Composition, form of production and packaging
Tablets are white, flat, oval, with a facet and a risk on one side, with engraving "0.5" on one side of the risks and "CBG" on the other.
cabergoline 500 mcg
Excipients: lactose - 75.8 mg, L-leucine - 3.6 mg, magnesium stearate (E572) - 0.1 mg.
2 pcs. - bottles of dark glass (1) - packs of cardboard.
8 pcs. - bottles of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
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 includes stimulation of the central dopamine receptors of the hypothalamus. At doses higher than those required to suppress prolactin secretion, the drug causes a central dopaminergic effect due to stimulation of dopamine D 2 receptors. The effect of the drug is dose-dependent. Reduction in prolactin in the blood is usually observed after 3 hours and persists for 2-3 weeks, and therefore, to suppress the secretion of milk, it is usually enough to take one dose of the drug. In the treatment of hyperprolactinemia, prolactin in the blood is normalized after 2-4 weeks of the drug in an effective dose. The normal level of prolactin can persist for several months after drug withdrawal.
Cabergoline has a highly selective effect and does not affect the basal secretion of other pituitary and cortisol hormones. The only pharmacodynamic effect, not associated with the therapeutic effect, is a decrease in blood pressure. The maximum hypotensive effect usually develops 6 hours after a single dose; the degree of BP reduction and the frequency of development of the hypotensive effect are dose-dependent.
After oral administration, cabergoline is rapidly absorbed from the digestive tract. C max in blood plasma is achieved in 0.5-4 hours. Food does not affect the absorption or distribution of cabergoline.
Pharmacokinetics has a linear character up to a dose of 7 mg / day.
The binding of cabergoline (at a concentration of 0.1-10 ng / ml) with plasma proteins is 41-42%.
In the urine, cabergoline metabolites are found: 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 (in comparison with cabergoline) inhibit the secretion of prolactin.
Cabergoline has a long T 1/2 . T 1/2 in healthy volunteers is 63-68 hours, T 1/2 in patients with hyperprolactinemia is 79-115 hours. With such a T 1/2, the equilibrium state is reached after 4 weeks.
In urine and feces 18% and 72% of the dose, respectively, were detected. The content of unchanged cabergoline in urine is 2-3%.
- suppression of physiological postpartum lactation (only for medical reasons);
- suppression of already established lactation (only for medical reasons);
- disorders associated with hyperprolactinaemia (including functional disorders such as amenorrhea, oligomenorrhoea, anovulation, galactorrhea);
- Prolactin secretion adenomas of the pituitary gland (micro- and macro-prolactinomas);
Cabergoline is ingested preferably during meals.
In the treatment of hyperprolactinemia-related disorders, the recommended initial dose is 500 mcg per week in 1 or 2 doses (for example, on Monday and Thursday). The dose is increased gradually, usually by 500 Ојg per week at intervals of 1 month until the optimal therapeutic effect is achieved. The maximum daily dose is 3 g.
The maintenance dose is 1 mg / week (0.25-2 mg / week); in some cases in patients with hyperprolactinaemia - up to 4.5 mg / week.
When using the drug Agalates in doses of more than 1 mg / week, it is recommended to divide the weekly dose into 2 or more receptions depending on the tolerability.
To suppress physiological postpartum or already established lactation, the recommended dose is 1 mg once during the first 24 hours after the birth of the child.
Given the indications for use, the experience of using cabergoline in patients older than 65 years is limited. The available data indicate that there is no specific risk.
Determination of the frequency of adverse reactions (according to the recommendations of the WHO): 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 - a hypersensitivity reaction, a skin rash.
On the part of the hematopoiesis 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 hemianopia, fainting; very rarely - a sudden attack of sleep, a pathological attraction to gambling.
From the cardiovascular system: often - postural hypotension, angina, damage to the heart valves (including with regurgitation), pericarditis, pericardial effusion, hot flashes, palpitations, peripheral edema.
From the side of the digestive system: very often - nausea, abdominal pain; often - dyspepsia, vomiting, gastritis, constipation; rarely - pain in the epigastric region; very rarely - retroperitoneal fibrosis.
On the part of the respiratory system: often - shortness of breath, infrequently - pleural effusion, lung fibrosis, epistaxis.
Other: often - asthenia, weakness, impaired liver function, pain in the mammary gland, impaired vision; very rarely - cramps in the muscles of the lower extremities, increased activity of CK.
- postpartum or uncontrolled hypertension;
severe hepatic impairment;
- adverse events on the part of the lungs, such as pleurisy or fibrosis (including in anamnesis) associated with the use of dopamine agonists;
- psychosis (including history) or the risk of their development;
- Pregnancy and developed on its background, preeclampsia and eclampsia;
- the period of lactation (breastfeeding);
- Children's age till 16 years;
- defeat of the heart valves due to prolonged therapy with cabergoline, confirmed by echocardiography;
- deficiency of lactase, glucose-galactose malabsorption syndrome;
- simultaneous use with antibiotics of a group of macrolides;
- hypersensitivity to the components of the drug;
- Hypersensitivity to other ergot alkaloids.
Caution should be given to patients with cardiovascular disease, arterial hypotension, Reynaud's syndrome, peptic ulcers or gastrointestinal bleeding, drowsiness, sudden onset of sleep, patients with end-stage renal failure or who are on hemodialysis, elderly patients over the age of 65, During a long time.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and lactation (breastfeeding).
Pregnancy should be excluded before taking the drug. It is recommended to avoid pregnancy during at least 1 month after discontinuation of treatment. There are limited data on the intake of the drug during pregnancy, received during the first 8 weeks after conception. The use of cabergoline was not accompanied by an increased risk of abortion, premature birth, multiple pregnancies or congenital disorders. Other data have not been received so far.
AT studies on animals of direct or indirect adverse effects of cabergoline on the course of pregnancy, development of the embryo / fetus, childbirth or postnatal development is not found.
Given the limited experience of using cabergoline in pregnancy, when planning it, the drug should be discarded. In the case of pregnancy during treatment, cabergoline is immediately withdrawn. In connection with the possibility of expansion of a pre-existing tumor, signs of an increase in the pituitary gland in pregnant women should be monitored.
Since cabergoline suppresses lactation, the drug should not be given to mothers who prefer breast-feeding infants. During treatment with cabergoline, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
Data on the efficacy and safety of cabergoline in patients with impaired renal function are limited. The pharmacokinetics of cabergoline does not change significantly with moderate or severe renal failure. Not studied in patients with terminal stage of renal failure or hemodialysis. Therefore, in such patients, the drug should be used with caution.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Data on the efficacy and safety of cabergoline in patients with impaired hepatic function. Therefore, in such patients, the drug should be used with caution.
APPLICATION FOR CHILDREN
The effectiveness and safety of the use of cabergoline in children under 16 years of age has not been studied.
APPLICATION IN ELDERLY PATIENTS
Caution should be given to elderly patients.
To open the bottle, first press the lid, then turn it, as shown on the lid. Capsule with silica gel from the bottle can not be removed or consumed.
Data on the efficacy and safety of cabergoline in patients with impaired hepatic or renal function are limited. In patients with severe hepatic insufficiency (grade C on the Child-Pugh scale), if necessary, prolonged therapy, Agalates should be used at lower doses.
The pharmacokinetics of cabergoline does not change significantly with moderate or severe renal failure, has not been studied in patients with terminal stage of renal failure or hemodialysis. Therefore, in such patients, the drug should be used with caution.
The effect of alcohol on overall tolerability of cabergoline is not 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 the start of treatment.
With long-term use of the drug Agalates and other ergot derivatives, which are active against serotonin 5-HT 2B receptors, the risk of fibrotic and serous inflammatory diseases such as exudative pleurisy, pleural fibrosis, pulmonary fibrosis, pericarditis, damage to one or more valvular heart valves (aortic, mitral, tricuspid), retroperitoneal fibrosis. The abolition of the drug Agalates in the case of the development of these diseases led to an improvement in the patients' condition.
Prior to the onset of prolonged therapy with Agalates, all patients should undergo a complete examination to detect cardiac valve lesions, to determine the functional state of the lungs and kidneys to prevent worsening of the course of concomitant diseases.
When new clinical symptoms appear on the part of the respiratory system, fluoroscopy of the lungs is recommended. In patients with pleural effusions / fibrosis, there was an increase in ESR, therefore, with elevated ESR without obvious clinical signs, an X-ray examination should also be performed, as well as the creatinine concentration in the blood plasma.
With prolonged therapy with Agalates, the gradual development of fibrotic disorders is possible, therefore, the appearance of symptoms such as shortness of breath, shortness of breath, coughing, chest pain, back pain, swelling of the lower limbs, signs of retroperitoneal fibrosis , malaise), heart failure.
After the beginning of therapy with Agalates for the prevention of fibrotic disorders, the condition of the heart valves should be monitored and an EchoCG examination performed within 3-6 months after the initiation of therapy. Further, the frequency of EchoCG control is set by the doctor individually for each patient, but not less than once every 6-12 months. In case of appearance or deterioration of valvular regurgitation, narrowing of the lumen or thickening of the valve wall, therapy with Agalates should be discontinued.
The need for the patient in other types of clinical examination is established by the doctor on an individual basis.
When using Agalates, drowsiness and episodes of sudden falling asleep may occur, 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 a decrease in the dose or withdrawal of Agalates.
Hyperprolactinaemia in combination with amenorrhea and infertility can be associated with tumors of the pituitary gland, so before the beginning of therapy with Agalates, a pituitary function test should be performed.
It is recommended to check the content of prolactin in the blood serum every month, tk. after achieving an effective therapeutic regimen, the normal concentration of prolactin is maintained for 2-4 weeks.
After the abolition of the drug Agalates, hyperprolactinaemia usually occurs again. However, in some patients there is a persistent decrease in prolactin concentration for several months.
The use of the drug Agalates restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Because pregnancy can occur before the resumption of menstruation, pregnancy tests are recommended during the amenorrhea period, and after the recovery of the menstrual cycle - in all cases, their delay is more than 3 days.Women who do not plan pregnancy are recommended to use effective non-hormonal contraceptives during treatment with Agalates and after it is finished. Women planning pregnancy, conception is recommended not earlier than 1 month after the abolition of the drug Agalates.
Impact on the ability to drive vehicles and manage mechanisms
Patients should be informed of the need for caution when driving a car or controlling machinery.
Patients who have already experienced drowsiness and / or episodes of sudden falling asleep with Agalates should stop driving a car or other activity that requires a high concentration of attention and speed of psychomotor reactions.
Preclinical safety data
As shown in preclinical studies, cabergoline is safe in a significant dose range and does not have a teratogenic, mutagenic or carcinogenic effect.
There is no information about an overdose of the drug. 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 the indications, measures should be taken to restore blood pressure. In addition, with severe symptoms from the central nervous system (hallucinations), dopamine antagonists may be required.
The effect of macrolide antibiotics on the content of cabergoline plasma in their combined use has not been studied. Given the possibility of increasing the level of cabergoline, the drug is not recommended 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 reduce blood pressure.
In clinical studies in patients with Parkinson's disease, pharmacokinetic interaction with levodopa or selegiline was not detected.
Pharmacokinetic interaction with other drugs based on the available information on the metabolism of cabergoline can not be predicted.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry place, in a tightly closed original bottle at a temperature of no higher than 25 В° C. Shelf life - 2 years.