Flutamid

General characteristics. Structure:

Active ingredient: 250,0 mg of a flutamid.

Excipients: a mannitol (Е 421), sodium lauryl sulfate, K-30 povidone, cellulose microcrystallic, silicon dioxide colloid, sodium krakhmalglikolit, magnesium stearate.

The nonsteroid anti-androgenic drug suppressing action of all androgens competitively blocking their communication with receptors of target cells not only in a prostate, but also in a hypothalamus and a hypophysis. It is appointed for treatment of primary prostate cancer, and also at other states when it is necessary to reduce effect of effect of male sex hormones.

Pharmacological properties:

Pharmacodynamics. Flutamid - anti-androgenic drug of nonsteroid structure. Flutamid and his metabolites have no agonistic or antagonistic properties concerning receptors of glucocorticoids, mineralkortikoid and estrogen. Flutamid blocks androgenic receptors of target cells in a prostate, a hypothalamus and a hypophysis and inhibits biological effects of endogenous androgens. However флутамид the gonadotrophin-releasing of hormone (GTRG) a hypothalamus or on sensitivity of a hypophysis to GTRG has no the oppressing effect on androgenoposredovanny secretion. It leads to increase in content of gonadotropic hormones (luteinizing and follicle-stimulating) owing to what there is testosterone hyperproduction stimulation.

Competing with androgens, флутамид and its metabolites inhibit linkng of dihydrotestosterone with nuclear receptors of androgens. Blockade of receptors can also happen at the level of a cellular membrane and in cell cytoplasm. The main metabolite - 2-gidroksiflutamid. Its affinity with receptors of androgens is 25 times higher, than at a flutamid that allows to consider it as an active form of a flutamid. The combination of a flutamid with chemical or surgical castration leads to manifestation of testicular and adrenal effects of androgens.

Pharmacokinetics. After oral administration флутамид it is well soaked up from digestive tract. The maximum concentration in plasma is reached for 2 hours. Experiences with use marked hyzone of a flutamid demonstrate his bystry metabolism in biologically active form - 2-gidroksiflutamid and other metabolites. The period of its half-decay makes 5–6 hours. There are about 10 metabolites of a flutamid. More than 90% of a flutamid and 2-gidroksiflutamid contact proteins of plasma. It Eliminirutsya preferential by kidneys. About 4% of the accepted dose are excreted with a stake.

Indications to use:

Treatment of the progressing prostate cancer as monotherapy (with or without orkhiektomiya) or in a combination with agonists of luteinizing hormone of LGRG (LHRH) rileasing-hormone at patients to whom did not appoint earlier any treatment which do not react or in whom resistance to hormonal therapy or its intolerance developed. In a combination therapy - as one of means for treatment of locally limited prostate cancer of B2 - C2 (T2b - T4), for reduction of volume of a tumor, strengthening of control over a tumor and increase in the period between exacerbations of a disease.

Route of administration and doses:

For oral administration. Drug is used as monotherapy, and in a combination with LGRG on one tablet (250 mg) by 3 times a day with an eight-hour interval. The general daily dose for adults makes 750 mg. As a part of a combination therapy with LGRG agonists Flutamid's reception is begun in 3 days prior to therapy with LGRG agonists.

At a heavy liver failure the advantage of treatment has to exceed risk of emergence of side reactions. The doctor determines treatment duration individually.

Features of use:

As a part of a combination therapy with LGRG agonists therapy by Flutamid begin a minimum in 3 days prior to reception of agonists of LGRG that promotes less expressed peristatic hyperemia, than at the parallel beginning of therapy.
Treatment has to be carried out under observation of the doctor. Special attention should be paid to effect of drug on function of a liver and a delay of liquid in an organism of patients who were not subjected to an orkhiektomiya (surgical or medicamentous).

An inspection of function of a liver should be carried out during the entire period of treatment by drug as such side reactions as cholestatic jaundice, a liver necrosis, change of level of transaminase and hepatic encephalopathy were noted.

The corresponding laboratory researches should be conducted in case of the first signs of an abnormal liver function (for example: an itch, dark coloring of urine, resistant lack of appetite, jaundice, moderate morbidity in the right upper quadrant of a stomach or the general weakness). Treatments by drug should not be begun the patient with transaminase levels in serum which by 2 - 3 times exceed an upper limit of norm.

If the patient has symptoms of jaundice or laboratory confirmed abnormal liver function in the absence of metastasises in her, in this case it is necessary to stop treatment by Flutamid or to lower his dose though certain recommendations concerning dosing do not exist. Disturbance of functions of a liver usually happens reversible after the termination of treatment by Flutamid, and some patients and have later dose declines.

If to patients medicamentous or surgical castration was not carried out, Flutamid's introduction can lead to increase in levels of testosterone and oestradiol in a blood plasma; sometimes there is a liquid delay in an organism. Therefore this drug should be used with care at heart diseases. At such patients at long reception of Flutamid the oligospermatism can be observed. In this case carrying out quantification of sperm is reasonable. During treatment it is not necessary to take alcohol.

Ability to influence speed of response at control of motor transport and work with other mechanisms. Usually, drug does not influence speed of response at control of motor transport or work with other mechanisms, but in isolated cases dizziness, weakness and a vision disorder is possible. In such cases it is necessary to abstain from control of motor transport or work with other mechanisms.

Drug is not recommended for inclusion in time of pregnancy and the period of feeding by a breast.

Children. Information about use of drug for children is absent therefore drug is not shown to use of this category of patients.

Side effects:

Monotherapy:
Infections and invasions. Not widespread: the surrounding herpes.

Benign and malignant tumors. Isolated cases: a new growth in chest glands at men.

Blood and lymphatic system. Not widespread: hypostasis, ecchymoma, limfedema.

Immune system. Not widespread: volchanochnopodobny syndrome.

Mental disturbances. Widespread: sleeplessness. Not widespread: depression, alarm.

Nervous system. Not widespread: dizziness.

Sight. Not widespread: sight misting.

Respiratory organs. Not widespread: диспноэ. Isolated cases: cough.

Alimentary system. Widespread: diarrhea, nausea, vomiting, increase in appetite. Not widespread: stomach ache, ulcer-like pain, heartburn, lock, hepatitis, anorexia, thirst.

Skin and hypodermic fabric. Not widespread: itch. Isolated cases: photosensitivity.

Reproductive system. The most widespread: gynecomastia, nagrubaniye of mammary glands, galactorrhoea. Not widespread: decrease in a libido, reduction спермоутворення.

General disturbances. Widespread: fatigue. Not widespread: a headache, weakness, fever, thirst, pain behind a breast, weakness.

As a part of a combination therapy:
Blood and lymphatic system. Not widespread: anemia, leukopenia, hypostasis, thrombocytopenia. Isolated cases: hemolitic anemia, makrotsitarna anemia, methemoglobinemia, sulfhemoglobinemia.

Metabolism disturbances. Isolated cases: hyperglycemia, diabetes mellitus aggravation.

Mental disturbances. Not widespread: depression, alarm, concern.

Nervous system. Not widespread: drowsiness, confusion of consciousness, nervousness, neurosis.

Respiratory organs. Isolated cases: intersticial damage of lungs.

Alimentary system. Very widespread: diarrhea, nausea, vomiting. Not widespread: abdominal cavity pain, jaundice, anorexia. Isolated cases: cholestatic jaundice, hepatic encephalopathy, a liver necrosis, cases of heavy injury of a liver with the lethal end.

Skin and hypodermic fabric. Not widespread: rash. Isolated cases: photosensitivity, erythema, ulcers, violent rash, epidermal necrosis.

Musculoskeletal system. Not widespread: arthralgia, mialgiya.

System of allocation. Not widespread: dysuria, change of frequency of an urination. Isolated cases: urine discoloration to amber and flavovirent.

Cardiovascular system. Not widespread: arterial hypertension.

Reproductive system. The most widespread: decrease in a libido, impotence, rushes of blood. Not widespread: gynecomastia.

Changes of laboratory indicators. Changes of the following indicators are observed: a glutamate-oksaloatsetattransaminaza (GOT), alaninaminotranspherase (GPT), gamma glutaminetransferase (GGT), bilirubin, residual nitrogen of urea, creatinine level in serum.

General disturbances. Not widespread: irritation in an injection site, feeling of heat.

Interaction with other medicines:

At patients who receive long therapy by warfarin, increase in a prothrombin time after Flutamid's use was noted. Therefore it is necessary to carry out selection of an optimum dose of anticoagulant.

It is necessary to avoid simultaneous use of Flutamid and potentially hepatotoxic drugs.

At compatible use of Flutamid and theophylline possible increase in concentration of theophylline in a blood plasma. Theophylline initially to metabolizuyetsya by CYP 1A2 which is the enzyme responsible for conversion of a flutamid to its active metabolite of a 2-gidroksiflutamid.

Contraindications:

Hypersensitivity to a flutamid or excipients which are a part of drug, a heavy liver failure.

Overdose:

In experiments on animals Flutamid resulted in hypoactivity, a piloerektion, slowed down a respiration rate, caused an ataxy and/or dacryagogue, anorexia, sedation, vomiting and a methemoglobinemia. Clinical data show that Flutamid's reception in a daily dose to 1500 mg does not cause serious side effects. Also the gynecomastia and a nagrubaniye of mammary glands and passing changes of levels of hepatic transaminases can be noted. Considering high extent of communication of a flutamid with proteins of plasma, it is necessary to expect insignificant effect of carrying out dialysis at patients with drug overdose. In the absence of vomiting it is necessary to cause it artificially (if the patient in consciousness). Holding the general actions for control and maintenance of vital parameters is shown.

Storage conditions:

To store at the room temperature (15–25 °C). To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 21 tablets in the blister; on 4 blisters in cardboard packaging.