Андрокур® Depot

General characteristics. Structure:

Active agent: tsiproterona acetate of 100 mg.
Excipients: castor oil of 353.40 mg, benzyl benzoate of 618.60 mg.
Description. Transparent, from colourless till yellowish color, liquid.

Pharmacological properties:

Pharmacodynamics. The drug Androkur® of Depot is the hormonal drug containing ципротерон, possessing anti-androgenic, gestagenny and anti-gonadotropic action.
Tsiproteron on the competitive mechanism oppresses action of androgens on their target organs, and also possesses the central anti-gonadotropic action leading to decrease in synthesis of testosterone in testicles and its contents in blood serum. As a result androgenic stimulation of tissue of prostate gland is suppressed.
At men at use of a tsiproteron oppression of sexual desire, potentiality and function of testicles is observed. These effects are completely reversible and pass after the treatment termination.
System toxicity
According to standard preclinical trials of toxicity at repeated long introduction there is no specific risk for the person.

Pharmacokinetics. Absorption. After intramuscular introduction ципротерон it is slowly and completely released. Absolute bioavailability of a tsiproteron after intramuscular introduction is considered full.
Distribution. The maximum concentration in plasma, equal 180±54 ng/ml, is reached in 2-3 days. Then decrease in concentration of drug in plasma with an elimination half-life of 4±1,1 days is observed. The general clearance of a tsiproteron makes 2,8±1,4 ml/min. of serum.
Tsiproteron almost completely contacts blood plasma albumine. Only 3,5-4% are in blood in a free look. As communication with proteins of plasma is nonspecific, changes of the GSPG level (the globulin connecting sex hormones) do not influence pharmacokinetics of a tsiproteron.
Considering long plasma elimination half-life of blood in a final phase of distribution and the accepted dose, it is possible to expect cumulation of a tsiproteron at use of repeated doses. Equilibrium concentration is reached approximately in 5 weeks of use of drug.
Metabolism / biotransformation. Tsiproteron is metabolized by a hydroxylation and conjugation. The main metabolite in a blood plasma - 15P-hydroxyderivative. The first phase of metabolism is catalyzed preferential by an isoenzyme of P450 CYP3A4 cytochrome. Removal. Small amounts are removed with bile in an invariable look. The most part of the entered dose is removed in the form of metabolites with bile and kidneys.

Indications to use:

Inoperable prostate cancer
The raised sexual desire at sexual deviations at men

Route of administration and doses:

The drug Androkur® of Depot, as well as all other Solutio oleosa, it is necessary to enter strictly intramusculary and very slowly. In certain cases the microembolism of a pulmonary artery Solutio oleosa can cause emergence of such signs and symptoms as cough, short wind and a stethalgia. Emergence and other signs and symptoms - including, vazovagalny reactions is possible (for example, an indisposition, the increased sweating, dizziness, paresthesias or a faint). These reactions can arise in time or at once after an injection and are reversible. In such cases usually use a maintenance therapy (for example, inhalation by oxygen). It is necessary to avoid intravascular administration of drug.

Anti-androgenic therapy at an inoperable prostate cancer On 300 mg (1 ampoule) deeply intramusculary each 7 days.
At improvement of a state or achievement of remission it is not recommended to interrupt treatment or to reduce a dose.

For decrease in the raised sexual desire at sexual deviations at men Usually each 10-14 days enter 300 mg (1 ampoule) deeply intramusculary. In exceptional cases, when this dose is not enough, it is possible to enter 600 mg (2 ampoules) each 10-14 days (preferably on 3 ml into the right and left buttock). At achievement of satisfactory result of treatment it is necessary to try to reduce a dose, gradually increasing intervals between injections.
For achievement of steady therapeutic effect it is necessary to use the drug Androkur® of Depot for a long time, whenever possible, with simultaneous carrying out psychotherapy.

Use for certain categories of patients
Children's and teenage age
The drug Androkur® of Depot is not recommended to be used at children and teenagers up to 18 years because of insufficient information by efficiency and safety at this category of patients. Treatment by the drug Androkur® of Depot is not recommended to be carried out before end of the period of puberty as it is impossible to exclude probability of adverse influence on growth and on yet not stable endocrine system.

Advanced age
There are no data on need to change a drug dose at elderly patients. Liver failure
Use of the drug Androkur® of Depot is contraindicated to patients with liver diseases (until indicators of a liver are not normalized).

Renal failure
There are no data on need to change a drug dose at this category of patients.

Features of use:

During treatment of Androkurom® of Depot it is regularly necessary to make assessment of function of a liver, bark of adrenal glands and a research of peripheral blood.
At the patients accepting Androkur® hepatotoxic cases (development of jaundice, hepatitis and liver failure) were noted. At use of drug in a dose of 100 mg and it was reported about cases from the death above. The majority of cases from the death was noted at men at a late stage of a prostate cancer. Toxicity depends on a dose and usually develops in several months after the beginning of therapy. Before an initiation of treatment, it is regular during treatment and at emergence of any symptoms or signs of a hepatotoxic it is necessary to conduct researches of function of a liver. At the confirmed hepatotoxic therapy tsiproterony is recommended to be cancelled if only a hepatotoxic is not caused by other reasons, for example, metastatic process. In the latter case treatment should be continued only under a condition if the expected positive effect exceeds risk.
Seldom or never after use of the drug Androkur® of Depot were noted high-quality and malignant tumors of a liver which in some cases could lead to life-threatening intra belly bleeding are even more rare. At complaints to an acute pain in an upper part of a stomach, increase in a liver or in the presence of symptoms of acute intra belly bleeding the differential diagnosis should be carried out taking into account a possible tumor of a liver.
It was reported about emergence of tromboembolic episodes at the patients using the drug Androkur® of Depot though existence of relationship of cause and effect was not revealed. At patients with the thromboembolic diseases of arteries or veins previous tromboticheskimi/(for example, a deep vein thrombosis, an embolism of a pulmonary artery, a myocardial infarction), with disturbances of cerebral circulation in the anamnesis or at late stages of malignant diseases the risk of emergence of tromboembolic episodes is increased.
During treatment by the drug Androkur® of Depot it was reported about development of anemia. Therefore during treatment by the drug Androkur® of Depot it is necessary to make a research of peripheral blood regularly.
Patients with a diabetes mellitus need careful medical observation as the need for peroral hypoglycemic means or insulin can change (you watch also the section "Contraindications").
Use of the drug Androkur® of Depot in high doses can sometimes be followed by an asthma. In similar cases when carrying out the differential diagnosis it is necessary to take into account the known promoting effect of progesterone and synthetic gestagen on the breath accompanied with a hypocapny and a compensatory respiratory alkalosis. Special treatment at this symptom complex is not required. During treatment by the drug Androkur® of Depot it is regularly necessary to check function of a bast layer of adrenal glands as, proceeding from preclinical data, possible suppression of function of adrenal glands in connection with kortikoidopodobny effect of the drug Androkur® of Depot in high doses is supposed.
The drug Androkur® of Depot, as well as all other Solutio oleosa, it is necessary to enter strictly intramusculary and very slowly. In certain cases the microembolism of a pulmonary artery Solutio oleosa can cause emergence of such signs and symptoms as cough, short wind and a stethalgia. Emergence and other signs and symptoms - including, vazovagalny reactions is possible (for example, an indisposition, the increased sweating, dizziness, paresthesias or a faint). These reactions can arise in time or at once after an injection and are reversible. In such cases usually use a maintenance therapy (for example, inhalation by oxygen).
At treatment by the drug Androkur® of Depot of patients with the raised sexual desire at sexual frustration alcohol intake can lead to decrease in effect of drug.

Influence on driving of motor transport and control of mechanisms
During treatment by the drug Androkur® of Depot it is necessary to be careful during the driving of the car and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions as at administration of drug of Androkur® of Depot the increased fatigue worsening these indicators can be observed.

Side effects:

The most often observed side effects: decrease in a libido, impotence and reversible suppression of a spermatogenesis.
The most serious side effects: a hepatotoxic, benign and malignant tumors of a liver which can lead to intra belly bleeding and development of thromboembolic processes.
The undesirable phenomena about which it was reported at use of the drug Androkur® of Depot,
are listed below. Frequency is determined as: very often (> 1/10), it is frequent (from> 1/100 to <1/10),
infrequently (from> 1/1000 to <1/100), it is rare (from> 1/10000 to <1/1000), is very rare (<1/10000). For
the undesirable effects revealed in the course of post-marketing observations and for
which it is not possible to estimate reliably frequency, it is specified "frequency is unknown".
From the hemopoietic system:
frequency is unknown - anemia
From immune system:
seldom - hypersensitivity reactions.
Disturbances of mentality:
often - a depression, the suppressed mood, feeling of concern (temporary). From vessels:
frequency is unknown - an oil microembolism of a pulmonary artery vazovagalny reactions of fibrinferments and a thromboembolism)). From system of breath: often - an asthma of I
From digestive tract:
frequency is unknown - intra belly bleeding
From a liver and biliary tract:
often - jaundice, hepatitis, a liver failure
From skin and hypodermic fabrics: infrequently - rash.
From a musculoskeletal system: frequency is unknown - osteoporosis.
From generative organs and molochy glands:
very often - reversible suppression of a spermatogenesis, decrease in a libido, erectile
dysfunction;
often - a gynecomastia.
Others:
often - increase or decrease in body weight, increased fatigue, inflows, the increased perspiration
very seldom - development of benign or malignant tumors of a liver; frequency is unknown - a meningioma.
The undesirable phenomena for which it is possible to find more detailed information in the section "Special Instructions" are marked with an asterisk the I Undesirable phenomena for which the causal interrelation with administration of drug of Androkur® of Depot is not proved, marked with asterisks - address the section "Contraindications".
For designation of specific side reaction the most suitable term from MedDRA - the Medical dictionary for regulatory activity is provided (version 8.0). Synonyms or the accompanying states are not listed, but they also should be taken into account.
At men against the background of treatment by the drug Androkur® of Depot sexual desire and a potentiality decrease, besides, function of gonads is suppressed. These changes have reversible character and take place after therapy cancellation.
Within several weeks as a result of anti-androgenic and anti-gonadotropic effects of the drug Androkur® of Depot there is a suppression of a spermatogenesis which is gradually recovered in several months after therapy cancellation.
At men administration of drug of Androkur® of Depot can lead to development of a gynecomastia (that sometimes is followed by the increased tactile sensitivity and morbidity of nipples), which usually passes after drug withdrawal or a dose decline. As well as when using other anti-androgenic drugs, the long deficit of androgens caused by the drug Androkur® of Depot can lead to development of osteoporosis. It was reported about development of meningiomas in connection with long (within several years) administration of drugs of Androkur® (in other dosage forms) in a dose of 25 mg and more (section "Contraindications" and "Special Instructions").

Interaction with other medicines:

Despite the lack of clinical trials of interactions, it is possible to expect that кетоконазол, итраконазол, Clotrimazolum, ритонавир and other strong CYP3A4 inhibitors will suppress metabolism of a tsiproteron of acetate which is metabolized by CYP3A4 isoenzyme. On the other hand, the inductors CYP3A4, such as rifampicin, Phenytoinum and drugs containing a St. John's Wort can reduce concentration of a tsiproteron of acetate. Proceeding from results of the researches in vitro, at high therapeutic doses of a tsiproteron of acetate (100 mg 3 times a day) the inhibition of isoenzymes of system of P450 cytochrome, such as CYP2C8, 2S9, 2S19, 3A4 and 2D6 is possible.
The risk of a myopathy and rabdomioliz connected using statines can increase at co-administration of high therapeutic doses of a tsiproteron of acetate with inhibitors of GMG-KOA-reduktazy (statines) which are metabolized preferential by CYP3A4 isoenzyme as they have the same way of metabolism.
 The need for peroral antidiabetic means can change or
insulin.

Contraindications:

 At treatment of an inoperable prostate cancer:
- hypersensitivity to a tsiproteron or to other components of drug;
- the liver diseases which are followed by disturbance of its function;
- syndrome Cudgel Johnson, Rotor syndrome;
- liver tumors in the anamnesis or now (except for metastasises of a prostate cancer in a liver);
- a cachexia (except for a cachexia at a prostate cancer);
- heavy chronic depression;
- thromboses and thrombembolia now;
- existence of a meningioma now or in the anamnesis;
- children and teenagers up to 18 years.
• At treatment of the raised sexual desire at sexual deviations at men:
- hypersensitivity to a tsiproteron or to other components of drug;
- the liver diseases which are followed by disturbance of its function;
- syndrome Cudgel Johnson, Rotor syndrome;
- liver tumors in the anamnesis or now;
- cachexia;
- heavy chronic depression;
- thrombosis and a thrombembolia in the anamnesis or now;
- a heavy diabetes mellitus with an angiopatiya;
- sickemia;
- existence of a meningioma now or in the anamnesis;
- children and teenagers up to 18 years.

With care
At patients with  an inoperable  prostate cancer  in the presence of thromboembolic  processes in the anamnesis, a severe form of a diabetes mellitus with an angiopatiya, a sickemia of Androkur® of Depot it is appointed only after assessment of an individual ratio of advantage and risk in each case. Patients with a diabetes mellitus, during treatment have to be under observation of the doctor.

Overdose:

Researches of acute toxicity after single use of drug showed what ципротерон can be considered as almost non-toxic substance. The risk of acute intoxication after single one-time accidental use of the dose several times exceeding a therapeutic dose is also improbable. There is no specific antidote. At a neobkhodimost it is recommended to carry out symptomatic therapy.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solutio oleosa for intramuscular introduction on 300 mg / 3 ml in ampoules of dark glass. On 3 ampoules in the cardboard pallet together with the application instruction in a cardboard pack.