Drug reference

Clonazepam

Benzodiazepine · Anxiolytic/Sedative

Also known as Rivotril, Klonopin, Clonil, Lonazep, Zapiz

START

Confirm seizure type (EEG if available) or panic disorder diagnosis. Baseline LFTs, CBC. Screen for substance abuse history, sleep apnea, COPD, concurrent CNS depressants. Start low (0.25-0.5 mg), titrate slowly.

TYPICAL MAX

4 mg/day (panic); 20 mg/day (seizures — rarely needed); 0.2 mg/kg/day (pediatric). In elderly: max 2-3 mg/day.

STOP IF

Suicidal ideation, severe respiratory depression, paradoxical agitation, severe allergic reaction, signs of dependence/abuse

WATCH

Mental status (suicidal ideation, depression, cognitive function), respiratory rate (especially with opioids/CNS depressants), gait and fall risk (elderly), LFTs (baseline and periodic), signs of tolerance/dependence

CDSCO approvedIndian drug schedule (H, H1, X, or OTC)ATC N03AE01

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · 20-60 min (oral onset)
PEAK: 2.5h · 1-4 h (mean ~2-3 h)
t½: 1.5d · 30-40 h (long-acting benzodiazepine)
DURATION: 12h · 6-12 h (anticonvulsant effect)

EXCRETION

Renal (metabolites); <2% unchanged; hepatic CYP3A4

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

FDA PLLR: Benzodiazepines can cause fetal harm. Risk of congenital malformations (oral clefts, cardiac defects), neonatal withdrawal syndrome (floppy infant syndrome, irritability, tremor, feeding difficulties), and long-term neurodevelopmental effects. Avoid during pregnancy, especially first trimester. If essential, use lowest dose for shortest time.

FDA category + note

Top interactionssee all 12 →

OpioidsContraindicatedDatabaseKimi deep-research + Cla
MethylnaltrexoneSevereTextbookG&G 14e
NalmefeneSevereTextbookG&G 14e
NaloxoneSevereTextbookG&G 14e

Available in India

755 branded formulations and 155 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Mechanism

Clonazepam is a high-potency benzodiazepine that acts as a positive allosteric modulator at the GABA-A receptor complex. It binds to the benzodiazepine recognition site located at the interface of the alpha (α) and gamma (γ) subunits of the GABA-A receptor, increasing the affinity of GABA for its binding site and enhancing the opening frequency of the chloride ion channel. This results in increased chloride conductance, neuronal membrane hyperpolarization, and reduced neuronal excitability, producing anticonvulsant, anxiolytic, sedative, and muscle relaxant effects. Clonazepam has particular efficacy against absence seizures and myoclonic seizures.

Indications

Lennox-Gastaut syndrome (petit mal variant)Akinetic seizuresMyoclonic seizuresAbsence seizures (petit mal) — when succinimides have failedPanic disorder (with or without agoraphobia)Adjunctive therapy for various seizure types in adults and childrenAcute mania (off-label, adjunctive)Restless legs syndrome (off-label)REM sleep behavior disorder (off-label)

Dosing

Adult: Seizures: Start 0.5 mg PO TID; increase by 0.5-1 mg every 3 days. Maintenance: 3-6 mg/day (max 20 mg/day). Panic disorder: Start 0.25 mg PO BID; increase to 1 mg/day after 3 days. Maintenance: 1-4 mg/day (max 4 mg/day).
Pediatric: Seizures (infants/children): 0.01-0.03 mg/kg/day divided BID-TID; increase by 0.25-0.5 mg every 3 days. Max: 0.1-0.2 mg/kg/day. Infants <10 years or <30 kg: start 0.01-0.03 mg/kg/day.
Renal adjustment: No specific adjustment required. Use caution in severe renal impairment (accumulation of metabolites possible).
Hepatic adjustment: Contraindicated in severe hepatic impairment. Use caution in mild-moderate hepatic disease; start at lowest dose and titrate slowly. Monitor for excessive sedation.
Geriatric: Start 0.25 mg PO daily-BID; titrate slowly. Increased risk of falls, cognitive impairment, respiratory depression. Consider lower max dose (2-3 mg/day). Beers Criteria: potentially inappropriate medication in elderly (increased fall risk, cognitive impairment).
Max dose: 20 mg/day (seizures); 4 mg/day (panic disorder); 0.2 mg/kg/day (pediatric seizures)

Pharmacokinetics

Onset

Oral: onset within 20-60 minutes. Anticonvulsant effect: within hours of reaching therapeutic plasma levels.

Peak effect

Oral: peak plasma at 1-4 hours (mean ~2-3 hours). Sublingual/orally disintegrating: faster onset (15-30 min).

Duration

Long-acting benzodiazepine; anticonvulsant effect persists 6-12 hours (allows BID-TID dosing despite long half-life).

Half-life

30-40 hours (mean elimination t½); up to 60 hours in some individuals. Active metabolite 7-aminoclonazepam has similar half-life.

Bioavailability

>90% (oral).

Protein binding

~85% (bound to plasma albumin).

Metabolism

Extensively hepatic via CYP3A4 (reduction of 7-nitro group to 7-amino metabolite), followed by acetylation (via NAT2), hydroxylation, and glucuronidation/sulfation. Less than 2% excreted unchanged.

Excretion

Primarily renal: metabolites (glucuronide and sulfate conjugates) in urine. Small amount in feces.

Contraindications

Hypersensitivity to clonazepam or other benzodiazepines
Significant hepatic impairment (impaired metabolism, increased toxicity)
Acute narrow-angle glaucoma (benzodiazepines may increase intraocular pressure)
Untreated sleep apnea (respiratory depression risk)
Severe respiratory insufficiency (COPD, chronic bronchitis, pneumonia)
Myasthenia gravis (may worsen muscle weakness)
Concurrent use with opioids (FDA black box warning — respiratory depression, coma, death)
Pregnancy (especially first trimester — risk of congenital malformations, neonatal withdrawal, floppy infant syndrome)

Side effects

Common

Somnolence, drowsiness, fatigueDizziness, ataxia, impaired coordinationCognitive impairment (memory problems, confusion)Behavioral changes (irritability, aggression in children)Increased saliva production (hypersalivation, especially in children)DepressionAnterograde amnesia

Serious

Respiratory depression (especially with opioids, alcohol, CNS depressants)
Severe hypersensitivity reactions (angioedema, anaphylaxis, Stevens-Johnson syndrome)
Paradoxical reactions (agitation, hallucinations, psychosis — especially in elderly and children)
Suicidal ideation and behavior (FDA warning for all antiepileptic drugs)
Dependence, tolerance, and withdrawal syndrome (seizures, agitation, tremor, insomnia on abrupt discontinuation)
Neonatal sedation and withdrawal (if used during pregnancy)
Severe hypotension and syncope (rare)

Pregnancy & lactation

Pregnancy

Lactation

Excreted in breast milk (infant plasma levels ~10-30% of maternal). May cause infant drowsiness, poor feeding, weight loss. Avoid if possible. If breastfeeding, monitor infant closely. AAP considers effects unknown but of concern.

Drug interactions

Opioids

Contraindicated

Database

FDA black box warning: combined use of benzodiazepines and opioids causes profound respiratory depression, coma, and death via synergistic CNS depression at different receptor sites (GABA-A and mu-opioid).

Avoid concurrent use. If absolutely necessary in supervised settings, limit to lowest doses, shortest duration, monitor respiratory rate and oxygen saturation, and ensure naloxone availability.

Source: Kimi deep-research + Cla

Methylnaltrexone

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.

Source: G&G 14e

Nalmefene

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.