Active substanceFlutamideFlutamide
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  • Dosage form: & nbsppills
    Composition:
    1 tablet contains:
    active substance: flutamide 250 mg;
    Excipients: lactose monohydrate 150 mg, cellulose
    microcrystalline - 50 mg, corn starch - 30 mg, sodium lauryl sulfate - 10 mg, silicon dioxide colloid - 5 mg, magnesium stearate - 5 mg.

    Description:
    Round biconvex tablets are pale yellow.

    Pharmacotherapeutic group:Antitumor agent, antiandrogen.
    ATX: & nbsp

    L.02.B.B.01   Flutamide

    Pharmacodynamics:
    Flutamide is a nonsteroidal drug with an antiandrogenic effect.The mechanism of action includes 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% a-hydroxylated metabolite binds to proteins. From the body, the drug is excreted mainly by the kidneys, about 4.2% is secreted through 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 a stable concentration).After oral administration of flutamide 250 mg 3 times a day, a stable level of drug concentration and its active metabolite in plasma is achieved after a fourth dose of the drug.

    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 HNRH 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 impairment
    - Child age (safety and efficacy not established)

    Carefully:
    in patients with reduced 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 withdrawal of treatment or dose reduction.
    Less often: diarrhea, nausea, vomiting, increased appetite, insomnia,
    increased 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 severe hepatic insufficiencytherapy with flutamide); 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, edema, 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:
    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 the 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 level of hepatic enzymes in serum (appropriate laboratory tests should be carried out1 time per month for the first 4 months and then regularly).
    In the case of increasing the level of liver enzymes by 2-3 times compared with the upper limit of the normal range and / or jaundice in the absence of liver metastases flutamide application should stop.
    Patients should receive the recommendation to immediately consult a doctor when the first symptoms of liver disease, such as itchy skin, dark urine, nausea, vomiting, persistent loss of appetite, yellowness of the skin or sclera, pain in the right upper quadrant, or flu-like symptoms.

    Form release / dosage:
    Tablets of 250 mg.
    Packaging:
    For 30 or 90 tablets in bottles of brown glass, ukuporennyh screw cap and fixing ring. 1 bottle with instructions for use in a cardboard pack.

    Storage conditions:
    At a temperature of no higher than 25 ° C in a dry, dark place. Keep out of the reach of children!

    Shelf life:
    5 years.
    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008383/08
    Date of registration:22.10.2008
    The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland
    Manufacturer: & nbsp
    Representation: & nbspAktavis, Open Company Aktavis, Open Company
    Information update date: & nbsp23.10.2015
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