Schedule H

Oral

Formulation Strength

Tablet 5 mg

Tablet 10 mg

Tablet 20 mg

Oral Suspension 5 mg/5 mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Adjunctive Treatment of Epilepsy (Including Lennox-Gastaut Syndrome and Refractory Focal/Generalised Seizures)

Parameter Details

Starting dose 10 mg/day in 1–2 divided doses (preferably at bedtime initially)

Titration Increase by 5–10 mg/day every 5–7 days based on seizure control and tolerability

Usual maintenance dose 20–30 mg/day in 1–2 divided doses

Maximum dose 40 mg/day

Clinical notes:

• Tolerance may develop with prolonged continuous use

• Works best as add-on therapy to valproate, lamotrigine, or levetiracetam

• Consider intermittent dosing strategies in long-term therapy to minimise tolerance

1. Acute Seizure Clusters / Catamenial Epilepsy Exacerbations (Intermittent Short-term Use)

Parameter Details

Starting dose 10 mg once daily or in 2 divided doses

Titration Not applicable (short-course therapy)

Usual maintenance dose 10–20 mg/day for 3–5 days during seizure cluster period

Maximum dose 20 mg/day for intermittent use

Clinical notes:

• Used for predictable seizure exacerbations (e.g., perimenstrual worsening)

• Short courses (3–5 days) help prevent tolerance development

• Specialist discretion required for timing and duration

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Anxiety disorders (refractory cases) 10–20 mg/day in 2 divided doses Short-term only (≤4 weeks) OFF-LABEL; Specialist only; Not first-line; Evidence: Benzodiazepine class effect; use only when other anxiolytics failed

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Adjunctive Therapy in Refractory Epilepsy (Including Lennox-Gastaut Syndrome)

Age ≥2 years — Weight-based Dosing

Body Weight Starting Dose Titration Usual Maintenance Maximum Dose

≤30 kg 5 mg/day (single dose at bedtime) Increase by 5 mg every 5–7 days 0.5–1 mg/kg/day in 1–2 divided doses 20 mg/day

30 kg 10 mg/day in 1–2 divided doses Increase by 5–10 mg every 5–7 days 20–30 mg/day in 1–2 divided doses 40 mg/day

Alternative Weight-based Calculation:

Parameter Details

Starting dose 0.1–0.2 mg/kg/day in 1–2 divided doses

Titration Increase by 0.1–0.2 mg/kg every 5–7 days

Usual maintenance dose 0.5–1 mg/kg/day

Maximum dose 1.5 mg/kg/day or 40 mg/day (whichever is lower)

Clinical notes:

• Use oral suspension for accurate dosing in younger children

• Evening or bedtime dosing preferred to minimise daytime sedation

• Re-evaluate need periodically to minimise long-term benzodiazepine dependence

Safety Monitoring:

• Somnolence and sedation levels

• Behavioural changes (irritability, aggression, paradoxical agitation)

• School performance and cognitive function

• Growth and development parameters

Secondary Indications — Paediatric (Off-label)

Not applicable

Age Restrictions:

• Not recommended in children below 2 years of age except under paediatric neurologist supervision in tertiary care settings

Severe impairment (eGFR <30) Start at lower dose (5 mg/day); slower titration; monitor for excessive sedation and accumulation

Haemodialysis Not significantly dialysed; use with caution

• Known hypersensitivity to clobazam, other benzodiazepines, or any excipients

• Myasthenia gravis

• Severe respiratory insufficiency

• Severe hepatic impairment

• Sleep apnoea syndrome (untreated)

• Acute narrow-angle glaucoma

• History of substance abuse or benzodiazepine dependence

• Depression or suicidal ideation (may worsen)

• Chronic respiratory disease (COPD, asthma)

• Elderly patients (increased sensitivity to sedation)

• History of paradoxical reactions to benzodiazepines

• Concurrent use of other CNS depressants

• Porphyria

• Gradual withdrawal essential — abrupt discontinuation may precipitate rebound seizures or withdrawal syndrome

Parameter Details

Risk category Use with caution; risk of congenital malformations not definitively ruled out

Known risks Possible increased risk of oral clefts (first trimester); neonatal withdrawal syndrome; floppy infant syndrome if used near term

Preferred alternatives Levetiracetam, lamotrigine (as per ICMR epilepsy guidelines)

When may be used Only if seizure control cannot be achieved with safer alternatives; benefit must outweigh fetal risk

Monitoring Folic acid supplementation (5 mg/day); fetal anomaly scan; neonatal monitoring for sedation, hypotonia, withdrawal symptoms

Parameter Details

Compatibility Compatible with breastfeeding with monitoring

Drug levels in milk Low to moderate; active metabolite (N-desmethylclobazam) may accumulate

Preferred alternatives Levetiracetam, lamotrigine (lower sedation risk in infant)

Infant monitoring Sedation, poor feeding, hypotonia, inadequate weight gain; consider monitoring if maternal dose >20 mg/day

Parameter Recommendation

Recommended starting dose 5 mg once daily (at bedtime)

Titration Slow increments — increase by 5 mg every 7–10 days

Maximum dose 20–30 mg/day (lower than standard adult maximum)

Extra risks Prolonged sedation; confusion and cognitive impairment; increased fall risk; paradoxical agitation; respiratory depression; reduced hepatic and renal clearance

Additional notes Consider alternative antiepileptics (levetiracetam, lamotrigine) in cognitively impaired elderly

Interacting Drug Mechanism/Effect Recommendation

Opioids (morphine, tramadol, fentanyl) Additive CNS and respiratory depression Avoid combination if possible; if essential, reduce doses of both; monitor respiratory status

Alcohol Additive sedation and respiratory depression Avoid concurrent use

Strong CYP2C19 inhibitors (fluconazole, omeprazole, fluvoxamine) Increased clobazam and N-desmethylclobazam levels Reduce clobazam dose; monitor for excessive sedation

Valproate Inhibits metabolism; increases active metabolite levels Monitor for sedation; may need clobazam dose reduction

Strong CYP3A4 inducers (rifampicin, phenobarbital) Reduced clobazam efficacy May need dose increase; monitor seizure control

Interacting Drug Mechanism/Effect Recommendation

Carbamazepine May reduce clobazam levels via CYP3A4 induction Monitor seizure control; may need higher clobazam dose

Phenytoin Bidirectional interaction — clobazam may increase phenytoin levels Monitor phenytoin levels; watch for toxicity

SSRIs (fluoxetine, sertraline) Additive sedation; CYP2C19 inhibition by some SSRIs Monitor for increased sedation

Antipsychotics Additive sedation and CNS depression Use with caution; monitor mental status

Oral contraceptives No significant pharmacokinetic interaction Advise about sedation; no dose adjustment needed

• Somnolence and drowsiness (most common)

• Fatigue and lethargy

• Dizziness

• Irritability (especially in children)

• Ataxia and coordination difficulties

• Increased salivation (particularly in children)

• Constipation

• Memory impairment

• Appetite changes

Adverse Effect Clinical Action

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (rare) Discontinue immediately; dermatology referral; hospitalisation

Paradoxical reactions (aggression, agitation, psychosis) Consider dose reduction or discontinuation; more common in children and elderly

Suicidal ideation / behaviour (especially in adolescents) Close psychiatric monitoring; discontinue if severe

Severe respiratory depression Discontinue; supportive care; more likely with concurrent opioids or in respiratory disease

Withdrawal seizures (on abrupt discontinuation) Never stop abruptly; gradual taper over weeks required

Physical dependence and tolerance Assess periodically; consider intermittent dosing strategies

Phase Parameters

Baseline Liver function tests; seizure frequency documentation; mental status and mood assessment; baseline cognitive function in children

After initiation/dose change Sedation level at 1 week; seizure frequency at 1 month; behavioural changes (especially in children); liver function if symptomatic

Long-term LFTs every 6–12 months; periodic reassessment of need for continuation (every 3–6 months); monitor for tolerance development; cognitive function in chronic paediatric use

Frisium Sanofi Tablets 5 mg, 10 mg

Lobazam Micro Labs Tablets 5 mg, 10 mg

Cloba Torrent Tablets 5 mg, 10 mg

Clozic Cipla Tablets 5 mg, 10 mg

Clobakem Alkem Tablets 5 mg, 10 mg

ClobaKid Various Oral suspension 5 mg/5 mL

• NPPA status: Included in NLEM for adjunctive epilepsy therapy

• Government supply: Available through public health facilities

1. Lower sedation than other benzodiazepines: Clobazam has less sedative effect compared to clonazepam or diazepam — preferred benzodiazepine for chronic epilepsy management.

1. Tolerance is common: Efficacy may diminish with continuous long-term use; intermittent dosing (e.g., during seizure clusters or perimenstrual periods) helps preserve effectiveness.

1. Paediatric formulation matters: Always use oral suspension for children requiring doses less than 5 mg to ensure accurate dosing.

1. Best as add-on therapy: Most effective when combined with valproate, lamotrigine, or levetiracetam in refractory epilepsy; not recommended as monotherapy.

1. Never stop abruptly: Gradual tapering over 2–4 weeks is essential to prevent rebound seizures and withdrawal symptoms; reduce by 5–10 mg per week.

1. CYP2C19 poor metabolisers: Patients who are CYP2C19 poor metabolisers may have significantly higher drug levels — start with lower doses and titrate cautiously.

Clobazam; epilepsy; Lennox-Gastaut syndrome; benzodiazepine; antiepileptic; adjunctive therapy; paediatric neurology; seizure clusters; NLEM India; Schedule H

RxIndia v1.0 — 04 Apr 2025

• CDSCO-approved product inserts

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine

• ICMR Epilepsy Guidelines

• IAP Guidelines for Paediatric Epilepsy

• AIIMS Drug Formulary

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian neurology specialist practice patterns