Expiration date: 01/2025

Structure and Composition:

Tablets. 1 tablet contains Cabergoline 0.5 mg

Excipients: Lactose anhydrous Leucine

Patients in the dark glass of 2 or 8 pieces. In the paper cartons 1 bottle.

Description pharmaceutical form:

White flat oblong tablets marked "P" and «U», separated by a notch on one side and "700" with short notches of the top and bottom - on the other hand.

Pharmacokinetics:

Cabergoline is rapidly absorbed from the gastrointestinal tract, the Cmax in plasma achieved through 0.5-4 h, binding to plasma proteins is 41-42%. T1 / 2 cabergoline assessed by urinary excretion rate of 63-68 hours in healthy volunteers and 79-115 hours in patients with hyperprolactinemia. Because of the long T1 / 2, CSS achieved after 4 weeks. After 10 days of drug administration in the feces and urine are detected respectively about 18 and 72% of the dose, and the proportion of unchanged drug in the urine of 2-3%. The main product of the metabolism of cabergoline identified in urine is a 6-allyl-8 & beta-carboxy-ergoline in concentrations up to 6.4% of the dose. Urinary metabolites additional 3 does not exceed 3% of the dose. It is found that the metabolic products have significantly less effect in relation to suppress prolactin secretion compared with cabergoline.

Food intake has no effect on the absorption and distribution of cabergoline.

Description of the pharmacological actions:

Cabergoline is a dopaminergic ergoline derivative and is characterized by severe and prolonged prolaktinsnizhayuschim action due to direct stimulation of the D2-dopamine receptors lactotropic pituitary cells. Moreover, in higher doses compared with the doses for reducing serum prolactin cabergoline has a central effect due to stimulation of dopaminergic D2-receptors.

Reduced plasma concentrations of prolactin observed for 3 hours after drug administration and persists for 7-28 days in healthy volunteers and patients with hyperprolactinemia until 14-21 days - in postpartum women.

Cabergoline has the strong selective effect, has no effect on basal secretion of other pituitary hormones and cortisol. Prolaktinsnizhayuschee effect of the drug is dose-dependent both in terms of severity and duration of action.

By the pharmacodynamic effects of cabergoline not related to the therapeutic effect relates only to blood pressure reduction. In single dose of the drug the maximum antihypertensive effect is noted within the first 6 hours, and is dose-dependent.

Testimony:

• prevention of physiological lactation after giving birth
  
• suppression of already established lactation post-partum
  
• treatment of disorders associated with hyperprolactinemia, including amenorrhea, oligomenorrhea, anovulation, galaktoreyu
  
• prolactin pituitary adenomas (micro - and macroprolactinoma), idiopathic hyperprolactinemia empty sella syndrome in combination with hyperprolactinemia.
  

Contraindications:

• Hypersensitivity to cabergoline or other components of the drug, as well as any ergot alkaloids
  
• Children up to age 16 years (safety and efficacy in these patients has not been established).
  

Carefully

As with other ergot derivatives, Dostinex should be used with caution in the following conditions and / or diseases:

• hypertension, which developed against the background of pregnancy, such as preeclampsia or post-partum hypertension (Dostinex is appointed only in cases where the potential benefits of the drug is much higher than the potential risk)
  
• severe cardiovascular disease, Raynaud's syndrome
  
• peptic ulcer, gastrointestinal bleeding
  
• severe hepatic impairment (we recommend the use of lower doses)
  
• severe psychotic or cognitive impairment (including history)
  
• Symptoms of cardiac and respiratory function due to fibrosis or the presence of such conditions in history
  
• simultaneous application of drugs, hypotensive effect (due to the risk of orthostatic hypotension).
  

Application of pregnancy and breastfeeding:

Since the controlled clinical trials with Dostinex in pregnant women has been conducted, use of 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 the pregnancy during treatment with Dostinex, should consider the appropriateness of discontinuation of the drug, also taking into account the benefit / risk ratio.

Pregnancy should be avoided for at least one month after discontinuation of Dostinex, given the long half-life of the drug and the presence of limited data about its effects on the fetus (although, according to available data, the use of Dostinex in a dose of 0.5-2 mg per week over disorders associated with hyperprolactinemia, was not accompanied by an increase in the frequency of miscarriage, premature delivery, multiple pregnancy and congenital malformations).

Data on drug excretion in breast milk is not, however, in the absence of the effect of the use of Dostinex for the prevention or suppression of lactation mothers should abandon breastfeeding. When violations associated with hyperprolactinemia, Dostinex should not be administered to mothers who wish to breastfeed.

Side effect:

In clinical trials using Dostinex to prevent physiological lactation (1 mg dose) and for the suppression of lactation (0,25 mg every 12 hours for 2 days) side effects were observed in approximately 14% of women. When applying Dostinex 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 frequency of side effects was 68%. Adverse events occurred mainly during the first 2 weeks of therapy and in most cases disappeared with continued therapy or after a few days after discontinuation of Dostinex. Adverse events were generally transient, according to severity - mild to moderate and were dose-dependent. At least once during the treatment of serious adverse events were reported in 14% of patients due to side effects of the treatment was stopped in about 3% of patients.

The most frequent side effects are presented below.

From the CCC: heartbeat rarely - orthostatic hypotension (with prolonged use Dostinex generally exerts a hypotensive effect), possibly asymptomatic decrease in blood pressure during the first 3-4 days after birth (garden - more than 20 mm Hg, Dad - more than 10 mmHg.).

From the nervous system: dizziness / vertigo, headache, fatigue, drowsiness, depression, fatigue, paresthesia, syncope.

From the digestive system: nausea, vomiting, epigastric pain, abdominal pain, constipation, gastritis, dyspepsia.

Other: mammalgia, epistaxis, flushing to the face, transient hemianopsia, vasospasm of the fingers and lower limbs muscle cramps (like other ergot derivatives, Dostinex may have a vasoconstrictor effect).

When long-term therapy with Dostinex deviation from the norm of standard laboratory parameters are rarely observed in women with amenorrhea there was a decrease in hemoglobin levels during the first few months after the restoration of menstruation.

In post-marketing study also recorded the following side effects associated with taking cabergoline: alopecia, increased creatinine phosphokinase activity in the blood, delusions, dyspnea, edema, fibrosis, abnormal liver function and abnormalities in liver function, hypersensitivity reactions, rash, respiratory disorder, respiratory failure , valvulopatiya.

Drug Interactions:

Information about the interaction of cabergoline and other ergot alkaloids is missing, it is not recommended the simultaneous use of these drugs during long-term therapy Dostinex.

Since Dostinex exerts therapeutic effects through direct stimulation of dopamine receptors, it can not be administered simultaneously with drugs that act as antagonists of dopamine (phenothiazines, butyrophenones, thioxanthenes, metoclopramide, etc.), As they may weaken the effect of Dostinex, aimed at reducing the level of prolactin.

As with other ergot derivatives, Dostinex should not be used simultaneously with antibiotics, macrolides (eg erythromycin) since This may result in increased systemic bioavailability of cabergoline.

Dosage and administration:

Inside, during a meal.

Lactation Prevention: 1 mg once daily (2 tablets of 0.5 mg.), on the first day after birth.

Suppression established lactation: 0.25 mg (Table 2.1.), 2 times a day every 12 h for two days (total dose - 1 mg). To reduce the risk of orthostatic hypotension in breastfeeding mothers, a single dose of Dostinex should not exceed 0.25 mg.

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

Depending on tolerability weekly dose may be administered once or divided into two or more receptions a week. Separation weekly dose to several doses recommended when administering the drug in a dose of 1 mg per week.

In patients with hypersensitivity to dopaminergic drugs probability of side effects can be reduced by starting Dostinex therapy at a lower dose (ie 0.25 mg 1 time per week), followed by a gradual increase in its to achieve a therapeutic dose. To improve the tolerability of the drug in the event of significant side effects may be a temporary reduction of the dose, followed by a more gradual increase in it (for example an increase of 0.25 mg per week every 2 weeks).

Overdose:

Symptoms include nausea, vomiting, diarrhea disorders, orthostatic hypotension, confusion, psychosis, hallucinations.

Treatment: supporting activities aimed at the elimination of the drug (gastric lavage) and, if necessary, to maintain blood pressure. Perhaps the appointment of dopamine antagonists.

Special instructions:

Before the appointment of Dostinex for the treatment of disorders associated with hyperprolactinemia, it is necessary to conduct a full investigation of the pituitary gland.

When increasing the dose, patients should be under the supervision of a physician to determine the lowest effective dose which provides a therapeutic effect.

After will be picked effective dosing regimen, it is recommended to carry out regular (1 time per month) determination of prolactin concentration in the blood serum. Normalization of prolactin levels is usually observed within 2-4 weeks of treatment.

After the abolition of Dostinex is usually observed recurrence of hyperprolactinemia, but some patients had persistent suppression of prolactin levels for several months. In most women, ovulatory cycles persist for at least 6 months after the abolition of Dostinex.

Dostinex restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Because pregnancy can occur before the restoration of menstruation, it is recommended to conduct pregnancy tests at least once every 4 weeks for a period of amenorrhea, and after the restoration of menstruation - every time a missed period is marked by more than 3 days. Women who wish to avoid pregnancy, you should use a barrier method of contraception during treatment with Dostinex, and after discontinuation of the drug to the recurrence of anovulation. Women who become pregnant should be under medical supervision for the early detection of the symptoms of the pituitary gland to increase, as during pregnancy may increase the size of pre-existing pituitary tumors.

Dostinex should be administered at lower doses in patients with severe hepatic insufficiency (class C according to Child-Pugh classification), which is a long-term therapy the drug. By applying such a single dose of 1 mg patients showed an increase in AUC as compared to healthy volunteers and patients with less severe hepatic insufficiency.

As with other ergot derivatives, after long-term use of cabergoline were observed in patients of pleural effusion / pleural fibrosis and valvulopatiya. In some cases, patients received prior therapy ergotoninovymi dopamine agonists. Therefore, Dostinex should be used with caution in patients with current symptoms and / or clinical symptoms of cardiac function, or a history of these conditions. After discontinuation of Dostinex for patients diagnosed with pleural effusion / pleural fibrosis and valvulopatiya noted improvement in symptoms.

The use of cabergoline causes drowsiness. In patients with Parkinson's disease the use of dopamine receptor agonists may cause a sudden fall asleep. In such cases, it is recommended to reduce the dose or discontinue therapy with Dostinex.

Research on the use of the drug in elderly patients with disorders associated with hyperprolactinemia have been conducted. Safety and efficacy in children under 16 years of age has not been established.

Effects on ability to drive and use other mechanisms. Patients taking Dostinex, who observed drowsiness, should be warned that they are advised to refrain from driving and performing the work (for example using machinery), in which a reduced emphasis could create for them or others the risk of serious injury or death.