Welson (Melatonin) p / o 3mg tablets, No. 30
Expiration Date: 05/2027
Russian Pharmacy name:
Велсон (Мелатонин) таблетки п/о 3мг, №30
The drug is taken orally with a sufficient amount of liquid.
In case of sleep disturbance, desynchronosis, take 3 mg 1 time / day 30-40 minutes before bedtime.
When used as an adaptogen when changing time zones, it is taken 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.
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.
White film-coated tablets, round, biconvex; in cross section, the core is from white to almost white with a brownish tinge.
1 tab.
melatonin 3 mg
Excipients: calcium hydrogen phosphate dihydrate - 64.67 mg, microcrystalline cellulose - 25 mg, povidone K25 - 3.33 mg, croscarmellose sodium - 2 mg, talc - 1 mg, colloidal silicon dioxide - 0.5 mg, calcium stearate - 0.5 mg.
hypersensitivity to drug components;
autoimmune diseases;
liver failure;
severe renal failure;
pregnancy;
breastfeeding period;
age up to 18 years (the effectiveness and safety of the drug has not been established).
Carefully
The effect of various degrees of renal failure on the pharmacokinetics of melatonin has not been studied, therefore, the drug should be used with caution in patients with this pathology.
pharmachologic effect
A synthetic analogue of the pineal hormone (pineal gland). Normally, the synthesis of melatonin in the pineal gland has a certain daily rhythm. Melatonin production is synchronized with the day / night cycle, with the peak plasma concentration occurring at night and the minimum at daytime. Information about the absence of light is perceived by the retina, from where the signal is sent through the retinohypothalamic tract to the suprachiasmatic nucleus, and then to the superior cervical ganglion. From the endings of the sympathetic nerves extending from the neurons of the superior cervical ganglion, norepinephrine is released into the parenchyma of the pineal gland, which triggers the synthesis of melatonin. Light inhibits the production of melatonin.
Impact on any link in the melatonin synthesis process can lead to a decrease in the production of this hormone and a violation of circadian rhythms. A decrease in the production of melatonin can be observed against the background of the following conditions:
excessive exposure to artificial light sources in the dark (especially the blue spectrum - TV screen, smartphone, computer);
disorders of the sleep-wake cycle (desynchronosis), which can occur under the influence of endogenous (for example, with delayed sleep phase syndrome, advanced sleep phase syndrome) and exogenous factors (for example, sleep disturbance during shift work, changing time zones);
elderly and senile age;
perimenopause and postmenopause in women;
the presence of bad habits (active smoking and alcohol consumption);
taking certain medications (NSAIDs, beta-blockers, benzodiazepines).
Melatonin normalizes circadian rhythms. It has an adaptogenic, sedative, hypnotic effect. Increases the concentration of GABA and serotonin in the midbrain and hypothalamus, alters 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 the biological rhythm and the normalization of night sleep. Improves the quality of sleep, accelerates falling asleep, reduces the number of nighttime awakenings, improves well-being after waking up in the morning, does not cause feelings of lethargy, fatigue and fatigue upon awakening, regulates neuroendocrine functions, and reduces stress reactions. Adapts the body of weather-sensitive people to changes in weather conditions.
It is not addictive and addictive.
Pharmacokinetics
Suction
Melatonin is rapidly absorbed from the gastrointestinal tract after oral administration. 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. Tmax in serum - 60 min (normal range 20-90 min). After taking melatonin at a dose of 3-6 mg, serum Cmax is usually 10 times more endogenous melatonin in serum at night. Concomitant food intake delays the absorption of melatonin.
The oral bioavailability of melatonin ranges from 9 to 33% (approximately 15%).
Distribution
In in vitro studies, the binding of melatonin to plasma proteins is 60%. Basically, melatonin binds to albumin, ? 1-acid glycoprotein and HDL. Vd about 35 liters. It is quickly distributed into saliva and penetrates the BBB, is determined in the placenta. The concentration in the cerebrospinal fluid is 2.5 times lower than in the plasma.
Metabolism
Melatonin is metabolized primarily in the liver. After ingestion, melatonin undergoes significant transformation during the 'first pass' 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 isoenzymes CYP1A1, CYP1A2 and, possibly, CYP2C19 of the cytochrome P450 system are involved in the metabolism of melatonin. The main metabolite of melatonin, 6-sulfatoxymelatonin, is inactive.
Highlighting
Melatonin is excreted by the kidneys. The average T1 / 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.
Pharmacokinetics in special patient groups
Pharmacokinetic parameters are influenced by age, caffeine intake, smoking, taking oral contraceptives. Accelerated absorption and impaired elimination are observed in critically ill patients.
In elderly patients, the rate of absorption can be reduced by 50%. Melatonin metabolism slows down with age. At different doses of melatonin, higher AUC and Cmax values ??were obtained in elderly patients, which reflects a reduced melatonin metabolism in this group of patients.
In patients with impaired renal function, there was no accumulation of melatonin during long-term treatment. These findings are consistent with the short T1 / 2 of melatonin in humans.
The liver is the main organ involved in the metabolism of melatonin, therefore liver disease leads to an increase in the concentration of endogenous melatonin. In patients with liver cirrhosis, the plasma concentration of melatonin increased significantly during the daytime.
Side effect
Classification of adverse reactions by organs and systems, indicating the frequency of their occurrence: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely ( ? 1/10000, <1/1000), very rarely (<1/10000), incl. isolated messages, frequency unknown (frequency cannot be estimated from available data).
Infectious and parasitic diseases: rarely - herpes zoster.
From the hematopoietic system: rarely - leukopenia, thrombocytopenia.
From the immune system: frequency unknown - hypersensitivity reactions.
From the side of metabolism: 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 - 'hot flashes', exertional angina, palpitations.
From the digestive system: infrequently - abdominal pain, 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: infrequently - pain in the limbs; rarely - arthritis, muscle spasm, neck pain, night cramps.
From the urinary system: infrequently - glucosuria, proteinuria; rarely - polyuria, hematuria, nocturia.
On the part of the genitals and mammary gland: 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.
Influence on the results of laboratory and instrumental studies: 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.
If any of the side effects indicated in the instructions are aggravated or any other side effects not indicated in the instructions are noted, the patient should be informed about this by the doctor.
Application during pregnancy and lactation
The drug VelsonЃ is contraindicated for use during pregnancy and during breastfeeding.
Application for violations of liver function
The use of the drug is contraindicated in liver failure.
Application for impaired renal function
The use of the drug is contraindicated in severe renal failure.
The drug should be used with caution in patients with varying degrees of renal failure.
Application in children
The use of the drug under the age of 18 is contraindicated.
Use in 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 patients of this group, it is possible to take the drug 60-90 minutes before bedtime.
special instructions
Exposure to bright light may reduce the effectiveness of WelsonЃ. In this regard, it is recommended to avoid bright lighting after taking WelsonЃ.
It is necessary to inform women wishing to become pregnant that the drug has a weak contraceptive effect.
There are no clinical data on the use of melatonin in patients with autoimmune diseases, and therefore the use of the drug in this category of patients is not recommended.
Influence on the ability to drive vehicles and use mechanisms
The drug VelsonЃ causes drowsiness, in this regard, during the period of treatment, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.
Overdose
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 in doses of 3000-6600 mg for several weeks. Loss of consciousness was observed with the use of melatonin in very high doses (up to 1 g).
Symptoms: in case of an overdose, drowsiness may develop.
Treatment: gastric lavage, activated carbon, symptomatic therapy. The clearance of the active substance is assumed within 12 hours after ingestion.
Drug interactions
Pharmacokinetic interaction
At concentrations significantly higher than therapeutic, melatonin induces the CYP3A isoenzyme in vitro. The clinical significance of this phenomenon is not fully understood. If signs of induction develop, consideration should be given to reducing the dose of concurrently used drugs.
Avoid combination with fluvoxamine, which increases the concentration of melatonin (increase in AUC by 17 times and Cmax by 12 times) due to inhibition of its metabolism by cytochrome P450 isoenzymes (CYP): CYP1A2 and CYP2C19.
Caution should be exercised while taking the following medicines:
5- and 8-methoxypsoralen, which increases the concentration of melatonin due to inhibition of its metabolism;
cimetidine (an inhibitor of CYP2D isoenzymes), which increases plasma melatonin levels by inhibiting the latter;
estrogens, which increase the concentration of melatonin by inhibiting its metabolism by isoenzymes CYP1A1 and CYP1A2;
inhibitors of the CYPA2 isoenzyme (eg, quinolones), which can increase the exposure of melatonin;
inducers of the CYP1A2 isoenzyme (for example, carbamazepine and rifampicin), which can reduce the plasma concentration of melatonin.
Smoking can reduce the concentration of melatonin due to the induction of the isoenzyme CYP1A2.
A wealth of data has been published on the effect of adrenergic and opioid receptor agonists / antagonists, antidepressants, prostaglandin inhibitors, benzodiazepines, tryptophan and ethanol on the secretion of endogenous melatonin. The study of the mutual influence of these drugs on the dynamics or kinetics of melatonin has not been carried out.
Pharmacodynamic interaction
You should refrain from drinking alcohol while taking melatonin. it reduces the effectiveness of the drug.
Melatonin enhances the sedative effects of benzodiazepine and non-benzodiazepine hypnotics such as zaleplon, zolpidem, and zopiclone. The combined use can lead to progressive impairment of attention, memory and coordination in comparison with zolpidem monotherapy.
The use of melatonin with thioridazine and imipramine can lead to increased feelings of calmness and difficulty in performing certain tasks compared with imipramine monotherapy, as well as an increase in the feeling of 'cloudy head' compared to thioridazine monotherapy.