Melatonin is a neurohormone primarily synthesized and secreted by the pineal gland in a circadian rhythm, with peak levels occurring during the night. The 5mg oral formulation is a synthetic version used pharmacologically to treat circadian rhythm sleep disorders by promoting sleep initiation and regulating the sleep-wake cycle. It acts as a chronobiotic (resets the body clock) and a mild hypnotic.
Adult: For Insomnia (≥55 years): 2mg to 5mg, taken 1-2 hours before bedtime. For Circadian Rhythm Disorders: 0.5mg to 5mg, taken 2-4 hours before desired bedtime (timing is critical). For Jet Lag: 0.5mg to 5mg, taken at bedtime after arrival at destination for several days. Start with the lowest effective dose.
Note: Take orally with or without food. However, taking on an empty stomach may lead to faster absorption. Take 1 to 2 hours before desired bedtime. Do not crush or chew sustained-release formulations (if available). Adhere strictly to timing for circadian rhythm applications.
Melatonin exerts its primary effects by acting as an agonist at melatonin receptors (MT1 and MT2) in the suprachiasmatic nucleus (SCN) of the hypothalamus, the body's master circadian clock. Activation of MT1 receptors promotes sleepiness and inhibits neuronal firing in the SCN. Activation of MT2 receptors is involved in phase-shifting circadian rhythms, thereby synchronizing the sleep-wake cycle to the external environment (light-dark cycle). It also has free radical scavenging antioxidant properties.
Pregnancy: Category N (Not classified by US FDA). Animal studies show questionable reproductive toxicity. Use in pregnancy is contraindicated unless the potential benefit justifies the potential risk to the fetus. Endogenous melatonin plays a role in pregnancy; exogenous effects are unclear.
Driving: May impair ability to drive or operate machinery. Do not drive for at least 4-5 hours after ingestion. Warn about next-day drowsiness.
| Fluvoxamine and other CYP1A2 inhibitors | Markedly increases melatonin plasma levels (by up to 17-fold), increasing risk of sedation and side effects. | Major |
| Cimetidine | Increases melatonin levels by inhibiting CYP1A2 and CYP2C19. | Moderate |
| CYP1A2 inducers (e.g., Smoking, Carbamazepine, Rifampicin) | Decrease melatonin plasma levels, potentially reducing efficacy. | Moderate |
| Central Nervous System (CNS) Depressants (e.g., Benzodiazepines, Zolpidem, Alcohol, Antipsychotics, Antihistamines) | Additive sedative effect, increasing risk of excessive drowsiness and impaired psychomotor performance. | Major |
| Anticoagulants/Antiplatelets (e.g., Warfarin) | Melatonin may increase INR and risk of bleeding; monitor INR closely. | Moderate |
| Antihypertensives (e.g., Nifedipine, Propranolol) | Melatonin may potentiate hypotensive effect; beta-blockers also inhibit endogenous melatonin production. | Moderate |
| Immunosuppressants (e.g., Cyclosporine, Tacrolimus) | Melatonin may stimulate immune function, potentially counteracting immunosuppressive therapy. | Moderate |
| Oral Contraceptives (Estrogens) | May inhibit melatonin metabolism, increasing its levels. | Moderate |
| Caffeine | May antagonize the sleep-promoting effects of melatonin. | Minor |
Same composition (Melatonin (5mg)), different brands: