Melatonin-SZ pills 3mg, 30pcs

Composition

1 tablet contains:

active ingredients:  

melatonin -Z mg;

excipients:  

microcrystalline cellulose-48.5 mg:

sodium carboxymethyl starch-6.5 mg;

calcium hydrophosphate dihydrate-41.0 mg;

magnesium stearate-1.0 mg

shell composition:  

hypromellose-1.53 mg;

polysorbate-80 (twin-80) – 0.64 mg;

talc – 0.51 mg;

titanium dioxide E 171-0.32 mg

Pharmacological action

Pharmacodynamics

Synthetic analog of pineal gland hormone (epiphysis); has adaptogenic, sedative, hypnotic effects. Normalizes circadian rhythms. Increases the concentration of gamma-aminobutyric acid (GABA) and serotonin in the midbrain and hypothalamus, changes the activity of pyridoxal kinase, which is involved in the synthesis of GABA, dopamine and serotonin.

Regulates the sleep-wake cycle, daily changes in locomotor activity and body temperature, has a positive effect on the intellectual and mnestic functions of the brain, on the emotional and personal sphere. Promotes the organization of biological rhythm and normalization of night sleep.

Improves sleep quality, accelerates falling asleep, and regulates neuroendocrine functions. Adapts the body of weather-sensitive people to changes in weather conditions. Pharmacokinetics Absorption

Melatonin is rapidly absorbed in the gastrointestinal tract after oral use. In the elderly, the absorption rate may 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, Cta> in blood plasma and saliva is reached after 20 minutes and 60 minutes, respectively.

The time to reach the maximum concentration of Tta> in the blood serum is 60 minutes (normal range is 20-90 minutes). After taking 3-6 mg of melatonin, the maximum concentration of Ctax in the blood serum is usually 10 times greater than the endogenous melatonin in the blood serum at night. Concomitant food intake delays melatonin absorption.

Bioavailability

The oral bioavailability of melatonin ranges from 9 to 33% (approximately 15%).

Distribution

In vitro studies showed a 60% association of melatonin with plasma proteins. Melatonin mainly binds to albumin, beta-acid glycoprotein, and high-density lipoproteins. The Vd distribution volume is about 35 liters. It is rapidly distributed in saliva and passes through the blood-brain barrier, and is detected in the placenta. The concentration in the cerebrospinal fluid is 2.5 times lower than in plasma.

Biotransformation

Melatonin is primarily metabolized in the liver. After ingestion, melatonin undergoes a significant transformation during its initial passage through the liver, where it is hydroxylated and conjugated with sulfate and glucuronide to form 6-sulfatoxymelatonin; the level of presystemic metabolism can reach 85%.

Experimental studies suggest that the cytochrome P450 isoenzymes CYP1A1, CYP1A2, and possibly CYP2C19 are involved in melatonin metabolism. The main metabolite of melatonin,6-sulfatoxymelatonin, is inactive.

Selection

Melatonin is released from the body by the kidneys. The average elimination half-life (T|/2) of melatonin is 45 minutes. Excretion is carried out in the urine, about 90% in the form of sulfate and glucuronic conjugates of 6-hydroxymelatonin, and about 2% – 10% was excreted unchanged.

Pharmacokinetic parameters are affected by age, caffeine intake, smoking, and oral contraceptive use. In critically ill patients, accelerated absorption and impaired elimination are observed.

Elderly patients

Melatonin metabolism is known to slow down with age. At different doses of melatonin, higher values of the area under the concentration-time curve (AUC) and Ctax were obtained in the elderly, which reflects a reduced melatonin metabolism in this group of patients.

Patients with impaired renal function During long-term treatment, melatonin accumulation was not observed. These findings are consistent with the short human melatonin half-life.

Patients with impaired liver function The liver is the main organ involved in melatonin metabolism, so liver diseases lead to an increase in the concentration of endogenous melatonin. In patients with cirrhosis of the liver, the plasma concentration of melatonin in the daytime significantly increased.

Indications

Sleep disorders, including those caused by a violation of the sleep-wake rhythm, such as desynchronosis (sudden jet lag).

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation.

Recommendations for use

Inside, for 30-40 minutes. In case of sleep disorders – 3 mg 1 time a day.

In case of desynchronization as an adaptogen when changing time zones-1 day before the flight and in the next 2-5 days-3 mg. The maximum daily dose is 6 mg.

Elderly patients. With age, melatonin metabolism decreases, which should 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.

Kidney failure. The effects of varying degrees of renal failure on the pharmacokinetics of melatonin have not been studied, so melatonin should be taken with caution in such patients. In patients with severe renal insufficiency, the use of the drug is not recommended.

Contraindications

Hypersensitivity to the components of the drug, autoimmune diseases, liver failure, severe renal failure, pregnancy, breast-feeding, children under 18 years of age.

WITH CAUTION

Melatonin-SZ should be used with caution in patients with varying degrees of renal insufficiency.

Side effects

Classification of the frequency of side effects according to WHO recommendations: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (

Infectious and parasitic diseases:  rarely — herpes zoster.

Blood and lymphatic system disorders:  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, restlessness, insomnia, unusual dreams, nightmares, anxiety; rarely-mood swings, aggression, agitation, tearfulness, stress symptoms, disorientation, early morning awakening, increased libido, low mood, depression.

Nervous system disorders:  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 visual organ:  rarely-decreased visual acuity, blurred vision, increased lacrimation.

Hearing disorders and labyrinth disorders:  rarely-vertigo, positional vertigo.

From the CCC side:  infrequently-arterial hypertension; rarely-angina pectoris of tension, palpitation, hot flashes.

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

Liver and biliary tract disorders:  infrequently — hyperbilirubinemia.

Skin and subcutaneous tissue disorders:  infrequently-dermatitis, night sweating, pruritus and generalized pruritus, rash, dry skin; rarely-eczema, erythema, dermatitis of the hands, psoriasis, generalized rash, itchy rash, nail damage; frequency unknown-angioedema, oral mucosal edema, tongue edema.

Musculoskeletal and connective tissue disorders:  infrequently-pain in the extremities; rarely-arthritis, muscle spasms, neck pain, night cramps.

From the side of the kidneys and urinary tract:  infrequently-glucosuria, proteinuria; rarely-polyuria, hematuria, nocturia.

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, increase in body weight; rarely-increased activity of hepatic transaminases, deviation from the norm of blood electrolyte content, deviation from the norm of laboratory test results.

Interaction

Pharmacokinetic interaction

-melatonin is known to induce the CYP3A isoenzyme in vitro at concentrations significantly higher than therapeutic levels. The clinical significance of this phenomenon is not fully understood. If signs of induction develop, consideration should be given to reducing the dose of concomitantly administered drugs.

– at concentrations significantly higher than therapeutic levels, melatonin does not induce CYP1A isoenzymes in vitro. Therefore, the interaction of melatonin with other drugs due to the effect of melatonin on CYP1A isoenzymes is apparently insignificant;