Not scheduled; available OTC at lower doses; higher doses often prescribed clinically

Oral

• Immediate-Release Tablets: 2 mg, 3 mg, 5 mg, 6 mg, 10 mg

• Sustained-Release (SR) Tablets: 2 mg, 3 mg, 5 mg

• Chewable / Orally Disintegrating Tablets: 3 mg (select brands)

• Combination products (melatonin + valerian): Available but not standard practice

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Insomnia (Short-term Management) — Adults

Particularly useful in elderly patients and circadian rhythm-related sleep disorders

Step Dose

Starting dose 3 mg orally, 30–60 minutes before intended bedtime

Titration If inadequate response after 1 week, increase by 2–3 mg increments

Usual maintenance dose 3–6 mg nightly

Maximum dose 10 mg/day

Key Clinical Notes:

• Duration of use: Typically 4–8 weeks; reassess need for continuation

• Immediate-release preferred for sleep-onset difficulties

• Sustained-release formulation preferred in elderly for sleep maintenance problems

• Onset of action: 30–90 minutes

• Non-habit forming; does not cause dependence

• Take in dim light environment for optimal effect

1. Delayed Sleep Phase Syndrome (DSPS) — Adults

Circadian rhythm disorder with delayed sleep-wake timing

Step Dose

Starting dose 2–3 mg orally, 1–2 hours before desired bedtime

Titration Adjust timing rather than dose if phase shift inadequate

Usual maintenance dose 2–5 mg nightly

Maximum dose 6 mg/day (higher doses rarely offer additional benefit)

Key Clinical Notes:

• Use immediate-release formulation for phase-shifting effect

• Duration: Usually 4–6 weeks; reassess circadian shift

• Combine with bright light therapy in morning for optimal results

• Gradual advancement of administration time recommended

1. Jet Lag — Adults

Temporary circadian misalignment due to transmeridian travel

Step Dose

Starting dose 3–5 mg at bedtime in destination time zone

Titration Not applicable

Usual maintenance dose 3–5 mg nightly

Maximum dose 5 mg/day

Key Clinical Notes:

• Begin on day of travel or first night at destination

• Continue for up to 5 nights

• Most effective when crossing ≥5 time zones (eastward travel)

• Use immediate-release formulation

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes Evidence Basis

Anxiety-related sleep disturbance 3–6 mg, 30–60 min before bedtime 2–4 weeks initially OFF-LABEL Indian psychiatric specialist practice

REM Sleep Behaviour Disorder (in Parkinson's Disease) 3–12 mg at bedtime Long-term with periodic review OFF-LABEL; Specialist only Small RCTs; movement disorder specialist practice

Pre-operative anxiolysis 3–6 mg, 60–90 min before procedure Single dose OFF-LABEL Meta-analyses; anaesthesia specialist practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Sleep Disorders Associated with Neurodevelopmental Conditions

Autism Spectrum Disorder (ASD), ADHD, and other developmental disorders

Specialist-initiated only — Paediatric psychiatrist or developmental paediatrician supervision required

2–5 years 0.5–1 mg, 30–60 min before bedtime Increase by 0.5–1 mg weekly based on response 1–3 mg nightly 5 mg/day

6–12 years 1–2 mg, 30–60 min before bedtime Increase by 1 mg weekly if needed 2–5 mg nightly 6 mg/day

12 years 2–3 mg, 30–60 min before bedtime Increase by 1–2 mg weekly if needed 3–5 mg nightly 10 mg/day

Key Clinical Notes:

• Immediate-release preferred for sleep-onset difficulties

• Sustained-release may be considered for sleep maintenance issues

• Safety and efficacy beyond 3 months not firmly established — reassess regularly

• Combine with behavioural interventions and sleep hygiene measures

Safety Monitoring:

• Behavioural changes and mood alterations

• Excessive daytime sleepiness

• Vivid dreams or nightmares

• Periodic re-evaluation of continued need (every 3 months)

Secondary Indications — Paediatric (Off-label)

Indication Age Group Dose Duration Notes Evidence Basis

Jet Lag >6 years 1–3 mg at bedtime during travel Up to 5 nights OFF-LABEL Limited evidence; occasional paediatric specialist use

Age Restriction Statement:

• Not recommended below 2 years of age except under specialist supervision in specific neurological conditions

• Always initiate under specialist guidance regardless of age

• No dose adjustment required in mild to moderate renal impairment

• Severe renal impairment: Use with caution due to limited data; start at lower dose

• Dialysis: No specific recommendations; use lowest effective dose

• Known hypersensitivity to melatonin or any formulation excipients

• Severe hepatic impairment

• Concurrent use with fluvoxamine (significant interaction risk)

• Autoimmune disorders — theoretical risk of immune modulation; use only if benefit confirmed by specialist

• Epilepsy — rare reports of increased seizure frequency at high doses; use with caution

• Depression or other mood disorders — monitor for worsening of depressive symptoms

• Concurrent use of other CNS depressants — additive sedation risk

• Activities requiring alertness — daytime drowsiness may impair driving or machinery operation

• Patients on anticoagulant therapy — monitor coagulation parameters

• Diabetes mellitus — may affect glucose metabolism in some patients

Parameter Recommendation

Risk category Safety not established in human pregnancy; animal data limited

Preferred alternatives Non-pharmacological sleep hygiene interventions; behavioural therapy

When may be used Only if benefit clearly outweighs risk; under specialist supervision; short-term use only

Monitoring Maternal sedation; hypotension; fetal monitoring as per standard antenatal care

Parameter Recommendation

Compatibility Likely compatible for short-term use; excreted in breast milk in low amounts

Expected levels in milk Low (endogenous melatonin naturally present in breast milk)

Preferred alternatives Non-pharmacological measures when possible

Recommended use Short-term; lowest effective dose (1–3 mg); take after last evening feed

Infant monitoring Sedation, altered sleep-wake patterns, feeding difficulties

• Recommended starting dose: 2 mg (sustained-release preferred for sleep maintenance)

• Titration: Slow; increase by 1–2 mg weekly if needed

• Maximum dose: 5–6 mg usually sufficient

• Special considerations:

• Increased sensitivity to CNS effects

• Preferred alternative to benzodiazepines due to non-habit forming nature

• Lower fall risk compared to traditional hypnotics

• Monitor for confusion and excessive daytime drowsiness

• Good tolerability profile overall

• Sustained-release formulations preferred for sleep maintenance issues

Interacting Drug(s) Effect / Mechanism Action

Fluvoxamine Strong CYP1A2 inhibitor; markedly increases melatonin plasma levels (up to 12-fold) Avoid combination; if essential, use very low melatonin dose with close monitoring

Warfarin and other oral anticoagulants Possible potentiation of anticoagulant effect Monitor INR closely; adjust anticoagulant dose as needed

CNS depressants (benzodiazepines, opioids, alcohol) Additive sedation and CNS depression Avoid concurrent use or use with extreme caution

Immunosuppressants Theoretical antagonism due to immune-stimulating properties of melatonin Use with caution in transplant patients; monitor closely

Interacting Drug(s) Effect / Mechanism Action

Oral contraceptives May increase melatonin levels via CYP1A2 inhibition Monitor for excessive sedation; may need dose reduction

Carbamazepine, Phenytoin, Phenobarbital CYP enzyme induction reduces melatonin efficacy Monitor response; may need higher melatonin dose

Rifampicin Strong CYP inducer; reduces melatonin effect Monitor for reduced efficacy

SSRIs / SNRIs (except fluvoxamine) Theoretical additive serotonergic effects; altered sleep patterns Monitor sleep quality and CNS effects

Ciprofloxacin CYP1A2 inhibitor; may increase melatonin levels Monitor for sedation

Caffeine CYP1A2 substrate; may alter melatonin metabolism Advise limiting caffeine intake, especially evening

Nifedipine Reduced antihypertensive effect reported Monitor blood pressure

• Drowsiness and daytime somnolence

• Headache

• Dizziness or light-headedness

• Nausea

• Vivid dreams or nightmares

• Dry mouth

• Irritability (especially in children)

• Mild abdominal discomfort

Adverse Effect Clinical Notes

Hypersensitivity reactions Rare; rash, pruritus, angioedema reported; discontinue if suspected

Severe daytime sedation May impair driving and machinery operation; reassess dose and timing

Worsening of depression Monitor mood in patients with psychiatric history; consider discontinuation if mood deteriorates

Seizures Rare; reported at high doses in predisposed patients

Phase Parameters

Baseline Sleep diary (subjective assessment); psychiatric history; current medications review; liver function (if hepatic concerns)

After initiation (1–2 weeks) Subjective sleep quality; daytime alertness; adverse effects; timing adjustment if needed

Short-term (4–8 weeks) Reassess continued need; evaluate for tolerance; sleep diary review

Long-term (if continued) Periodic reassessment every 3 months; monitor mood; evaluate ongoing indication; liver function annually if high doses used

Paediatric-specific Behavioural assessment; growth monitoring; reassess indication every 3 months

Brand Name Manufacturer Notes

Meloset® Aristo Pharmaceuticals Immediate-release

Restikind-M® Mankind Pharma Immediate-release

Circadin® Neurim (imported) Sustained-release 2 mg

Melatonin (generic) Cipla, Himalaya, others Various strengths

Melacare® Intas Available in multiple strengths

N-Sleep® Macleods Immediate-release

Note: Strengths and preparations vary widely between OTC supplements and prescription products; verify formulation type when prescribing.

• Not listed under NLEM 2022

• Not under NPPA price control

• Price varies significantly by brand and formulation type

• Available in both government and private sector pharmacies

1. Not a sedative-hypnotic: Melatonin regulates circadian rhythm rather than inducing deep sedation; manage patient expectations accordingly — effect builds over several days.

1. Formulation selection matters: Use immediate-release for sleep-onset difficulties and phase-shifting; use sustained-release for sleep maintenance problems, particularly in elderly.

1. Dose ceiling effect: Higher doses (>6 mg) rarely provide additional benefit and may increase adverse effects; if 5–6 mg is ineffective, reconsider diagnosis rather than escalating dose.

1. Timing is critical: Administer 30–60 minutes before intended bedtime in dim light environment; earlier administration (1–2 hours) may be needed for phase-shifting in DSPS.

1. Preferred in elderly and addiction-prone patients: Safe alternative to benzodiazepines and Z-drugs due to absence of dependence potential, lower fall risk, and minimal cognitive impairment.

1. OTC vs prescription considerations: OTC preparations may have variable quality and bioavailability; pharmaceutical-grade products preferred for clinical use.

melatonin; insomnia; circadian rhythm; sleep disorders; jet lag; DSPS; elderly-safe; non-habit-forming; paediatric-specialist; hepatic-caution; non-benzodiazepine

RxIndia v1.0 — 10 Jan 2025

• CDSCO formulations database

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• API Textbook of Medicine, 11th Edition

• AIIMS Clinical Guidelines — Psychiatry and Sleep Medicine

• ICMR Mental Health Practice Modules

• IAP Guidelines (paediatric use supportive reference)

• WHO EMLc (supportive material for paediatric indications)

• Indian psychiatric specialist protocols

• Published RCTs and meta-analyses (noted for off-label indications)