Flutamide - instructions for use, doses, side effects, contraindications

Competitively blocks androgen receptors cells of target tissues and prevents the binding of androgens. Prevents the manifestation of the biological effects of androgens in androgen-sensitive organs (including the prostate gland and seminal vesicles). After taking flutamide, there is an increase in plasma levels of testosterone and estradiol.The ability of flutamide to interfere with the action of testosterone at the cellular level serves as a supplement to the drug castration caused by analogues of gonadotropin-releasing hormone.

With external application prevents hair growth. The effect is achieved after 2-3 months and is manifested by thinning and enlightening the hair, facilitating their hair removal, slowing growth, partial loss.

Pharmacokinetics:When ingested quickly and completely absorbed from the digestive tract. Metabolised in the liver. At least 6 metabolites have been identified. The main metabolite found in the blood plasma is alpha-hydroxyls(2-hydroxyflutamide) is biologically active. Binding to plasma proteins is 94-96% (flutamide) and 92-94% (2-hydroxyflutamide). The maximum concentration of 2-hydroxyflutamide is 2 hours. The half-life of 2-hydroxyflutamide is 6 hours (in elderly patients 8 hours after a single dose and 9.6 hours after reaching a stable concentration). It is excreted mainly by kidneys in the form of metabolites, 4.2% - with feces for 72 hours.

Indications:

Tablets: palliative treatment of progressive prostate cancer (including metastases) in the form of monotherapy (with or without orchiectomy) or in combination with agonists gonadotropin-releasing hormone; treatment of locally advanced prostate cancer B2-C2 (T2b-T4). Differential diagnosis of hypogonadism in men.

Ointment: hirsutism.

ICD-10

II.C60-C63.C61 Malignant neoplasm of prostate

XII.L60-L75.L68.0 Hirsutism

XXI.Z40-Z54.Z51.5 Palliative Care

Contraindications:

Ingestion: hypersensitivity, severe liver, kidney, thyroid gland.Child age (safety and efficacy not established).

Outer (ointment): kidney disease, pregnancy.

Carefully:Cardiovasculara tendency to thrombosis, a decreased function of the liver. Conditions predisposinge to intoxication with aniline (one of the metabolites flutamide - methylaniline derivative): deficiency of glucose-6-phosphate dehydrogenase, smoking, hemoglobinopathy (M hemoglobin).

Pregnancy and lactation:

Recommendations for FDA category - H. In view of the potential risk to the fetus (feminization of male fetuses), women of childbearing age during treatment are recommended to use contraceptives.

Information about penetration into breast milk is not present.In view of the potential risk of adverse effects on the child during treatment with flutamide, breastfeeding is recommended to be discontinued.

Dosing and Administration:

Inside: prostate cancer - 250 mg 3 times a day; differential diagnosis of male hypogonadism - 10 mg / kg per day in 3 doses for 3 days, with the study of daily excretion of lutropin and / or total gonadotropins before and on the background of the third day of the drug intake. It is acceptable to sample for 5 days, with the study of daily excretion of lutropin and total gonadotropins on the background of the fifth day of intake.

Outer: the ointment is applied in a thin layer, lightly rubbing, on the skin of the face with excessive hair, 2-3 times a day; After reaching the effect (2-3 months), the ointment can be applied once a day. Treatment is carried out in courses lasting 6-8 months with a break of 1 month.

Side effects:

From the side endocrine system: gynecomastia and / or galactorrhea, decreased libido, impotence.

From the side digestive system: nausea, vomiting, jaundice, diarrhea, increased activity of hepatic transaminases, increased or no appetite.

From the side water-electrolyte exchange: fluid retention.

Other: rarely - headache, thromboembolism, impaired renal function, sleep disorders, subcutaneous hemorrhage, lupus-like syndrome, methemoglobinemia, suppression of spermatogenesis (with prolonged treatment), paresthesia.

For external use: skin allergic reactions (redness, burning sensation, rash).

Overdose:

The dose, the reception of which would threaten life, is not defined. Doses not exceeding 1500 mg per day (2 times higher than recommended) and administered within 36 weeks of clinical studies cause gynecomastia, chest stress and increased activity of hepatic enzymes (noted when prescribed in the recommended doses).

Acute overdose: decreased activity, piloerection, ataxia, lacrimation, anorexia, vomiting, methemoglobinemia, slowing of breathing.

Chronic intoxication in dogs: myocardial damage in the form of chronic myxomatous degeneration, intra-atrial fibrosis, acidophilic degeneration of the myocardium, vasculitis and perivasculitis.

There is no specific antidote.

Symptomatic treatment, induction of vomiting, monitoring of vital functions.

Interaction:

Amphotericin B. When combined use increases the risk of kidney damage and the likelihood of developing bronchospasm and hypotension.

Busulfan. Against the background of flutamide, the risk of developing veno-occlusive disease of the liver increases.

Warfarin. Flutamide enhances the effect of warfarin; when combined, a dose reduction may be required.

Dakarbazin increases (mutually) the probability of damage to the liver.

Dakarbazin. Flutamide increases (mutually) the risk of manifestation of hepatotoxicity.

Doxorubicin. Strengthens (mutually) the risk of side effects.

With the combined use of theophylline and flutamide, the concentration of theophylline in the blood can increase.

Special instructions:

When treating prostate cancer, it is necessary to monitor liver function (laboratory tests should be performed once a month for the first four months and then regularly). In the case of an increase in the level of hepatic enzymes 2-3 times in comparison with the upper limit of normal values and / or the appearance of jaundice in the absence of metastases to the liver, the use of flutamide should be discontinued. With the appearance of the first symptoms of liver dysfunction, such as itchy skin, darkening of urine,nausea, vomiting, persistent loss of appetite, yellowing of the skin or whites of the eyes, pain in the right upper quadrant or flu-like symptoms of vague origin should immediately consult a doctor.

When evaluating the results of differential diagnosis of male hypogonadism, it is necessary to focus on the following indicators: in healthy people with normal basal excretion of gonadotropins after administration of the drug, an increase in their excretion of 1.5 times or more is observed; when primary hypogonadism, the initial excretion of gonadotropins is significantly increased, less often - normal, the use of the drug leads to a further increase in their release by 1.5-2 times or more; with secondary hypogonadism, the initial excretion of gonadotropins is reduced, rarely - normal, there is no significant increase in their release after taking the drug.

The use of flutamide in humans leads to a decrease in the number of spermatozoa.

There may be a change in the color of urine from amber to yellow-green.

Instructions

Flutamide (Flutamidum)