Active substanceCabergolineCabergoline
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  • Dosage form: & nbsppills
    Composition: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.
    Description:
    White flat oval tablets with chamfer and risk on one side, with engraving "0.5" on one side of the risks and "CBG" on the other.

    Pharmacotherapeutic group:Dopamine receptor agonist
    ATX: & nbsp

    G.02.C.B.03   Cabergoline

    Pharmacodynamics:
    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 dopaminergic receptors of the hypothalamus. At doses higher than those required to inhibit prolactin secretion, the drug causes a central dopaminergic effect due to stimulation of dopamine B2 receptors. The effect of the drug is dose-dependent. Reduction of prolactin in the blood is usually observed after 3 hours and persists for 2-3 weeks,in this connection for the suppression of milk secretion, it is usually sufficient 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 lowering blood pressure (BP). 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.
    Pharmacokinetics:

    Suction

    After oral administration cabergoline quickly absorbed from the gastrointestinal tract (GIT). The maximum concentration in the blood plasma is achieved after 0.5-4 hours. The food has no effect on the absorption or distribution of cabergoline.

    Distribution

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

    Metabolism

    In the urine, cabergoline metabolites are found: 6-allyl-8p-carboxy-ergoline in an amount of 4-6% of the dose, 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.

    Excretion

    Cabergoline has a long half-life: T1 / 2 was 63-68 h in healthy volunteers and 79-115 h in patients with hyperprolactinemia.

    At this half-life, the equilibrium state is reached after 4 weeks. AT urine and feces were detected, respectively, 18% and 72% of the dose. The content of unchanged cabergoline in urine is 2-3%.

    Pharmacokinetics has a linear character up to a dose of 7 mg / day.

    Preclinical safety data

    As shown in preclinical studies, cabergoline is safe in a wide range of doses and does not have a teratogenic, mutagenic or carcinogenic effect.

    Indications:
    - 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 adenomas of the pituitary gland (micro- and macro-prolactinomas).

    - Idiopathic hyperprolactinemia.
    Contraindications:Postpartum or uncontrolled hypertension; hypersensitivity to cabergoline, other ergot alkaloids or any component of the drug; severe violations of liver function; adverse events from the lungs, such as pleurisy or fibrosis (including in anamnesis) associated with the use of dopamine agonists; psychoses (including history) or the risk of their development; pregnancy and developed on its background, preeclampsia and eclampsia; the period of breastfeeding; children's age till 16 years; damage to the valves of the heart due to prolonged therapy with cabergoline, confirmed by echocardiography; simultaneous use with antibiotics-macrolides; lactose intolerance; deficiency of lactase; glucose-galactose malabsorption syndrome.
    Carefully:Patients with cardiovascular disease, arterial hypotension, Raynaud's syndrome, peptic ulcers or gastrointestinal bleeding, drowsiness, sudden onset of sleep,patients with terminal stage of renal failure or who are on hemodialysis, patients older than 65 years; prolonged treatment with cabergoline.
    Pregnancy and lactation:
    The drug is contraindicated in pregnancy and lactation.
    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, obtained 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.
    In studies on animals, the direct or indirect adverse effects of cabergoline on the course of pregnancy, embryo / fetal development, childbirth, or postnatal development have not been established.
    Given the limited experience of using cabergoline in pregnancy, when planning it, the drug should be discarded. In case of pregnancy during treatment cabergoline immediately cancel.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.
    Because the cabergoline suppresses lactation, the drug should not be given to mothers who prefer breast-feeding infants. During treatment with cabergoline, breastfeeding should be discontinued.
    Dosing and Administration:

    Cabergoline is ingested preferably during meals.

    Adults

    Treatment of disorders associated with hyperprolactinemia.

    The recommended initial dose is 0.5 mg per week in one or two doses (for example, on Monday and Thursday). Dosage increases gradually, usually 0.5 mg / week at intervals of 1 month to achieve the optimal therapeutic effect. The maximum daily dose should not exceed 3 mg. The maintenance dose is 1 mg / week (0.25 - 2 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 receptions depending on the tolerability. To suppress the physiological after a generic or already established lactate The recommended dose is -1 mg once during the first 24 hours after the birth of the child.

    Use in patients with impaired hepatic or renal function

    Information is provided 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 older than 65 years is limited. The available data indicate that there is no specific risk.

    Side effects:The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not meless than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely (including isolated cases) - less than 0.01%.

    From the immune system: infrequently - hypersensitivity reaction, skin rash.

    From the side of the blood and lymphatic system: infrequently - erythromelalgia.

    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 pectoris, damage to the heart valves (including with regurgitation), pericarditis, pericardial effusion, "hot flashes", palpitations, peripheral edema.

    From the digestive tract: very often - nausea, pain in the abdomen; 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, fibrosis of the lung, nosebleed.

    Other: often - asthenia, weakness, dysfunctionliver function, pain in the mammary gland, impaired vision; very rarely - cramps in the muscles of the lower limbs, increased activity of creatine phosphokinase.

    Overdose: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.If indicated, measures should be taken to restore blood pressure. In addition, with severe symptomatology of the central nervous system (hallucinations), dopamine antagonists may be required.
    Interaction:
    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 interactions with other drugs on the basis of available information on the metabolism of cabergoline can not be predicted.
    Special instructions:
    To open the vial, first press the lid, then rotate it, as shown on the lid. A bag of silica gel from a vial can not be removed or consumed.
    Data on the efficacy and safety of Agalates in patients with impaired hepatic or renal function are limited. In patients with severe hepatic insufficiency (Child-Pugh class C), 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. It is not studied in patients with terminal stage of renal failure or hemodialysis. Therefore, in such patients, Agalates should be used with caution. The effect of alcohol on the overall tolerance of the drug Agalates 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 5HT2B receptors, the risk of fibrotic and seizure-inflammatory diseases such as exudative pleurisy, pleural fibrosis, pulmonary fibrosis, pericarditis, damage to one or more valves heart (aortic, mitral, tricuspid), retroperitoneal fibrosis. Abolition of the drug Agalates in the case of the development of the above 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 the rate of erythrocyte sedimentation (ESR),therefore at an elevated erythrocyte sedimentation rate without overt clinical signs should conduct radiography of the chest, as well as to determine the concentration of creatinine in plasma.
    During prolonged therapy with Agalates possible gradual development of fibrotic disorders, so during treatment should monitor the appearance of symptoms such as dyspnea, shortness of breath, cough, chest pain, back pain, lower extremity edema, signs of retroperitoneal fibrosis (pain , malaise), heart failure. After the start of therapy with Agalates to prevent fibrotic disorders should monitor the status of the heart valves and spend echocardiography (echocardiography) study for the first time in 3-6 months after 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 deterioration or valvular regurgitation, thickening or narrowing of the lumen of the valve wall Agalates drug therapy should be discontinued. The need for the patient in other types of clinical examination is established by the doctor on an individual basis.With the use of Agalates, drowsiness and episodes of "sudden falling asleep" can occur, especially in patients with Parkinson's disease (see "Impact on the ability to drive vehicles and mechanisms").
    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, therefore, before the beginning of therapy with Agalates, a pituitary function check should be performed. It is recommended to check the serum content of prolactin every month, since after achieving an effective therapeutic regimen, the normal concentration of prolactin persists for 2-4 weeks.
    After the abolition of the drug Agalates, hyperprolactinaemia usually occurs again.
    However, in some patients there has been a persistent decrease in prolineact concentrations 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.
    Effect on the ability to drive transp. cf. and fur:
    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.
    Form release / dosage:
    Tablets 0.5 mg.
    Packaging:
    For 2 or 8 tablets in bottles of dark glass (type III) with a neck sealed with a membrane of aluminum foil and kraft paper, with a lid of polypropylene,equipped with a system against opening by children; the vial contains a bag of silica gel.
    1 bottle with instructions for use in a cardboard pack.
    Storage conditions:
    At a temperature of no higher than 25 ° C in a dry place in a tightly closed original vial.

    Keep out of the reach of children.
    Shelf life:2 years.

    Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-001307/09
    Date of registration:20.02.2009/10.12.2012
    Expiration Date:Unlimited
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp21.01.2017
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