| Composition | : | Each prolonged release tablet contains Melatonin 2 mg. |
|---|---|---|
| Excipients | : | Ammonio methacrylate copolymer, Calcium hydrogen phosphate dehydrate, Lactose monohydrate, Silica colloidal dioxide, Talc, Magnesium stearate. |
| Pharmacokinetic properties | : | Absorption: The absorption of orally ingested melatonin is complete in adults and may be decreased by up to 50% in the elderly. The kinetics of melatonin are linear over the range of 2-8 mg. Bioavailability is in the order of 15%. There is a significant first pass effect with an estimated first pass metabolism of 85%. T max occurs after 3 hours in a fed state The rate of melatonin absorption and Cmax is affected by food. The presence of food delayed the absorption of the melatonin resulting in a later and lower peak plasma concentration in the fed state. Distribution: The in vitro plasma protein binding of melatonin is approximately 60%. Melatonin MP is mainly bound to albumin, alpha1-acid glycoprotein and high density lipoprotein. Biotransformation: Experimental data suggest that isoenzymes CYP1A1, CYP1A2 and possibly CYP2C19 of the cytochrome P450 system are involved in melatonin metabolism. The principal metabolite is 6-sulphatoxy-melatonin (6-S-MT), which is inactive. The site of biotransformation is the liver. The excretion of the metabolite is completed within 12 hours after ingestion. Elimination: Terminal half-life (t½) is 3.5-4 hours. Elimination is by renal excretion of metabolites, |
| MECHANISM OF ACTION | : | The activity of melatonin at the MT1, MT2 and MT3 receptors is believed to contribute to its sleep-promoting properties, as these receptors (mainly MT1 and MT2) are involved in the regulation of Melatonin MP rhythms and sleep regulation. |
| Indications | : | Melatonin MP is indicated as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over. |
| Contraindications | : | Hypersensitivity to the active substance or to any of the excipients |
| Warnings and precautions | : | Melatonin MP may cause drowsiness. Therefore the product should be used with caution if the effects of drowsiness are likely to be associated with a risk to safety. No clinical data exist concerning the use of Melatonin in individuals with autoimmune diseases. Therefore, Melatonin is not recommended for use in patients with autoimmune diseases. Melatonin contains lactose. Patients with rare hereditary problems of galactose intolerance, the LAPP lactase deficiency or glucose-galactose malabsorption should not take this medicine. |
| PREGNANCY | : | The use of melatonin MP in pregnant women and by women intending to become pregnant is not recommended. |
| NURSING MOTHERS | : | Endogenous melatonin was measured in human breast milk thus exogenous melatonin is probably secreted into human milk. Therefore, breast-feeding is not recommended in women under treatment with melatonin |
| Effects on ability to drive and use machines | : | Melatonin MP has moderate influence on the ability to drive and use machines. Melatonin may cause drowsiness, therefore the product should be used with caution if the effects of drowsiness are likely to be associated with a risk to safety. |
| UNDESIRABLE EFFECTS | : | The most common adverse reactions were headache, nasopharyngitis, back pain, and arthralgia |
| Drug interactions | : | Interaction studies have only been performed in adults. Melatonin has been observed to induce CYP3A in vitro at supra-therapeutic concentrations. this can give rise to reduced plasma concentrations of concomitantly administered medicinal products. Melatonin's metabolism is mainly mediated by CYP1A enzymes. Therefore, interactions between melatonin and other active substances as a consequence of their effect on CYP1A enzymes is possible. Caution should be exercised in patients on fluvoxamine, which increases melatonin levels by inhibiting its metabolism by hepatic cytochrome P450 (CYP) isozymes CYP1A2 and CYP2C19. The combination should be avoided. Caution should be exercised in patients on 5- or 8-methoxypsoralen (5 and 8-MOP), which increases melatonin levels by inhibiting its metabolism. Caution should be exercised in patients on cimetidine a CYP2D inhibitor, which increases plasma melatonin levels, by inhibiting its metabolism. Cigarette smoking may decrease melatonin levels due to induction of CYP1A2. Caution should be exercised in patients on oestrogens (e.g. contraceptive or hormone replacement therapy), which increase melatonin levels by inhibiting its metabolism by CYP1A1 and CYP1A2. CYP1A2 inhibitors such as quinolones may give rise to increased melatonin exposure. CYP1A2 inducers such as carbamazepine and rifampcin may give rise to reduced plasma concentrations of melatonin. There is a large amount of data in the literature regarding the effect of adrenergic agonists/antagonists, opiate agonists/antagonists, antidepressant medicinal products, prostaglandin inhibitors, benzodiazepines, tryptophan and alcohol, on endogenous melatonin secretion. Whether or not these active substances interfere with the dynamic or kinetic effects of Melatonin or vice versa has not been studied. Alcohol should not be taken with Melatonin, because it reduces the effectiveness of Melatonin on sleep. Melatonin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics, such as zaleplon, zolpidem and zopiclone. |
| DOSAGE AND ADMINISTRATION | : | The recommended dose is 2 mg once daily, 1-2 hours before bedtime and after food. This dosage may be continued for up to thirteen weeks. Paediatric population: The safety and efficacy of Melatonin in children aged 0 to 18 years has not yet been established. No data are available. Renal impairment: The effect of any stage of renal impairment on melatonin pharmacokinetics has not been studied. Caution should be used when melatonin is administered to such patients. Hepatic impairment: There is no experience of the use of Melatonin in patients with liver impairment. Published data demonstrates markedly elevated endogenous melatonin levels during daytime hours due to decreased clearance in patients with hepatic impairment. Therefore, Melatonin is not recommended for use in patients with hepatic impairment. Method of Administration: Oral use. Tablets should be swallowed whole to maintain prolonged release properties. Crushing or chewing should not be used to facilitate swallowing. |
| OVERDOSE | : | Several cases of overdose have been reported post-marketing. Somnolence was the most reported adverse event. Most were mild to moderate in severity. Melatonin has been administered at 5 mg daily doses in clinical trials over 12 months without significantly changing the nature of the adverse reactions reported. Administration of daily doses of up to 300 mg of melatonin without causing clinically significant adverse reactions have been reported in the literature. If overdose occurs, drowsiness is to be expected. Clearance of the active substance is expected within 12 hours after ingestion. No special treatment is required. |
| STORAGE CONDITIONS | : | Store at temperature below 25ºC, away from light. |
| PACKAGING | : | A carton box of 30 Prolonged Release Tablet packed in blister with a leaflet. |