Inside.

In case of sleep disturbance - 3 mg 1 time / day 30-40 minutes before bedtime.

With desynchronosis, as an adaptogen when changing time zones - 1 day before the flight and in the next 2-5 days - 3 mg 30-40 minutes before bedtime.

The maximum daily dose is 6 mg.

Elderly patients: with age, there is a decrease in melatonin metabolism, which must be taken into account when choosing a dosage regimen for elderly patients. Taking this into account, in elderly patients, it is possible to take the drug 60-90 minutes before bedtime.

Renal failure: the effect of varying degrees of renal failure on the pharmacokinetics of melatonin has not been studied, therefore melatonin should be used with caution in these patients. The use of the drug is contraindicated in patients with severe renal insufficiency.

• Hypersensitivity to drug components;
• autoimmune diseases;
• liver failure;
• severe renal failure;
• pregnancy;
• period of breastfeeding;
• children under 18 years of age.

Use Melatonin-SZ with caution in patients with varying degrees of renal failure.

Application during pregnancy and lactation

The drug is contraindicated for use during pregnancy and during breastfeeding.

Application for violations of liver function

Use is contraindicated in liver failure.

Application for impaired renal function

Use is contraindicated in severe renal failure.

Classification of the incidence of side effects according to WHO recommendations: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥ 1/10 000 to <1/1000), very rare (<1/10 000), including isolated messages; the frequency is unknown (according to the available data, it is not possible to establish the frequency of occurrence).

Infectious and parasitic diseases: rarely - herpes zoster.

From the hematopoietic and lymphatic system: rarely - leukopenia, thrombocytopenia.

From the immune system: frequency unknown - hypersensitivity reactions.

From the side of metabolism and nutrition: rarely - hypertriglyceridemia, hypokalemia, hyponatremia.

Mental disorders: infrequently - irritability, nervousness, anxiety, insomnia, unusual dreams, nightmares, anxiety; rarely - mood swings, aggression, agitation, tearfulness, stress symptoms, disorientation, early morning awakening, increased libido, low mood, depression.

From the nervous system: infrequently - migraine, headache, lethargy, psychomotor hyperactivity, dizziness, drowsiness; rarely - fainting, memory impairment, impaired concentration, delirium, "restless legs" syndrome, poor sleep quality, paresthesia.

From the side of the organ of vision: rarely - decreased visual acuity, blurred vision, increased lacrimation.

On the part of the organ of hearing and labyrinth disorders: rarely - vertigo, positional vertigo.

From the side of the cardiovascular system: infrequently - arterial hypertension; rarely - exertional angina, palpitations, hot flashes.

From the gastrointestinal tract: infrequently - abdominal pain, abdominal pain in the upper abdomen, dyspepsia, ulcerative stomatitis, dry mouth, nausea; rarely - gastroesophageal disease, gastrointestinal disorder or disorder, bullous stomatitis, ulcerative glossitis, vomiting, increased peristalsis, bloating, salivary hypersecretion, bad breath, abdominal discomfort, stomach dyskinesia, gastritis.

From the liver and biliary tract: infrequently - hyperbilirubinemia.

On the part of the skin and subcutaneous tissues: infrequently - dermatitis, sweating at night, itching and generalized itching, rash, dry skin; rarely - eczema, erythema, hand dermatitis, psoriasis, generalized rash, itchy rash, nail damage; the frequency is unknown - Quincke's edema, edema of the oral mucosa, edema of the tongue.

From the musculoskeletal system and connective tissue: infrequently - pain in the limbs; rarely - arthritis, muscle spasm, neck pain, night cramps.

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

From the genitals and mammary gland: infrequently - menopausal symptoms; rarely - priapism, prostatitis; frequency unknown: galactorrhea.

General reactions: infrequently - asthenia, chest pain; rarely: fatigue, pain, thirst.

Laboratory and instrumental data: infrequently - deviation from the norm of laboratory parameters of liver function, increase in body weight; rarely - an increase in the activity of hepatic transaminases, a deviation from the norm in the content of electrolytes in the blood, a deviation from the norm in the results of laboratory tests.

Pharmacokinetic interaction

It is known that at concentrations significantly exceeding therapeutic ones, melatonin induces the CYP3A isoenzyme in vitro. The clinical significance of this phenomenon is not fully understood. If signs of induction develop, consider reducing the dose of concurrently used drugs.

At concentrations significantly higher than therapeutic, melatonin does not induce CYP1A isoenzymes in vitro. Therefore, the interaction of melatonin with other drugs due to the effect of melatonin on isoenzymes of the CYP1A group appears to be insignificant.

Melatonin metabolism is mainly mediated by CYP1A isoenzymes. Therefore, the interaction of melatonin with other drugs is possible due to the effect of melatonin on isoenzymes of the CYP1A group.

Caution should be exercised in relation to patients taking fluvoxamine, which increases the concentration of melatonin (increase in AUC by 17 times and Cmax by 12 times) by inhibiting its metabolism by cytochrome P450 isoenzymes: CYP1A2 and CYP2C19. This combination should be avoided.

Caution should be exercised in relation to patients taking 5- and 8-methoxypsoralen, which increases the concentration of melatonin due to inhibition of its metabolism.

Caution should be exercised in relation to patients taking cimetidine (an inhibitor of CYP2D isoenzymes), since it increases plasma melatonin levels by inhibiting the latter.

Smoking can reduce the concentration of melatonin due to the induction of the isoenzyme CYP1A2.

Caution should be exercised in relation to patients taking estrogens (for example, contraceptives or hormone replacement therapy), which increase the concentration of melatonin by inhibiting their metabolism by isoenzymes CYP1A1 and CYP1A2.

Inhibitors of CYPA2 isoenzymes, such as quinolones, can increase melatonin exposure.

CYP1A2 isoenzyme inducers, such as carbamazepine and rifampicin, are able to reduce plasma melatonin concentrations.

In the modern literature, there is a lot of data concerning the effect of agonists / antagonists of adrenergic and opioid receptors, antidepressants, inhibitors of prostaglandins, benzodiazepines, tryptophan and alcohol on the secretion of endogenous melatonin. Studies of the mutual influence of these drugs on the dynamics or kinetics of melatonin have not been conducted.

Pharmacodynamic interaction

You should not drink alcohol while taking melatonin. it reduces the effectiveness of the drug.

Melatonin potentiates the sedative effects of benzodiazepine and non-benzodiazepine hypnotics such as zaleplon, zolpidem, and zopiclone. In the course of a clinical study, clear signs of a transient pharmacodynamic interaction between melatonin and zolpidem were observed one hour after their administration. The combined use can lead to progressive disorders of attention, memory and coordination in comparison with zolpidem monotherapy.

In studies, melatonin was prescribed in conjunction with thioridazine and imipramine, drugs that affect the central nervous system. In none of the cases was there a clinically significant pharmacokinetic interaction. However, concomitant use with melatonin resulted in increased feelings of calmness and difficulty in performing certain tasks compared with imipramine monotherapy, as well as increased feelings of "cloudiness" in comparison with thioridazine monotherapy.

Symptoms: according to the available literature data, the use of melatonin in a daily dose of up to 300 mg did not cause clinically significant adverse reactions. Hyperemia, abdominal cramps, diarrhea, headache and scotoma were observed with the use of melatonin at doses of 3000-6600 mg for several weeks. When very high doses of melatonin (up to 1 g) were used, involuntary loss of consciousness was observed.

In case of an overdose, drowsiness may develop.

Treatment: gastric lavage and the use of activated carbon, symptomatic therapy.

Elimination of the active substance is expected within 12 hours after oral administration.