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Active ingredients
Cabergolin
Release form
Pills
Composition
1 tablet contains: Active substances: cabergoline - 500 mcg. Auxiliary substances: lactose - 75.9 mg, leucine - 3.6 mg.
Pharmacological effect
Dopamine receptor agonist. Cabergoline is a dopaminergic ergoline derivative, characterized by a pronounced and prolonged prolactin-lowering effect. The mechanism of action is associated with direct stimulation of the dopamine D2 receptors of the lactotropic pituitary cells. In doses exceeding those for reducing the level of prolactin in the blood plasma, it has a central dopaminergic effect due to the stimulation of dopamine D2 receptors. A decrease in the concentration of prolactin in the blood plasma is noted 3 h after administration of the drug and persists for 7-28 days in healthy volunteers and patients with hyperprolactinemia, and up to 14-21 days in women in the postpartum period. Prolactin-lowering effect is dose-dependent both in terms of severity and duration of action. Cabergoline has a strictly selective effect, does not affect the basal secretion of other pituitary and cortisol hormones. Only a decrease in blood pressure is related to pharmacological effects of cabergoline. With a single use of the drug, the maximum hypotensive effect is observed during the first 6 hours and is dose-dependent.
Pharmacokinetics
Absorption and distribution After ingestion, cabergoline is rapidly absorbed from the gastrointestinal tract. Cmax in plasma is achieved in 0.5-4 hours. Binding to plasma proteins is 41-42%. Css is reached after 4 weeks of therapy due to prolonged T1 / 2. Food intake does not affect absorption and distribution of cabergoline. Metabolism The main product of cabergoline metabolism identified in urine is 6-allyl-8β-carboxy-ergoline at a concentration of up to 4-6% of the accepted doses. The content in the urine of 3 additional metabolites does not exceed 3% of the dose. Metabolism products have a significantly lower effect on suppressing secretion of prolactin compared to cabergoline. T1 / 2 output, estimated by the rate of kidney excretion, is 63-68 h in healthy volunteers and 79-115 h in patients with hyperprolactinemia. 10 days after taking the drug in urine and feces are found, respectively, 18% and 72% of the dose, with the proportion of unchanged cabergoline in the urine is 2-3%.
Indications
- Prevention of physiological postpartum lactation; - Suppression of established postpartum lactation; - Treatment of disorders associated with hyperopia, including amenorrhea, oligomenorrhea, anovulation and galactorrhea; - Prolactin-secreting adenomas of the pituitary gland (micro- and macroprolactinomas), and idiopathic hypoprotection of the body of the hip; hyperprolactinemia.
Contraindications
- hypersensitivity to cabergoline or other components of the drug, as well as to any ergot alkaloids - dysfunction of the heart and respiration due to fibrotic changes or the presence of such conditions in history; - with prolonged therapy: anatomical signs of pathology of the valvular apparatus of the heart (such as thickening of the valve leaflet , narrowing of the valve lumen, mixed pathology (narrowing and stenosis of the valve), confirmed by an echocardiographic study (EchoCG), conducted prior to the start of therapy; - lactose intolerance, de lactase phycite, glucose-galactose malabsorption.— childhood and adolescence under 16 years of age (safety and efficacy have not been established). Doverex; should be prescribed with caution in the following conditions and / or diseases: - arterial hypertension that developed during pregnancy, for example, pre-eclampsia or postpartum arterial hypertension (Dostinex; appointed only in cases where the potential benefit from the use of the drug significantly exceeds the possible risk); - severe cardiovascular diseases, Raynaud's syndrome; - peptic ulcer, gastrointestinal bleeding; - severe liver failure (use of lower doses is recommended); yellow psychotic or cognitive impairment (including history); simultaneous use with drugs that have a hypotensive effect (due to the risk of orthostatic hypotension).
Use during pregnancy and lactation
Since controlled clinical studies using the drug Dostinex; in pregnant women was not carried out, the appointment of the drug during pregnancy is possible only in cases of extreme necessity, when the expected benefit to the mother outweighs the potential risk to the fetus. If the pregnancy occurred during the treatment with the drug Dostinex ;,The feasibility of discontinuing the drug should be considered, also taking into account the benefit / risk ratio. According to available data, Dostinex's use in a dose of 0.5-2 mg per week for disorders associated with hyperprolactinemia was not accompanied by an increase in the frequency of miscarriages, premature birth, multiple pregnancy and congenital malformations. There is no information on the release of the drug in breast milk, but in the absence of the effect of the use of the drug Dostinex; to prevent or suppress lactation should refuse breastfeeding. For disorders associated with hyperprolactinemia, Dostinex; should not be assigned to mothers who do not want to stop lactation.
Dosage and administration
Is taken orally, during meals. Prevention of lactation: 1 mg (2 tab.) Once on the first day after birth. Suppression of established lactation: 250 mcg (1/2 tab.) 2 times / day every 12 hours for 2 days ( total dose is 1 mg). In order to reduce the risk of orthostatic hypotension in breastfeeding mothers, a single dose of Dostinex should not exceed 250 mcg. Treatment of disorders associated with hyperprolactinemia: the recommended initial dose is 500 mcg per week in 1 (1 tab.) Or 2 doses (1/2 tab., for example, on Monday and Thursday). Increasing the weekly dose should be carried out gradually - by 500 mcg with an interval of 1 month to achieve the optimal therapeutic effect. The therapeutic dose is usually 1 mg per week, but can range from 250 μg to 2 mg per week. The maximum dose for patients with hyperprolactinemia is 4.5 mg per week. Depending on tolerance, the weekly dose can be taken once or divided into 2 or more doses per week. The division of a weekly dose into several doses is recommended when prescribing a drug in a dose of more than 1 mg per week. In patients with hypersensitivity to dopaminergic drugs, the likelihood of side effects can be reduced by starting Dostinex therapy; at a lower dose (250 μg 1 time per week), followed by a gradual increase until a therapeutic dose is reached. To improve the tolerability of the drug in the event of severe side effects, a temporary dose reduction is possible, followed by a gradual increase, for example, by 250 mcg per week every 2 weeks.
Side effects
During clinical studies using the drug Dostinex; to prevent physiological lactation (1 mg once) and to suppress lactation (250 mcg every 12 hours for 2 days), adverse reactions were observed in approximately 14% of women. When using the drug 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 incidence of adverse reactions was 68%. Adverse reactions occurred mainly during the first 2 weeks of therapy and in most cases disappeared as therapy continued or several days after discontinuation of the drug Dostinex; Adverse reactions were usually transient, mild or moderate in severity and dose-dependent. At least once during the course of therapy, severe side effects were observed in 14% of patients; due to adverse reactions, treatment was discontinued in approximately 3% of patients. The most frequent adverse reactions are presented below. From the cardiovascular system: palpitations; rarely, orthostatic hypotension (with prolonged use, the drug has a hypotensive effect); asymptomatic decrease in blood pressure during the first 3-4 days after delivery (systolic - more than 20 mm Hg, diastolic - more than 10 mm Hg). From the nervous system: dizziness / vertigo, headache, fatigue, drowsiness, depression, asthenia, paresthesias, fainting, nervousness, anxiety, insomnia, impaired concentration oral cavity, diarrhea, flatulence, toothache pain, sensation of irritation of the pharyngeal mucosa. Other: mastodynia, nasal bleeding, rush of blood to the skin of the face, transient hemianopsia, vascular spasms of the fingers, muscle cramps of the lower limbs (like other ergot derivatives, Dostinex; flu-like symptoms, malaise, periorbital and peripheral edema, anorexia, acne, pruritus, joint pain. During long-term therapy with the use of the drug Dostinex; abnormal standard laboratory parameters were rarely observed; in women with amenorrhea, a decrease in hemoglobin level was observed during the first few months after the restoration of menstruation. The following adverse reactions were reported in the post-marketing study,associated with the use of cabergoline: alopecia, increased activity of CK in the blood, mania, dyspnea, edema, fibrosis, abnormal liver function, abnormal liver function indicators, hypersensitivity reactions, rash, respiratory disorders, respiratory failure, valvulopathy, pathological gambling addiction, hypersexuality. increased libido, aggressiveness, psychotic disorders, pericarditis, attacks of sudden sleep, weight loss or increase, nasal congestion.
Overdose
Symptoms (more likely, symptoms of dopamine receptor hyperstimulation): nausea, vomiting, dyspeptic symptoms, orthostatic hypotension, confusion, psychosis, hallucinations. Treatment: measures should be taken to eliminate the drug (gastric lavage) and to maintain blood pressure. The use of dopamine antagonists is recommended.
Interaction with other drugs
Information about the interaction of cabergoline and other ergot alkaloids is absent, therefore the simultaneous use of these drugs during long-term therapy with the Dostinex drug; not recommended. Because cabergoline has a therapeutic effect by direct stimulation of dopamine receptors, the drug should not be administered simultaneously with drugs acting as dopamine antagonists (including phenothiazines, butyrophenones, thioxanthenes, metoclopramide), because they can weaken the effect of cabergoline, aimed at reducing the concentration of prolactin. Like other ergot derivatives, cabergoline cannot be used simultaneously with macrolide antibiotics (for example, erythromycin), as this may lead to an increase in the systemic bioavailability of cabergoline.
special instructions
Before the appointment of the drug Dostinex; In order to treat disorders associated with hyperprolactinemia, it is necessary to conduct a full study of the function of the pituitary gland. In addition, the state of the cardiovascular system, including echoCG, should be assessed in order to detect dysfunction of the valvular apparatus asymptomatic. As with other ergot derivatives, after long-term use of cabergoline in patients was observed pleural effusion / pleural fibrosis and valvulopathy.In some cases, patients received prior therapy with ergotonin dopamine agonists. Therefore, Dostinex; should not be used in patients with existing signs and / or clinical symptoms of dysfunction of the heart or respiration associated with fibrotic changes or with such conditions in history. The drug should be discontinued if there are signs of the appearance or worsening of blood regurgitation, narrowing of the lumen of the clalans or thickening of the valve leaflets. It has been established that the ESR increases with the development of pleural effusion or fibrosis. If an unexplained increase in ESR is detected, it is recommended to perform a chest X-ray. A study of the concentration of creatinine in the blood plasma and an assessment of renal function can also help in the diagnosis. After discontinuation of the drug Dostinex; symptoms improved in patients with pleural effusion / pleural fibrosis or valvulopathy. It is not known whether cabergoline may worsen the condition of patients with signs of blood regurgitation. Cabergoline should not be used in the detection of fibrous lesions of the cardiac valve apparatus. Fibrotic disorders may develop asymptomatically. In this regard, the condition of patients receiving long-term treatment with cabergoline should be regularly monitored and special attention should be paid to the following symptoms: - pleuro-pulmonary disorders: such as shortness of breath, difficulty in breathing, persistent cough or chest pain; - renal insufficiency or obstruction of ureteral vessels or abdominal organs, which may be accompanied by pain in the side or in the lumbar region and swelling of the lower extremities, any swelling or soreness on palpation in the abdominal region, which may show elstvovat on the development of a retroperitoneal fibrosis; -perikardialny fibrosis and fibrosis of the valves of the heart valves often manifest heart failure. In this regard, it is necessary to exclude fibrosis of valvular valves (and constrictive pericarditis) when symptoms of heart failure appear. Regular monitoring of the patient's condition for the development of fibrotic disorders should be carried out. The first time echoCG should be performed 3-6 months after the start of therapy.Then, this study should be carried out depending on the clinical assessment of the patient’s condition, paying particular attention to the symptoms described above at least every 6-12 months of therapy. The need for other monitoring methods (for example, physical examination, including auscultation of the heart, x-rays, computed tomography) is evaluated individually for each patient. When increasing the dose, patients should be under the supervision of a physician in order to establish the minimum effective dose that provides therapeutic Effect. After an effective dosing regimen is selected, it is recommended that a regular (1 time per month) determination of serum prolactin concentration be recommended. Normalization of prolactin concentration is usually observed within 2-4 weeks of treatment. After discontinuation of the drug Dostinex; recurrence of hyperprolactinemia is usually observed, however, in some patients persistent inhibition of prolactin concentration is observed for several months. In most women, ovulatory cycles persist for at least 6 months after discontinuation of the drug Dostinex; Dostrax; restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Since pregnancy can occur before menstruation is restored, it is recommended that pregnancy tests be performed at least once every 4 weeks during the amenorrhea period, and after menstruation is restored every time there is a delay in menstruation for more than 3 days. Women wishing to avoid pregnancy should use barrier methods of contraception during treatment with the drug Dostinex; as well as after discontinuation of the drug before repeating anovulation. Women who have become pregnant should be under the supervision of a physician for the timely detection of symptoms of an increase in the pituitary gland, since during pregnancy it is possible to increase the size of pituitary tumors that already exist. should be administered in lower doses to patients with severe hepatic insufficiency (Child-Pugh class C), who are indicated for prolonged therapy with the drug. With a single dose of 1 mg in these patients, an increase in AUC was observed compared with healthy volunteers and patients with less severe liver failure. The use of cabergoline causes drowsiness. In patients with Parkinson's disease, the use of dopamine receptor agonists can cause sudden sleep.In such cases, it is recommended to reduce the dose of the drug Dostinex; or discontinue therapy. There were no studies on the use of the drug in elderly patients with disorders associated with hyperprolactinemia. Use in pediatricsSafety and efficacy of the drug in children and adolescents under 16 years of age has not been established. Dostinex ;, should refrain from driving vehicles and mechanisms and other potentially dangerous activities requiring concentration of attention and the speed of psychomotor reactions.