Schedule H and Schedule X (Psychotropic substance under NDPS Act)

Oral

• Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

• Mouth-dissolving tablets (MDT): 0.25 mg, 0.5 mg, 1 mg, 2 mg

• Oral drops (solution): 2.5 mg/mL (10 mL bottle)

• Injection: NOT AVAILABLE in India (not CDSCO-approved)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Epilepsy — Adjunctive or Monotherapy

(Particularly effective for myoclonic seizures, absence seizures, Lennox-Gastaut syndrome, infantile spasms)

Parameter Recommendation

Starting dose 0.5 mg at bedtime OR 0.25 mg twice daily

Titration Increase by 0.25–0.5 mg every 3–5 days based on seizure control and tolerability

Usual maintenance dose 1–4 mg/day in 2–3 divided doses

Maximum dose 20 mg/day (specialist supervision required for doses >6 mg/day)

Clinical Notes:

• More effective as adjunctive therapy; tolerance may develop with long-term use

• Bedtime dosing preferred initially to minimise daytime sedation

• Avoid abrupt discontinuation — risk of withdrawal seizures; taper gradually over 2–4 weeks

• May lose efficacy over time (tolerance); reassess periodically

1. Panic Disorder (With or Without Agoraphobia)

Parameter Recommendation

Starting dose 0.25 mg twice daily OR 0.5 mg at bedtime

Titration Increase by 0.25–0.5 mg every 3 days based on response and tolerability

Usual maintenance dose 1–2 mg/day in 1–2 divided doses

Maximum dose 4 mg/day (specialist prescription for doses >2 mg/day)

Clinical Notes:

• Not first-line for panic disorder; SSRIs/SNRIs preferred as initial therapy

• Indicated when rapid symptom control needed or SSRIs not tolerated/ineffective

• Duration: Short-term preferred (4–12 weeks); plan taper early

• Dependence risk increases significantly beyond 4 weeks of continuous use

Secondary Indications — Adults (Off-label, if any)

Indication Dose Duration Label Status Evidence Basis

Acute catatonia 1–2 mg/day in divided doses; may increase to 4–6 mg/day if needed Short-term; taper after resolution OFF-LABEL; Specialist only Indian psychiatry practice; benzodiazepine-responsive catatonia well-documented

REM sleep behaviour disorder 0.25–0.5 mg at bedtime; may increase to 1 mg Long-term maintenance may be needed OFF-LABEL; Specialist only International RCTs; limited Indian data

Essential tremor (refractory) 0.5–1 mg/day in divided doses Long-term if effective OFF-LABEL; Specialist only Used when propranolol/primidone not tolerated or ineffective

Akathisia (antipsychotic-induced) 0.5–1 mg/day Duration of antipsychotic therapy OFF-LABEL; Specialist only Indian psychiatry practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Epilepsy — Various Seizure Types

(Including myoclonic seizures, absence seizures, Lennox-Gastaut syndrome, infantile spasms)

Age/Weight Starting Dose Titration Usual Maintenance Maximum Dose

Infants 6–12 months 0.01 mg/kg/day in 2–3 divided doses Increase by 0.25 mg every 3–5 days 0.05–0.1 mg/kg/day 0.2 mg/kg/day

Children 1–5 years (10–20 kg) 0.25 mg at bedtime Increase by 0.25 mg every 3–5 days 0.5–1.5 mg/day in 2–3 doses 0.1 mg/kg/day or 3 mg/day

Children 6–12 years (20–40 kg) 0.5 mg at bedtime Increase by 0.25–0.5 mg every 3–5 days 1–3 mg/day in 2–3 doses 0.15 mg/kg/day or 6 mg/day

Adolescents >12 years 0.5–1 mg at bedtime Increase by 0.5 mg every 3–5 days 1.5–4 mg/day in 2–3 doses 0.2 mg/kg/day or 20 mg/day

Clinical Notes:

• Oral drops (2.5 mg/mL) preferred for precise weight-based dosing in young children

• 1 drop ≈ 0.1 mg (verify with specific product)

• Bedtime dosing initially to minimise daytime sedation affecting school performance

• Increased salivation common in children; monitor for drooling

Safety Monitoring:

• Monitor for excessive sedation, behavioural changes, paradoxical agitation

• Respiratory monitoring in infants and children with respiratory compromise

• Regular assessment of seizure control and developmental milestones

• Monitor for signs of dependence with long-term use

Minimum Age: Not recommended in infants <6 months except under paediatric neurologist supervision with appropriate monitoring.

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Label Status Evidence Basis

Severe anxiety in neurodevelopmental disorders (autism, intellectual disability) 0.01–0.02 mg/kg/day in divided doses; max 0.05 mg/kg/day Short-term; regular reassessment OFF-LABEL; Specialist only Indian paediatric psychiatry practice; IAP guidelines

Status epilepticus (when IV benzodiazepines unavailable) 0.1 mg/kg buccal/sublingual (crushed tablet or oral drops); max 2 mg Single dose; emergency use OFF-LABEL; Specialist only Limited evidence; emergency use when other options unavailable

Severe impairment (eGFR <30) Use with caution; start at lower dose; increased sensitivity due to metabolite accumulation

Haemodialysis Not significantly dialysed; no supplemental dose required

• Known hypersensitivity to clonazepam, other benzodiazepines, or any excipient

• Acute narrow-angle glaucoma (untreated)

• Severe respiratory insufficiency

• Severe sleep apnoea syndrome (uncontrolled)

• Myasthenia gravis

• Severe hepatic impairment (decompensated cirrhosis)

• Acute intoxication with alcohol, opioids, or other CNS depressants

• Chronic respiratory disease (COPD, bronchiectasis) — risk of respiratory depression

• History of substance use disorder — high dependence potential

• Depression or suicidal ideation — may exacerbate; monitor closely

• Elderly patients — increased sensitivity; higher fall risk

• Concurrent use with opioids or other CNS depressants — additive respiratory depression

• Porphyria — may precipitate acute attack

• Cognitive impairment — may worsen confusion

• History of paradoxical reactions to benzodiazepines

• Long-term use (>4 weeks) — risk of tolerance and dependence; plan taper strategy early

• Abrupt discontinuation — risk of rebound seizures and withdrawal symptoms

Parameter Recommendation

Risk category High risk (Category D equivalent); known teratogenic potential

Known risks First trimester: increased risk of oral clefts; Third trimester: neonatal hypotonia, respiratory depression, withdrawal ("floppy infant syndrome")

Preferred alternatives For epilepsy: Levetiracetam, Lamotrigine (with folic acid supplementation); For anxiety: Non-pharmacological; SSRIs if medication essential

When it may be used Only if benefit clearly outweighs risk; uncontrolled seizures pose significant risk to mother and fetus

Monitoring Fetal anomaly scan; fetal growth monitoring; neonatal observation for hypotonia, respiratory depression, withdrawal symptoms (feeding difficulties, irritability, tremors)

Parameter Recommendation

Compatibility Use with caution; not absolutely contraindicated

Drug levels in milk Low to moderate; infant exposure estimated at 2–5% of maternal weight-adjusted dose

Preferred alternatives For epilepsy: Levetiracetam, Carbamazepine; For anxiety: SSRIs (sertraline preferred)

Infant monitoring Monitor for sedation, poor feeding, hypotonia, poor weight gain

Recommendations If essential, use lowest effective dose; monotherapy preferred; avoid breastfeeding at time of peak maternal plasma levels (2–4 hours post-dose)

• Starting dose: 0.25 mg once daily (usually at bedtime); some may require 0.125 mg

• Titration: Very slow; increase no more than 0.25 mg every 5–7 days

• Usual maintenance dose: 0.5–1 mg/day; rarely exceed 2 mg/day

• Extra risks:

• Increased sensitivity to CNS effects

• Higher risk of falls and hip fractures

• Paradoxical agitation and confusion more common

• Daytime sedation and cognitive impairment

• Impaired driving and operating machinery

• Association with increased dementia risk with long-term use

• Recommendations:

• Avoid long-term use for anxiety or insomnia

• Review need regularly; plan for discontinuation

• Consider non-benzodiazepine alternatives where possible

Interacting Drug/Class Mechanism/Effect Recommendation

Opioids (morphine, tramadol, codeine, fentanyl) Additive CNS and respiratory depression; risk of fatal overdose Avoid combination if possible; if essential, reduce doses of both and monitor closely

Alcohol Synergistic CNS depression Avoid concomitant use; counsel patients

Clozapine Increased risk of cardiovascular collapse, respiratory depression Avoid initiation of clonazepam in patients on clozapine; if essential, start at very low dose with close monitoring

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) Increased clonazepam levels; prolonged sedation Reduce clonazepam dose; monitor for toxicity

CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital, rifampicin) Decreased clonazepam levels; reduced efficacy May need to increase clonazepam dose; monitor seizure control

Interacting Drug/Class Mechanism/Effect Recommendation

Valproate Additive CNS depression; may increase clonazepam levels Monitor for excessive sedation; may need dose reduction

SSRIs (fluoxetine, fluvoxamine) CYP inhibition; may increase clonazepam levels Monitor for sedation; consider dose adjustment

Other antiepileptics (lamotrigine, levetiracetam) Additive CNS effects Generally used together; monitor for sedation

Antipsychotics Additive sedation and hypotension Monitor blood pressure and sedation

Sedating antihistamines Additive CNS depression Avoid combination or use with caution

Theophylline May reduce benzodiazepine effect (antagonism) Monitor clinical response

Antihypertensives Additive hypotensive effect Monitor blood pressure

• Drowsiness and fatigue (most common; up to 50%)

• Dizziness and unsteadiness

• Impaired coordination and ataxia

• Cognitive impairment (memory, concentration difficulties)

• Increased salivation and drooling (especially in children)

• Depression or emotional blunting

• Muscle weakness

• Slurred speech

• Respiratory depression (especially with co-sedatives or in respiratory disease) — may require ventilatory support

• Paradoxical reactions (aggression, agitation, hostility, psychosis) — discontinue if occurs

• Severe allergic reactions including Stevens-Johnson syndrome (rare)

• Physical dependence and withdrawal syndrome (seizures, psychosis, tremors) — taper gradually

• Suicidal ideation or worsening depression — monitor and reassess

• Neonatal complications if used late in pregnancy (hypotonia, respiratory depression, withdrawal)

• Anterograde amnesia

After initiation/dose change Monitor for excessive sedation, ataxia, behavioural changes; seizure frequency; paradoxical reactions (within first 2 weeks)

Long-term Periodic assessment of continued need; signs of tolerance or dependence; cognitive function; seizure control; psychiatric status; liver function annually if high doses

Pregnancy Fetal anomaly scan; growth monitoring; neonatal observation post-delivery

• Rivotril® (Sun Pharma/Roche)

• Clonotril® (Torrent)

• Lonazep® (Intas)

• Epitril® (Sanofi)

• Clozep® (Cipla)

• Zapiz® (USV)

• Clonafit® (Mankind)

• Petril® (Micro Labs)

• Clonax® (Win Medicare)

• Multiple generic formulations from various manufacturers

NLEM Status: Clonazepam 0.5 mg tablet is included in NLEM 2022; NPPA price-controlled.

Government Supply: Available through government hospitals and Jan Aushadhi stores.

• Never discontinue abruptly — taper gradually over 2–4 weeks (reduce by 0.125–0.25 mg every 3–5 days) to prevent withdrawal seizures, especially in epilepsy patients

• Not first-line for generalised anxiety disorder or insomnia — SSRIs/SNRIs and non-benzodiazepine hypnotics preferred; clonazepam reserved for panic disorder or specific seizure types

• Tolerance to antiseizure effect may develop over months; periodic reassessment of efficacy needed; may require dose increase or switching to alternative agent

• In children, oral drops allow precise weight-based dosing and easier administration; calculate dose carefully (2.5 mg/mL = 0.1 mg per drop approximately)

• Warn patients about impaired driving and operating machinery; effects may persist into following day due to long half-life (18–50 hours)

• High potential for misuse and diversion — prescribe minimum necessary quantity; regular review of prescription pattern required under Schedule X regulations

clonazepam; benzodiazepine; epilepsy; myoclonic seizures; panic disorder; Schedule X; CNS depressant; dependence-risk; paediatric-neurologist; pregnancy-Category-D; NLEM India

RxIndia v1.0 — 29 May 2025

• CDSCO product database

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022

• API Textbook of Medicine

• AIIMS Neurology and Psychiatry Protocols

• ICMR Guidelines for Epilepsy Management

• IAP Guidelines for Paediatric Neurology

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive pharmacologic reference)

• RCT evidence for REM sleep behaviour disorder and essential tremor (off-label indications only)