Agalates tablets 0.5mg, No. 2

suppression of physiological postpartum lactation (only for medical reasons);

suppression of already established lactation (only for medical reasons);

disorders associated with hyperprolactinemia (including functional disorders such as amenorrhea, oligomenorrhea, anovulation, galactorrhea);

prolactin-secreting pituitary adenomas (micro- and macroprolactinomas);

idiopathic hyperprolactinemia.

Inside, preferably with meals.

Adults

Treatment of disorders associated with hyperprolactinemia: The recommended starting dose is 0.5 mg per week in 1 or 2 divided doses (for example, on Monday and Thursday). The dosage is increased gradually, usually by 0.5 mg / week at intervals of 1 month, until the optimal therapeutic effect is achieved. The maximum daily dose should not exceed 3 mg.

Maintenance dose - 1 mg / week (0.25Ц2 mg / week); in some cases in patients with hyperprolactinemia up to 4.5 mg / week.

When using the drug Agalates in doses above 1 mg / week, it is recommended to divide the weekly dose into 2 or more doses, depending on the tolerance.

To suppress the physiological postpartum or already established lactation: the recommended dose is 1 mg once during the first 24 hours after the birth of the child.

Use in patients with impaired liver or kidney function. Information is presented in the sections 'Contraindications' and 'Special instructions'.

Use in patients over 65 years of age. Given the indications for use, experience with cabergoline in patients over 65 years of age is limited. Available data indicate no specific risk.

postpartum or uncontrolled arterial hypertension;

hypersensitivity to cabergoline, other ergot alkaloids or any component of the drug;

severe liver dysfunction;

adverse events from the lungs, such as pleurisy or fibrosis (including a history), associated with the use of dopamine agonists;

psychoses (including history) or the risk of their development;

pregnancy and developing on its background preeclampsia and eclampsia;

breastfeeding period;

children under the age of 16;

damage to the heart valves due to long-term therapy with cabergoline, confirmed by echocardiography;

simultaneous use with antibiotics of the macrolide group;

lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

With caution: in patients with cardiovascular diseases, arterial hypotension, Raynaud's syndrome, peptic ulcers or gastrointestinal bleeding, drowsiness, sudden sleep attacks, end-stage renal failure or on hemodialysis, patients over 65 years of age; with prolonged treatment with cabergoline.

pharmachologic effect

Dopamine receptor agonist. Cabergoline is a synthetic ergot alkaloid, an ergoline derivative, a long-acting dopamine agonist that inhibits the secretion of prolactin. The mechanism of action of cabergoline involves the stimulation of central dopamine receptors in the hypothalamus. At doses higher than those required to suppress prolactin secretion, the drug induces a central dopaminergic effect due to the stimulation of dopamine D2 receptors. The effect of the drug is dose-dependent. A decrease in the content of prolactin in the blood is usually observed after 3 hours and lasts for 2-3 weeks, therefore, to suppress milk secretion, a single dose of the drug is usually sufficient. In the treatment of hyperprolactinemia, the content of prolactin in the blood is normalized after 2-4 weeks of using the drug in an effective dose.Normal prolactin levels can persist for several months after drug withdrawal. Cabergoline is highly selective and does not affect the basal secretion of other pituitary hormones and cortisol. The only pharmacodynamic effect not associated with a therapeutic effect is a decrease in blood pressure. The maximum hypotensive effect usually develops 6 hours after a single dose of the drug; the degree of blood pressure reduction and the incidence of the hypotensive effect are dose-dependent.The maximum hypotensive effect usually develops 6 hours after a single dose of the drug; the degree of blood pressure reduction and the incidence of the hypotensive effect are dose-dependent.The maximum hypotensive effect usually develops 6 hours after a single dose of the drug; the degree of blood pressure reduction and the incidence of the hypotensive effect are dose-dependent.

Pharmacokinetics

Absorption After oral administration, cabergoline is rapidly absorbed from the gastrointestinal tract. Cmax in blood plasma is reached after 0.5-4 hours. Food does not affect the absorption or distribution of cabergoline. Pharmacokinetics is linear up to a dose of 7 mg / day. Distribution The binding of cabergoline (at a concentration of 0.1-10 ng / ml) with plasma proteins is 41-42%. Metabolism Cabergoline metabolites were found in urine: 6-allyl-8? -Carboxy-ergoline in an amount of 4-6% of the dose taken, as well as three other metabolites with a total content of less than 3%. All metabolites to a much lesser extent (compared to cabergoline) inhibit the secretion of prolactin. Excretion Cabergoline has a long T1 / 2. T1 / 2 in healthy volunteers is 63-68 hours, T1 / 2 in patients with hyperprolactinemia is 79-115 hours. With this T1 / 2, the equilibrium state is achieved after 4 weeks.In urine and feces, 18% and 72% of the dose taken were found, respectively. The content of unchanged cabergoline in urine is 2-3%.

Side effect

Determination of the frequency of adverse reactions (in accordance with WHO recommendations): very often (? 10%), often (? 1%, but <10%), infrequently (? 0.1%, but <1%), rarely (? 0.01%, but <0.1%), very rarely (including isolated cases) - <0.01%. From the immune system: infrequently - hypersensitivity reaction, skin rash. From the hematopoietic system: infrequently - erythromegaly. From the nervous system: often - hallucinations, sleep disorders, confusion, dizziness, dyskinesia, increased libido, headache, drowsiness, depression; infrequently - hyperkinesis, psychotic disorder, delirium, paresthesia, transient hemianopsia, fainting; very rarely - sudden onset of sleep, pathological attraction to gambling. From the side of the cardiovascular system: often - postural hypotension, angina pectoris, damage to the heart valves (including with regurgitation),pericarditis, pericardial effusion, hot flashes, palpitations, peripheral edema. From the digestive system: very often - nausea, abdominal pain; often - dyspepsia, vomiting, gastritis, constipation; rarely - pain in the epigastric region; very rarely - retroperitoneal fibrosis. From the respiratory system: often - shortness of breath, infrequently - pleural effusion, pulmonary fibrosis, epistaxis.

Others: often - asthenia, weakness, impaired liver function, pain in the mammary gland, visual impairment; very rarely - cramps in the muscles of the lower extremities, increased activity of CPK.

Application during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding). Pregnancy should be excluded before starting the drug. It is recommended to avoid pregnancy for at least 1 month after stopping treatment. There are limited data on taking the drug during pregnancy, obtained during the first 8 weeks after conception. The use of cabergoline was not associated with an increased risk of abortion, premature birth, multiple pregnancy, or congenital disorders. No other data have been received to date. In animal studies, no direct or indirect adverse effects of cabergoline on pregnancy, embryo / fetal development, childbirth or postnatal development have been found. Given the limited experience with cabergoline during pregnancy, the drug should be discontinued when planning it.If pregnancy occurs during treatment, cabergoline is immediately canceled. In connection with the possibility of expansion of a pre-existing tumor, signs of an enlarged pituitary gland in pregnant women should be monitored. Because cabergoline suppresses lactation, the drug should not be given to mothers who prefer to breastfeed their babies. Breastfeeding should be discontinued during treatment with cabergoline.

Application for violations of liver function

Data on the efficacy and safety of cabergoline in patients with impaired liver function. Therefore, in such patients, the drug should be used with caution.

Application for impaired renal function

There are limited data on the efficacy and safety of cabergoline in patients with impaired renal function. The pharmacokinetics of cabergoline are not significantly altered in moderate or severe renal impairment. Has not been studied in patients with end-stage renal disease or hemodialysis. Therefore, in such patients, the drug should be used with caution.

Application in children

The efficacy and safety of using cabergoline in children under 16 years of age has not been studied.

Use in elderly patients

The drug should be prescribed with caution to elderly patients.

special instructions

To open the bottle, you must first press the cap, then turn it as shown on the cap. Do not remove or consume the capsule with silica gel from the bottle. There are limited data on the efficacy and safety of cabergoline in patients with impaired hepatic or renal function. In patients with severe hepatic impairment (class C on the Child-Pugh scale), if long-term therapy is required, Agalates should be used in lower doses. The pharmacokinetics of cabergoline does not change significantly in moderate or severe renal failure, has not been studied in patients with end-stage renal failure or in hemodialysis. Therefore, in such patients, the drug should be used with caution. The effect of alcohol on the overall tolerance of cabergoline has not been established.The use of the drug Agalates can cause symptomatic arterial hypotension, especially when taken together with drugs that lower blood pressure. It is recommended to regularly measure blood pressure in the first 3-4 days after starting treatment.

With prolonged use of Agalates and other ergot derivatives that are active against serotonin 5-HT2B receptors, the risk of developing fibrotic and serous-inflammatory diseases, such as exudative pleurisy, pleural fibrosis, pulmonary fibrosis, pericarditis, damage to one or more valves, increases heart (aortic, mitral, tricuspid), retroperitoneal fibrosis. Cancellation of the drug Agalates in the case of the development of the listed diseases led to an improvement in the condition of the patients. Before starting long-term therapy with Agalates, all patients should undergo a complete examination to detect lesions of the heart valves, to determine the functional state of the lungs and kidneys to prevent the deterioration of the course of concomitant diseases.When new clinical symptoms of the respiratory system appear, a fluoroscopy of the lungs is recommended. In patients with pleural effusion / fibrosis, an increase in ESR was noted, in this regard, with an increased ESR without obvious clinical signs, an X-ray examination should also be performed, and the concentration of creatinine in the blood plasma should also be determined. With prolonged therapy with Agalates, a gradual development of fibrotic disorders is possible, therefore, during treatment, the appearance of symptoms such as shortness of breath, shortness of breath, cough, chest pain, back pain, edema of the lower extremities, signs of retroperitoneal fibrosis (back pain , malaise), heart failure.After starting therapy with Agalates, in order to prevent fibrotic disorders, the condition of the heart valves should be monitored and an EchoCG examination should be performed within 3-6 months after the start of therapy. Further, the frequency of EchoCG monitoring is set by the doctor individually for each patient, but not less than once every 6-12 months. In the event of the appearance or worsening of valve regurgitation, narrowing of the lumen or thickening of the valve wall, therapy with Agalates should be discontinued. The patient's need for other types of clinical examination is determined by the physician on an individual basis. When using the drug Agalates, drowsiness and episodes of sudden falling asleep may appear, especially in patients with Parkinson's disease. When using the drug Agalates, there was an increase in libido, hypersexuality, pathological attraction to gambling.These symptoms were reversible and disappeared with dose reduction or discontinuation of Agalates. Hyperprolactinemia in combination with amenorrhea and infertility can be associated with pituitary tumors, therefore, before starting therapy with Agalates, it is necessary to examine the function of the pituitary gland. It is recommended that serum prolactin levels be checked every month as after reaching an effective therapeutic regimen, the normal concentration of prolactin is maintained for 2-4 weeks. After discontinuation of the drug Agalates, hyperprolactinemia usually reappears. However, in some patients, a persistent decrease in prolactin concentration is observed over several months. The use of Agalates restores ovulation and fertility in women with hyperprolactinemic hypogonadism.Since 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 delay of more than 3 days. Women who are not planning to become pregnant are advised to use effective non-hormonal contraception during and after treatment with Agalates. For women planning pregnancy, conception is recommended no earlier than 1 month after discontinuation of Agalates. Influence on the ability to drive vehicles and use mechanisms Patients should be informed about the need for caution when driving or operating mechanisms. Patients who have already experienced drowsiness and / or episodes of sudden falling asleep during treatment with Agalates,should refuse to drive a car or other activity that requires increased concentration of attention and speed of psychomotor reactions. Preclinical safety data As shown in preclinical studies, cabergoline is safe over a significant dose range and has no teratogenic, mutagenic or carcinogenic effects.

Overdose

There is no information on drug overdose. Based on the results of animal experiments, one can expect the appearance of symptoms due to hyperstimulation of dopamine receptors: nausea, vomiting, decreased blood pressure, impaired consciousness / psychosis or hallucinations. Treatment: according to indications, measures should be taken to restore blood pressure. In addition, severe CNS symptoms (hallucinations) may require the use of dopamine antagonists.

Drug interactions

The effect of macrolide antibiotics on the plasma content of cabergoline when used together 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 direct stimulation of dopamine receptors, so it should not be used in combination with dopamine receptor antagonists (phenothiazines, butyrophenones, thioxanthenes, metoclopramide). There is no information on the interaction of cabergoline with other ergot alkaloids, however, long-term use of this combination is not recommended. 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, no pharmacokinetic interaction with levodopa or selegiline was found. Pharmacokinetic interactions with other drugs cannot be predicted based on the available information on the metabolism of cabergoline.