Flutamid

General characteristics. Structure:

Active ingredient: 250 mg of a flutamid in 1 tablet.

The drug possessing anti-androgenic and antineoplastic action.

Pharmacological properties:

Pharmacodynamics. Competitively blocks androgenic receptors of cells of target tissues and interferes with linkng of androgens with them. Prevents manifestation of biological effects of androgens in androgenchuvstvitelny bodies (including a prostate and seed bubbles). After reception of a flutamid increase in plasma levels of testosterone and oestradiol is noted. Ability of a flutamid to interfere with effect of testosterone at the cellular level serves as addition to the medicinal castration caused by analogs a gonadotrophin-rileasing of hormone (GNRG).

Pharmacokinetics. At intake it is quickly and completely soaked up from a GIT. It is metabolized in a liver. At least 6 metabolites are identified. The main metabolite found in a blood plasma — alpha and hydroxylated derivative (2-oksiflutamid) — is biologically active. Linkng with proteins of plasma makes 94–96% (флутамид) and 92–94% (2-oksiflutamid). Cmax  of a 2-oksiflutamid — the 2nd p. T1/2  of a 2-oksiflutamid — 6 h (patients of advanced age have 8 h after a single dose and 9,6 h at achievement of stable concentration). 4,2% — with excrements during 72 h are removed preferential by kidneys in the form of metabolites.

At external use interferes with growth of hair. The effect is reached in 2–3 months and shown by thinning and an enlightenment of hair, simplification of their epilation, growth delay, partial loss.

Indications to use:

Tablets: palliative treatment of the progressing prostate cancer (including with metastasises) in the form of monotherapy (when performing or without orkhiektomiya) or in a combination with GNRG agonists; treatment of a locally-spread prostate cancer (T2b  — T4). Differential diagnosis of a hypogonadism at men.

Ointment: hirsutism.

Route of administration and doses:

Inside: a prostate cancer — on 250 mg 3 times a day; differential diagnosis of a men's hypogonadism — on 10 mg/kg / сутв 3 receptions within 3 days, with a research of daily excretion of a lyutropin and/or total gonadotrophins to and against the background of the day before yesterday administration of drug. Conducting test within 5 days, with a research of daily excretion of a lyutropin and total gonadotrophins against the background of the fifth day of reception is admissible.

Outwardly: ointment is applied a thin layer, slightly rubbing, on sites of face skin with excess pilosis, 2–3 times a day; after achievement of effect (2–3 months) it is possible to apply ointment 1 time a day. Treatment is carried out by courses lasting 6-8 months with a break 1 month.

Features of use:

At cancer therapy of a prostate it is necessary to control function of a liver (laboratory analyses should be carried out within the first four months once a month and further it is regular). In case of increase in level of liver enzymes by 2–3 times in comparison with an upper limit of normal values and/or emergence of jaundice in the absence of metastasises in a liver, use of a flutamid it is necessary to stop.

At emergence of the first symptoms of an abnormal liver function, such as skin itch, urine darkening, nausea, vomiting, permanent loss of appetite, yellowing of integuments or whites of the eyes, painful feelings in right hypochondrium or grippopodobny symptoms of not clear origin it is necessary to see a doctor immediately.

At assessment of results of differential diagnosis of a men's hypogonadism, it is necessary to be guided by the following indicators: at healthy people at normal basal excretion of gonadotrophins after administration of drug increase in their allocation by 1,5 times and more is observed; at primary hypogonadism initial excretion of gonadotrophins is considerably raised, is more rare — normal, use of drug leads to further increase in their allocation by 1,5–2 times and more; at a secondary hypogonadism initial excretion of gonadotrophins is lowered, is more rare — normal, essential increase in their allocation after administration of drug is not observed.

Change of coloring of urine from amber to flavovirent can be observed.

Category of action on a fruit on FDA — D.

Side effects:

Gynecomastia and/or morbidity in the field of chest glands, a galactorrhoea, a liquid delay, decrease a libido, impotence, nausea, vomiting, diarrhea or a lock, increase or lack of appetite, an abnormal liver function and/or kidneys, jaundice, sleeplessness, a headache, paresthesia, allergic reactions, hypodermic hemorrhages, a methemoglobinemia, a volchanochnopodobny syndrome, suppression of a spermatogenesis (at prolonged treatment).

At external use: skin allergic reactions (reddening, burning sensation, rash).

Interaction with other medicines:

At systemic action strengthening of anticoagulative effect of warfarin is possible (the dose of anticoagulant should be selected under control of a prothrombin time).

Contraindications:

At intake: hypersensitivity, serious illness of a liver, kidneys, thyroid gland.

Outwardly (ointment): diseases of kidneys, pregnancy.

Restrictions to use. Cardiovascular diseases, tendency to fibrinferments, reduced function of a liver.

Overdose:

Treatment: if the patient in consciousness and without spontaneous vomiting, it is necessary to cause vomiting. Control of the vital functions, symptomatic therapy is necessary. The hemodialysis and peritoneal dialysis are inefficient (owing to high extent of linkng with proteins of plasma).

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 250 mg, 10 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.