The drug is indicated in combination with prednisone or Prednisolone for: castrate-resistant treatment, metastatic prostate cancer in adult men, no symptoms or symptoms of slight / slight intensity, after failure of androgen suppression therapy, in which the use of chemotherapy is not yet indicated clinically; treatment, refractory castration, prostate cancer with metastases in adult men whose disease progresses during or after chemotherapy with docetaxel.
Composition:
1 tabl contains 250 mg of abiraterone acetate; the preparation contains lactose and sodium.
Action:
Inhibitor of androgen biosynthesis. The abirateron acetate isin vivo rapidly hydrolyzed to abiraterone, which selectively inhibits the activity of the CYP17 enzyme (with 17α-hydroxylase and C17,20-lyase activity), necessary for the biogenesis of androgens in the testes, adrenal glands and tumor tissues of the prostate gland. Inhibition of CYP17 also results in increased production of mineralocorticosteroids in adrenal glands. After oral administration, the drug achieves Cmax during 2 hours. Food significantly increases AUC and Cmax abiraterone. Abiraterone in approximately 99.8% is bound to plasma proteins. It is metabolized, among others through sulfurization, hydroxylation and oxidation, mainly in the liver. It is excreted mainly via faeces (88%). T0,5 is 15 hours.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Women who are or may be likely to be pregnant. Severe liver dysfunction.
Precautions:
Due to the risk of hypertension, hypokalemia and stagnation of fluids during treatment with abiraterone, caution should be exercised in patients with cardiovascular diseases (severe or unstable angina pectoris, left ventricular ejection fraction <50%, NYHA class III or IV heart failure, recent myocardial infarction, ventricular arrhythmia), treated with cardiac glycosides, with severe renal dysfunction. Before starting treatment and then at least once a month, you should monitor your blood pressure, blood potassium levels and symptoms of fluid stasis; treat hypertension and alleviate hypokalemia. The blood aminotransferase levels should be assessed before starting treatment, every 2 weeks for the first 3 months of treatment and then monthly. If hepatotoxicity occurs, depending on its severity, dose modification or complete discontinuation of abiraterone therapy is recommended (see dosage). Patients with active or symptomatic viral hepatitis have not been included in clinical trials, therefore there is no evidence to support the desirability of abiraterone in this population. In patients with moderate or severe hepatic impairment (Child-Pugh B or C), drug exposure may be significantly increased; no recommendation on dosage can be made - the preparation should be avoided in these patients. Patients discontinuing prednisone or prednisolone should be observed for signs of adrenal insufficiency. If abiraterone continues to be administered after discontinuation of corticosteroids, patients should be monitored for signs of excess mineralocorticoid. If patients using prednisone or prednisolone may be exposed to extreme stress, it may be advisable to increase the dose of corticosteroids before, during and after the stressful situation. In men with advanced prostate cancer with metastases (castrated prostate cancer), a reduction in bone density may occur; treatment with abiraterone in combination with glucocorticosteroids may enhance this effect. Patients who have previously used ketoconazole to treat prostate cancer may be expected to have a weaker response. The sodium content of the preparation (27.2 mg, i.e.> 1 mmol in a dose of 4 tablets) should be taken into consideration by people on a low sodium diet. Due to the lactose content, the preparation should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose.
Pregnancy and lactation:
The drug is not used in women. Abiraterone is contraindicated in pregnant women or women who could become pregnant, because the use of a CYP17 inhibitor by a pregnant woman may cause changes in hormone levels that may interfere with fetal development. It is not known whether abiraterone or its metabolites are detectable in semen. It is necessary to use a condom in the case of sexual activity of a patient with a pregnant woman. In the case of sexual activity of a patient with a woman in childbearing period, it is necessary to use a condom simultaneously with another effective method of contraception.
Side effects:
Very common: urinary tract infection, hypokalemia, hypertension, peripheral edema. Common: hypertriglyceridemia, heart failure (including congestive heart failure, left ventricular dysfunction and decreased ejection fraction), angina pectoris, arrhythmia, atrial fibrillation, tachycardia, ALT increase, fractures. Uncommon: adrenal insufficiency. Mineralocorticoid reactions can usually be effectively treated; concomitant use of corticosteroids reduces the frequency and severity of these side effects.
Dosage:
Orally. Adult men: the recommended dose is 1000 mg (4 tablets of 250 mg) given once only once a day. The medicine must not be taken with food. Taking a medicine with food increases the total exposure of the body to abiraterone. The preparation should be taken in combination with a low dose of prednisone or prednisolone. The recommended dose of prednisone or prednisolone is 10 mg per day. In non-surgically treated patients, pharmacological castration with LHRH analogues should be continued during treatment. The aminotransferases should be assessed before starting treatment, every 2 weeks for the first three months of treatment and then monthly. Blood pressure, serum potassium and fluid stasis should be assessed monthly. However, patients with a significant risk of congestive heart failure should be examined every 2 weeks for the first 3 months of therapy and then monthly. In patients with pre-existing hypokalaemia or hypokalaemia, which developed during treatment with the product, potassium levels should be maintained at ≥4.0 mM. In patients who have grade ≥3 toxicity. including hypertension, hypokalemia, edema and other non-mineralocorticoid-related activities, treatment should be withheld and appropriate measures instituted. Do not resume treatment with the preparation until the severity of symptoms decreases to grade 1 or baseline values. If the daily dose of both abiraterone acetate, prednisone or prednisolone is omitted, the usual recommended daily dose should be resumed the Next day.Hepatotoxicity. In patients who develop hepatotoxic effects during treatment (ALT or AST elevations more than 5 times above ULN), treatment should be stopped immediately. Resumption of treatment after return of liver function tests to baseline values may be continued at a reduced daily dose of 500 mg once a day. In patients who have resumed treatment, serum transaminases should be tested every 2 weeks for 3 months and then monthly. If hepatotoxicity recurs with a reduced dose of 500 mg daily, treatment should be discontinued. In case of severe hepatotoxicity (ALT or AST elevation more than 20 times above ULN), during treatment, the drug should be discontinued and should not be restarted.Hepatic dysfunction. No dose adjustment is required in patients with pre-existing mild hepatic impairment, Child-Pugh Class A. There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate given to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). Dose adjustment recommendations can not be made. The use of the drug should be carefully evaluated in patients with moderate hepatic impairment, the benefits of which should clearly outweigh the possible risks. Do not use the drug in patients with severe hepatic impairment.Impaired renal function. No dose adjustment is required in patients with impaired renal function. There are no clinical data in patients with prostate cancer and severe renal impairment. Caution should be exercised in these patients.Children and youth - there is no appropriate use in this population, as prostate cancer is absent in children and adolescents.Method of administration. The drug should be taken at least 2 hours after a meal and should not be eaten for at least 1 hour after it has been taken. The tablets should be swallowed whole with water.
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