Expiration date: 05/2022

Structure and Composition: 

Tablets. 1 tablet contains active substance: Cabergoline 0.5 mg

Excipients: lactose - 75.8 mg L-leucine - 3.6 mg magnesium stearate (E572) - 0.1 mg

2 and 8 pcs. in dark glass bottles (type III) with a neck, sealed membrane of aluminum foil and a film (polyester / PE), with a lid equipped with a system of opening against children. The vial contains a capsule with a cylindrical shape and seal of silica wool. In a cardboard bundle one bottle.

Description pharmaceutical form:

White flat oval tablets with a facet and Valium on one side, engraved with "0.5" on one side of the risks and "CBG" on the other.

Pharmacokinetics:

Suction

After oral administration cabergoline is rapidly absorbed from the gastrointestinal tract. Cmax plasma levels achieved after 0.5-4 hours. Food does not affect the distribution of absorption or cabergoline.

Distribution

Binding of cabergoline (at a concentration of 0.1-10 ng / ml) to plasma proteins is 41-42%.

Metabolism

The urinary metabolites detected cabergoline 6-allyl-8 & beta-karboksiergolin in the amount of 4-6% of the dose, as well as three other metabolite with a total content of less than 3%.

All metabolites are considerably less (compared with cabergoline) inhibit the secretion of prolactin.

breeding

Cabergoline has a long T1 / 2 - 63-68 hours in healthy volunteers and 79-115 hours in patients with hyperprolactinemia.

In this T1 / 2 equilibrium state is reached after 4 weeks. In urine and faeces found respectively 18 and 72% of the dose. Contents cabergoline unchanged in urine is 2.3%.

The pharmacokinetics is linear up to a dose of 7 mg / day.

Preclinical safety data

As shown in preclinical studies, cabergoline is safe in a large range of doses and has no teratogenic, mutagenic or carcinogenic effects.

Description of the pharmacological actions:

Cabergoline - synthetic ergot alkaloid derivative ergoline dopamine agonist, a long-acting receptor-inhibiting prolactin secretion. The mechanism of action of cabergoline includes stimulation of central dopamine receptors of the hypothalamus. At doses higher than those required for suppression of prolactin secretion, the drug is a central dopaminergic effect due to stimulation of the dopamine D2-receptor. The drug has a dose-dependent manner. Decreasing the amount of prolactin in blood is usually observed after 3 hours and maintained for 2-3 weeks, and therefore to suppress the secretion of milk is usually sufficient single dose of the drug. In the treatment of hyperprolactinemia content normalized prolactin within 2-4 weeks of the drug in an effective dose. Normal prolactin levels may persist for several months after discontinuation of the drug.

Cabergoline has a highly selective effect and no effect on basal secretion of other pituitary hormones and cortisol. The only pharmacodynamic effect is not related to the therapeutic effect is the reduction of blood pressure. The maximum antihypertensive effect usually develops within 6 hours after a single dose of the drug and the degree of blood pressure lowering the incidence of dose-dependent hypotensive effect.

Testimony:

  • suppression of physiological lactation post-partum (only for medical reasons)
  • suppression of already established lactation (only for medical reasons)
  • disorders associated with hyperprolactinemia (including functional disorders like amenorrhea, oligomenorrhea, anovulation, galactorrhoea)
  • prolactin pituitary adenomas (micro- and macroprolactinoma)
  • idiopathic hyperprolactinemia.

Contraindications:

  • postpartum, or uncontrolled hypertension
  • Hypersensitivity to cabergoline, other ergot alkaloids or to any component of the drug
  • severe liver function abnormalities
  • adverse events by the lungs, such as pleurisy or fibrosis (including history), associated with taking dopamine agonists
  • psychoses (including history), or the risk of their development
  • Pregnancy and develop its pre-eclampsia and eclampsia
  • breast-feeding.

Efficacy and safety of cabergoline in children under 16 years of age has not been studied.

Precautions: in patients with cardiovascular disease, hypotension, Raynaud's syndrome, peptic ulcer or gastrointestinal bleeding, end-stage renal failure or hemodialysis, in elderly patients.

Application of pregnancy and breastfeeding:

The drug is contraindicated during pregnancy and lactation.

Pregnancy should be excluded before the start of dosing. It is recommended to avoid pregnancy for at least 1 month after cessation of treatment. There are limited data on the reception of the drug during pregnancy obtained during the first 8 weeks after conception. The use of cabergoline has not been accompanied by an increased risk of abortion, premature delivery, multiple pregnancy or congenital abnormalities. Other data received to date.

In animal studies, direct or indirect adverse effects of cabergoline on pregnancy, embryo / fetal, parturition or postnatal development were found.

Given the limited experience with the use of cabergoline in pregnancy, when it is planning drug should be discontinued. In case of pregnancy during treatment with cabergoline immediately overturned. In connection with the expansion of pre-existing tumors should be monitored signs of increased pituitary gland in pregnant women.

Since cabergoline inhibits lactation, the drug should not be administered to mothers who choose to breast-feeding infants. During treatment with cabergoline should stop breastfeeding.

Side effect:

Adverse effects are usually dose-dependent and decreases with its gradual reduction.

Suppression of lactation: adverse events develop in approximately 14% of patients. The most frequent - lowering blood pressure (12%), dizziness (6%) and headache (5%). Prolonged treatment effects of the frequency increases to 70%.

Frequent (more than 1/100, less than 1/10)

From the nervous system, depression, headaches and dizziness, paresthesia, fatigue, somnolence.

From the CCC: low blood pressure, palpitations and chest pain.

On the part of the digestive tract: nausea, vomiting, gastralgia, gastritis, constipation.

Skin and subcutaneous tissue: skin redness.

Uncommon (more than 1/1000, less than 1/100)

From the side view: hemianopsia.

From the CCC: nosebleeds.

Rare (more than 1/10000, less than 1/1000)

Allergic reactions: skin rash.

From the CCC: fainting.

From the musculoskeletal system: cramps in the fingers and calves.

On the part of the digestive tract: abnormal liver function.

Reduction of blood pressure (systolic over 20 diastolic mm Hg over 10 mm Hg) was recorded after 3-4 days after a single dose of cabergoline 1 mg in women after childbirth.

Adverse events were usually develop within the first two weeks, then decrease or disappear. Cancel the drug due to side effects was required in 3% of cases.

post-marketing surveillance

cabergoline treatment was accompanied by excessive daytime sleepiness and episodes of suddenly falling asleep, particularly in patients with Parkinson's disease. There are reports of increasing libido in patients with Parkinson's disease with dopamine agonists in the treatment including cabergoline, especially at high doses. Also observed in the treatment of cabergoline pleural effusions, pleural fibrosis, valvulopatiya, respiratory disorders (including respiratory failure).

Drug Interactions:

Effect of macrolide antibiotics on cabergoline plasma content in their combination has not been studied. Given the possibility of increasing the level of cabergoline, the drug is not recommended for use in combination with macrolides.

The mechanism of action of cabergoline is associated with the direct stimulation of dopamine receptors, so it should not be used in combination with a dopamine receptor antagonists (phenothiazines, butyrophenones, thioxanthenes, metoclopramide).

There is no information about the interactions of cabergoline with other ergot alkaloids, however it is not recommended long-term use of such combinations.

Given the pharmacodynamics of cabergoline (hypotensive effect), it is necessary to take into account the interaction with drugs that lower blood pressure.

In clinical studies in patients with Parkinson's disease pharmacokinetic interaction with levodopa or selegiline were found. Pharmacokinetic interactions with other drugs on the basis of the available information about the metabolism of cabergoline is impossible to predict.

Dosage and administration:

Inside, preferably during meals.

Adults

The treatment of disorders associated with hyperprolactinemia. The recommended starting dose - 0.5 mg per week in one or two doses (for example on Monday and Thursday). The dosage is gradually increased, usually 0.5 mg / week in intervals of 1 month to achieve optimum therapeutic effect. Maintenance dose - 1 mg / week (0.25-2 mg / week) in individual cases, patients with hyperprolactinemia to 4.5 mg / week.

When using the drug at doses above 1 mg / week sharing recommended weekly dose into 2 or more methods, depending on tolerance.

For suppression of lactation. The recommended dose - 1 mg once daily for the first 24 hours after birth.

Use in patients with impaired hepatic or renal function

The information is presented in the "Contraindications" and "Cautions".

Use in elderly

Given the indications for use, experience with cabergoline in elderly patients is limited. Available data show no specific risks.

Overdose:

Data on drug overdose not. Based on the results of animal experiments, we can expect the appearance of symptoms caused by hyperstimulation of dopamine receptors: nausea, vomiting, decreased blood pressure, impaired consciousness / psychosis or hallucinations. If shown, it should take steps to restore blood pressure. Furthermore, in severe CNS symptoms (hallucinations) may require the use of dopamine antagonists.

Special instructions:

To open the bottle, first click on the cover, and then turn it as shown on the cover. The capsule with the bottle of silica is not removed and is not consumed inside.

Data on the efficacy and safety of cabergoline in patients with impaired hepatic or renal function is limited. The pharmacokinetics of cabergoline has not changed significantly in moderate or severe renal insufficiency. It has not been studied in patients with end-stage renal failure or dialysis. Therefore, in these patients the drug should be used with caution. The effects of alcohol on overall tolerability of cabergoline has not been established.

Cabergoline can cause symptomatic hypotension, especially when co-administered with drugs that lower blood pressure. It is recommended to regularly measure blood pressure in the first 3-4 days after initiation of treatment.

Hyperprolactinemia in combination with amenorrhea and infertility may be associated with tumors of the pituitary, so prior to treatment with cabergoline must determine the cause of hyperprolactinemia.

It is recommended to check serum prolactin content every month, since after achieving an effective therapeutic regimen normal prolactin level is maintained for 2-4 weeks.

After the abolition of hyperprolactinemia drug usually occurs again. However, some patients experience a persistent decline in prolactin concentrations in a few months. Cabergoline restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Because pregnancy can occur before the resumption of menstruation, pregnancy tests are recommended during the period of amenorrhea, and after the restoration of the menstrual cycle - in all cases of delays of more than 3 days. Patients who do not want to get pregnant, it is recommended to use effective non-hormonal contraception during treatment with cabergoline and after its completion. Women planning a pregnancy, it is recommended to conceive not earlier than 1 month after discontinuation of the drug. A number of patients ovulatory cycle was maintained for 6 months after discontinuation of the drug.

With prolonged use of cabergoline, as well as other ergot derivatives, pleural effusion may appear / pulmonary fibrosis and valvular heart disease. Sometimes these events occurred in patients previously treated with dopamine agonists from the group of ergot alkaloids. Cancel cabergoline in case of the indicated pathology led to an improvement of signs and symptoms.

When new clinical symptoms of the respiratory system is recommended X-ray light. Patients with pleural effusion / fibrosis showed an increase of ESR in this regard at an elevated ESR, without overt clinical signs should also conduct X-ray examination.

When using cabergoline and drowsiness may occur sudden episodes of sleep, especially in patients with Parkinson's disease. Sudden falling asleep during daily activities, in some cases develops without warning, is rare.

The preparation contains lactose. Patients with rare hereditary form of galactose intolerance, lactase deficiency or malabsorption of glucose-galactose should not take Cabergoline.

Effects on ability to drive a car and to management of mechanisms

Cabergoline reduces blood pressure, which may disturb the reaction rate in some patients. This should be considered in situations requiring concentration, such as driving a car or operating machinery. Patients should be informed of the need to observe caution when driving or operating machinery.

Patients who have already been observed drowsiness and / or sudden sleep episodes during treatment with cabergoline should abandon the car or other driving-related risk activity, when disturbances of the reaction rate can be for them and others at risk of serious injury or death. Sometimes it is advisable to decrease the dosage or withdrawal of the drug.

Storage conditions:

In tightly closed original vial.

Agalates
(Cabergoline)