Index of drugs

Treatment of metastatic metastatic prostate cancer in adult males with no symptoms or mild symptoms after treatment failure with androgen deprivation and for which chemotherapy is not yet clinically indicated. Treatment of metastatic prostate cancer with metastases in adult males who have progressed during or after treatment with docetaxel.

1 soft capsule contains 40 mg of enzalutamide; the drug contains sorbitol.

A strong inhibitor of androgen receptor signaling. It blocks several steps of the signaling pathway through the androgen receptor. Enzalutamide competitively blocks the binding of androgens to the androgen receptor, blocks the transfer of the active receptor to the nucleus, and the binding of the active androgen receptor to the DNA, even in the case of overexpression of androgen receptors, and in prostate cancer resistant to antiandrogen treatment. Treatment with enzalutamide reduces the growth of prostate cancer cells, can cause death of these cells and regression of cancer. In non-clinical studies, enzalutamide did not show agonist androgen receptor activity. After a single oral administration, medium T_0,5 in the final phase is 5.8 days (range: 2.8-10.2 days). Steady state is reached after about 1 month. Enzalutamide administered daily, orally, accumulates about 8.3-fold compared to a single dose. C_max enzalutamide is observed 1-2 h after administration. The absorption value of enzalutamide after oral administration was determined to be at least 84.2%. Enzalutamide and its active metabolite can penetrate the blood-brain barrier. Enzalutamide binds in 97-98% with plasma proteins, mainly albumin. The active metabolite is 95% bound to plasma proteins. Enzalutamide is extensively metabolised. There are two major metabolites in human plasma: N-desmethylenzalutamide (active metabolite) and a carboxylic acid derivative (inactive metabolite). Enzalutamide is metabolised by cytochrome CYP2C8 and to a lesser extent cytochrome CYP3A4 / 5. Both play a role in the formation of the active metabolite. The drug is excreted in 71% in the urine (mainly in the form of an inactive metabolite, with traces of enzalutamide and its active metabolite), 13.6% - in the faeces (0.39% of the dose in the form of unchanged enzalutamide).

Hypersensitivity to the active substance or to any of the excipients. Pregnant women or women who could become pregnant.

Caution should be exercised when administering to a patient with history of epileptic seizures or other factors described in the history that predispose to their occurrence, including, but not limited to: primary brain injury, stroke, primary brain tumors or metastases to the brain, or alcoholism. In addition, the risk of seizures may be increased in patients who are taking concomitant medications that lower the seizure threshold. Enzalutamide is a powerful enzyme inducer and may cause the lack of efficacy of many commonly used drugs. When introducing enzalutamide treatment, a review of concomitant medications should be carried out. In general, the use of enzalutamide should be avoided at the same time as medications that are sensitive substrates of many metabolizing enzymes or carriers if their therapeutic effect is of great concern to the patient and if dosage adjustment is not easily achieved by monitoring the efficacy or concentration of these drugs in the plasma. Combination with Warfarin and anticoagulant coumarin derivatives should be avoided; when co-administered with CYP2C9 metabolisers (such as warfarin or acenocoumarol), additional prothrombin time (INR) monitoring should be introduced. Caution should be exercised in patients with severe renal impairment (no study). Caution should be exercised in patients with moderate hepatic impairment (Child-Pugh Class B). It is not recommended for patients with severe hepatic impairment (Child-Pugh Class C) (no data available). From clinical trials 3.phases have been excluded from patients with recent myocardial infarction (in the last 6 months) or unstable angina (in the last 3 months), NYHA class III or IV heart failure, except when the left ventricular ejection fraction (LVEF) was ≥45%, patients with bradycardia or untreated or not recoverable hypertension. This should be taken into account when prescribing enzalutamide to these patients. The safety and efficacy of the preparation during chemotherapy have not been established. Co-administration of enzalutamide has no clinically relevant effect on the pharmacokinetics of intravenously administered docetaxel; however, an increased incidence of docetaxel-induced neutropenia can not be excluded. There is no significant use of enzalutamide in children and adolescents in the treatment of metastatic prostate cancer with metastases in adult males. The preparation contains sorbitol - it should not be used in patients with rare hereditary problems of fructose intolerance.

Enzalutamide is not indicated for use in women. It is contraindicated in women who are pregnant or may become pregnant. It is not known whether enzalutamide or its metabolites are present in sperm. If a patient undergoing sexual intercourse with a pregnant woman during treatment and for 3 months after it ends, he should use a condom. If a patient has sexual intercourse with a woman of childbearing age during treatment and for 3 months after the end of treatment, he must use a condom and another effective method of contraception. Animal studies have shown deleterious effects on reproduction and the negative effects on the reproductive system of male rats and dogs.

Very common: headache, hot flushes, hypertension. Common: anxiety, memory disorders, memory loss, attention disorders, restless legs syndrome, gynecomastia, dry skin, pruritus, fractures, falls. Uncommon: leukopenia, neutropenia, visual hallucinations, cognitive impairment, epileptic seizures. Frequency unknown: muscle pain, muscle cramps, muscle weakness, back pain.

Orally. Adult males: 160 mg (4 capsules) in a single daily dose. In non-surgically treated patients, pharmacological castration with LHRH analogues should be continued during treatment. If you do not take your medicine at the usual time, take your prescribed dose as soon as possible. If a dose is missed on a given day, treatment should be resumed the Next day by taking the usual daily dose. If you have symptoms of Grade ≥3 toxicity. or side effects difficult to tolerate, discontinue the use of the drug for a week or until the symptoms are reduced to grade ≤ 2. Then, use the drug again in the same or, if justified, reduced dose (120 mg or 80 mg).Co-administration with strong CYP2C8 inhibitors. If possible, avoid such a connection. If concomitant use of strong CYP2C8 inhibitors is necessary, the dose of enzalutamide should be reduced to 80 mg once a day. In the event of discontinuation of co-administration with strong CYP2C8 inhibitors, the dose of enzalutamide used before initiating treatment with strong CYP2C8 inhibitors should be resumed.Special groups of patients. No dose adjustment is necessary in elderly patients. No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh A); be cautious in patients with moderate hepatic impairment (Child-Pugh B); Do not use in patients with severe hepatic impairment (Child-Pugh C). No dose adjustment is necessary for patients with mild or moderate renal impairment; be cautious in patients with severely impaired renal function or in the final stage of renal disease.Way of giving. The capsules should be swallowed whole with water; take with or without food.