides dosing; no routine target here.

Safety

Boxed warning
Boxed: opioid-associated respiratory depression, abuse/misuse/addiction, and dependence/withdrawal. No reliable single incidence estimate; risk depends on exposure and co-sedatives. Avoid abrupt withdrawal after repeated use.
Contraindications
Benzodiazepine hypersensitivity; significant liver disease; acute narrow-angle glaucoma.
Serious precautions & monitoring
Tolerance can reduce benefit. Avoid significant liver disease; monitor sedation and behavior.

Common / selected adverse effects

  • Seizure-treatment experience: drowsiness; ataxia; behavioral problems

Drug interactions: toxicity & clinical action

Partner / combinationClinical effectClinical action
Opioids / alcohol / other sedativesAdditive respiratory depression and profound sedation.Avoid unnecessary combinations; monitor closely.
CYP3A inhibitors / enzyme-inducing ASMsInhibitors may increase exposure; inducers reduce it.Monitor sedation or breakthrough seizures when the partner is added/removed.
ValproateAbsence status has been reported with the combination.Investigate prolonged staring/confusion or seizure worsening; do not assume sedation alone.

Pregnancy & contraception

Fetal / neonatal risk
Clonazepam exposure late in pregnancy can cause neonatal respiratory depression, hypotonia or withdrawal. Published benzodiazepine observational data do not show a clear association with major birth defects, but do not establish absence of risk.
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.

Extrapolation

Trial summary

Study design / duration
Legacy seizure indication; no contemporary pivotal seizure trial summarized in the current label.
Primary endpoint
No single pivotal endpoint is identified in the cited source.
Results
The current label does not provide a modern placebo-controlled Phase 3 seizure-efficacy estimate. Its quantified placebo-controlled trials concern panic disorder and should not be presented as antiseizure efficacy.

Mechanism of action

  • A 1,4-benzodiazepine that enhances GABA-dependent gating of benzodiazepine-sensitive GABA-A chloride channels at the classical α/γ subunit-interface site. This is distinct from the GABA-binding site and from GABA-B receptors.
  • The classical teaching is increased opening/burst frequency for benzodiazepines versus longer openings for barbiturates. Single-channel behavior depends on preparation and conditions, so this is a useful distinction rather than an absolute kinetic rule.
  • Route, onset, duration, active metabolites and clearance distinguish these drugs clinically, but those pharmacokinetic differences are not separate receptor mechanisms.

Pharmacology

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

Pharmacokinetics

Bioavailability
Approximately 90% absolute oral bioavailability.
Elimination half-life
Typically 30–40 hours (U.S. label); the UK SmPC reports a broader 20–60-hour range.
Volume of distribution
Approximately 3 L/kg (UK SmPC).
Active metabolite(s)
No major clinically established active metabolite. Amino metabolites are inactive; the UK SmPC describes trace hydroxylated nitro derivatives with pharmacologic activity, without an established clinical contribution.
Active-metabolite half-life
Not reported for the trace potentially active derivatives in the cited labeling.
Protein binding
~85%
Metabolism / elimination
Hepatic; CYP3A involvement

Do not interpret “no major active metabolite” as proof that every metabolite is pharmacologically inert.

Molecular structure

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

Product history

Initial U.S. approval
1975
Brands
Klonopin
Manufacturer / marketer
H2-Pharma (distributor); licensed by CHEPLAPHARM
Generic availability
Yes: tablets and ODT.
Related drugs
1,4-benzodiazepine; clobazam differs structurally (1,5).

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: Klonopin tablets ↗

Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 1/2023. This is a draft reference; final review is pending.