Meladapt (Tablets) Instructions for Use

Marketing Authorization Holder

Atoll LLC (Russia)

Manufactured By

Ozon, LLC (Russia)

ATC Code

N05CH01 (Melatonin)

Active Substance

Melatonin (BP British Pharmacopoeia)

Dosage Form

Meladapt

Film-coated tablets, 3 mg: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, or 300 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with a score on one side; the cross-section shows two layers: a core of white or white with a yellowish tint and a film coating.

Excipients: calcium hydrogen phosphate dihydrate – 143.25 mg, microcrystalline cellulose (MCC-102) – 100 mg, magnesium stearate – 2.5 mg, croscarmellose sodium – 1.25 mg.

Coating composition: polyvinyl alcohol – 2.7 mg, macrogol 4000 – 1.3 mg, titanium dioxide – 1 mg.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.
30 pcs. – blister packs (1) – cardboard packs.
30 pcs. – blister packs (2) – cardboard packs.
30 pcs. – blister packs (3) – cardboard packs.
30 pcs. – blister packs (4) – cardboard packs.
30 pcs. – blister packs (5) – cardboard packs.
30 pcs. – blister packs (10) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
20 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
40 pcs. – jars (1) – cardboard packs.
50 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
70 pcs. – jars (1) – cardboard packs.
80 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

Adaptogenic agent

Pharmacotherapeutic Group

Adaptogenic agent

Pharmacological Action

Synthetic analogue of the pineal gland hormone melatonin.

It has an adaptogenic, sedative, and hypnotic effect.

It normalizes circadian rhythms. It increases the concentration of GABA and serotonin in the midbrain and hypothalamus, and changes the activity of pyridoxal kinase, which is involved in the synthesis of GABA, dopamine, and serotonin. It is known that GABA is an inhibitory neurotransmitter in the CNS, and a decrease in the activity of serotonergic mechanisms may be important in the pathogenesis of depressive states and disorders.

It regulates the sleep-wake cycle, daily changes in locomotor activity and body temperature, and has a positive effect on the intellectual and mnestic functions of the brain, and on the emotional and personal sphere. It contributes to the organization of the biological rhythm and the normalization of night sleep. It improves sleep quality, reduces the frequency of headaches and dizziness, and improves mood. It accelerates falling asleep, reduces the frequency of nighttime awakenings, improves well-being after morning awakening, and does not cause feelings of lethargy, weakness, and fatigue upon awakening. It makes dreams more vivid and emotionally rich.

It adapts the body to rapid time zone changes, reduces stress reactions, and regulates neuroendocrine functions.

It has immunostimulating and antioxidant properties.

The main physiological effect of melatonin is the inhibition of gonadotropin secretion. In addition, the secretion of other adenohypophysis hormones – corticotropin, TSH, and GH – is reduced, but to a lesser extent.

The secretion of melatonin is subject to a circadian rhythm, which in turn determines the rhythmicity of gonadotropic effects and sexual function. The synthesis and secretion of melatonin depend on illumination – excess light inhibits its formation, while decreased illumination increases the synthesis and secretion of the hormone. In humans, 70% of the daily production of melatonin occurs at night.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. It easily penetrates histohematic barriers (including the blood-brain barrier). T_1/2 is short.

Indications

For sleep disorders, including those caused by disruption of the sleep-wake rhythm, such as desynchronosis (rapid time zone change).

ICD codes

Dosage Regimen

Take the tablets orally. Swallow the tablet whole with a sufficient amount of water. Do not chew or crush the tablet.

Take a single daily dose of 1.5 mg to 3 mg once a day. Administer the dose 30 to 40 minutes before your intended bedtime. This timing is critical for the drug’s synchronizing effect on the sleep-wake cycle.

For the management of sleep disturbances, including difficulty falling asleep, the standard adult dose is 3 mg taken before bedtime. Adjust the dose individually based on therapeutic response and tolerability.

For the prevention and reduction of desynchronosis symptoms associated with rapid time zone changes, begin taking the tablets on the day of travel and continue for several days after arriving at the destination. Take the tablet before bedtime at the destination.

The maximum daily dose should not exceed 6 mg. Do not exceed this maximum dose. The duration of continuous use should be determined by a physician, typically not exceeding several weeks for primary insomnia.

In elderly patients, initiate therapy at the lower end of the dosage range due to a potential age-related decrease in melatonin metabolism. Exercise caution and monitor for increased sensitivity.

Avoid consumption of alcohol during treatment, as it reduces the effectiveness of melatonin. Refrain from driving vehicles or operating machinery after taking the dose due to the risk of drowsiness and decreased alertness.

Adverse Reactions

From the hematopoietic system rarely – leukopenia, thrombocytopenia.

From the immune system frequency unknown – hypersensitivity reactions.

From metabolism rarely – hypertriglyceridemia, hypokalemia, hyponatremia.

From the psyche infrequently – irritability, nervousness, restlessness, insomnia, unusual dreams, nightmares, anxiety; rarely – mood changes, aggression, agitation, tearfulness, stress symptoms, disorientation, early morning awakening, increased libido, depressed mood, depression.

From the nervous system infrequently – migraine, headache, lethargy, psychomotor hyperactivity, dizziness, drowsiness; rarely – fainting, memory impairment, attention disturbance, delirium, restless legs syndrome, poor sleep quality, paresthesia.

From the organ of vision rarely – decreased visual acuity, blurred vision, increased lacrimation.

From the ear and labyrinth disorders rarely – vertigo, positional vertigo.

From the cardiovascular system infrequently – increased blood pressure; rarely – flushing, exertional angina, palpitations.

From the digestive system infrequently – abdominal pain, upper abdominal pain, dyspepsia, ulcerative stomatitis, dry mouth, nausea; rarely – gastroesophageal reflux disease, gastrointestinal disturbances or disorders, bullous stomatitis, ulcerative glossitis, vomiting, increased intestinal peristalsis, abdominal distension, hypersalivation, bad breath, abdominal discomfort, gastric dyskinesia, gastritis.

From the liver and biliary tract infrequently – hyperbilirubinemia.

From the skin and subcutaneous tissues infrequently – dermatitis, night sweats, skin itching and generalized itching, skin rash, dry skin; rarely – eczema, erythema, hand dermatitis, psoriasis, generalized rash, pruritic rash, nail disorder; frequency unknown – angioedema (Quincke’s edema), oral mucosal edema, tongue edema.

From the musculoskeletal system infrequently – limb pain; rarely – arthritis, muscle spasm, neck pain, night cramps.

From the urinary system infrequently – glucosuria, proteinuria; rarely – polyuria, hematuria, nocturia.

From the reproductive system infrequently – menopausal symptoms; rarely – priapism, prostatitis; frequency unknown – galactorrhea.

From laboratory parameters infrequently – abnormal liver function tests, increased body weight; rarely – increased liver transaminases, abnormal blood electrolytes, abnormal laboratory test results.

Other infrequently – asthenia, chest pain; rarely – herpes zoster, increased fatigue, feeling of thirst.

Contraindications

Hypersensitivity to melatonin; severe renal impairment (CrCl <30 ml/min), autoimmune diseases (no clinical data), hepatic insufficiency, pregnancy, breastfeeding period, age under 18 years (efficacy and safety not established).

With caution renal insufficiency (CrCl >30 ml/min), elderly age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Not recommended for use in women wishing to become pregnant, due to the slight contraceptive effect of melatonin.

Use in Hepatic Impairment

Contraindicated for use in patients with hepatic insufficiency.

Use in Renal Impairment

Contraindicated for use in patients with severe renal impairment (CrCl < 30 ml/min). Should be used with caution in renal insufficiency (CrCl > 30 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age (efficacy and safety not established).

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

During the use of melatonin, it is recommended to avoid exposure to bright light.

Women planning a pregnancy should be informed about the weak contraceptive effect of melatonin.

Alcohol should not be consumed during the use of melatonin, as it reduces its effectiveness.

With age, the metabolism of melatonin decreases, which must be taken into account when choosing a dosage regimen for elderly patients.

Effect on ability to drive vehicles and operate machinery

When using melatonin, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions (risk of drowsiness).

Drug Interactions

Caution should be exercised in patients taking fluvoxamine, which, when used concomitantly with melatonin, increases its plasma concentration by inhibiting its metabolism by cytochrome P450 isoenzymes: CYP1A2 and CYP2C19. Their simultaneous use should be avoided.

Caution is required in patients taking 5- and 8-methoxypsoralen, which increases the plasma concentration of melatonin by inhibiting its metabolism.

Caution should be exercised in patients taking cimetidine (an inhibitor of the CYP2D isoenzyme), as it increases the plasma concentration of melatonin by inhibiting the latter.

Tobacco smoking reduces the plasma concentration of melatonin by inducing the CYP1A2 isoenzyme.

Caution is required in patients taking estrogens (e.g., contraceptives or HRT), which increase the plasma concentration of melatonin by inhibiting their metabolism by CYP1A1 and CYP1A2 isoenzymes.

Inhibitors of the CYP1A2 isoenzyme, for example, quinolones, can increase the exposure of melatonin when used concomitantly.

Inducers of the CYP1A2 isoenzyme, such as carbamazepine and rifampicin, can reduce the plasma concentration of melatonin when used concomitantly.

Ethanol, when used concomitantly with melatonin, reduces its effectiveness.

Melatonin potentiates the sedative effect of benzodiazepine and non-benzodiazepine hypnotic drugs, such as zaleplon, zolpidem, and zopiclone.

Concomitant use of melatonin and zolpidem may lead to progressive impairment of attention, memory, and coordination compared to zolpidem monotherapy.

Concomitant use of melatonin with thioridazine and imipramine led to an increased feeling of calmness and difficulty in performing certain tasks compared to imipramine monotherapy, as well as an increased feeling of “fogginess in the head” compared to thioridazine monotherapy.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.