Androfarm (tablets)

General characteristics. Structure:

Active ingredient: cyproterone;

1 tablet contains a tsiproteron of acetate in terms of 100% substance of 50 mg or 100 mg;

excipients: starch corn, lactoses monohydrate, silicon dioxide colloid anhydrous, povidone, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Androfarm – steroid anti-androgenic drug 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 that leads to reduction of secretion of androgens and strengthens anti-androgenic action. Thanks to it at men drug contains growth of a carcinoma of a prostate stimulated by endogenous androgens and even causes regress of a tumor and its metastasises, at women weakens symptoms of a hirsutism and other displays of hyper androgenic pathology.

Pharmacokinetics. Tsiproterona acetate is completely soaked up at oral administration of different doses. After use of 50 mg of a tsiproteron of acetate the maximum concentration in a blood plasma makes about 140 ng/ml and about 3 hours remain. Further concentration of substance in blood serum decreases for 24-120 hours, the final elimination half-life makes 43,9±12,8 hours. The clearance of a tsiproteron of acetate makes 3,5±1,5 ml/min. of blood serum. Tsiproterona acetate almost completely contacts plasma albumine. About 3,5-4% of the general level of a steroid remain in a stand-at-ease. As linkng 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).

It is metabolized in the different ways, including a hydroxylation and conjugation.

The main metabolite in a blood plasma – 15β-гидроксипроизводное. Metabolism of 1 phase is catalyzed, mainly, by CYP3A4 enzyme of P450 cytochrome.

Insignificant part of the accepted dose is removed in not changed state with bile. The most part of substance is excreted in the form of metabolites with urine and bile in the ratio 3:7. The elimination half-life of metabolites makes 1,7 days of plasma.
Pharmaceutical characteristics.

Main physical and chemical properties: tablets of a round form with a flat surface with risky and a facet, white or almost white color. On a surface of tablets the mramornost is allowed.

Indications to use:

Tablets of 50 mg.

Purpose of drug to men.

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

For treatment of an inoperable prostate cancer.

Purpose of drug to women.

The expressed androgenization symptoms, such as severe forms of a hirsutism, the androgenetichesky allopecia of heavy degree which is often followed by the expressed forms of an acne and/or seborrhea.

Tablets of 100 mg.

For treatment of an inoperable prostate cancer.

Route of administration and doses:

Apply inside. A pill should be taken after food, washing down with a small amount of liquid.

The maximum daily dose makes 300 mg.

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

The initial dose makes 50 mg twice a day. In case of need the daily dose can be raised to 200 mg (100 mg 2 times a day) or for a short span to 300 mg (on 100 mg 3 times a day). After achievement of satisfactory result of treatment the therapeutic effect has to be supported by means of the minimum dose. In most cases reception of 25 mg twice a day is sufficient (50 mg a day). It is necessary to appoint a maintenance dose or to cancel drug 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 accept drug throughout a long time if it is possible – with simultaneous carrying out psychotherapy.

For treatment of an inoperable prostate cancer.

Accept 100 mg of drug 2-3 times a day (a daily dose – 200-300 mg).

At improvement of a state or remission of a disease it is not necessary to reduce the appointed dose of drug or to interrupt treatment.

For the purpose of the prevention of growth of level of male sex hormones in an initiation of treatment agonists a gonadotrophin-rileasing of hormone (GnRH): at first carry out monotherapy by drug Androfarm: on 100 mg twice a day (a daily dose – 200 mg) for 5-7 days. After that for 3-4 weeks – on 100 mg of drug Androfarm twice a day (a daily dose – 200 mg) in a combination with an agonist a gonadotrophin-rileasing of hormone (GnRH) in the recommended dose.

For elimination of inflows of heat at patients during treatment by analogs a gonadotrophin-rileasing of hormone (GnRH) or after an orkhiektomiya: 50-150 mg of drug Androfarm in days with increase in a dose, in case of need – to 100 mg 3 times a day (a daily dose – 300 mg).

Purpose of drug to women.

Women of reproductive age. Drug use Androfarm contraindicated during pregnancy therefore prior to treatment it is necessary to exclude pregnancy.

To begin to accept drug follows in the first day of a cycle (the first day of menstrual bleeding). Only women with an amenorrhea can begin treatment at once after purpose of drug. In this case the first day of use of drug is considered in the first afternoon of a cycle. Further treatment is carried out according to the scheme recommended below.

From 1st to the 10th day of a cycle (that is for 10 days) accept daily    100 mg of drug. Besides, for stabilization of a menstrual cycle and necessary contraceptive protection of the woman accept the drug Diane-35 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 drugs are recommended to be accepted daily at the same time.

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

At improvement of a condition of the patient the daily dose of drug Androfarm which is accepted for the first 10 days of a combination therapy with Diane-35 can be lowered to 50 mg or 25 mg. Perhaps, there will be sufficient a reception continuation only of Diane-35.

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

The passed tablets. If delay in reception of a dragee of Diane-35 makes more than 12 hours, contraceptive protection in this cycle can be reduced. In this case it is necessary to pay attention to appropriate sections in the instruction for a medical use of the drug Diane-35.

At the missed reception of tablets of drug Androfarm decrease in its therapeutic effectiveness and developing of intermenstrual bleedings is possible. It is not necessary to accept a double dose of drug to compensate the admission of a tablet. Administration of drug is resumed in usual time in a combination with a dragee of Diane-35.

Women 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 drug Androfarm. At the same time the average daily dose of drug, 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 drug 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 testimonial of need for dose adjustment for patients with a renal failure.

Features of use:

Use during pregnancy or feeding by a breast.

The Androfarm is contraindicated during pregnancy or feeding by a breast.
Children.

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

In some cases during drug use the Androfarm in high doses can be observed an asthma, it needs to be considered when carrying out differential diagnosis. It is considered that such states do not demand treatment.

There are messages on development of anemia at use of a tsiproteron of acetate. 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 a diabetes mellitus demand careful medical observation during treatment by Androfarm as there can be a need for correction of a dose of peroral antidiabetic means or insulin.

It was reported about development of the thromboembolic phenomena in patients who applied a tsiproteron acetate though the causal interrelation with administration of drug is not established.

Patients with arterial or venous тромботическими / 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 group of the increased risk of development further of the thromboembolic phenomena. It is necessary to approach with extra care purpose of drug 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.

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

At patients who applied 100 mg and more tsiproteron of acetate in days cases of development of a hepatotoxic, including jaundice, hepatitis and a liver failure which sometimes led to a lethal outcome are registered. The majority of these cases concerned treatment of men with a prostate cancer. Toxicity of drug 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 treatment and if any symptoms of a hepatotoxic are observed, it is necessary to conduct researches of function of a liver. If a hepatotoxic is confirmed, in the absence of other reason of its emergence (for example, in the presence of metastasises) use of a tsiproteron of acetate is recommended to be cancelled. Treatment can be continued only if the advantage of therapy exceeds possible risk.

In isolated cases development high-quality was observed, and is even more rare – malignant tumors of a liver. In some cases the intra belly bleedings caused by these tumors threatened life. At emergence of pain in an upper part of a stomach, increase in a liver or symptoms of intra belly bleeding during treatment by Androfarm it is necessary to consider probability of existence of a tumor of a liver.

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 a day or above. If the meningioma, treatment not обходимо is diagnosed for the patient who is treated by drug Androfarm to stop.

During treatment by Androfarm it is not necessary to take alcohol.

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

If during a combination therapy within 3 weeks of reception of tablets the krovomazaniye is observed, use of drugs should not be interrupted. However when developing long bleeding or repeated intermenstrual bleedings it is necessary to conduct gynecologic examination for the purpose of an exception of an organic disease.

At use of Diane-35 in a combination therapy it is necessary to pay attention to the relevant data in the instruction for a medical use of this drug.

Drug Androfarm contains lactose therefore to patients with rare hereditary diseases of intolerance of a galactose, deficit of lactase of Lapp or malabsorption of glucose galactose it is not necessary to use this drug.
Ability to influence speed of response at control of motor transport or work with other mechanisms.

During treatment by Androfarm increased fatigue, change of mood can be observed that has to be considered by patients whose activity is connected with control of vehicles or with other mechanisms.

Side effects:

Frequency of side reactions is defined as it is very frequent (≥ 1/10), is frequent (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100), is rare (≥ 1/10000, <1/1000) and is very rare (<1/10000).

New growths: very seldom – benign and malignant tumors of a liver; frequency is unknown – high-quality cerebral meningiomas in connection with prolonged use (within several years) drug in a dose of 25 mg or above.

From system of blood and lymphatic system: frequency is unknown – anemia.

From immune system: seldom – hypersensitivity reactions.

Metabolic and alimentary disturbances: often – increase or a degrowth of a body.

Mental disorders: very often – decrease a libido, erectile dysfunction (these phenomena disappear after the treatment termination); often – oppressed mood, concern (temporary).

Vascular disturbances: frequency is unknown – the thromboembolic phenomena (the causal interrelation with administration of drug is not established.

From respiratory system: often – an asthma.

From the alimentary system: frequency is unknown – intra belly hemorrhage.

From gepatobiliarny system: often – a hepatotoxic, including jaundice, hepatitis, a liver failure.

From skin and hypodermic cellulose: infrequently – rash.

From a musculoskeletal system and connecting fabric: frequency is unknown – osteoporosis.

From reproductive system and mammary glands: very often – reversible oppression of a spermatogenesis (after the treatment termination it is gradually recovered for several months); often – a gynecomastia (sometimes in a combination with hypersensitivity of nipples at a touch) that, as a rule, passes after drug withdrawal; frequency is unknown – ovulation suppression, tension of mammary glands, a krovomazaniye (at women).

General frustration and local reactions: often – increased fatigue, heat inflows, the strengthened sweating.

Interaction with other medicines:

At treatment Androfarmy there can be a need for correction of a dose of peroral anti-diabetic drugs or insulin.

In spite of the fact that clinical trials of interaction of drug with medicines were not conducted, but as it is metabolized with the participation of CYP3A4 enzyme, it is expected that кетаконазол, итраконазол, Clotrimazolum, ритонавир and other strong CYP3A4 inhibitors oppress metabolism of a tsiproteron of acetate. On the other hand, the inductors CYP3A4, 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 use of high therapeutic doses of a tsiproteron of acetate (100 mg three times a day) the inhibition of such enzymes of system of P450 cytochrome as CYP2C8, 2C9, 2C19, 3A4 and 2D6 is possible.

At simultaneous use of HMGCoA inhibitors (statines) and high therapeutic doses of a tsiproteron of acetate because of an identical way of metabolism of these substances the risk of a myopathy or rabdomioliz associated with statines can increase.

Contraindications:

General contraindications: hypersensitivity to any of drug components; liver diseases; syndrome Cudgel Johnson, Rotor syndrome; liver tumors, including in the anamnesis (only in that case when the tumor is not caused by metastasises of a prostate cancer); a 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 use for the purpose of decrease in a sexual inclination at pathological deviations in the sexual sphere at men except the above-stated contraindications: severe forms of diabetes with vascular complications; drepanocytic anemia, 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.

At purpose of a cyclic combination therapy for treatment of the expressed symptoms of an androgenization it is necessary to pay attention to the contraindications specified in the instruction for a medical use of the drug Diane-35 which is applied in a combination with drug Androfarm.

Overdose:

Tsiproterona acetate – almost nontoxic substance. After single use in a dose which several times exceeds therapeutic cases of acute intoxication were not noted.

Storage conditions:

Period of validity 3 years. Not to use drug after the termination of the period of validity specified on packaging. To store in the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets on 50 mg in the blister, on 2 or 5 blisters in a pack.

On 10 tablets on 100 mg in the blister, on 3 or 6 blisters in a pack.