Melonin

Approved Indications:

• Primary insomnia in adults and elderly
• Jet lag (short-term management of circadian rhythm disruption)
• Delayed Sleep-Wake Phase Disorder (DSWPD)
• Sleep disorders in children with neurodevelopmental conditions (e.g., autism spectrum disorder, ADHD)
• Non-24-hour sleep-wake rhythm disorder (especially in totally blind individuals)

Clinically Accepted Off-Label Uses:

• Shift work sleep disorder
• Preoperative anxiety or sedation
• Sleep disturbance in dementia
• Sleep support in depression or seasonal affective disorder
• Adjunct in migraine prophylaxis and cluster headaches
• Adjunctive antioxidant therapy (e.g., male infertility, neurodegenerative conditions)

Route of Administration: Oral (tablet, capsule, liquid, or sublingual)

Adults:

• Insomnia: 2–5 mg orally at bedtime, 30–60 minutes before sleep
• Jet Lag: 0.5–5 mg on the day of travel, 1 hour before bedtime at the destination; continue for 2–5 days
• DSWPD: 0.5–3 mg, 1–3 hours before desired sleep time
• Shift Work Sleep Disorder: 1–3 mg before intended daytime sleep

Elderly:

• Start with 0.5–2 mg nightly; prolonged-release form preferred

Children (off-label use):

• Neurodevelopmental sleep disorder: 1–6 mg at bedtime (max 10 mg/day); initiate with lowest dose under medical supervision

Special Populations:

• Renal Impairment: No dosage adjustment required
• Hepatic Impairment: Use with caution (hepatic metabolism)

Melatonin is a hormone produced by the pineal gland in response to darkness. Exogenous melatonin binds to MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN) of the hypothalamus. Activation of MT1 receptors promotes sleep onset, while MT2 receptor stimulation shifts the timing of the circadian rhythm. By mimicking endogenous melatonin activity, the drug helps regulate sleep-wake cycles, particularly in individuals with sleep phase disorders or external disruptions such as jet lag.

• Absorption: Rapidly absorbed after oral administration
• Bioavailability: ~15% (varies widely due to first-pass metabolism)
• Onset: 30–60 minutes
• Peak Plasma Time: 0.5 to 2 hours
• Distribution: Crosses the blood-brain barrier
• Protein Binding: ~60%
• Metabolism: Primarily hepatic via CYP1A2 to 6-hydroxymelatonin
• Half-life: 20–50 minutes (immediate-release); 3–4 hours (prolonged-release)
• Excretion: Mainly in urine as 6-sulfatoxymelatonin

• Pregnancy: Not assigned a formal FDA category. Animal data show no fetal harm, but human studies are limited. Use only if clearly needed.
• Lactation: Melatonin is excreted into breast milk. Use with caution; insufficient human data. Not generally recommended while breastfeeding unless prescribed.

• Primary Class: Hypnotic / Sleep-inducing agent
• Subclass: Endogenous hormone; Circadian rhythm modulator

• Hypersensitivity to melatonin or any formulation component
• Severe hepatic impairment
• Use in pregnancy or lactation without medical supervision
• Children with seizure disorders (unless under close monitoring)
• Autoimmune diseases (use with caution due to immunomodulation)

• Daytime Drowsiness: May impair ability to drive or operate machinery
• Seizure Risk: Use with caution in patients with epilepsy
• Hormonal Effects: May influence reproductive hormone levels; avoid prolonged use in adolescents
• Bleeding Risk: Theoretical increase with anticoagulants
• Immunomodulation: Avoid in autoimmune diseases
• Use Duration: Should not be used indefinitely without clinical evaluation

Common Adverse Effects:

• CNS: Headache, drowsiness, dizziness, vivid dreams
• GI: Nausea, abdominal cramps
• General: Fatigue, irritability

Serious/Rare Adverse Effects:

• Mood disturbances, depression, or suicidal ideation (rare)
• Allergic reactions (rash, pruritus, swelling)
• Hypotension or bradycardia
• Hormonal imbalances with long-term use

Onset & Severity: Typically mild and transient; dose-dependent

• CNS Depressants (e.g., benzodiazepines, alcohol): Additive sedative effects
• CYP1A2 Inhibitors (e.g., fluvoxamine): Increase melatonin levels
• CYP1A2 Inducers (e.g., rifampin, carbamazepine): Reduce melatonin effect
• Warfarin: May enhance anticoagulant effect—monitor INR
• Hormonal Contraceptives: May increase melatonin levels

• AASM (American Academy of Sleep Medicine): Recommends melatonin for circadian rhythm disorders, not for general adult insomnia
• WHO: Includes melatonin as supportive medication in pediatric palliative care
• EMA/FDA: Emphasize safe short-term use, particularly in elderly with insomnia
• Research Focus: Investigational use in COVID-19-related sleep disorders and inflammation

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Protect from moisture
• Light Protection: Store away from direct sunlight
• Handling: Keep in original container; do not freeze
• Refrigeration: Not required