Circadin
Circadin: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Circadine
ATX code: N05CH01
Active ingredient: melatonin (melatonin)
Manufacturer: SwissCo Services (Switzerland)
Description and photo update: 2018-21-11
Prices in pharmacies: from 696 rubles.
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Circadin is a sleeping pill.
Release form and composition
Circadin is produced in the form of prolonged-release tablets: biconvex round, almost white or white (21 pcs. In a blister, 1 blister in a cardboard box).
Composition of 1 tablet:
- active substance: melatonin - 2 mg;
- additional components: calcium hydrogen phosphate dihydrate, copolymer of methyl methacrylate trimethylammonioethyl methacrylate chloride and ethyl acrylate, colloidal silicon dioxide, lactose monohydrate, magnesium stearate, talc.
Pharmacological properties
Pharmacodynamics
Melatonin is a synthetic analogue of the hormone produced by the pineal gland, which is similar in chemical structure to serotonin. The secretion of melatonin in physiological conditions increases after a short period of time after the onset of the dark period of the day, reaches a maximum at approximately 2-4 am and decreases during the second half of the night. It is assumed that the substance is involved in the regulation of circadian rhythms and the perception of the day-night cycle. Melatonin exhibits a strong hypnotic effect and allows you to fall asleep quickly.
It is believed that the effect of this substance on the MT1, MT2 and MTZ receptors leads to an increase in the hypnotic effect, since these receptors (mainly MT1 and MT2) control circadian rhythms and sleep. Since endogenous melatonin levels decline with age, Circadin can significantly improve sleep quality in the setting of primary insomnia, especially in those over the age of 55.
Circadin in a daily dose of 2 mg, taken in the evening hours, helps to increase the duration and improve the quality of sleep. In this case, patients note an increase in activity during wakefulness in the absence of deterioration of psychomotor reactions throughout the day.
Pharmacokinetics
After oral administration in adults, the active substance is rapidly absorbed in the gastrointestinal tract (gastrointestinal tract); in elderly patients, absorption may be reduced by 50%. The bioavailability of melatonin is 15%. When the agent is used in the dose range of 2–8 mg, the kinetic parameters retain the linear nature of the dynamics. A pronounced effect of the first passage through the liver is observed, the value of primary metabolism according to research data is 85%.
The period of reaching the maximum concentration (T max) when using the product after meals is 3 hours. Food intake affects the absorption and maximum concentration (Cmax) of melatonin in plasma when used at a dose of 2 mg. Against the background of concomitant food intake, the absorption of the substance decreases, which causes a later T max (3 hours compared to 0.75 hours) and a lower C max (1020 pg / ml compared to 1176 pg / ml).
In the course of in vitro studies, it was found that melatonin binds to plasma proteins by 60% - mainly with alpha1-acid glycoprotein, albumin and high density lipoproteins. On the background of long-term treatment, its cumulation was not observed.
Based on the data of experimental studies, it can be assumed that the metabolism of melatonin is carried out with the participation of isoenzymes CYP1A1, CYP1A2 and, probably, also CYP2C19 of the cytochrome P450 system. The main metabolite of the substance is 6-sulfatoxymelatonin, which is inactive. The pre-systemic metabolism takes place in the liver, the elimination of the metabolite is completed approximately 12 hours after oral administration.
The half-life (T ½) of a substance can be 3.5-4 hours. Excretion is carried out by the kidneys, while 89% of the dose received is excreted in the form of sulfate and conjugates of glucuronide 6-hydroxymelatonin and 2% - unchanged.
In women, the C max of melatonin was observed 3-4 times higher than in men. There was also a five-fold variability in C max between different persons of the same sex. However, no other differences in clinically significant parameters of pharmacodynamics in women and men, except for differences in Cmax of a substance in blood plasma, were found.
Indications for use
According to the instructions, Circadin is recommended for short-term treatment of primary insomnia, characterized by poor sleep quality in patients over the age of 55 (as a monotherapy drug).
Contraindications
- autoimmune diseases;
- liver dysfunction;
- congenital lactase deficiency, glucose-galactose malabsorption syndrome, congenital galactose intolerance;
- age up to 18 years;
- hypersensitivity to any of the constituents of Circadine.
Instructions for the use of Circadine: method and dosage
Circadin is taken by mouth.
The recommended dosage is 1 tablet (2 mg) once a day in the evening, after meals, 1-2 hours before bedtime. In order to support the sustained release of melatonin, the tablet must be swallowed whole. Do not chew or crush the tablets to make swallowing easier.
The duration of therapy is no more than 13 weeks.
Side effects
- immune system: with an unknown frequency - hypersensitivity reactions (including edema of the tongue, edema of the oral mucosa, Quincke's edema);
- hematopoietic system: rarely - thrombocytopenia, leukopenia;
- parasitic and infectious diseases: rarely - herpes zoster;
- metabolism: rarely - hyponatremia, hypokalemia, hypertriglyceridemia;
- nervous system: infrequently - dizziness, lethargy, headache, migraine, drowsiness, psychomotor hyperactivity; rarely - poor sleep quality, impaired concentration, memory impairment, dreamy (oneiroid) confusion, paresthesia, restless legs syndrome, fainting;
- psyche: infrequently - anxiety, restlessness, nervousness, irritability, unusual dreams, insomnia, nightmares; rarely - early morning awakening, mood changes, tearfulness, low mood, stress symptoms, agitation, aggression, increased libido, depression, disorientation;
- digestive system: infrequently - dry mouth, ulcerative stomatitis, abdominal pain (including in the upper abdomen), nausea, dyspepsia, hyperbilirubinemia; rarely - bloating, bad breath, salivary hypersecretion, ulcerative glossitis, blisters on the oral mucosa, abdominal discomfort, abnormal intestinal murmurs, indigestion, vomiting, gastrointestinal disturbance / disorder, gastritis, gastroesophageal reflux disease;
- cardiovascular system: infrequently - arterial hypertension; rarely - hot flashes, palpitations, exertional angina;
- labyrinth disorders and the organ of hearing: vertigo, positional vertigo;
- organ of vision: rarely - increased lacrimation, blurred vision, decreased visual acuity;
- musculoskeletal system: infrequently - pain in the limb; rarely - neck pain, muscle spasm, night cramps, arthritis;
- skin and subcutaneous tissues: infrequently - night sweating, dry skin, rash, itching (including generalized), dermatitis; rarely - erythema, nail lesions, hand dermatitis, eczema, itchy / generalized rash, psoriasis;
- reproductive system: infrequently - menopausal symptoms; rarely - prostatitis, priapism; with an unknown frequency - galactorrhea;
- general disorders: infrequently - chest pain, asthenia; rarely - thirst, pain, fatigue;
- urinary system: infrequently - proteinuria, glucosuria; rarely - hematuria, polyuria, nocturia;
- laboratory and instrumental data: infrequently - an increase in body weight, a deviation from the norm of laboratory parameters of liver function; rarely - deviation from the norm in the level of electrolytes in the blood, deviations from the norm of these laboratory tests, increased activity of hepatic transaminases.
Overdose
Overdose cases of Circadine have not been recorded. In clinical trials that lasted more than 12 months, the drug was taken at a dosage of 5 mg per day; no significant changes in the nature of the registered undesirable effects were noted.
The literature contains information on the use of melatonin in daily doses up to 300 mg without the development of clinically significant disorders. It is assumed that in case of an overdose of the drug, drowsiness may occur. After oral administration, elimination of the active substance from the body can probably proceed for 12 hours. No special therapy is required.
special instructions
Against the background of taking Circadine, drowsiness may develop, as a result of which the drug must be used with caution in cases where the appearance of this side effect may pose a threat to the patient's safety.
The results of clinical studies on the use of Circadine in patients with autoimmune diseases have not been provided, therefore, it is not recommended to prescribe the drug to patients from this risk group.
Influence on the ability to drive vehicles and complex mechanisms
During the period of using the product, due to the risk of drowsiness, it is required to refrain from driving and performing other potentially dangerous types of work.
Application during pregnancy and lactation
According to preclinical studies, the adverse effects of melatonin on pregnancy, childbirth, fetal development, or postnatal development have not been established. However, due to the lack of clinical data on the effects of Circadine on pregnancy, its use in pregnant women and women planning to become pregnant is not recommended.
Since endogenous melatonin is found in human milk, it is assumed that exogenous melatonin is also able to pass into human milk. In animal studies, the transfer of melatonin through the placenta or breast milk from mother to fetus has been established. As a result, it is not recommended to use Circadin during breastfeeding.
Pediatric use
Circadine is contraindicated in children and adolescents under 18 years of age due to the lack of information confirming the safety and efficacy of its use in patients of this age category.
With impaired renal function
With a long course of therapy, the accumulation of the drug was not revealed, which is associated with its short half-life from the body. But since the effect of impaired renal function (of any severity) on the pharmacokinetics of the drug has not been studied, patients with renal insufficiency are advised to take Circadin with caution.
For violations of liver function
Due to the fact that the metabolism of the drug is carried out mainly in the liver, the presence of its diseases leads to an increase in the level of endogenous melatonin. In patients with liver cirrhosis, a significant increase in the plasma concentration of melatonin in the daytime was found, as well as, when compared with the control group, a significant decrease in the excretion of 6-sulfatoxymelatonin.
Circadine is contraindicated in patients with hepatic impairment.
Use in the elderly
It was found that the process of biotransformation of a substance slows down with age, as a result of which, in the elderly, C max and the area under the concentration-time curve (AUC) of melatonin are higher than in adult patients:
- patients 18–45 years old: C max - 500 pg / ml, AUC - 3000 pg × h / ml;
- patients 55–69 years old: C max - 1200 pg / ml, AUC - 5000 pg × h / ml.
Drug interactions
Pharmacokinetic interaction of melatonin with other active substances:
- fluvoxamine: the concentration of melatonin increases (C max increases by 12, AUC - by 17 times) due to the suppression of its metabolism by cytochrome P450 (CYP) isoenzymes CYP2C19 and CYP1A2 (it is recommended to avoid the combined use of these funds);
- cimetidine (a CYP2D inhibitor), 5- and 8-methoxypsoralen, estrogens (including hormone replacement therapy and contraceptives): the level of melatonin in the blood plasma increases as a result of inhibition of its metabolism (with these combinations, caution should be exercised);
- quinolones (CYP1A2 inhibitors): increased exposure to melatonin;
- rifampicin, carbamazepine (inducers of CYP1A2): the plasma concentration of melatonin in the blood decreases.
Smoking can lead to a decrease in melatonin concentration (through stimulation of CYP1A2).
Currently, there are many published data related to the effect on the production of endogenous melatonin of the following substances: agonists / antagonists of opioid and adrenergic receptors, prostaglandin inhibitors, antidepressants, benzodiazepines, tryptophan and ethanol. Studies of the interaction of these substances on the kinetics and dynamics of Circadine have not been carried out.
Pharmacodynamic interaction of melatonin with other substances:
- benzodiazepine and non-benzodiazepine hypnotics (zolpidem, zaleplon, zopiclone): the sedative effect of these substances is enhanced; when combined with zolpidem, a progressive disorder of memory, attention and coordination may occur (when compared with monotherapy with this substance);
- ethanol: the effect of Circadine is weakened; during the period of treatment, you should refrain from drinking alcohol;
- imipramine, thioridazine (drugs affecting the central nervous system): no clinically significant pharmacokinetic interaction was found, however, against the background of this combination, an aggravation of the feeling of "clouding in the head" was noted when compared with the action of thioridazine alone, as well as difficulty in performing some tasks and an increase in feelings of calm when compared with imipramine monotherapy;
- non-steroidal anti-inflammatory drugs: this combination is not recommended.
Analogs
Analogs of Circadine are: Melaxen Balance, Kakspal Neo, Melarithm, Melaxen, Mellarena, Sonnovan.
Terms and conditions of storage
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
The shelf life is 5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Circadine
There are relatively few reviews about Circadine, and they are mostly positive. Patients who took the drug (mostly elderly people suffering from primary insomnia) describe it as an effective hypnotic with a mild effect. The drug, according to reviews, causing gradually increasing drowsiness, accelerates falling asleep, improves sleep quality, reduces the number of awakenings at night, and the next day after taking it helps to increase mood and increase activity, without leading to the appearance of lethargy.
Almost all patients attribute its high cost to the disadvantages of Circadine; there are no reports of the occurrence of undesirable reactions.
Price for Circadin in pharmacies
In pharmacies, the price of Circadin for a pack containing 21 tablets can vary from 710 to 800 rubles.
Circadin: prices in online pharmacies
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Drug name Price Pharmacy |
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Circadin tablets prolonged action 2mg 21 pcs. 696 r Buy |
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Circadin 2 mg extended-release tablets 21 pcs. 696 r Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
