Adult: ≥55 years As prolonged-release tab: 2 mg once daily, taken 1-2 hours before bedtime. Recommended Max treatment duration: 13 weeks.
Oral Short-term management of jet lag
Adult: As immediate-release tab: 1-5 mg, taken on arrival at the destination at the habitual bedtime. As oral solution: 3 mg once daily, may be increased to 6 mg once daily if necessary; 1st dose is taken after arrival at destination at the habitual bedtime. Max duration: 5 days. Doses must not be taken before 8:00 P.M. or after 4:00 A.M. at destination. Max of 16 treatment courses per year.
Concomitant use with fluvoxamine or alcohol.
Patient with autoimmune disease, epilepsy. Cigarette smokers. Not recommended in patients with hepatic impairment. Renal impairment. Elderly. Pregnancy and lactation.
Significant: CNS depression, exacerbation of autoimmune disease; may increase seizure frequency. Gastrointestinal disorders: Abdominal pain, constipation, diarrhoea, nausea, vomiting. General disorders and administration site conditions: Asthenia. Infections and infestations: Influenza. Musculoskeletal and connective tissue disorders: Arthralgia, back or neck pain, muscle cramp, pain in extremity. Nervous system disorders: Headache, somnolence, dizziness, migraine. Psychiatric disorders: Nervousness, anxiety, restlessness. Respiratory, thoracic and mediastinal disorders: Respiratory tract infection, nasopharyngitis, pharyngitis, pharyngolaryngeal pain, cough, rhinitis.
Patient Counseling Information
This drug may cause CNS depression (e.g. drowsiness), if affected, do not drive or operate machinery.
Increased plasma concentrations with CYP1A2 inhibitors (e.g. ciprofloxacin, norfloxacin, verapamil, contraceptives or hormone replacement therapy), 5- or 8-methoxypsoralen (5- or 8-MOP), cimetidine, and caffeine. Decreased plasma concentrations with CYP1A2 inducers (e.g. carbamazepine, phenytoin, rifampicin, omeprazole). May reduce the hypotensive effect of Ca channel antagonists (e.g. nifedipine). May enhance the sedative effects of benzodiazepines and non-benzodiazepine hypnotics (e.g. zolpidem, zopiclone, zaleplon). Concomitant use with vitamin K antagonists (e.g. warfarin) may lead to increased or decreased prothrombin levels. Potentially Fatal: Fluvoxamine significantly increases melatonin levels.
Alcohol reduces the effect of melatonin; avoid concomitant use.
Description: Melatonin is a hormone secreted by the pineal gland. Its agonist activity at the MT1, MT2 and MT3 receptors is believed to contribute to its sleep-promoting properties, as these receptors (primarily MT1 and MT2) are involved in the control of circadian rhythms and sleep regulation. Pharmacokinetics: Absorption: Completely absorbed. Food delays rate of absorption (prolonged-release tab). Bioavailability: 15%. Time to peak plasma concentration: Prolonged-release tab: 2.6-3 hours (fed state); 0.75-1.6 hours (fasting state). Distribution: Crosses the placenta; may enter breastmilk. Plasma protein binding: Approx 60% (mainly to albumin, α1-acid glycoprotein and high-density lipoprotein). Metabolism: Metabolised in the liver by CYP1A1, CYP1A2 and possibly CYP2C19 isoenzymes to 6-sulphatoxy-melatonin (inactive metabolite). Excretion: Via urine (89% as inactive metabolite, 2% as unchanged drug). Elimination half-life: 3.5-4 hours.