Active substanceFlutamideFlutamide
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  • Dosage form: & nbsppills
    Composition:
    1 tablet contains:
    active substance: flutamide 250 mg,
    auxiliary substances: microcrystalline cellulose, corn starch, lactose monohydrate, sodium lauryl sulfate, silicon dioxide colloid, magnesium stearate.

    Description:
    Round, light yellow pills with a bevel.

    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, progestagenic 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 reached after 2 hours, is a biologically active a-hydroxylated derivative (2-hydroxyflutamide). 94-96% flutamide and 92-94% of the a-hydroxylated metabolite binds to proteins. From the body, the drug is excreted mainly by the kidneys, about 4.2% is secreted with feces for 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 a stable 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 with 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 the tendency to thrombosis and cardiovascular diseases, as well as in conditions predisposing to intoxication aniline (one metabolite of flutamide - metilanilinovoe derivative): deficiency of glucose-6-phosphate dehydrogenase, smoking, hemoglobinopathies (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 the administration of Flutamide Pliva begins 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 the drug is used in mop therapy
    Most often: gynecomastia and / or pain in the region of the breast, sometimes accompanied by galactorrhea. These phenomena disappear after withdrawal 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 activity of transaminases (these side effects are usually reversible after discontinuation of therapy, but there have been reports of fatal outcomes due to severeliver failure with flutamide therapy); subcutaneous hemorrhages, 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 GnRH agonists
    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 failure, hepatitis, cholestatic jaundice, liver necrosis, hepatic encephalopathy, increased photosensitivity, methemoglobinemia.

    Overdose:
    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 action with the simultaneous use of warfarin and flutamide, the dose of anticoagulant should be selected under the control of prothrombin time.
    Avoid simultaneous administration of flutamide with other hepatotoxic drugs, as well as alcohol.
    Against the background of simultaneous administration of theophylline and flutamide, there is an increase in the level of theophylline in the blood, which may be due to the presence of a common pathway of metabolism in these drugs.

    Special instructions:
    Treatment with Flutamide Pliva should be carried out under the control of hepatic enzyme activity in blood serum (once a month for the first 4 months and then regularly).
    If the hepatic enzyme activity is increased 2-3 times in comparison with the upper limit of normal values ​​and / or the appearance of jaundice in the absence of metastases in the liver, the use of Flutamide Pliva should be discontinued.
    Patients should receive a recommendation immediately, consult a doctor with the first symptoms of liver dysfunction, such as pruritus, darkening of the urine, nausea, vomiting, persistent loss of appetite, icterus of the skin or sclera, pain in the right hypochondrium or influenza-like symptoms.
    In patients who have not undergone surgical or drug castration, spermatogenesis should be performed during long-term treatment. The administration of flutamide can lead to an increase in the level of testosterone and estradiol in the blood, in connection with this, fluid retention in the body is possible.Particular attention should be given to patients with cardiovascular diseases, also prone to edema formation.

    Form release / dosage:
    Tablets of 250 mg.

    Packaging:
    For 10 tablets in a blister of PVC / aluminum foil.
    For 10 blisters (100 tablets) with instructions for use in a cardboard bundle.

    Storage conditions:
    List B.
    Store at a temperature not higher than 25 ° C, 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:П N011946 / 01
    Date of registration:15.05.2009
    The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia
    Manufacturer: & nbsp
    Information update date: & nbsp22.10.2015
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