Достинекс®

General characteristics. Structure:

International unlicensed name: каберголин; white flat oblong tablets with the marking "Р" and "U" divided by a notch on the one hand and "700" with short notches from above and from below numbers – on the other hand.

Active agent: каберголин 0,5 mg; excipients: leucine, lactose anhydrous.

Pharmacological properties:

Pharmacodynamics. Kabergolin is to dofaminergichesky derivatives of an ergolin and is characterized by the expressed and long prolaktinsnizhayushchy action caused by direct stimulation of D2 - dopamine receptors of lactotropic cells of a hypophysis. Besides, at reception of higher doses in comparison with those for decrease in level of prolactin in serum, каберголин has the central dofaminergichesky effect owing to stimulation of D2 receptors.

Decrease in concentration of prolactin in a blood plasma is noted during 3 h after administration of drug and remains within 7-28 days at healthy volunteers and patients with a giperprolaktinemiya, and to 14-21 days - at women in a puerperal period.

Kabergolin possesses strictly selective effect, does not exert impact on basal secretion of other hormones of a hypophysis and cortisol. Prolaktinsnizhayushchy effect of drug is dozozavisimy as concerning expressiveness, and action duration.

Only the lowering of arterial pressure (ABP) belongs to the pharmakodinamichesky influences of a kabergolin which are not connected with therapeutic effect. At a single dose of drug the maximum hypotensive effect is noted within the first 6 hours and is dozozavisimy.

Pharmacokinetics. Kabergolin is quickly soaked up from digestive tract, the maximum concentration in plasma is reached in 0,5 - 4 hours, communication with proteins of a blood plasma makes 41 – 42%. The elimination half-life of a kabergolin estimated on removal speed with urine makes 63 - 68 hours at healthy volunteers and 79 - 115 hours at patients with a giperprolaktinemiya. Owing to a long elimination half-life the condition of equilibrium concentration is reached in 4 weeks. In 10 days after administration of drug in urine and Calais respectively about 18% and 72% of the accepted dose are found, and the share of not changed drug in urine makes 2 – 3%. The key product of metabolism of a kabergolin identified in urine is 6-аллил-8β-карбокси-эрголин in concentration to 4 - 6% of the accepted dose. Content in urine of 3 additional metabolites does not exceed 3% of the accepted dose. It is established that products of metabolism have considerably smaller effect concerning suppression of secretion of prolactin in comparison with kabergoliny.

Meal does not influence absorption and distribution of a kabergolin.

Indications to use:

Prevention of a physiological lactation after the delivery;
Suppression of already established puerperal lactation;
Treatment of the disturbances connected with a giperprolaktinemiya including an amenorrhea, an oligomenorrhea, anovulation, a galactorrhoea;
Prolaktinsekretiruyushchy adenomas of a hypophysis (micro - and makroprolaktinoma); idiopathic giperprolaktinemiya; a syndrome of an "empty" Turkish saddle in combination with a giperprolaktinemiya.

Route of administration and doses:

Inside, during food.

Prevention of a lactation: 1 mg once (2 tablets on 0,5 mg), in the first day after the delivery.

Suppression of the established lactation: on 0,25 mg (1/2 tablets) two times a day every 12 hours within two days (the general dose is equal to 1 mg). For the purpose of decrease in risk  of orthostatic hypotension at the nursing mothers, the single dose of Dostineksa® should not exceed 0,25 mg.

Treatment of the disturbances connected with a giperprolaktinemiya: the recommended initial dose makes 0,5 mg a week in one step (1 tablet of 0,5 mg) or in two steps (on 1/2 tablets of 0,5 mg, for example, on Monday and Thursday). Increase in a week dose has to be carried out gradually – on 0,5 mg with a monthly interval before achievement of optimum therapeutic effect. The therapeutic dose usually makes 1 mg a week, but can fluctuate from 0,25 to 2 mg a week. The maximum dose for patients with a giperprolaktinemiya should not exceed 4,5 mg a week.

Depending on portability, the week dose can be accepted once or to divide into 2 and more inclusion in week. Division of a week dose into several receptions is recommended at purpose of drug in a dose more than 1 mg a week.

At patients with hypersensitivity to dofaminergichesky drugs the probability of development of by-effects can be reduced, having begun therapy of Dostineksom® in lower dose (for example, on 0,25 mg once a week), with the subsequent its gradual increase up to achievement of a therapeutic dose. For improvement of portability of drug at emergence of the expressed by-effects perhaps temporary dose decline with the subsequent its more gradual increase (for example, increase by 0,25 mg a week each two weeks).

Features of use:

Before purpose of Dostineksa® for the purpose of treatment of the disturbances connected with a giperprolaktinemiya it is necessary to conduct a full research of function of a hypophysis.

At increase in a dose patients have to be under observation of the doctor for the purpose of establishment of the smallest effective dose providing therapeutic effect.

After the effective mode of dosing is picked up, it is recommended to carry out definition of concentration of prolactin regular (once a month) in blood serum. Normalization of level of prolactin is usually observed within 2-4 weeks of treatment.

After cancellation of Dostineksa® the giperprolaktinemiya recurrence is usually observed, however at some patients permanent suppression of level of prolactin within several months is noted. At most of women ovulatory cycles remain within not less than 6 months after cancellation of Dostineksa®.

Достинекс® recovers an ovulation and fertility at women with a giperprolaktinemichesky hypogonadism. As pregnancy can occur before recovery of periods, it is recommended to carry out tests for pregnancy at least once in 4 weeks during the amenorrhea period, and after recovery of periods - every time when the periods delay more, than for 3 days is noted. The women wishing to avoid pregnancy should use barrier methods of contraception during treatment of Dostineksom®, and also after drug withdrawal before repetition of anovulation. Women at whom there occurred pregnancy have to be under observation of the doctor for early detection of symptoms of increase in a hypophysis as during pregnancy increase in the sizes of already existing hypophysis tumors is possible.

Достинекс® patients should appoint in lower doses with a heavy liver failure (a class C on Child-Pugh classification) to which long therapy is shown by drug. At single use to such patients of a dose of 1 mg increase in AUC (the area under a curve "concentration / time") in comparison with healthy volunteers and patients with less expressed liver failure was noted.

As well as at use of other derivatives of an ergot, after long reception of a kabergolin at patients a pleural exudate / pleural fibrosis and a valvulopatiya were observed. In certain cases patients received the previous therapy by ergotoninovy agonists of dopamine. Therefore Dostineks® should be applied with care to patients with the available signs and/or clinical symptoms of dysfunction of heart or with such states in the anamnesis. After the termination of reception of Dostineksa® at patients with the diagnosis a pleural exudate / pleural fibrosis and a valvulopatiya improvement of symptoms was noted.

Use of a kabergolin causes drowsiness. With Parkinson's disease use of agonists of dopamine receptors can cause sudden backfilling in patients. In similar cases it is recommended to lower a dose of Dostineksa® or to stop therapy.

Researches on use of drug for patients of advanced age with the disturbances connected with a giperprolaktinemiya were not conducted. Safety and efficiency of drug at children are younger than 16 years is not established. 

Influence on ability to drive the car and other mechanisms

The patients accepting Dostineks® at whom drowsiness is observed have to be warned that they are recommended to refrain from driving of the car and from work performance (for example, with mechanisms) during which the lowered attention could create for them or the serious damages surrounding risk or death.  

Side effects:

During clinical trials using Dostineksa® for prevention of a physiological lactation (once) and for suppression of a lactation (on 0,25 mg each 12 hours within 2 days) side effects were noted by 1 mg approximately at 14% of women. At use of Dostineksa® within 6 months in the dose of 1-2 mg a week divided into 2 receptions for treatment of the disturbances connected with a giperprolaktinemiya, the frequency of by-effects made 68%. By-effects arose, generally within the first 2 weeks of therapy and in most cases disappeared in process of continuation of therapy or in several days after cancellation of Dostineksa®. By-effects usually were passing, on severity - poorly or are moderately expressed and had dozozavisimy character. At least once during therapy heavy by-effects were noted at 14% of patients; because of side effects treatment was stopped approximately at 3% of patients.

The most frequent side effects are given below:

From cordial vascular system: heartbeat; seldom - orthostatic hypotension (at prolonged use of Dostineks® usually has hypotensive effect); perhaps asymptomatic decrease in the ABP during the first 3-4 days after the delivery (systolic - more than on 20 mm hg, diastolic – more than 10 mm hg).

From a nervous system: dizziness / вертиго, headache, increased fatigue, drowsiness, depression, adynamy, paresthesias, faint.

From the alimentary system: nausea, vomiting, pains in epigastric area, an abdominal pain, a lock, gastritis, dyspepsia.

Others: a mastodynia, nasal bleeding, "inflows" of blood to face skin, a tranzitorny hemianopsia, vasospasms of fingers and a myotonia of the lower extremities (as well as other derivatives of an ergot, Dostineks® can have vasoconstrictive effect).

At long therapy using Dostineksa® the aberration of standard laboratory indicators was noted seldom; at women with an amenorrhea decrease in level of hemoglobin within the first several months after recovery of periods was observed.

In a post-market research also following side effects connected with reception of a kabergolin are registered: an alopecia, increase in activity creatinine phosphokinase in blood, a mania, диспноэ, hypostases, fibrosis, abnormal liver functions and deviations of indicators of function of a liver, hypersensitivity reaction, rash, respiratory disturbances, respiratory insufficiency, a valvulopatiya.

Interaction with other medicines:

Information on interaction of a kabergolin and other alkaloids of an ergot is absent therefore simultaneous use of these medicines during long therapy is not recommended.

As Dostineks® has therapeutic effect by direct stimulation of dopamine receptors, it is impossible to appoint it along with the drugs operating as antagonists of dopamine (fenotiazina, phenyl propyl ketones, thioxanthenes, Metoclopramidum, etc.) since they can weaken the action of Dostineksa® directed to decrease in level of prolactin.

As well as other derivatives of an ergot, it is impossible to apply along with antibiotics macroleads (for example, erythromycin) since it can lead to increase in system bioavailability of a kabergolin.

Contraindications:

- Hypersensitivity to a kabergolin or other components of drug, and also to any alkaloids of an ergot.

- Safety and efficiency of drug at children are younger than 16 years is not established. 

With care. As well as it is necessary to appoint other derivatives of an ergot, Dostineks® with care at the following states and/or diseases: 

the arterial hypertension which developed against the background of pregnancy, for example, a preeclampsia or puerperal arterial hypertension (Dostineks® is appointed only when the potential advantage of drug use considerably exceeds possible risk);
serious cardiovascular illness, Reynaud's syndrome;
round ulcer, gastrointestinal bleedings;
heavy liver failure (use of lower doses is recommended);
heavy psychotic or cognitive disturbances (including in the anamnesis);
symptoms of dysfunction of heart and breath owing to fibrous changes or existence of such states in the anamnesis;
simultaneous use with the drugs having hypotensive effect (because of risk of development of orthostatic hypotension).
 

Pregnancy and lactation
As controlled clinical trials using Dostineksa® at pregnant women were not conducted, purpose of drug during pregnancy is possible only in emergency cases, taking into account a ratio advantage/risk for the woman and a fruit.

If pregnancy occurred against the background of treatment of Dostineksom®, it is necessary to consider expediency of drug withdrawal, also considering a ratio advantage/risk.

Approach of pregnancy should be avoided within, at least, one month after the termination of reception of Dostineksa®, considering a long elimination half-life of drug and existence of limited data on its impact on a fruit (though, according to the available data, use of Dostineksa® in a dose of 0,5 - 2 mg a week concerning the disturbances connected with a giperprolaktinemiya was not followed by increase in frequency of abortions, premature births, polycarpous pregnancy and inborn malformations).

There are no data on removal of drug with breast milk, however, in the absence of effect of use of Dostineksa® for prevention or suppression of a lactation mothers should refuse breastfeeding. At the disturbances connected with a giperprolaktinemiya, mothers wishing to nurse should not appoint Dostineks®.

Overdose:

Symptoms: nausea, vomiting, dispeptic frustration, orthostatic hypotension, confusion of consciousness, psychosis, hallucinations.

At overdose it is necessary to hold the auxiliary events directed to drug removal (gastric lavage) and, if necessary, maintenance of arterial pressure. Appointment of antagonists of dopamine is possible. 

Storage conditions:

Validity term - 2 years. Not to use after a period of validity. At a temperature not above 25 °C in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 0,5 mg; on 2 or on 8 tablets in the bottle of dark glass like I closed screwing on an aluminum cover with the plastic insert containing the drying agent and porous paper at the bottom; from above the bottle is supplied with an additional plastic cap like "pilfer-proof".

1 bottle with the application instruction in a cardboard pack.