Description overdue on 04/10/2014

• Composition
• Product form
• Pharmacological action
• Pharmacodynamics and pharmacokinetics
• Indications
• Contraindications
• Side effects
• Instructions on Tsirkadin (method and dosage)
• Overdose
• Cooperation
• Terms of sale
• Storage conditions
• Shelf life
• Analogs
• Reviews
• Price, where to buy

Composition

The composition of one tablet of sleeping pills include 2 mg Melatonin ; to auxiliary substances include a copolymer of methyl methacrylate, 40 mg trimetilammonioetilmetakrilata chloride, 40 mg of calcium hydrogen phosphate dihydrate, 80 mg of lactose monohydrate, 2 mg silica and 4 mg of talc, and 2 mg of magnesium stearate.

Product form

The drug comes in tablet form, which are white or almost white and round, bi-convex shape.
21 Tablets packaged into blisters thing, which in turn are placed into cardboard boxes with instructions to Tsirkadin.

Pharmacological action

Melatonin - a synthetic analogue of a hormone secreted by the pineal gland, and has a chemical structure close to serotonin . Physiological conditions promote secretion Melatonin Which increases immediately with the onset of dark period. His maximum secretion reaches approximately 2 to 4 o'clock in the morning, and a decrease occurs in the second half of the night. It is known that melatonin   able to control circadian rhythms and take day-night cycle. Melatonin   It has a strong hypnotic effect and contributes to the rapid fall asleep.

This effect is achieved due to the fact that melatonin   It affects receptors MT1, MT2 and overcurrent, and these receptors play an important role in the regulation of circadian rhythms. It is proved that with age, the content of this substance in the body is greatly reduced, so Tsirkadin is very popular among the older generation (over 55) and people who suffer from primary insomnia .

When receiving 2 mg per day Tsirkadina afternoon patients since the first days of receiving notice that the increased duration of sleep, and sleep quality improved. Many patients also say that taking the drug at a constant improvement is not just a dream, but the activity during waking and there is no deterioration of psychomotor reactions throughout the day.

Pharmacodynamics and pharmacokinetics

Absorption

At reception Melatonin inside it is determined that the substance in adults quickly and without any problems absorbed in the intestine, but in the elderly the rate of absorption of the drug can be reduced by 40-50%.

If the dosage range at reception Melatonin   is from 2 to 8 mg, the kinetic parameters of the linear character not lose momentum. Tsirkadina Bioavailability is about 15%. Note that during the studies noted a significant effect of the so-called "first pass" metabolism of the primary evaluation in which 80-85%. TCmax fixed at around 3:00. It is also noted that the meal may have a strong impact on the absorption of Melatonin And at Cmax plasma levels. Simultaneous food intake and absorption of tablets Tsirkadina Melatonin   It slows down and this can lead not only to a relatively late TCmax, but a lower Cmax.

Distribution of

During in vitro studies, it was determined that the connection of the active substance to plasma proteins reaches 60%. The strongest link Melatonin   occurs with albumin, HDL (high density lipoprotein), and alpha 1-acid glycoprotein.

It is proved that long-term treatment drug accumulation occurs. This is due to the fact that T1 / 2 Melatonin   a person is very short. After 1 and 3 weeks of continuous treatment with this Hypnotics 2 hours after administration of the tablet (about 23:00) was conducted taking blood as a result of which its concentration was determined. She was 431 ± 83.1 pg.

Metabolism

In experimental studies it has been suggested that the process of metabolism Melatonin isozymes contribute to such as CYP1A1, CYP1A2, and CYP2C19. The major metabolite Melatonin   It is inactive 6-sulfatoxymelatonin. Presistemnomu metabolism   in the liver, and excretion of total metabolite ends approximately 12 hours after receiving Tsirkadina.

Withdrawal

T1 / 2 Tsirkadina reaches 3-3, 5:00. When Withdrawal major role played by the kidneys (89% as conjugates of 6-glucuronide and sulfate gidroksimelatonina). The rest of the Tsirkadina derived from the human body in an unmodified form.

Pharmacokinetics in special clinical situations

Please note that the Cmax of the drug in women may increase 3-4 times compared with the values ​​enshrined in men.

Due to the fact that the process of metabolism   in older patients (55-68 years); greatly slows with age, the AUC and Cmax values ​​have higher (AUC can reach 5000 pg × h / ml and Smah- 1200 pg / ml).

Since the liver - a main body which is involved in the metabolism   Tsirkadina, the serious liver disease can cause a major increase in the concentration of Melatonin   (endogenous). It is noted that its maximum concentration Melatonin   plasma levels achieved during the day and in patients with liver cirrhosis should be extremely careful at this time. Also in patients with cirrhosis of the liver   It was observed a strong decrease in excretion of 6-sulphatoxymelatonin, when compared to the control group.

Indications

It is recommended to use the drug Tsirkadin:

• with short-term treatment of primary insomnia Which is characterized by low sleep quality in elderly patients (55 - 68 years).

Contraindications

Do not use the drug Tsirkadin:

• in congenital galactose intolerance ;
• in the presence of   glucose-galactose syndrome malabsorption ;
• congenital lactose deficiency ;
• at autoimmune diseases ;
• at   renal failure ;
• at hepatic insufficiency ;
• at pregnancy ;
• at   Lactation (during breastfeeding);
• at the age of 18;
• at hypersensitivity   to any component of the formulation.

Side effects

During the reception of the drug Tsirkadin patients may experience discomfort:

Cardio-vascular system :
from tides (periodic skin redness).

From the digestive system:
from abdominal pain, constipation, dry mouth, disorders and digestive disorders, vomiting, increased peristalsis, flatulence, salivary gland overproduction, halitosis .

For the skin:
from hyperhidrosis, eczema, erythema, itchy rash and itching, dry skin, nail infections, sweating at night.

CNS:
from irritability, excitability, fatigue, insomnia, abnormal dreams, migraine, psychomotor hyperactivity, dizziness, sleepiness, mood variability, aggressive behavior, agitation, tearfulness, early morning awakening, increased libido, memory impairment, reduced attention span, poor quality of sleep.

On the part of the vision:
from reduction in visual acuity, blurred vision, increased lacrimation .

On the part of the ear and labyrinth disorders:
from dizziness   a change in body position.

Laboratory findings:
from leukopenia and thrombocytopenia, hyperbilirubinemia, hypertriglyceridemia, elevated liver enzymes, changes in laboratory parameters of liver function .

Other:
from fatigue, weight gain, muscle cramps, neck pain, priapism, fatigue, shingles, swelling .

Instructions on Tsirkadin (method and dosage)

Tsirkadin drug is taken orally 1 tablet prolonged action, which contains 2 mg Melatonin . The instructions for use Tsirkadina indicated that it is recommended to take the drug in the afternoon after a meal. The best course of treatment according to hypnotic is 3 weeks.

Overdose

Today has not been a single case of an overdose of a drug Tsirkadin. During the research group of subjects Tsirkadin applied at a dose of 5 mg per day for about 12 months. As a result, none of the subjects showed no changes and serious side effects. It is proved that the application of opiates Tsirkadin a daily dose in the range of 200-300 mg did not cause any clinically significant side effects.

Possible reaction of an overdose may be the development of a strong sleepiness But since the clearance of the active substance varies within 12 hours, the symptom will completely disappear within 10-12 hours after administration of hypnotic inside. Special treatment of overdose is not required.

Cooperation

Pharmacokinetic interactions

It is proved that in the employment drug Tsirkadina at concentrations that are significantly higher than the therapeutic dose, melatonin   is able to induce CYP3A in vitro. To date, experts have not yet identified the clinical significance of this fact and, therefore, advise in the development of signs of induction to discuss with your doctor the issue of reducing the doses of drugs that are applied at the same time with sleeping pills.

Even at high concentrations Melatonin   is not peculiar to the induction of enzymes group CYP1A in vitro. Thus, its interaction with other active substances likely but minimal.

With special care to make this a hypnotic should be patients who are already using in their drug regimen such as fluvoxamine, as it had in the joint admission may cause a major increase in the concentration of   Melatonin . The experiment was definitely that fluvoxamine may provoke an increase in AUC of 15-17 times, and Cmax in the blood at 10-12. This effect is achieved by inhibiting the metabolism of melatonin such isoenzymes cytochrome As P450 (CYP) - CYP1A2 and CYP2C19.

Also, caution should be observed and patients who take a 5- or 8-methoxypsoralen. This substance can also provoke an increase in the concentration of melatonin as a result of inhibition of metabolism.
To increase level Melatonin   plasma may concomitant use of cimetidine (CYP2D inhibitor), which also has an inhibiting effect on the process.

Note that smoking   thereby reducing the concentration of melatonin due to the stimulation of CYP1A2.
Additionally, consult your doctor should patients who are taking Estrogens   ( Contraceptives   or hormone replacement therapy), which also cause an increase in the concentration of melatonin.

The reason for a significant increase in exposure of melatonin can be inhibitors of CYP1A2 ( quinolones ).
Reducing the concentration of active substance in the blood plasma can CYP1A2 inducers ( carbamazepine, rifampicin ).

Research on Interaction Tsirkadina inhibitors prostaglandins, benzodiazepines, agonists, antagonists , and Antidepressants . tryptophan   and ethanol   It is not carried out, but in the modern scientific literature provides many examples that relate to the impact of these substances on the secretion Melatonin .

Pharmacodynamic interactions

Experts advise during the course of treatment of a sedative to completely abandon the use of alcohol As at the joint reception greatly reduced the effectiveness of the drug.

Tsirkadin can greatly increase the sedative effect as the benzodiazepine and non-benzodiazepine hypnotic drugs. It is better to abandon a joint reception and Tsirkadina Zaleplon, Zolpidem and   Zopiclone As the combination of these drugs can cause progressive disorder such as attention, memory and coordination.

Increase the feeling of tranquility and cause serious difficulties in carrying out certain tasks can be combined Tsirkadina appointment with drugs that affect the central nervous system ( Thioridazine, imipramine ).

It should also refuse to co-administration with NSAIDs.

Terms of sale

The preparation is available in pharmacies by prescription only.

Storage conditions

Tsirkadin drug should be stored in a maximum reach of children and adolescents at a temperature not exceeding 25 ° C.

Shelf life

The drug Tsirkadin has a sufficiently large rock shelf life of 5 years.

Analogs Tsirkadina

The main drug is analogue Melaxen But also enjoyed popularity Tsirkadina analogues such as Melaxen Balance   and Melatonin .

Reviews Tsirkadine

Average rating Tsirkadina forums is 4, 6 and 5-point scale.

The advantages of the drug Visitors forums include:

• soft effect;
• the absence of after-effects;
• saving effect after the course.

The downside of the drug panellists are:

• high cost.

After analyzing the responses about Tsirkadine forums, we can conclude that most often it is used with older people to get rid of primary insomnia.

Information about the preparation Tsirkadin Wikipedia there.

Price Tsirkadina where to buy

The average retail price Tsirkadina in Ukraine is 540 UAH.

Buy medicine Tsirkadin in Moscow can be over 640 rubles.