Dostinex tablets 0.5mg, No. 2

• Prevention of physiological lactation after childbirth;

• Suppression of already established postpartum lactation;

• Treatment of disorders associated with hyperprolactinemia, including amenorrhea, oligomenorrhea, anovulation, galactorrhea;

• Prolactin-secreting pituitary adenomas (micro- and macroprolactinomas); idiopathic hyperprolactinemia; syndrome of 'empty' sella turcica in combination with hyperprolactinemia.

Inside, during meals.

Prevention of lactation: 1 mg once (2 tablets, 0.5 mg each), on the first day after childbirth.

Suppression of established lactation: 0.25 mg (1/2 table) 2 times a day every 12 hours for two days (total dose - 1 mg). In order to reduce the risk of orthostatic hypotension in breastfeeding mothers, a single dose of DostinexЃ should not exceed 0.25 mg.

Treatment of disorders associated with hyperprolactinemia: the recommended initial dose is 0.5 mg per week in one dose (1 tablet 0.5 mg each) or in two doses (1/2 tablet 0.5 mg each, for example on Monday and Thursday). The increase in the weekly dose should be carried out gradually - by 0.5 mg - at monthly intervals until the optimal therapeutic effect is achieved. The therapeutic dose is usually 1 mg per week, but can range from 0.25 to 2 mg per week. The maximum dose for patients with hyperprolactinemia should not exceed 4.5 mg per week.

Depending on the tolerance, the weekly dose can be taken once or divided into 2 or more doses per week. The division of the weekly dose into several doses is recommended when prescribing the drug at a dose of more than 1 mg per week.

In patients with hypersensitivity to dopaminergic drugs, the likelihood of side effects can be reduced by starting therapy with DostinexЃ at a lower dose (for example, 0.25 mg once a week), followed by a gradual increase until the therapeutic dose is reached. To improve the tolerance of the drug in the event of severe side effects, a temporary decrease in the dose is possible, followed by a more gradual increase in it (for example, an increase of 0.25 mg per week every 2 weeks).

Each tablet contains:
Active ingredient : cabergoline 0.5 mg;
Excipients : leucine, anhydrous lactose.

• Hypersensitivity to cabergoline or other components of the drug, as well as to any ergot alkaloids.

• The safety and efficacy of the drug in children under 16 years of age has not been established.

With caution
Like other ergot derivatives, DostinexЃ should be used with caution in the following conditions and / or diseases:

• arterial hypertension that developed during pregnancy, for example, preeclampsia or postpartum arterial hypertension (DostinexЃ is prescribed only in cases where the potential benefit of using the drug significantly outweighs the possible risk);

• severe cardiovascular disease, Raynaud's syndrome;

• peptic ulcer, gastrointestinal bleeding;

• severe hepatic impairment (lower doses are recommended);

• severe psychotic or cognitive impairment (including history);

• symptoms of dysfunction of the heart and respiration due to fibrotic changes or the presence of such conditions in the anamnesis;

• simultaneous use with drugs that have an antihypertensive effect (due to the risk of developing orthostatic hypotension).

Trade name of the drug : DOSTINEXЃ

International Non-Proprietary Name (INN) : cabergoline

Dosage form : tablets

Description : white flat oblong tablets marked УPФ and УUФ, separated by a notch on one side and У700Ф with short notches on the top and bottom of the number on the other side.

Composition : Each tablet contains:
Active ingredient : cabergoline 0.5 mg;
Excipients : leucine, anhydrous lactose.

Description :

Pharmacotherapeutic group : dopamine receptor agonist
ATX code G02CB03

Pharmacological properties
Pharmacodynamics
Cabergoline is a dopaminergic derivative of ergoline and is characterized by a pronounced and long-term prolactin-lowering effect due to direct stimulation of D2-dopamine receptors of pituitary lactotropic cells. In addition, when taken at higher doses than to lower serum prolactin levels, cabergoline has a central dopaminergic effect due to D2 receptor stimulation.
A decrease in the concentration of prolactin in blood plasma is observed within 3 hours after taking the drug and persists for 7-28 days in healthy volunteers and patients with hyperprolactinemia, and up to 14-21 days in women in the postpartum period. Cabergoline has a strictly selective effect, does not affect the basal secretion of other pituitary hormones and cortisol. The prolactin-lowering effect of the drug is dose-dependent both in terms of severity and duration of action.
The pharmacodynamic effects of cabergoline, which are not associated with a therapeutic effect, include only a decrease in blood pressure (BP). With a single dose of the drug, the maximum hypotensive effect is observed within the first 6 hours and is dose-dependent.

Pharmacokinetics
Cabergoline is rapidly absorbed from the gastrointestinal tract, the maximum plasma concentration is reached after 0.5-4 hours, the connection with blood plasma proteins is 41-42%. The half-life of cabergoline, assessed by the rate of excretion in the urine, is 63-68 hours in healthy volunteers and 79-115 hours in patients with hyperprolactinemia. Due to the long half-life, the state of equilibrium concentration is reached after 4 weeks. 10 days after taking the drug in the urine and feces, about 18% and 72% of the dose taken, respectively, are found, and the proportion of the unchanged drug in the urine is 2-3%.
The main metabolic product of cabergoline identified in urine is 6-allyl-8?-carboxy-ergoline at a concentration of up to 4-6% of the dose taken. The content of 3 additional metabolites in urine does not exceed 3% of the dose taken. It was found that metabolic products have a significantly lower effect in suppressing the secretion of prolactin in comparison with cabergoline.
Food intake does not affect the absorption and distribution of cabergoline.

Indications for use

• Prevention of physiological lactation after childbirth;

• Suppression of already established postpartum lactation;

• Treatment of disorders associated with hyperprolactinemia, including amenorrhea, oligomenorrhea, anovulation, galactorrhea;

• Prolactin-secreting pituitary adenomas (micro- and macroprolactinomas); idiopathic hyperprolactinemia; syndrome of 'empty' sella turcica in combination with hyperprolactinemia.

Contraindications

• Hypersensitivity to cabergoline or other components of the drug, as well as to any ergot alkaloids.

• The safety and efficacy of the drug in children under 16 years of age has not been established.

With caution
Like other ergot derivatives, DostinexЃ should be used with caution in the following conditions and / or diseases:

• arterial hypertension that developed during pregnancy, for example, preeclampsia or postpartum arterial hypertension (DostinexЃ is prescribed only in cases where the potential benefit of using the drug significantly outweighs the possible risk);

• severe cardiovascular disease, Raynaud's syndrome;

• peptic ulcer, gastrointestinal bleeding;

• severe hepatic impairment (lower doses are recommended);

• severe psychotic or cognitive impairment (including history);

• symptoms of dysfunction of the heart and respiration due to fibrotic changes or the presence of such conditions in the anamnesis;

• simultaneous use with drugs that have an antihypertensive effect (due to the risk of developing orthostatic hypotension).

Pregnancy and lactation
Since there have been no controlled clinical trials with the use of DostinexЃ in pregnant women, prescribing the drug during pregnancy is possible only in cases of extreme necessity, taking into account the benefit / risk ratio for the woman and the fetus.
If pregnancy occurs during treatment with DostinexЃ, the advisability of discontinuing the drug should be considered, also taking into account the benefit / risk ratio.
Pregnancy should be avoided for at least one month after discontinuation of DostinexЃ, given the long half-life of the drug and limited data on its effects on the fetus (although, according to available data, DostinexЃ at a dose of 0.5-2 mg per week for disorders associated with hyperprolactinemia, was not accompanied by an increase in the frequency of miscarriages, premature births, multiple pregnancies and congenital malformations).
There is no information on the elimination of the drug in breast milk, however, in the absence of the effect of using DostinexЃ to prevent or suppress lactation, mothers should refuse breastfeeding. For disorders associated with hyperprolactinemia, DostinexЃ should not be prescribed to mothers who wish to breastfeed.

Route of administration and dosage
Inside, during meals.
Prevention of lactation : 1 mg once (2 tablets of 0.5 mg), on the first day after childbirth.
Suppression of established lactation : 0.25 mg (1/2 tablet) twice a day every 12 hours for two days (the total dose is 1 mg). In order to reduce the risk of orthostatic hypotension in breastfeeding mothers, a single dose of DostinexЃ should not exceed 0.25 mg.
Treatment of disorders associated with hyperprolactinemia: The recommended starting dose is 0.5 mg per week in one dose (1 tablet 0.5 mg) or in two divided doses (1/2 tablet 0.5 mg, for example, on Monday and Thursday). The increase in the weekly dose should be carried out gradually - by 0.5 mg at monthly intervals until the optimal therapeutic effect is achieved. The therapeutic dose is usually 1 mg per week, but can range from 0.25 to 2 mg per week. The maximum dose for patients with hyperprolactinemia should not exceed 4.5 mg per week.
Depending on the tolerance, the weekly dose can be taken once or divided into 2 or more doses per week. The division of the weekly dose into several doses is recommended when prescribing the drug at a dose of more than 1 mg per week.
In patients with hypersensitivity to dopaminergic drugs, the likelihood of side effects can be reduced by starting DostinexЃ therapy at a lower dose (for example, 0.25 mg once a week), followed by a gradual increase until the therapeutic dose is reached. To improve the tolerability of the drug in the event of severe side effects, a temporary decrease in the dose is possible, followed by a more gradual increase in it (for example, an increase of 0.25 mg per week every two weeks).

Side effects
In clinical studies with DostinexЃ to prevent physiological lactation (1 mg once) and to suppress lactation (0.25 mg every 12 hours for 2 days), side effects were observed in approximately 14% of women. When using DostinexЃ for 6 months at a dose of 1-2 mg per week, divided into 2 doses, for the treatment of disorders associated with hyperprolactinemia, the incidence of side effects was 68%. Side effects occurred mainly during the first 2 weeks of therapy and in most cases disappeared as therapy continued or a few days after DostinexЃ was discontinued. Side effects were usually transient, mild or moderate in severity and dose-dependent. At least once during therapy, severe side effects were observed in 14% of patients; due to side effects, treatment was discontinued in about 3% of patients.
The most common side effects are presented below:
From the cardiovascular system: heartbeat; rarely - orthostatic hypotension (with prolonged use, DostinexЃ usually has a hypotensive effect); possible asymptomatic decrease in blood pressure during the first 3-4 days after childbirth (systolic - more than 20 mm Hg, diastolic - more than 10 mm Hg).
From the nervous system : dizziness / vertigo, headache, fatigue, drowsiness, depression, asthenia, paresthesia, fainting.
From the digestive system : nausea, vomiting, epigastric pain, abdominal pain, constipation, gastritis, dyspepsia.
Others: mastodynia, epistaxis, 'flushing' of blood to the skin of the face, transient hemianopsia, vasospasm of the fingers and muscle cramps of the lower extremities (like other ergot derivatives, DostinexЃ can have a vasoconstrictor effect).
With long-term therapy with DostinexЃ, deviation from the norm of standard laboratory parameters was rarely observed; women with amenorrhea experienced a decrease in hemoglobin levels during the first few months after menstruation was restored.
In a post-marketing study, the following side effects associated with taking cabergoline were also recorded: alopecia, increased creatinine phosphokinase activity in the blood, mania, dyspnea, edema, fibrosis, abnormal liver function and abnormal liver function indicators, hypersensitivity reactions, rash, respiratory disorders, respiratory failure, valvulopathy.

Overdose Overdose
symptoms: nausea, vomiting, dyspeptic disorders, orthostatic hypotension, confusion, psychosis, hallucinations.
In case of an overdose, ancillary measures should be taken to remove the drug (gastric lavage) and, if necessary, maintain blood pressure. Prescription of dopamine antagonists is possible.

Interaction with other medicinal products
There is no information on the interaction of cabergoline and other ergot alkaloids, therefore, the simultaneous use of these medicinal products during long-term therapy with DostinexЃ is not recommended.
Since DostinexЃ has a therapeutic effect by direct stimulation of dopamine receptors, it cannot be administered simultaneously with drugs acting as dopamine antagonists (phenothiazines, butyrophenones, thioxanthenes, metoclopramide, etc.), because they can weaken the effect of DostinexЃ in reducing prolactin levels.
Like other ergot derivatives, DostinexЃ cannot be used concomitantly with macrolide antibiotics (for example, erythromycin), because this may lead to an increase in the systemic bioavailability of cabergoline.

Special instructions
Before prescribing DostinexЃ for the treatment of disorders associated with hyperprolactinemia, it is necessary to conduct a complete study of the function of the pituitary gland. When increasing the dose, patients should be under the supervision of a physician in order to establish the lowest effective dose that provides a therapeutic effect.
After an effective dosing regimen has been selected, it is recommended to carry out a regular (once a month) determination of the concentration of prolactin in the blood serum. Normalization of prolactin levels is usually observed within 2-4 weeks of treatment.
After discontinuation of DostinexЃ, a relapse of hyperprolactinemia is usually observed, but in some patients there is a persistent suppression of prolactin levels for several months. In most women, ovulatory cycles persist for at least 6 months after DostinexЃ is discontinued.
DostinexЃ restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Since pregnancy can occur before menstruation is restored, it is recommended that pregnancy tests be performed at least once every 4 weeks during the amenorrhea period, and after menstruation is restored, whenever menstruation is delayed by more than 3 days. Women wishing to avoid pregnancy should use barrier methods of contraception during treatment with DostinexЃ, as well as after discontinuation of the drug until anovulation recurs. Women who have become pregnant should be under the supervision of a doctor for the timely detection of symptoms of an enlarged pituitary gland, since during pregnancy it is possible to increase the size of already existing pituitary tumors.
DostinexЃ should be prescribed in lower doses in patients with severe hepatic impairment (class C according to Child-Pugh classification), for whom long-term drug therapy is indicated. With a single dose of 1 mg to such patients, there was an increase in AUC (area under the concentration / time curve) compared with healthy volunteers and patients with less severe hepatic impairment.
As with other ergot derivatives, patients with long-term administration of cabergoline have had pleural effusion / pleural fibrosis and valvulopathy. In some cases, patients have received prior therapy with ergotinine dopamine agonists. Therefore, DostinexЃ should be used with caution in patients with existing signs and / or clinical symptoms of cardiac dysfunction or with a history of such conditions. After discontinuation of DostinexЃ, patients with a diagnosis of pleural effusion / pleural fibrosis and valvulopathy showed improvement in symptoms.
The use of cabergoline causes drowsiness. In patients with Parkinson's disease, the use of dopamine receptor agonists may induce sudden sleep. In such cases, it is recommended to reduce the dose of DostinexЃ or discontinue therapy. Studies on the use of the drug in elderly patients with disorders associated with hyperprolactinemia have not been conducted. The safety and efficacy of the drug in children under 16 years of age has not been established.

Influence on the ability to drive a car and other mechanisms
Patients taking DostinexЃ who experience drowsiness should be warned that they are advised to refrain from driving a car and from performing work (for example, with mechanisms), in which reduced attention could create risk of serious injury or death to them or those around them.

Release form
Tablets 0.5 mg;
2 or 8 tablets in a type I amber glass vial, closed with a screw-on aluminum cap with a plastic insert containing a drying agent and porous paper at the bottom. 1 bottle with instructions for use in a cardboard box.

Shelf life is
2 years. Do not use after the expiration date.

Storage conditions
At a temperature not exceeding 25 ? C, out of the reach of children.

Conditions for dispensing from pharmacies
with a prescription