Pharmacological properties

Pharmacodynamics. androfarm — steroid anti-androgenic medicine with the double mechanism of action. the competitive antagonist of receptors of androgens, blocks biological effect of testosterone and other androgens in target cells. besides, the tsiproterona acetate has gestagenny and anti-gonadotropic activity which leads to reduction of secretion of androgens and strengthens anti-androgenic action. thanks to it at men medicine constrains stimulated endogenous androgens growth of a carcinoma of a prostate and even leads to regress of a tumor and its metastases, at women reduces expressiveness of a hirsutism and other manifestations of hyper androgenic pathology.

Pharmacokinetics. After oral administration Androfarm is completely soaked up in intestines. After application of 50 mg of a tsiproteron of _{acetate C max} in blood plasma about 140 ng/ml make and about 3 h remain. Further concentration of substance in blood serum decreases during 24–120 h, final the T _½ makes 43.9±12.8 h. The clearance of a tsiproteron of acetate is 3.5±1.5 ml/min. of blood serum.

acetate is slowly released by

After introduction of a tsiproteron in oil from oil solution. The bioavailability of medicine is 100%. The C _max a tsiproteron of acetate in blood plasma is reached in 2–3 days. About 4 days are allocated on monophase type with T _½ . After 4 injections the level of a tsiproteron of acetate in blood plasma is stabilized. After that hormone level in blood serum decreases with final T _½ 4±1.1 days. The full clearance of a tsiproteron of acetate is 2.8±1.4 ml/min. of blood serum.

Tsiproteron's

acetate almost completely contacts blood plasma albumine. About 3.5-4% of the general level of steroid remain in a stand-at-ease. As linking with proteins nonspecific, change of level of the globulin connecting sexual steroids does not influence pharmacokinetics of a tsiproteron of acetate.

Absolute bioavailability of a tsiproteron of acetate almost full (88% of the accepted dose).

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It is metabolized in various ways, including hydroxylation and conjugation. The main metabolite in blood plasma — 15b-hydroxyderivative. Metabolism of the I phase is catalyzed mainly by CYP enzyme 3A4 of P450 cytochrome.

Insignificant part of the accepted dose is removed by

in not changed view with bile. The most part of substance is removed in the form of metabolites with urine and bile in the ratio 3:7. The t _½ metabolites makes 1.7 days of blood plasma

Indication

Tablet of 50 mg

Prescribing of medicine to men. For decrease in sexual inclination at pathological deviations in the sexual sphere.

For treatment of an inoperable prostate cancer.

Prescribing of medicine to women. Expressed symptoms of an androgenization, such as severe forms of a hirsutism, androgenetichesky alopecia of heavy degree which is often followed by the expressed forms acne and/or seborrheas.

Tablet of 100 mg

For treatment of an inoperable prostate cancer.

Use

is Applied inside. a pill should be taken after a meal, washing down with a small amount of liquid.

Maximum daily dose makes 300 mg.

For decrease in sexual inclination at pathological deviations in the sexual sphere at men.

Initial dose makes 50 mg 2 times a day. In case of need the daily dose can be raised to 200 mg (100 mg 2 times a day) or for the short period up to 300 mg (on 100 mg 3 times a day). After achievement of the satisfactory treatment outcome the therapeutic effect has to be maintained by means of the minimum dose. In most cases reception of 25 mg 2 times a day (50 mg/days) is sufficient. It is necessary to appoint a maintenance dose or to cancel medicine gradually. At the same time the daily dose at an interval of several weeks decreases by 50 mg or, better, by 25 mg. For stabilization of therapeutic effect it is necessary to take the medicament throughout a long time if it is possible — with simultaneous carrying out psychotherapy.

For treatment of an inoperable prostate cancer. Accept 100 mg of medicine 2–3 times a day (a daily dose — 200–300 mg).

At improvement of a state or remission of a disease should not reduce the appointed dose of medicine or to interrupt treatment.

for the purpose of prevention of increase in level of male sex hormones in an initiation of treatment agonists gonadotropin-RG: at first carry out monotherapy by medicine Androfarm: on 100 mg 2 times a day (a daily dose — 200 mg) for 5–7 days. After that for 3–4 weeks — on 100 mg of medicine Androfarm 2 times a day (a daily dose — 200 mg) in a combination with agonist gonadotropin-RG in the recommended dose.

For elimination of inflows of heat at patients during treatment by analogs gonadotropin-RG or after an orkhiektomiya: 50–150 mg of medicine Androfarm in day with increase in a dose, in case of need — up to 100 mg 3 times a day (a daily dose — 300 mg).

Prescribing of medicine to women. Women of reproductive age. Medicine use Androfarm contraindicated during pregnancy therefore prior to treatment it is necessary to exclude pregnancy.

to Begin to take the medicament follows in the first day of a cycle (first day of menstrual bleeding). Only women with an amenorrhea can begin treatment at once after prescribing of medicine. In this case the first day of use of medicine is considered in the first afternoon of a cycle. Further treatment is carried out on the scheme recommended below.

C the 1st till the 10th day of a cycle (that is for 10 days) is accepted daily on 100 mg of medicine. Besides, for stabilization of a menstrual cycle and necessary contraceptive protection of the woman take the medicament containing a progestogen combination with estrogen on 1 dragee a day from 1st to the 21st day of a cycle.

At the combined cyclic therapy the medicaments is recommended to be taken daily at the same time.

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After the 21st day of use of medicine provided a 7-day break in treatment during which there comes cancellation bleeding. Exactly in 4 weeks after the beginning of the first course of treatment, that is on the same day weeks, the new cycle of combination therapy begins, despite the fact that, bleeding stopped or not.

daily dose of the medicament Androfarm taken for the first 10 days of combination therapy with the medicine containing a progestogen combination with estrogen can be reduced by

At improvement of a condition of the patient to 50 mg or 25 mg. Perhaps, there will be sufficient a reception continuation only of the medicine containing a progestogen combination with estrogen.

Absence of bleeding of cancellation. If during a break in use of medicines there is no cancellation bleeding, treatment should be suspended and before resuming of therapy it is necessary to exclude pregnancy.

Passed tablets. If delay in reception of a dragee of the medicine containing a progestogen combination with estrogen makes more than 12 h, contraceptive protection in this cycle can be reduced. In this case it is necessary to pay attention to appropriate sections in the instruction for medical use of the medicine containing a progestogen combination with estrogen.

At the missed reception of tablets of medicine Androfarm decrease in its therapeutic effectiveness and developing of intermenstrual bleedings is possible

. It is not necessary to take a double dose the medicament to compensate the admission of a tablet. Administration of medicament is resumed in usual time in combination with the medicine containing a progestogen combination with estrogen.

Woman in the period of a postmenopause or after a hysterectomy. Women in the period of a postmenopause or after a hysterectomy can receive monotherapy by medicine Androfarm. At the same time the average daily dose of medicine, depending on severity of a disease, makes from 50 mg to 25 mg of 1 times a day within 21 days. After that the 7-day break in treatment is provided.

Patients of advanced age. There are no data on need for dose adjustment for patients of advanced age.

Patients with a liver failure. Use of medicine is contraindicated to patients with liver diseases (until parameters of function of a liver do not return to norm).

Patients with a renal failure. There are no data confirming need for dose adjustment for patients with a renal failure.

Contraindication

General contraindications: hypersensitivity to any of medicine components; liver diseases; a syndrome of a dabin — Johnson, a rotor syndrome; liver tumors, including in the anamnesis (only when the tumor is not caused by metastases of a prostate cancer); serious general condition (if it is not connected with an inoperable prostate cancer); heavy chronic depression; thromboembolic states at present; a meningioma at present or in the anamnesis.

At application for the purpose of decrease in sexual inclination at pathological deviations in the sexual sphere at men, except the above-stated contraindications: severe forms of diabetes with vascular complications; a sickemia, thromboembolic states at present or in the anamnesis.

For women: severe forms of diabetes with vascular complications; a sickemia, thromboembolic states at present or in the anamnesis, jaundice or a persistent itch during the previous pregnancy in the anamnesis; herpes during pregnancy in the anamnesis.

When assigning cyclic combination therapy for treatment of the expressed symptoms of an androgenization should pay attention to the contraindications specified in the instruction for medical use of the medicine containing a progestogen combination with estrogen which is applied in a combination with medicine Androfarm.

Side effects

Frequency of side reactions is defined by

as it is very frequent (≥1/10), is frequent (≥1/100, 1/10), infrequently (≥1/1000, 1/100), is rare (≥1/10,000, 1/1000) and is very rare (1/10,000).

New growth: very seldom — benign and malignant tumors of a liver; frequency is unknown — benign cerebral meningiomas in connection with prolonged use (within several years) medicine in doses of 25 mg or above.

from blood and lymphatic system: frequency is unknown — anemia.

from the immune system: seldom — reactions of hypersensitivity.

Metabolic and alimentary violations: often — increase or degrowth of a body.

Mental disorders: very often — decrease a libido, erectile dysfunction (these phenomena disappear after the therapy termination); often — suppressed mood, a condition of concern (temporary).

Vascular violations: frequency is unknown — the thromboembolic phenomena (the causal interrelation with administration of medicament is not established).

from a respiratory system: often — short wind.

from a GIT: frequency is unknown — intra belly bleeding.

from a gepatobiliarny system: often — hepatotoxicity, including jaundice, hepatitis, a liver failure.

from skin and hypodermic cellulose: infrequently — rash.

from a musculoskeletal system and connective tissue: frequency is unknown — osteoporosis.

from a reproductive system and mammary glands: often — reversible oppression of a spermatogenesis (after the treatment termination it is gradually restored within several months); often — a gynecomastia (it is sometimes combined with hypersensitivity of chest nipples at touch) that, as a rule, passes after medicament withdrawal.

General violations and local reactions: often — increased fatigue, inflows of heat, the strengthened sweating.

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Special instructions

In some cases during use of medicine androfarm in high doses the short wind can be observed. it needs to be considered when performing differential diagnostics. it is considered that such states do not demand treatment.

messages about development of anemia at application of a tsiproteron of acetate Are available. Considering it, it is regularly necessary to control blood indicators with obligatory determination of quantity of erythrocytes throughout the entire period of treatment.

Patients with diabetes demand careful medical observation during treatment by Androfarm as there can be a need for dose adjustment of oral anti-diabetic means or insulin.

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It was reported about development of the thromboembolic phenomena in the patients applying a tsiproteron acetate though the interrelation with administration of medicament is not established.

Patients with arterial or venous tromboticheskimi / the thromboembolic phenomena (for example a deep vein thrombosis, an embolism of a pulmonary artery, a myocardial infarction) or cerebrovascular diseases in the anamnesis and patients with tumors at a late stage belong to

to group of the increased risk of development further of the thromboembolic phenomena. It is necessary to approach with extra care prescribing of medicine a sick inoperable prostate cancer with the thromboembolic phenomena in the anamnesis. In each separate case it is necessary to weigh the expected advantage of treatment and potential risk.

Androfarm has kortikoidopodobny effect therefore throughout the entire period of treatment it is necessary to check function of bark of adrenal glands regularly.

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At the patients applying 100 mg and more tsiproteron of acetate in day registered cases of development of hepatotoxicity, including jaundice, hepatitis and a liver failure which sometimes led to a lethal outcome. The majority of these cases concerned treatment of men with a prostate cancer. The toxicity of medicine depends on a dose and develops usually after several months of treatment. Before an initiation of treatment, it is regular throughout the entire period of therapy and if any symptoms of hepatotoxicity are observed, it is necessary to conduct researches of function of a liver. If hepatotoxicity is confirmed, in the absence of other reason of its emergence (for example in the presence of metastases) application of a tsiproteron of acetate is recommended to be cancelled. Treatment can be continued, only if the advantage of therapy exceeds possible risk.

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In isolated cases noted development benign, and is even more rare — malignant tumors of a liver. In some cases the intra belly bleedings caused by these tumors threatened life. At appearance of pain in the top part of a stomach, increase in a liver or symptoms of intra belly bleeding during medicament treatment Androfarm it is necessary to consider the probability of presence of a tumor of a liver.

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It was reported about development of the meningiomas (one or multiple) associated with prolonged use (for several years) a tsiproterona of acetate in a dose of 25 mg/days or above. If the meningioma, treatment not obkhodimo is diagnosed for the patient who is treated by medicine Androfarm to stop.

during medicament treatment Androfarm should not take alcohol.

Prescribing of medicine to women. Before an initiation of treatment it is necessary to perform the general medical and gynecologic examination (including inspection of mammary glands and the cytologic analysis of a neck of the uterus) and to exclude pregnancy.

If during combination therapy during 3 weeks of reception of tablets the krovomazaniye is noted, use of medicines it is not necessary to interrupt. However when developing long bleeding or repeated intermenstrual bleedings it is necessary to perform gynecologic examination for the purpose of an exception of an organic disease.

At use of the medicine containing a progestogen combination with estrogen in combination therapy should pay attention to the relevant data in the instruction for medical use of this medicine.

Drug Androfarm contains lactose therefore to patients with rare hereditary diseases of intolerance of a galactose, deficiency of Lappa lactases or malabsorption of glucose galactose it is not necessary to use this drug.

Use during pregnancy and feeding by a breast. Androfarm is contraindicated during pregnancy and feeding by a breast.

Children. Androfarm is not appointed before completion of puberty as negative impact of medicine on growth and the endocrine system of the patient is not excluded. Drug is not recommended to be used at children.

Ability to influence speed of response at control of vehicles or work with other mechanisms. During medicament treatment Androfarm can be noted increased fatigue, change of mood that has to be considered by patients whose activity is connected with control of vehicles or work with other mechanisms.

Interaction

At treatment androfarmy need for dose adjustment of oral anti-diabetic medicines or insulin can arise.

In spite of the fact that clinical trials of interaction of medicine with medicines were not conducted, but as it is metabolized with the participation of CYP enzyme 3A4, it is expected that ketakonazol, itrakonazol, Clotrimazolum, ritonavir and other strong CYP inhibitors 3A4 oppress metabolism of a tsiproteron of acetate. On the other hand, inductors CYP 3A4, such as rifampicin, Phenytoinum and medicines containing a St. John's wort can reduce the level of a tsiproteron of acetate.

based on results of the research in vitro, it is possible to assume that at application of high therapeutic doses of a tsiproteron of acetate (100 mg 3 times a day) the inhibition of such enzymes of a system of P450 cytochrome as CYP 2C8, 2C9, 2C19, 3A4 and 2D6 is possible.

At simultaneous use of GMG-KoA inhibitors (statines) and the tsiproterona of acetate because of an identical way of metabolism of these substances can increase in high therapeutic doses the risk of a myopathy or a rhabdomyolysis associated with statines.

Overdose

Tsiproteron's

acetate — almost non-toxic substance. after single application in the dose several times exceeding therapeutic the cases of sharp intoxication were not noted.

Storage conditions

B the place protected from light at a temperature not above 25 °C.