Velson pills 3mg, 30pcs

Composition

One film-coated tablet contains: Active ingredient:  melatonin – 3 mg. Auxiliary substances: calcium hydrophosphate dihydrate-64.67 mg, microcrystalline cellulose-25.00 mg, povidone K 25-3.33 mg, croscarmellose sodium-2.00 mg, talc-1.00 mg, colloidal silicon dioxide-0.50 mg, calcium stearate-0.50 mg. Shell composition: opadray white (03 A 280002) – 3.00 mg [hypromellose (hydroxypropylmethylcellulose – – 40%, microcrystalline cellulose-32%, titanium dioxide-20%, macrogol (polyethylene glycol) – 8%].

Pharmacological action

Pharmacotherapeutic group: adaptogenic agent.

ATX Code: N05CH01

Pharmacological properties

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 rate

Melatonin is rapidly absorbed in the gastrointestinal tract after oral use. In elderly patients, the rate of absorption 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, the maximum concentration (Cmax) in blood plasma and saliva is reached after 20 minutes and 60 minutes, respectively. The time to reach the maximum concentration (TMAX) in the blood serum is 60 minutes (normal range is 20-90 minutes). After taking 3-6 mg of melatonin, the Cmax 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, α1-acid glycoprotein, and high-density lipoproteins. The volume of distribution 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 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 half-life (T 1/2) 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 Cmax were obtained in elderly patients, which reflects a reduced melatonin metabolism in this group of patients.

Patients with impaired renal function

Melatonin accumulation was not observed during long-term treatment. These data are consistent with the short T 1/2 of melatonin in humans.

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

For sleep disorders, including those caused by a violation of the “sleep-wake” rhythm, such as desynchronosis (sudden change of time zones).

Use during pregnancy and lactation

The drug Velson® is contraindicated for use during pregnancy and lactation.

Contraindications

Velson® should be used with caution in patients with varying degrees of renal insufficiency.

Side effects

Classification of adverse reactions by organ and system, indicating the frequency of their occurrence: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (Infectious and parasitic diseases:  rarely – herpes zoster. Disorders of the blood and lymphatic system:  rarely-leukopenia, thrombocytopenia. Immune system disorders:  frequency unknown-hypersensitivity reactions. Metabolic and nutritional disorders:  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. Visual disturbances:  rarely-decreased visual acuity, blurred vision, increased lacrimation. Hearing disorders and labyrinth disorders:  rarely-vertigo, positional vertigo. Cardiac disorders:  rarely-angina pectoris of tension, palpitation. Vascular disorders:  infrequently-arterial hypertension; rarely-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 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. Kidney and urinary tract disorders:  infrequently-glucosuria, proteinuria; rarely-polyuria, hematuria, nocturia. Disorders of the genitals and mammary glands:  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-increased activity of “liver” transaminases, deviation from the norm of blood electrolyte content, deviation from the norm of laboratory test results. If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Pharmacokinetic interaction

Melatonin is known to induce the CYP3A isoenzyme in vitro at concentrations significantly higher than therapeutic levels, but 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 medications.

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.

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

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

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

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

Smoking can reduce the concentration of melatonin by inducing the CYP1A2 isoenzyme.

Caution should be exercised in patients taking estrogens (e. g., contraceptives or hormone replacement therapy) that increase melatonin concentrations by inhibiting their metabolism by the CYP1A1 and CYP1A2 isoenzymes.

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

Inducers of the CYP1A2 isoenzyme, such as carbamazepine and rifampicin, can reduce the plasma concentration of melatonin.

There is a wealth of data in the current literature regarding the effects of adrenergic and opioid receptor agonists/ antagonists, antidepressants, prostaglandin inhibitors, benzodiazepines, tryptophan, and alcohol on endogenous melatonin secretion. Studies of the mutual effect of these drugs on the dynamics or kinetics of melatonin have not been conducted.

Pharmacodynamic interaction

While taking melatonin, you should not drink alcohol, as 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 a clinical study, clear signs of a transient pharmacodynamic interaction between melatonin and zolpidem were observed one hour after use. Combined use may result in progressive attention, memory, and coordination disorders compared to zolpidem monotherapy.

In studies, melatonin was co-administered with thioridazine and imipramine, drugs that affect the central nervous system. No clinically significant pharmacokinetic interaction was observed in any of the cases. However, concomitant use with melatonin resulted in an increased sense of calm and difficulty in performing certain tasks compared to imipramine monotherapy, as well as an increased feeling of” blurring in the head ” compared to thioridazine monotherapy.

How to take, course of use and dosage

Inside, with a sufficient amount of liquid. For sleep disorders: 3 mg 1 time a day for 30-40 minutes before bedtime. When desynchronizing as an adaptogen when changing time zones: 1 day before the flight and in the next 2-5 days,3 mg for 30-40 minutes before bedtime. The maximum daily dose is 6 mg. Elderly patients melatonin metabolism decreases with age, 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. Patients with impaired renal function The effect of varying degrees of renal failure on the pharmacokinetics of melatonin has 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.

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 when melatonin was administered at doses of 3000-6600 mg for several weeks. When using very high doses of melatonin (up to 1 g), involuntary loss of consciousness was observed. Symptoms: in case of overdose, drowsiness may develop. Treatment: gastric lavage, activated charcoal, symptomatic therapy. Clearance of the Active ingredient is expected within 12 hours after oral use.

Special instructions

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

It is necessary to inform women who want to get pregnant about the presence of a weak contraceptive effect of the drug.

There are no clinical data on the use of melatonin in patients with autoimmune diseases, and therefore, the use in this category of patients is not recommended.

Influence on the ability to drive vehicles and mechanisms

The drug Velson® causes drowsiness, therefore, during the treatment period, you should refrain from driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 4 years. Do not use after the expiration date indicated on the package.

Active ingredient

Melatonin

Dosage form

Tablets

Purpose

For adults

Indications

Insomnia