Androcur (cyproterone) tablets

The composition and form of issue:

Androkur

Tablets. 1 tablet contains:

cyproterone acetate 10 mg

excipients: lactose monohydrate starch, corn polyvidone 25000 magnesium stearate silicon dioxide colloidal (Aerosil)

blistere in with the scale of calendar 15 PCs in a box 1 blister.

Tablets. 1 tablet contains:

cyproterone acetate 50 mg

excipients: lactose monohydrate starch, corn polyvidone 25000 magnesium stearate, micronized silicon dioxide (Aerosil)

in dark glass bottles of 20 and 50 PCs in a box 1 vial or blister of 10 PCs., in box 2, or 5 blisters.

Tablets. 1 tablet contains:

cyproterone acetate 100 mg

excipients: lactose corn starch povidone 25000 magnesium stearate

blistere in 10 PCs., in box 6 blisters.

Androkur Depot

Solution for injection oil. 1 amp. (3 ml) contains:

cyproterone acetate 300 mg

excipients: benzyl benzoate castor oil for injection

in a box of 3 vials of dark glass complete with ampulnam knife.

Description pharmaceutical form:

Androkur (10 mg): round white or slightly yellowish pill, scored on one side and engraved in the form of a hexagon, inside of which the letters “BW” on the other.

Androkur (50 mg): round white or slightly yellowish pill, scored on one side and engraved in the form of a hexagon, inside of which the letters “BV” on the other.

Androkur (100 mg): capsuleline, white to light-yellow tablets. On both sides the risks stamped “LA” on the reverse side of a hexagon.

Androkur Depot: transparent, colorless to yellowish, liquid.

Pharmacokinetics:

Androkur, 10 mg

After oral administration of cyproterone acetate is completely absorbed in a wide dose range. Cmax in serum after intake of 10 mg is approximately 1.5 hours and is about 75 ng/ml Total Cl — 3.6 ml/min/kg Metabolized by various pathways including hydroxylation and conjugation. The main metabolite is 15&beta-hydroxy derivative.

A certain amount of the dose excreted unchanged in the bile. Most of the dose is excreted as metabolites in urine and bile in the ratio of 3:7, T1/2 is 1.9 days. The rate of elimination of metabolites from the plasma has a similar value of (T1/2 — 1.7 days).

Cyproterone acetate is almost exclusively bound to plasma albumin. In the free state is about 3.5–4%. Since the link with proteins is nonspecific, changes in the concentration of globulin, linking sex hormones do not affect the pharmacokinetics of cyproterone acetate.

Due to the long duration of excretion in the final phase of elimination from plasma, as well as daily use, probably increasing the concentration of cyproterone in the serum in 2-2,5 times for one cycle of treatment.

The absolute bioavailability of cyproterone acetate is almost complete.

Androkur, 50 mg

Cyproterone acetate is completely absorbed after ingestion. It binds almost exclusively to albumin in plasma. In the free state is about 3.5–4 %. Since the link with proteins is nonspecific, changes in the concentration of globulin, linking sex hormones do not affect the pharmacokinetics of cyproterone acetate.

T1/2 — (43,9±12,8) h. Total clearance of cyproterone acetate from serum — (3,5±1,5) ml/min/kg. biotransformation in the liver and excreted mainly as metabolites in the bile and urine at a ratio of 3:7, part is excreted unchanged in the bile.

The absolute bioavailability of cyproterone acetate is almost complete (about 88%).

Androkur, 100 mg

The drug is completely absorbed after oral administration. Cmax of the drug in plasma is reached after an average of (2,8±1,1) h. protein Binding (mostly to albumin) serum — about 96%.

T1/2 — (42,8±9,7) h. Total clearance of cyproterone acetate from serum — (3,8±2,2) ml/min/kg. biotransformation in the liver and excreted mainly as metabolites in the bile and urine at a ratio of 3:7, part is excreted unchanged in the bile.

Androkur Depot

After the/m introduction cyproterone acetate slowly and fully released. Cmax = (180±54) ng/ml is achieved in 2-3 days. Then, a decrease in the drug concentration in the plasma with T1/2 — (4±1,1) of the day. Equilibrium concentration achieved in 5 weeks. Cyproterone acetate is almost completely bound to albumin in plasma. Only 3.5–4% are in the blood in a free form. Since the bond with plasma proteins is non-specific, changes in the level of globulin that binds sex hormones do not affect the pharmacokinetics of cyproterone acetate.

Most of the displays in the form of metabolites with urine and faeces, small quantities — in the bile in unchanged form.

Description pharmacological action:

Androkur, 10 mg

The active ingredient Androcur 10 mg reduces the influence of male sex hormones (androgens), which also produced in the female body. Therefore, women Androkur 10 mg eliminates the pathological changes which are caused by increased formation of androgens or an increased sensitivity to them: strong hair on the face and other body parts, as well as acne and seborrhea, which are largely dependent on androgens enhanced the function of the sebaceous glands.

Androkur, 50 and 100 mg

Androkur Depot

Cyproterone acetate is a competing mechanism of action inhibits the action of androgens at their target organs, and has a Central antigonadotropnym action, leading to a decrease of testosterone synthesis in the testes and its content in the blood serum. This results in inhibition of androgen stimulation of the prostate tissue. In men, the use of cyproterone acetate observed inhibition of libido, potency and testicular function. These effects are completely reversible and disappear after cessation of treatment.

Indications:

Androkur, 10 mg

• Manifestations of of moderate severity androgenization in women, such as:
• hirsutism moderate (abnormal hair on the face and body of moderate severity)
• androgenic alopecia moderate (due to androgens alopecia of moderate severity)
• severe and moderate forms of acne (acne) and seborrhea.

With acne and seborrhea average weight shown supplementation Androkura in cases where it is not observed clinical improvement in response to different treatment was not achieved satisfactory results when using only the drug Diane-35.

Androkur, 50 mg

inoperable prostate cancer.

increased libido for sexual deviations.

Androkur, 100 mg

metastatic or inoperable prostate cancer (without and after orchiectomy, as well as in combination with agonists of gonadotropin-releasing hormone).

Androkur Depot

increased libido in sexual deviations

antiandrogen therapy for inoperable carcinoma of the prostate.

Contraindications:

Androkur, 10 mg

• pregnancy
• breastfeeding
• liver disease (including syndrome, Dubin-Johnson, Rotor’s syndrome, tumor in liver disease or currently)
• idiopathic jaundice or persistent itching during a previous pregnancy
• herpes pregnant women in history
• cachexia
• severe chronic depression
• tromboembolia (incl. history)
• a severe form of diabetes with diabetic angiopathy
• sickle cell anemia
• hypersensitivity to any component of the drug
• adolescence (before completion of puberty).

Androkur, 50 and 100 mg

• Andrecorded
• hypersensitivity to cyproterone or to other component parts of the drug
• liver disease accompanied by dysfunction of
• syndrome Dubin-Johnson
• syndrome Rotor
• liver tumors in history or at present (with the exception of metastases of prostate cancer)
• cachexia (with the exception of cachexia in prostate cancer)
• severe chronic depression
• thrombosis and thromboembolism currently.

Use of the preparation Androkur 50 mg and Androkur Depot with the purpose of reducing sex drive in sexual deviations is contraindicated:

if the patient has severe forms of diabetes

sickle-cell anemia.

WITH CAUTION

The drug should be used Androkur 100 mg in the following diseases:

• tromboamboliceski processes in history
• severe forms of diabetes with vascular complications
• sickle-cell anemia.

Application of pregnancy and breast-feeding:

Androkur, 10 mg

Contraindicated in pregnancy. At the time of treatment should stop breastfeeding.

Side effects:

Androkur, 10 mg

There may be changes in body weight and libido, tension and breast tenderness, depression.

Rarely, allergic reactions and itching.

You should consider the side effects that contained in the instructions for use of the drug Diane-35.

Androkur, 100 mg

At the beginning of treatment may experience abdominal pain, nausea, fatigue, dry skin, lethargy, depression or state anxiety, decreased ability of concentration.

Rarely can be observed allergic reactions, increase or decrease body weight. Perhaps the appearance of gynecomastia and the suppression of spermatogenesis, a reversible decrease in libido and potency. Prolonged suppression of the production of androgens in rare cases, can cause osteoporosis. In a few cases at high doses observed a feeling of lack of air and the liver.

Androkur 50 mg, Androkur Depot

The following undesirable effects (see table) was observed in patients on the background of the use of cyproterone acetate (post-marketing data), but their relationship with Androkurom could not be neither confirmed nor refuted.

To indicate specific adverse reactions is the most appropriate term from MedDRA — medical dictionary for regulatory activities (version 8.0). Synonyms or similar state not be listed, but these should also be taken into account. In men with treatment Androkurom reduced libido and potency, moreover, suppressed the gonadal function. These changes are reversible and disappear after discontinuation of therapy.

Within a few weeks the result of the antiandrogenic and antigonadotropnym action Androcur is the suppression of spermatogenesis, which is gradually recovering several months after discontinuation of therapy. In men receiving Androcur can lead to the development of gynecomastia (which is sometimes accompanied by enhanced tactile sensitivity and nipple soreness), which usually takes place after drug withdrawal or dose reduction. As with other antiandrogen drugs, Androkurom caused by prolonged deficiency of androgens can lead to the development of osteoporosis.

It was reported on the development of benign cerebral meningiomas in connection with long-term (several years) taking Androcur in the dose of 25 mg or more.

Cm. also the section “Special instructions”.

Drug interactions:

Androkur, 10 mg

May change the need for oral antidiabetic agents or insulin.

Androkur, 50 mg

Androkur Depot

Despite the lack of clinical studies interactions, it can be expected that ketoconazole, Itraconazole, clotrimazole, ritonavir and other strong inhibitors of CYP3A4 will inhibit the metabolism of cyproterone acetate, which is metabolized by CYP3A4. On the other hand, inducers of CYP3A4, such as rifampicin, phenytoin and products containing St. John’s wort can reduce the concentration of cyproterone acetate.

Based on the results of in vitro studies, at high therapeutic doses of cyproterone acetate (100 mg 3 times per day) possible inhibition of isozymes of cytochrome P450, such as CYP2C8, 2C9, 2C19, 2D6 and ZA4.

Associated with statin use the risk of myopathy and rhabdomyolysis may be increased by concomitant administration of high therapeutic doses of cyproterone acetate with inhibitors of HMG-COA reductase inhibitors (statins), which are metabolized mainly by CYP3A4, as they have the same way of metabolism.

Patients with diabetes may change the need for oral antidiabetic agents or insulin.

Androkur, 100 mg

Antigonadotropnym action of cyproterone acetate is enhanced by its combined use with agonists of gonadotropin-releasing hormone. Under the action of cyproterone acetate reduced the initial increase in testosterone production caused by agonists of gonadotropin-releasing hormone.

Method of application and dose:

Androkur

Inside, after eating, squeezed small amounts of liquid.

Androkur, 10 mg

To provide adequate contraception and prevent intermenstrual bleeding accept Androkur in combination with the drug Diane-35.

The appointment of both preparations begin in the 1st day of the cycle (1st day of menstrual bleeding).

As a rule, in addition to Diane-35 daily take 1 table. Androcur at the same time from the 1st to the 15th day of the treatment cycle.

In the pack each tablet is marked with the day of the week on which it should be adopted. After administration 15 tab. within 15 days, in the remaining 6 days will only accept to Diana-35.

When 21 days of receiving a calendar pack of Diane-35 over, it should be a 7 day break from taking pills, during which should begin bleeding.

After a 7-day interval regardless of whether the bleeding stopped or still continues, the pills resume of the following calendar packs Androkur and Diane-35.

If during a break the bleeding has not occurred, which happens very rarely, you should stop the treatment and do not resume taking the pill until then, until will not be excluded pregnancy.

If a woman forgot to take the pill Diane-35 in normal times, it should be done no later than during the next 12 h. If the time of normal reception to Diana-35 has been more than 12 hours, contraceptive effect in this cycle may be impaired. You need to pay attention to the instructions regarding the contraceptive reliability, as well as recommendations on missed pills are included in information on the drug Diane-35. If, after this cycle of bleeding is missing, before resuming taking the pills should exclude pregnancy.

Skipping pills Androkur can lead to reduced therapeutic effect and cause intermenstrual bleeding. Missed pills Androkur leave not taken (i.e., should not take a double dose to compensate for the missed tablet) and resume taking the drug at the usual time with Diane-35.

Duration of treatment determines the physician depending on the severity of the pathological signs of androgenization and response to treatment. Usually the drugs must be taken for several months. The therapeutic effect in acne and seborrhea usually appears more quickly than hirsutism and alopecia.

After clinical improvement should try to continue treatment only in the drug Diane-35.

Androkur, 50 and 100 mg

For reduced libido in sexual deviations: as a rule, initial dose 1 table. (50 mg 2 times a day). If necessary, the dose can be increased to 200-300 mg/day (2 table. Androcur 50 mg 2-3 times a day) for a short period. Upon reaching a satisfactory result, you should try to reduce the dose to the minimum effective. In most cases it is enough to take 50 mg/day (1/2 tab. 2 times a day). When selecting a maintenance dose or if you cancel therapy, the dose should be reduced gradually.

With this purpose, the daily dose is recommended to reduce to 1 table. or better 0.5 table. within a few weeks.

To achieve sustainable therapeutic effect should be taken Androkur for a long time, if possible, while conducting psychotherapy.

Antiandrogen therapy of inoperable prostatic cancer: 200-300 mg/day (2 table. Androcur 50 mg or 1 table. Androcur 100 mg 2-3 times a day, for a long time).

With the improvement in or achievement of remission should not interrupt treatment or reduce dosage.

If signs of disease progression preparation Androkur, 100 mg should be discontinued.

To reduce the initial increase of androgens during therapy with agonists of gonadotropin-releasing hormone (GnRH): initially 200 mg per day (2 table. Androcur 50 mg or 1 table. Androcur 100 mg 2 times a day) as monotherapy for 5-7 days, then 200 mg daily for 3-4 weeks in combination with an agonist of GnRH in the manufacturer’s recommended dosage.

For treatment of “hot flashes” on the background of therapy with GnRH analogues or orchiectomy after: 50-100 mg/day (1-3 tabl. Androcur 50 mg or 0.5–1.5 table. Androcur 100 mg per day), if necessary, with a consequent increase in doses up to 300 mg per day (2 table. Androcur 50 mg or 1 table. Androcur 100 mg 3 times a day).

Androkur Depot

In/m, slowly, deep into muscle.

Like all oily solutions Androkur Depot is administered only in/m! In rare cases during the injection or immediately after it may be short-term reactions (urge to cough, coughing fits, feeling of shortage of air). Very slow introduction of the drug allows to avoid such reactions. It is necessary to avoid intravascular injection.

Decreased sex drive in sexual deviations: the usual 300 mg (1 amp.) I/m every 10-14 days. In exceptional cases, when this dose is not enough you can enter 600 mg (2 amp.) every 10-14 days (preferably 3 ml in the right and left buttock). Upon reaching a satisfactory result of treatment should try to reduce the dose, gradually increasing the interval between injections.

To achieve sustainable therapeutic effect should be taken Androkur Depot for a long time, if possible, while conducting psychotherapy.

Antiandrogen therapy for inoperable carcinoma of the prostate: 300 mg/m every 7 days.

With the improvement in or achievement of remission should not interrupt treatment or reduce dosage.

Overdose:

Androkur, 10 mg

In studies of acute toxicity after a single dose of drug it was found that cyproterone acetate, the active ingredient of the preparation Androkur can be considered practically non-toxic substance. The risk of acute intoxication after a single accidental ingestion of multiple therapeutic doses is also unlikely. Overdose in case of single application of a large number of tablets Androcur 10 mg was not reported.

Symptoms (in case of accidental intake of a large dose of the drug): nausea, intermenstrual bleeding in women.

Treatment: symptomatic, no specific antidote.

Androkur, 50 and 100 mg

Androkur Depot

Studies of acute toxicity after a single application of the drug showed that cyproterone acetate can be considered practically non-toxic substance. Also a remote risk of acute intoxication after a single accidental dose several times the recommended therapeutic dose.

Special instructions:

Androkur, 10 mg

Before treatment should conduct a General medical and gynecological examination (including breast examination and a smear of cervical mucus). It is also necessary to exclude pregnancy.

Patients with diabetes may change the need for oral hypoglycemic agents or insulin. Patients with diabetes during treatment with Androkur drug should be under a doctor’s supervision.

During treatment should use caution when doing activities that require increased attention.

During treatment requires periodic monitoring of liver function.

In rare cases, against the backdrop of sex steroids, which include cyproterone acetate, observed the development of liver tumors. Despite the fact that the connection with the supplementation has not been proven, in case of severe pain in the abdomen that do not disappear within a short time should immediately consult a doctor.

The drug Androkur is contraindicated in pregnancy. To prevent unwanted pregnancy, as well as intermenstrual bleeding should simultaneously apply the contraceptive drug Diane-35, which causes bleeding and due to the fact that it contains the same active substance antiandrogen (cyproterone acetate) enhances the therapeutic effect of the preparation Androkur.

If combination therapy during the 3-week period of taking the pills observed spotting, treatment should not be interrupted. However, persistent or recurrent late bleeding, you must contact your doctor for a gynaecological examination.

Because of the need for additional intake of Diane-35 should also take into account all the relevant information for this drug.

Caution — diabetes.

Androkur, 50 mg, Androkur Depot

Androkurom treatment is not recommended until the completion of puberty, because we can not exclude the likelihood of an adverse impact on growth and on more nestabilizirovannoy the endocrine system.

During treatment Androkurom should regularly assess liver function, adrenal and examination of peripheral blood. In patients receiving daily 200-300 mg cyproterone acetate have also been cases of hepatotoxicity, including jaundice, hepatitis and hepatic failure, sometimes fatal. The majority of these cases were registered in men with carcinoma of the prostate.

Toxicity is dose-dependent and usually develops several months after the start of therapy. Before the beginning of treatment and when any symptoms or signs of hepatotoxicity is necessary to conduct studies of the functions of the liver. If confirmed hepatotoxicity therapy cyproterone acetate is usually recommended to cancel, unless the hepatotoxicity not due to other causes, such as metastatic process. In this case, treatment should continue only if expected benefits outweigh the risks.

In rare cases after administration of sex hormones (which also includes the active component Androkura) were benign and even more rarely malignant liver tumors, in some cases leading to life-threatening intra-abdominal hemorrhage. If complaints of acute pain in the upper abdomen, liver enlargement or signs of acute intra-abdominal bleeding, the differential diagnosis should be considered possible liver tumor.

Patients suffering from diabetes, need careful medical supervision.

Reported occurrence of thromboembolic phenomena in patients receiving Androkur, although the causal relationships have been identified. In patients with previous thrombotic/thromboembolic diseases of arteries or veins (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction), disorders of cerebral circulation in the anamnesis or in the later stages of malignant disease the risk of thromboembolic complications is increased.

Androkurom in the treatment of patients with increased sexual desire in sexual disorders the use of alcohol can lead to reduced drug action.

Before the appointment Androkura patients with inoperable carcinoma of the prostate with thromboembolic syndrome in anamnesis, and in the presence of sickle-cell anemia or severe diabetes with vascular changes, in each individual case it is necessary to carefully evaluate the possible risks and expected benefits of treatment.

During treatment Androkurom be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions, because the drug may lead to deterioration of these indicators.

It is necessary to avoid intravascular injection Androkur Depot.

Androkur, 100 mg

Treatment Androkurom should be under the control of the liver, adrenal cortex and picture peripheral blood.

If there are signs of hepatotoxicity, the drug should be discontinued.

In patients with diabetes mellitus may require dose adjustment of insulin or other hypoglycemic drugs (glucose monitoring should be performed more often than usual).

Androkura negative impact on fertility after cessation of treatment were observed.

During treatment should refrain from activities, require increased attention.