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

One tablet contains: active ingredient: flutamide 250 mg excipients: lactose monohydrate 200 mg, potato starch 80 mg, microcrystalline cellulose 80 mg, sodium lauryl sulfate 15 mg, corn starch 70 mg povidone KZO -25 mg, silicon dioxide colloid-5 mg, cross-povidone-20 mg, magnesium stearate-5 mg

Description:

Round biconvex from pale yellow to yellow pills with a risk.

Pharmacotherapeutic group:Antitumor agent, antiandrogen.

ATX: & nbsp

L.02.B.B.01 Flutamide

Pharmacodynamics:

Flutamide is a non-steroidal antiandrogenic antitumor drug. Competitively blocks the interaction of androgens with their cellular receptors. The mechanism of action is based on inhibition of androgen uptake and / or inhibition of androgen binding in target cell nuclei. Its ability to inhibit the action of testosterone at the cellular level is in addition to the drug "castration" caused by gonadotropin-releasing hormone (GnRH) agonists. The target organ of the pharmacological action of flutamide is the prostate gland and seminal vesicles. Flutamide does not possess estrogenic, antiestrogenic, progestogen and anti-gestagenic activity.

Pharmacokinetics:

The drug is completely and rapidly absorbed after ingestion, undergoing biotransformation in the liver. The main metabolite found in blood plasma, the maximum concentration of which is achieved after 2 hours, is a biologically active a-hydroxylated derivative (2-oxyflutamide). 94-96% flutamide and 92-94% of the a-hydroxylated metabolite binds to plasma proteins.From the body, the drug is excreted mainly by the kidneys, about 4.2% is excreted by the intestine within 72 hours. The half-life of the active metabolite from the plasma is about 6 hours (in elderly patients - 8 hours after a single dose and 9.6 hours at an equilibrium concentration). After multiple administration of flutamide 250 mg three times a day, a stable level of drug concentration and its active metabolite in plasma is achieved after a fourth dose of flutamide.

Indications:

Treatment of metastatic prostate cancer when suppression of testosterone is indicated:

at the beginning of treatment in combination with GnRH agonists;
as an additional treatment for patients already receiving therapy with GnRH agonists;
in patients with surgical castration;
treatment of patients in whom other types of hormone therapy were ineffective or when intolerance of such treatment.

Contraindications:

Hypersensitivity to flutamide or any other component of the drug.
Severe hepatic insufficiency.
Child age (safety and efficacy not established)

Carefully:

in patients with impaired liver function, with a tendency to thrombosis and cardiovascular diseases, as well as in conditions predisposing to intoxication aniline (one of the metabolites flutamide - methylaniline derivative): deficiency of glucose-6-phosphate dehydrogenase, smoking, hemoglobinopathy (M- hemoglobin).

Dosing and Administration:

Inside, 250 mg 3 times a day every 8 hours. In case of achieving a positive effect, the drug is used until signs of progression of the tumor develop.

In the case of combined therapy with GnRH agonists, both drugs can be given concomitantly, or Flutamide is administered three days before the first admission of the GnRH agonist.

Side effects:

The incidence of side effects is described in accordance with the following gradation: most often (10% and higher), less often (from 1 to 10%), rarely (less than 1%).

When using the drug in monotherapy

Most often: gynecomastia and / or pain in the region of the breast, sometimes accompanied by galactorrhea. These phenomena disappear after the cessation of treatment. or dose reduction.

Less often: diarrhea, nausea, vomiting, increased appetite, insomnia, fatigue, transient liver dysfunction, hepatitis.

Rarely: hepatitis or jaundice (including cholestatic), liver necrosis, hepatic encephalopathy, increased transaminase activity (these side effects are usually reversible after discontinuation of therapy, but there have been reports of fatal outcomes due to severe hepatic insufficiency with flutamide therapy); subcutaneous hemorrhage, shingles, skin itching, lupus-like syndrome; anorexia, heartburn, constipation, indigestion; decreased libido, headache, hot flashes (fever, increased sweating), increased blood pressure, dizziness, weakness, visual acuity, thirst, chest pain, swelling (fingers, feet, shins), anxiety, depression and thrombocytopenia . With prolonged treatment, suppression of spermatogenesis was noted. Some cases of hemolytic anemia, macrocytic anemia, methemoglobinemia, reaction of increased photosensitivity (including erythema, ulceration of the skin, bullous rash, epidermal necrolysis) have been noted. Sometimes in patients there is a change in the color of urine from amber to yellow-green.

When treated in combination with agonists, GYRH

Most often: "hot flashes" (fever, increased sweating), decreased libido, impotence, diarrhea, nausea, vomiting. The incidence of these side effects, with the exception of diarrhea (more pronounced when used in conjunction with flutamide), is the same as with monotherapy with GnRH agonists.

Less, often: gynecomastia, anemia, leukopenia, thrombocytopenia, lack of appetite, swelling, symptoms of neuromuscular disorders, difficulty urinating, increased blood pressure and side effects from the central nervous system (drowsiness, depression, confusion, anxiety, neurosis).

Rarely: respiratory failure, hepatic insufficiency, hepatitis,

Cholestatic jaundice, liver necrosis, hepatic encephalopathy, increased photosensitivity, methemoglobinemia.

Overdose:

Symtomas (when taken at a dose of 1500 mg / day for 36 weeks): gynecomastia, chest tightness, increased activity of aspartate aminotransferase.

In case of an overdose, if the patient is conscious and without spontaneous vomiting, vomiting should be induced. It is necessary to use symptomatic therapy with constant monitoring of the patient and vital functions.Due to the high degree of association with plasma proteins, hemodialysis is practically ineffective.

Interaction:

In view of the possible enhancement of the anticoagulant effect with simultaneous use of warfarin and flutamide, the dose of anticoagulant should be selected under the control of prothrombin time.

Special instructions:

Treatment with flutamide should be carried out under the control of the activity of "hepatic" enzymes in the blood serum (once a month for the first 4 months and then regularly).

In the case of increased activity of "liver" enzymes in 2-3 times compared with the upper limit of normal values and / or the appearance of jaundice in the absence of metastases in the liver, Flutamide should be discontinued. Patients should receive a recommendation to consult a doctor immediately when the first symptoms of liver dysfunction occur, such as pruritus, darkening of the urine, nausea, vomiting, persistent loss of appetite, jaundice of the skin or sclera, pain in the right hypochondrium or influenza-like symptoms.

During treatment with Flutamide, drowsiness, neurosis and confusion may occur,therefore, it is recommended to refrain from driving and doing other activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 250 mg.

Packaging:

10 tablets in a blister pack. For 2 or 10 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000156

Date of registration:13.01.2011

The owner of the registration certificate:MEDINTORG, ZAO MEDINTORG, ZAO Russia

Representation: & nbspMEDINTORG, ZAOMEDINTORG, ZAO

Information update date: & nbsp22.10.2015

Illustrated instructions

Instructions

Flutamide (Flutamide)