Composition:
per tablet Active ingredient: melatonin - 3.00 mg. Excipients: microcrystalline cellulose - 172.72 mg, calcium hydrogen phosphate - 54.68 mg, croscarmellose sodium - 7.20 mg, colloidal silicon dioxide - 1.20 mg, magnesium stearate - 1.20 mg. Shell excipients: hypromellose (hydroxypropyl methylcellulose) - 4.00 mg, titanium dioxide - 2.90 mg, polysorbate 80 - 1.32 mg, macrogol 4000 (polyethylene glycol 4000) - 0.89 mg, talc - 0.89 mg.
Pharmacodynamics:
Melatonin is a synthetic analogue of the hormone of the pineal gland (pineal gland); synthesized from amino acids of plant origin. It has adaptogenic, sedative, hypnotic effect.
Normalizes circadian rhythms. It increases the concentration of gamma-aminobutyric acid (GABA) and serotonin in the midbrain and hypothalamus, changes the activity of pyridoxalkinase, which is involved in the synthesis of GABA, dopamine and serotonin. It regulates the sleep-wake cycle, daily changes in locomotor activity and body temperature, positively affects the intellectual-mnestic functions of the brain, and the emotional-personal sphere. Promotes the organization of biological rhythm and the normalization of night sleep, has a hypnotic effect.
It improves the quality of sleep, speeds up falling asleep, reduces the number of nightly awakenings, improves well-being after morning awakening, does not cause a feeling of lethargy, fatigue and fatigue upon awakening. Makes dreams more vivid and emotionally saturated. Adapts the body to a quick change of time zones, reduces stress reactions, regulates neuroendocrine functions. Adapts the body of weather-sensitive people to changes in weather conditions. It exhibits immunostimulating and antioxidant properties. Not addictive and addictive.
Pharmacokinetics:
The absorption of melatonin after oral administration is rapidly absorbed in the gastrointestinal tract. In older people, the absorption rate can be reduced by 50%. The kinetics of melatonin in the range of 2-8 mg is linear. When taken orally at a dose of 3 mg Cmax in blood plasma and saliva is achieved after 20 minutes and 60 minutes, respectively. The time to reach the maximum concentration of Tmax in serum is 60 minutes (normal range is 20-90 minutes).
After taking 3-6 mg of melatonin, the maximum concentration of Cmax in blood serum is usually 10 times higher than endogenous melatonin in blood serum at night. Concomitant food intake delays the absorption of melatonin. Bioavailability Oral bioavailability of melatonin ranges from 9 to 33% (approximately 15%).
Distribution In vitro studies, the association of melatonin with plasma proteins is 60%. Basically, melatonin binds to albumin, α1 - acid glycoprotein and high density lipoproteins. The distribution volume of Vd is about 35 liters. It is quickly distributed in saliva and passes through the blood-brain barrier, is determined in the placenta. The concentration in cerebrospinal fluid is 2.5 times lower than in plasma.
Biotransformation Melatonin is metabolized primarily in the liver. After oral administration, melatonin undergoes a significant transformation during the initial passage through the liver, where it is hydroxylated and conjugated with sulfate and glucuronide to form 6-sulfate-hydroxymelatonin; the level of presystemic metabolism can reach 85%.
Experimental studies suggest that the isoenzymes CYP1A1, CYP1A2 and, possibly, CYP2C19 of the cytochrome P450 system take part in the process of metabolism of melatonin. The main metabolite of melatonin is 6-sulfatoxymelatonin, inactive. Excretion Melatonin is excreted from the body by the kidneys.
The average half-life (T½) of melatonin is 45 minutes. Excretion is carried out with urine, about 90% in the form of sulfate and glucuronic conjugates of 6-hydroxymelatonin, and about 2-10% is excreted unchanged. Pharmacokinetic parameters are affected by age, caffeine intake, smoking, and oral contraceptives. In critically ill patients, accelerated absorption and impaired elimination are observed.
Elderly patients Melatonin metabolism is known to slow with age. At different doses of melatonin, higher values of the area indicators under the concentration-time curve (AUC) and Cmax were obtained in the elderly, which reflects a reduced melatonin metabolism in this group of patients. Patients with impaired renal function With prolonged treatment, cumulation of melatonin was not observed. These data are consistent with the short elimination half-life of melatonin in humans.
Side effects:
Classification of the incidence of side effects according to the recommendations of the World Health Organization: Very often (≥1 / 10), often (from ≥1/10 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely ( ≥1 / 10000 to <1/1000), very rarely (<1/10000), including individual messages; the frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence).
Infectious and parasitic diseases: rarely: herpes zoster.
Disorders from the blood and lymphatic system: rarely: leukopenia, thrombocytopenia.
Immune system disorders: frequency unknown: hypersensitivity reactions. Metabolic and nutritional disorders: rarely: hypertriglyceridemia, hypokalemia, hyponatremia. Mental disturbance: infrequently: irritability, nervousness, anxiety, insomnia, unusual dreams, nightmares, anxiety; rarely: mood changes, aggression, agitation, tearfulness, stress symptoms, disorientation, early morning awakening, increased libido, decreased mood, depression.
Disorders of the nervous system: infrequently: migraine, headache, lethargy, psychomotor hyperactivity, dizziness, drowsiness; rare: fainting, memory impairment, impaired concentration, delirium, restless legs syndrome, dream condition, poor quality of sleep, paresthesia. Violations of the organ of vision: rarely: decreased visual acuity, blurred vision, increased lacrimation.
Hearing impairment and labyrinth disorders: rarely: vertigo, positional vertigo. Disorders from the cardiovascular system: infrequently: arterial hypertension; rarely: angina pectoris, palpitations, hot flashes.
Disorders of the gastrointestinal tract: infrequently: abdominal pain, abdominal pain in the upper abdomen, dyspepsia, ulcerative stomatitis, dry mouth, nausea; rarely: gastroesophageal disease, gastrointestinal upset or upset, bullous stomatitis, ulcerative glossitis, vomiting, increased peristalsis, bloating, hypersecretion of saliva, halitosis, abdominal discomfort, gastric dyskinesia, gastritis. Violations of the liver and biliary tract: infrequently: hyperbilirubinemia.
Violation of the skin and subcutaneous tissues: infrequently: dermatitis, sweating at night, itching and generalized itching, rash, dry skin; rarely: eczema, erythema, dermatitis of the hands, psoriasis, generalized rash, itchy rash, nail damage; frequency unknown: Quincke's edema, swelling of the oral mucosa, swelling of the tongue.
Violations of the musculoskeletal and connective tissue: infrequently: pain in the limbs. rarely: arthritis, muscle spasm, neck pain, night cramps. Violations of the kidneys and urinary tract: infrequently: glucosuria, proteinuria; rarely: polyuria, hematuria, nocturia.
Disorders from the genitals and breast: infrequently: menopausal symptoms; rarely: priapism, prostatitis; frequency unknown: galactorrhea. General disorders and disorders at the injection site: infrequently: asthenia, chest pain; rarely: fatigue, pain, thirst.
Laboratory and instrumental data: infrequently: deviation from the norm of laboratory parameters of liver function, weight gain; rarely: increased activity of “liver” transaminases, a deviation from the norm of the content of electrolytes in the blood, a deviation from the norm of the results of laboratory tests.
Special conditions:
During the period of use of the drug Melatonin Evalar, it is recommended to avoid exposure to bright light. It is necessary to inform women who want to become pregnant about the presence of a weak contraceptive effect in the drug.
There is no clinical data on the use of melatonin in patients with autoimmune diseases, and therefore, the use of this category of patients is not recommended. Influence on the ability to drive vehicles, mechanisms. During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Indications:
For sleep disorders, including caused by rhythm disturbance "sleep-wakefulness", such as desynchronosis (a sharp change in time zones).
Contraindications:
Hypersensitivity to the components of the drug, autoimmune diseases, liver failure, severe renal failure, children under 18 years of age, pregnancy, period of breastfeeding. With caution. The effect of varying degrees of renal failure on the pharmacokinetics of melatonin has not been studied, so melatonin should be used with caution in such patients.
Use during pregnancy and during breastfeeding The drug is contraindicated for use during pregnancy and during breastfeeding.
Dosage:
Inside. In case of sleep disturbance - 3 mg once a 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 the metabolism of melatonin, which must be considered when choosing a dosage regimen for elderly patients. With this in mind, 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, so melatonin should be used with caution in such patients. Patients with severe renal failure are not recommended.
Overdose:
According to available literature data, the use of melatonin in a daily dosage of up to 300 mg did not cause clinically significant adverse reactions. When taking melatonin in doses from 3000 mg to 6600 mg for several weeks, symptoms such as hyperemia, abdominal cramps, diarrhea, headache, scotoma were observed. When using very high doses of melatonin (up to 1 g), involuntary loss of consciousness was observed. With an overdose, drowsiness may develop. Treatment - gastric lavage and the use of activated charcoal, symptomatic therapy. The clearance of the active substance is expected within 12 hours after ingestion.
