Welson, 3 mg 30 pcs.

Pharmacotherapeutic group: adaptogenic agent. ATX code: N05CH01 Pharmacological properties

Pharmacodynamics

A synthetic analog of the pineal body hormone (epiphysis); has adaptogenic, sedative, sedative 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, involved in the synthesis of GABA, dopamine and serotonin. It regulates the sleep-wake cycle, daily changes in locomotor activity and body temperature, has a positive effect on the intellectual and mental functions of the brain and on the emotional-personal sphere.

It helps to organize the biological rhythm and normalize night sleep. Improves the quality of sleep, speeds up falling asleep and regulates neuroendocrine functions. It adapts the body of people sensitive to changes in weather conditions.

Pharmacokinetics

Absorption

Melatonin is rapidly absorbed in the gastrointestinal tract after oral administration. In elderly patients the absorption rate may be reduced by 50%. The kinetics of melatonin in the 2-8 mg range are linear. When administered orally at a dose of 3 mg, the maximum concentration (Cmax) in plasma and saliva is reached after 20 min and 60 min, respectively. Time to reach maximum concentration (TCmax) in blood serum is 60 min (normal range 20-90 min). After taking 3-6 mg of melatonin, serum Cmax is usually 10 times higher than endogenous melatonin in serum at night. Concomitant food intake delays the absorption of melatonin.

Bioavailability

The bioavailability of melatonin when taken orally ranges from 9 to 33% (approximately 15%).
Distribution

In in vitro studies, the binding of melatonin to plasma proteins is 60%. Melatonin mainly binds to albumin, α1-acid glycoprotein and high density lipoproteins. The volume of distribution is about 35 liters. It is rapidly distributed in saliva and passes through the blood-brain barrier and is determined in the placenta. Concentration in cerebrospinal fluid is 2.5 times lower than in plasma.

Biotransformation

Melatonin is metabolized primarily in the liver. After ingestion, melatonin undergoes significant conversion during primary passage through the liver, where it is hydroxylated and conjugated to sulfate and glucuronide to form 6-sulfatoxymelatonin; presystemic metabolism can be as high as 85%. Experimental studies suggest that the CYP1A1, CYP1A2 isoenzymes and possibly CYP2C19 of the cytochrome P450 system are involved in the metabolism of melatonin. The main metabolite of melatonin, 6-sulfatoxymelatonin, is inactive.

The excretion

Melatonin is excreted from the body by the kidneys. The average elimination half-life (T1/2) of melatonin is 45 minutes. Excretion is with the urine, about 90% as sulfate and glucuron conjugates of 6-hydroxymelatonin, and about 2-10% is excreted unchanged.

Pharmacokinetic parameters are affected by age, caffeine intake, smoking, and taking oral contraceptives. In critical 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 area under the concentration-time curve (AUC) and Cmax were obtained in elderly patients, which reflects the reduced metabolism of melatonin in this group of patients.

Patients with impaired renal function

No cumulation of melatonin was noted with long-term treatment. These data are consistent with the short T1/2 of melatonin in humans.

Patients with impaired liver function

The liver is the main organ involved in melatonin metabolism, so liver disease leads to increased concentrations of endogenous melatonin. In patients with liver cirrhosis, plasma concentrations of melatonin were significantly increased during the daytime.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

Pharmacokinetic interaction

Melatonin is known to induce the CYP3A isoenzyme in vitro at concentrations significantly greater than therapeutic. The clinical significance of this phenomenon is not fully understood. If signs of induction develop, a dose reduction of concomitantly administered drugs should be considered.

In 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 CYP1A isoenzymes appears to be insignificant.

The metabolism of melatonin is mainly mediated by CYP1A isoenzymes. Therefore, melatonin may interact with other medicinal products due to the effect of melatonin on the CYP1A isoenzymes.

Patients should be cautious when taking fluvoxamine which increases melatonin concentrations (17-fold AUC and 12-fold Cmax increase) due to inhibition of its metabolism by cytochrome P450 isoenzymes (CYP): CYP1A2 and CYP2C19. This combination should be avoided.

Patients taking 5- and 8-methoxypsoralen, which increases melatonin concentrations due to inhibition of its metabolism, should be treated with caution.

Patients taking cimetidine (a CYP2D isoenzyme inhibitor) should be treated with caution because it increases melatonin plasma levels by inhibiting the latter.

Smoking may decrease melatonin concentration due to induction of CYP1A2 isoenzyme.

Patients taking estrogens (e.g., contraceptives or hormone replacement therapy) which increase melatonin concentrations by inhibiting their metabolism by CYP1A1 and CYP1A2 isoenzymes should be treated with caution.

CYPA2 isoenzyme inhibitors, such as quinolones, can increase melatonin exposure.

CYP1A2 isoenzyme inducers, such as carbamazepine and rifampicin, can decrease the plasma concentration of melatonin.

Modern literature is full of data concerning the effects of adrenergic and opioid receptor agonists/antagonists, antidepressants, prostaglandin inhibitors, benzodiazepines, tryptophan and alcohol on endogenous melatonin secretion. No studies of the reciprocal effects of these drugs on melatonin dynamics or kinetics have been performed.

Pharmacodynamic interaction

Alcohol should not be consumed while taking melatonin because it decreases the effectiveness of the drug.

Melatonin potentiates the sedative effects of benzodiazepine and non-benzodiazepine sleeping pills such as zaleplon, zolpidem and zopiclone. In a clinical study, there were clear signs of transient pharmacodynamic interaction between melatonin and zolpidem one hour after their administration. Combined use may lead to progressive impairment of attention, memory and coordination compared with zolpidem monotherapy.

In studies, melatonin has been co-administered with thioridazine and imipramine, drugs that affect the central nervous system. No clinically significant pharmacokinetic interaction was observed in either case. However, concomitant use with melatonin resulted in an increased sense of calmness and difficulty performing certain tasks compared with imipramine monotherapy, and an increased sense of “blurring in the head” compared with thioridazine monotherapy.

Special Instructions

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

Women who want to get pregnant should be informed about the weak contraceptive effect of the drug.

There is no clinical data available on the use of melatonin in patients with autoimmune diseases; therefore, use in this patient population is not recommended.

Wellson® causes somnolence and therefore during therapy one should avoid driving and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reaction.

Contraindications

Side effects

Overdose

Pregnancy use

Similarities