Agalates

General characteristics. Structure:

Active agent каберголин 0,5 mg;
excipients: lactose, L-leucine, magnesium stearate (E572)

Description: white flat oval tablets with a facet and risky on one party, with an engraving "0.5" on the one hand from risks and "CBG" - with another.

Pharmacological properties:

Pharmacodynamics. Kabergolin - synthetic alkaloid of an ergot, derivative an ergolina, the agonist of dopamine of long action inhibiting prolactin secretion. The mechanism of action of a kabergolin includes stimulation of the central dofaminergichesky receptors of a hypothalamus. In doses higher, than are required for prolactin secretion suppression, drug causes the central dofaminergichesky effect caused by stimulation dopamine D2 receptors. Effect of drug has dozozavisimy character. Decrease in content of prolactin in blood is usually observed in 3 h and remains within 2-3 weeks in this connection for suppression of secretion of milk reception of one dose of drug suffices usually. At treatment of a giperprolaktinemiya the content of prolactin in blood is normalized in 2-4 weeks of use of drug in an effective dose. Normal level of prolactin can remain within several months after drug withdrawal.
Kabergolin possesses highly the selection action and does not influence basal secretion of other hormones of a hypophysis and cortisol. The only pharmakodinamichesky effect which is not connected with therapeutic action is the lowering of arterial pressure (ABP). The maximum hypotensive effect develops usually in 6 hours after a single dose of drug; extent of decrease in the ABP and frequency of development of hypotensive effect of a dozozavisima.

Pharmacokinetics.
Absorption
After intake каберголин it is quickly soaked up from the digestive tract (DT). The maximum concentration in a blood plasma is reached in 0,5-4 h. Food does not exert impact on absorption or distribution of a kabergolin.
Distribution
Binding of a kabergolin (at concentration of 0,1-10 ng/ml) with proteins of plasma makes 41-42%.
Metabolism
In urine metabolites of a kabergolin are found: @-allyl-8r-carboxy-ergolin in number of 4-6% of the accepted dose, and also three other metabolites with the general content less than 3%.
All metabolites in much smaller degree (in comparison with kabergoliny) inhibit prolactin secretion.
Removal

Kabergolin possesses a long elimination half-life: Т½ made 63-68 h at healthy volunteers and 79-115 h is at patients with a giperprolaktinemiya.

At such elimination half-life the equilibrium state is reached in 4 weeks. In urine and Calais 18% and 72% of the accepted dose are revealed, respectively. The maintenance of not changed kabergolin in urine makes 2-3%.
The pharmacokinetics has linear character to a dose of 7 mg/days.
Preclinical data on safety
As shown in preclinical trials, каберголин it is safe in the considerable range of doses and has no teratogenic, mutagen or cancerogenic effect.

Indications to use:

- Suppression of a physiological puerperal lactation (only on medical indications).
- Suppression of already established lactation (only on medical indications).
- The disturbances connected with a giperprolaktinemiya (including such functional frustration as an amenorrhea, an oligomenorrhea, anovulation, a galactorrhoea).
- Prolaktinsekretiruyushchy adenomas of a hypophysis (micro and makroprolaktinoma). Idiopathic giperprolaktinemiya.

Route of administration and doses:

Kabergolin accept inside preferably during food.
Adults
Treatment of the disturbances connected with a giperprolaktinemiya
The recommended initial dose - 0,5 mg a week in one or two receptions (for example, on Monday and Thursday). The dosage increases gradually, usually by 0,5 mg/week at an interval of 1 month before achievement of optimum therapeutic effect. A maintenance dose - 1 mg/week (0,25 - 2 mg/week); in some cases at patients with a giperprolaktinemiya to 4,5 mg/week.
When using drug in doses it is higher than 1 mg/week, it is recommended to divide a week dose into 2 or more receptions depending on portability.
For suppression of a lactation: the recommended dose - 1 mg once during the first 24 h after the child's birth.
Use for patients with abnormal liver functions or kidneys
Information is provided in the sections "contraindications" and "special instructions".
Use for elderly
Considering indications to use, experience of use of a kabergolin for elderly patients is limited. The available data confirm lack of specific risk.

Features of use:

To open a bottle, at first press a cover, then turn it, as shown in a cover. Not to take and not to use the capsule with silica gel from a bottle inside.
Data on efficiency and safety of a kabergolin at patients with abnormal liver functions or kidneys are limited. The pharmacokinetics of a kabergolin significantly does not change at a moderate or heavy renal failure. It is not studied at patients with an end-stage of a renal failure or at a hemodialysis. Therefore at such patients drug should be used with care. Influence of alcohol on the general portability of a kabergolin is not established.
Kabergolin can cause symptomatic arterial hypotension, especially at joint reception with medicines, the reducing ABP. It is regularly recommended to measure the ABP in the first 3-4 days after an initiation of treatment.
Can be connected by Giperprolaktinemiya in combination with an amenorrhea and infertility with hypophysis tumors therefore prior to treatment kabergoliny it is necessary to find out the giperprolaktinemiya reason.
It is recommended to check the content of prolactin in blood serum every month as after achievement of the effective therapeutic mode the normal level of prolactin remains within 2-4 weeks.
After drug withdrawal the giperprolaktinemiya usually arises again. However at some patients permanent decrease in concentration of prolactin within several months is observed.
Kabergolin recovers an ovulation and fertility at women with a giperprolaktinemichesky hypogonadism. As pregnancy can occur before resuming of periods, it is recommended to carry out tests for pregnancy to the amenorrhea period, and after recovery of a menstrual cycle - in all cases of their delay more than for 3 days. Women who do not want to become pregnant are recommended to apply effective non-hormonal contraceptives during treatment kabergoliny and after its termination. The women planning pregnancy are recommended to conceive not earlier than in 1 month after drug withdrawal. At a number of patients the ovulatory cycle remained within 6 months after drug withdrawal.
At prolonged use of a kabergolin, as well as other derivatives of an ergot, there can be pleural exudates / pulmonary fibrosis and defeats of valves of heart. Sometimes these phenomena were noted at the patients who were earlier receiving dopamine agonists from group of an ergot. Cancellation of a kabergolin in case of development of the specified pathology led to improvement of signs and symptoms.
At emergence of new clinical symptoms from respiratory system the roentgenoscopy of lungs is recommended. At patients with pleural exudates / fibrosis noted increase in the blood sedimentation rate (BSR), in this regard at the raised SOE without strong clinical signs it is also necessary to conduct radiological examination. When using a kabergolin drowsiness and episodes of sudden backfilling, especially at patients with Parkinson's disease can appear. The sudden backfilling during daily activity developing in certain cases without harbingers is noted seldom.
Drug contains lactose. Patients with rare hereditary forms of intolerance of a galactose, deficit of lactase or at disturbance of absorption of glucose galactose should not accept каберголин.
And to control of mechanisms Kabergolin reduces influence on ability to driving of the car the ABP that can break speed of response at some patients. This needs to be considered in the situations demanding concentration of attention such as driving of the car or control of mechanisms. Patients should be informed on need of respect for care during the driving of the car or control of mechanisms.
Patients at whom drowsiness and/or episodes of sudden backfilling at treatment kabergoliny were already observed have to refuse driving of the car or another, connected with risk activity when disturbances of speed of response can represent for them and other people risk of serious injuries or death. Decrease in a dosage or drug withdrawal is sometimes reasonable.

Side effects:

Undesirable effects usually depend on a dose and decrease at its gradual decrease.
Suppression of a lactation: the undesirable phenomena develop approximately at 14% of patients. The most frequent: decrease in the ABP (12%), dizziness (6%) and headache (5%). At prolonged treatment the frequency of these effects increases up to 70%.
Frequent (more than 1/100, less than 1/10)
From a nervous system: depression, headache and dizziness, paresthesias, feeling of fatigue, drowsiness.
From cardiovascular system (CCC): lowered by the ABP, increase of heartbeat and a stethalgia.
From a GIT: nausea, vomiting, gastralgia, gastritises, locks. From skin and hypodermic cellulose: dermahemia of the person.
Infrequent (more than 1/1000, less than 1/100)
From sight: hemianopsia.
From CCC: nasal bleedings.
Rare (more than 1/10000, less than 1/1000)
Allergic reactions: skin rash.
From CCC: faints.
From a musculoskeletal system: spasms in fingers and gastrocnemius muscles.
From a GIT: abnormal liver function.
Decrease in the ABP (systolic more than on 20 mm of mercury. and diastolic more than on 10 mm of mercury.) it is noted in 3-4 days after a single dose of a kabergolin in a dose 1 mg at women after the delivery.
The undesirable phenomena usually develop within the first two weeks, then decrease or disappear. Drug withdrawal in connection with side effect was required in 3% of cases.
Post-marketing observation
Treatment kabergoliny was followed by excess drowsiness in the afternoon and episodes of sudden backfilling, especially at patients with Parkinson's disease. Patients have messages on increase in a libido with Parkinson's disease at treatment by dopamine agonists, including каберголин, especially in high doses. Also at treatment kabergoliny pleural exudates, pleural fibrosis, a valvulopatiya, respiratory disturbances are noted (including respiratory insufficiency).

Interaction with other medicines:

Influence of makrolidny antibiotics on content in plasma of a kabergolin at their sharing is not studied. Considering a possibility of increase in level of a kabergolin, drug is not recommended to be used in combination with macroleads.
The mechanism of action of a kabergolin is connected with direct stimulation of dopamine receptors therefore it should not be applied in a combination with antagonists of dopamine receptors (a fenotiazina, phenyl propyl ketones, thioxanthenes, Metoclopramidum).
There is no information about interactions of a kabergolin with other alkaloids of an ergot, nevertheless, prolonged use of such combination is not recommended.
Considering a pharmacodynamics of a kabergolin (hypotensive action), it is necessary to take into account interaction with medicines, the reducing ABP.
In clinical trials at patients with Parkinson's disease of pharmacokinetic interaction with a levodopa or selegiliny it is not revealed. Pharmacokinetic interactions with other drugs on the basis of the available information on metabolism of a kabergolin cannot be predicted.

Contraindications:

- Puerperal or uncontrollable arterial hypertension.
- Hypersensitivity to a kabergolin, other alkaloids of an ergot or any component of drug.
- Heavy abnormal liver functions.
- The undesirable phenomena from lungs, such as the pleurisy or fibroses (including in the anamnesis) connected with reception of agonists of dopamine.
- Psychoses (including in the anamnesis) or risk of their development.
- Pregnancy and the preeclampsia and an eclampsia which developed on its background.
- Breastfeeding.
- Efficiency and safety of use of a kabergolin for children up to 16 years is not studied.

With care: at patients with cardiovascular diseases, arterial hypotension, Reynaud's syndrome, round ulcers or gastrointestinal bleedings, at patients with an end-stage of a renal failure or being on a hemodialysis, at elderly patients.

Use at pregnancy and a lactation
Drug is contraindicated at pregnancy and a lactation.
Before administration of drug it is necessary to exclude pregnancy. It is recommended to avoid approach of pregnancy within not less than 1 month after the treatment termination. There are limited data on administration of drug during pregnancy received within the first 8 weeks after conception. Use of a kabergolin was not followed by increase in risk of abortions, premature births, multiple pregnancies or inborn disturbances. Other data are not obtained so far.
In researches on animals of direct or indirect adverse impact of a kabergolin on the course of pregnancy, development of an embryo/fruit, childbirth or post-natal development it is not revealed.
Considering limited experience of use of a kabergolin at pregnancy, at its planning drug should be cancelled. In case of approach of pregnancy during treatment каберголин immediately cancel. Due to a possibility of expansion of earlier existing tumor it is necessary to monitorirovat signs of increase in a hypophysis at pregnant women.
As каберголин suppresses a lactation, mothers who prefer breastfeeding of babies should not appoint drug. During treatment kabergoliny it is necessary to stop breastfeeding.

Overdose:

There are no data on overdose of drug. Proceeding from results of experiments on animals, it is possible to expect emergence of the symptoms caused by hyper stimulation of dopamine receptors: nausea, vomiting, decrease in the ABP, disturbance consciousnesses/psychoses or hallucinations. If it is shown, it is necessary to take measures for recovery of the ABP. Besides, at the expressed symptomatology from TsNS (hallucination) use of antagonists of dopamine can be required

Storage conditions:

At a temperature not above 30 °C in the dry place in densely closed original bottle. To store in the place, unavailable to children. Period of validity 2 years. Not to use after a period of validity

Issue conditions:

According to the recipe

Packaging:

Tablets of 0,5 mg.
On 2 and 8 tablets in bottles of dark glass (type III) with the neck sealed by a membrane from aluminum foil and films (polyether/polyethylene) with a cover from PEVP supplied with system against opening by children, the bottle contains the capsule of a cylindrical form with silica gel and a sealant from cotton wool.
1 bottle with the application instruction in a cardboard pack.