Schedule H

Oral

• Tablets: 5 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Insomnia (Short-term Treatment) — Adults

Step Dose

Starting dose 5 mg at bedtime

Titration Usually not required; may increase after 3–5 days if inadequate response

Usual maintenance dose 5–10 mg at bedtime

Maximum dose 10 mg/day

Key Clinical Notes:

• Duration should be limited to 2–4 weeks including taper period

• Elderly or debilitated patients: Start at 2.5–5 mg

• Address underlying causes of insomnia before initiating pharmacotherapy

• Gradual tapering required if used beyond 2 weeks

1. Myoclonic Seizures and Nocturnal Seizures (Adjunctive Therapy) — Adults

Step Dose

Starting dose 5 mg at bedtime

Titration Increase by 2.5–5 mg every 5–7 days based on response and tolerability

Usual maintenance dose 5–15 mg/day (single bedtime dose or divided)

Maximum dose 20 mg/day

Key Clinical Notes:

• Used as add-on therapy with primary antiepileptic drugs

• Particularly useful when seizures occur predominantly at night

• Monitor for tolerance development with prolonged use

Secondary Indications — Adults Only (Off-label)

Not documented in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Adjunctive Therapy in Myoclonic Epilepsy / Nocturnal Seizures

Specialist-initiated only — Paediatric neurologist supervision required

1–5 years 0.25 mg/kg/day at bedtime Increase by 0.25 mg/kg every 5–7 days as tolerated 0.25–0.5 mg/kg/day 1 mg/kg/day or 10 mg/day (whichever lower)

5–12 years 2.5–5 mg at bedtime Increase by 2.5 mg every 5–7 days 5–10 mg/day 1 mg/kg/day or 15 mg/day (whichever lower)

12 years 5 mg at bedtime Increase by 2.5–5 mg every 5–7 days 5–15 mg/day 20 mg/day

Safety Monitoring:

• Monitor closely for excessive sedation, respiratory depression, behavioural changes

• Assess coordination and cognitive function regularly

• Periodic review of seizure control and need for continued therapy

Secondary Indications — Paediatric (Off-label)

Not applicable.

Age Restriction Statement:

• Not recommended below 1 year of age except under specialist supervision in neonatal neurological disorders

• Not recommended for primary insomnia in children

Mild to moderate impairment No dose adjustment required

Severe impairment (eGFR <30) Use with caution; increased CNS sensitivity; start at lower dose

Dialysis-dependent Avoid prolonged use; risk of metabolite accumulation; not significantly dialyzable

• Known hypersensitivity to nitrazepam or other benzodiazepines

• Severe hepatic insufficiency

• Myasthenia gravis

• Severe respiratory insufficiency

• Obstructive sleep apnoea syndrome (untreated)

• Acute narrow-angle glaucoma

• Concurrent use with opioids in opioid-naïve patients (relative; avoid where possible)

• Elderly patients — increased sensitivity, risk of falls, confusion, paradoxical reactions

• History of alcohol or substance use disorder — high dependence potential

• Depression or suicidal ideation — may worsen mood; monitor closely

• Chronic pulmonary disease — risk of respiratory depression

• Renal impairment — may have prolonged action

• History of paradoxical reactions to benzodiazepines

• Concurrent CNS depressant use

• Tolerance and dependence develop with prolonged use (>2–4 weeks)

• Abrupt discontinuation after prolonged use — risk of rebound insomnia, anxiety, seizures

Parameter Recommendation

Risk category Avoid use; crosses placenta freely

Known risks Floppy infant syndrome, neonatal sedation, withdrawal symptoms, possible teratogenicity (cleft palate — data inconclusive)

Preferred alternatives Behavioural interventions first-line; if pharmacotherapy essential, short-term zolpidem under specialist care

When may be used Only if no alternative and benefit clearly outweighs risk; specialist obstetric-psychiatry input essential

Monitoring Neonatal monitoring for sedation, hypotonia, feeding difficulties, withdrawal

Parameter Recommendation

Compatibility Not recommended — excreted into breast milk

Expected levels in milk Moderate; long half-life leads to accumulation risk in infant

Preferred alternatives Non-pharmacological measures; if essential, short-acting benzodiazepines (lorazepam) with caution

Infant monitoring Sedation, poor feeding, lethargy, poor weight gain, respiratory depression

• Recommended starting dose: 2.5 mg at bedtime

• Titration: Slow; increase only if clearly needed after 5–7 days

• Maximum dose: 5 mg/day generally sufficient

• Special risks:

• Increased sensitivity to CNS effects

• Higher risk of falls and fractures

• Cognitive impairment and confusion

• Paradoxical disinhibition (agitation, aggression)

• Daytime sedation affecting daily activities

• Duration: Limit to shortest possible; reassess need frequently

Interacting Drug(s) Effect / Mechanism Action

Opioid analgesics (morphine, tramadol, fentanyl) Profound sedation, respiratory depression, coma, death Avoid combination; if essential, use lowest doses with close monitoring

Clozapine Severe respiratory depression, cardiovascular collapse Contraindicated — avoid combination

Other CNS depressants (barbiturates, other benzodiazepines) Additive CNS and respiratory depression Avoid concurrent use

Alcohol Marked potentiation of sedation and respiratory depression Absolute avoidance advised

Strong CYP3A4 inhibitors (ketoconazole, itraconazole) Increased nitrazepam plasma levels Avoid or reduce nitrazepam dose; monitor for toxicity

Sodium valproate Enhanced CNS depressant effects Use with caution; monitor sedation levels

Interacting Drug(s) Effect / Mechanism Action

Phenytoin, carbamazepine Reduced nitrazepam levels via CYP enzyme induction Monitor for reduced efficacy; may need dose adjustment

Rifampicin Decreased nitrazepam efficacy (strong CYP inducer) Monitor clinical response; consider alternative hypnotic

Antihypertensives Possible additive hypotensive effect Monitor blood pressure

Oral contraceptives Possible altered benzodiazepine metabolism Monitor for changes in sedation

Antihistamines (first-generation) Additive sedation Use with caution; advise patient about drowsiness

Proton pump inhibitors May slightly increase benzodiazepine levels Usually not clinically significant; monitor

• Daytime drowsiness and sedation

• Dizziness or light-headedness

• Muscle weakness and hypotonia

• Impaired coordination and ataxia

• Confusion (especially in elderly)

• Headache

• Fatigue

• Anterograde amnesia

• Hangover effect (next-day residual sedation)

Adverse Effect Clinical Notes

Respiratory depression Especially with concurrent CNS depressants or in respiratory-compromised patients; may require ventilatory support

Paradoxical reactions Aggression, agitation, hallucinations, disinhibition — discontinue immediately

Dependence and withdrawal syndrome Seizures, severe anxiety, psychosis on abrupt discontinuation — gradual taper essential

Severe hypotension Rare; more common with parenteral benzodiazepines

Anaphylaxis Very rare; requires immediate discontinuation and emergency management

Phase Parameters

Baseline Liver function tests; sleep history; assess for substance use disorder; respiratory function if pulmonary disease present

After initiation (3–7 days) Sedation level; coordination; cognitive function; sleep quality; paradoxical reactions

Short-term (2–4 weeks) Efficacy assessment; need for continued therapy; signs of tolerance or dependence

Long-term (if continued) Reassess every 4 weeks; monitor for cognitive decline (elderly); liver function periodically; assess for dependence

Epilepsy use Seizure frequency; serum levels of concomitant AEDs if applicable; neurological status

Brand Name Manufacturer

Nitravet® Intas Pharmaceuticals

Nitra® Sun Pharma

Nite® Micro Labs

Nitrosun® Sun Pharma

Note: Several generic versions available across India.

Strength Approximate Price (per tablet)

• Listed under NLEM 2022 (Hypnotics and Sedatives section)

• NPPA price control applicable

• Available in government supply and private sector

1. Not first-line for chronic insomnia: Reserve for short-term use (2–4 weeks maximum); behavioural interventions and sleep hygiene should be first approach.

1. Long half-life consideration: Half-life of 18–34 hours leads to next-day sedation ("hangover effect"); warn patients about driving and operating machinery.

1. Taper gradually: After use beyond 2 weeks, reduce dose by 25% weekly to avoid rebound insomnia, anxiety, and withdrawal seizures.

1. Useful in paediatric epilepsy: Particularly effective as adjunctive therapy for nocturnal and myoclonic seizures under specialist supervision.

1. Avoid in elderly if possible: If essential, use lowest effective dose for shortest duration; high risk of falls, confusion, and paradoxical reactions.

1. Screen for substance use: Assess for history of alcohol or drug dependence before prescribing; high abuse potential.

nitrazepam; benzodiazepine; hypnotic; insomnia; myoclonic seizures; nocturnal seizures; paediatric epilepsy; elderly-caution; dependence-risk; respiratory-depression; NLEM India

RxIndia v1.0 — 10 Jan 2025

• CDSCO product database and approved inserts

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• NLEM 2022

• API Textbook of Medicine, 11th Edition

• IAP Guidelines for Paediatric Epilepsy Management

• AIIMS Drug Formulary

• Goodman & Gilman's The Pharmacological Basis of Therapeutics