ANDROCURT DEPOT 100mg/ml 3ml 3 pcs. solution for intramuscular injection oil

Composition, release form and packaging

Solution - 1 ml .:

• Active ingredient: cyproterone acetate 100 mg;
• Excipients: castor oil 353.40 mg, benzyl benzoate 618.60 mg.

Oil solution for intramuscular administration of 300 mg / 3 ml in dark glass ampoules.

3 ampoules in a cardboard pallet together with instructions for use in a cardboard box.

Description of the dosage form

Transparent, colorless to yellowish liquid.

Pharmacotherapeutic group

Antiandrogen. 

Pharmacokinetics

Absorption. After intramuscular administration, cyproterone is slowly and completely released. The absolute bioavailability of cyproterone after intramuscular administration is considered complete.

Distribution. The maximum plasma concentration, equal to 180 ± 54 ng / ml, is reached after 2-3 days. Then there is a decrease in the concentration of the drug in plasma with a half-life of 4 ± 1.1 days. The total clearance of cyproterone from serum is 2.8 ± 1.4 ml / min / kg.

Cyproterone almost completely binds to blood plasma albumin. Only 3.5-4% are free in the blood. Since the connection with plasma proteins is nonspecific, changes in the level of SHBG (globulin that bind sex hormones) do not affect the pharmacokinetics of cyproterone.

Considering the long plasma half-life in the final phase of distribution and the dose taken, the cumulation of cyproterone can be expected when repeated doses are used. Equilibrium concentration is reached after about 5 weeks of using the drug.

Metabolism / biotransformation. Cyproterone is metabolized by hydroxylation and conjugation. The main metabolite in blood plasma is 15β-hydroxy derivative. The first phase of metabolism is catalyzed predominantly by the cytochrome P450 isoenzyme CYP3A4.

Excretion. Small amounts are excreted in the bile unchanged. Most of the administered dose is excreted as metabolites in the bile and kidneys.

Pharmacodynamics

The drug Androkur® Depo is a hormonal drug containing cyproterone, which has antiandrogenic, gestagenic and antigonadotropic effects.

Cyproterone, by a competitive mechanism, inhibits the action of androgens on their target organs, and also has a central antigonadotropic effect, leading to a decrease in testosterone synthesis in the testes and its content in blood serum. As a result, androgenic stimulation of the prostate tissue is suppressed.

In men, when using cyproterone, there is an inhibition of sexual desire, potency and testicular function. These effects are completely reversible and disappear after stopping treatment.

Systemic toxicity

According to standard preclinical toxicity studies with repeated long-term administration, there is no specific risk to humans.

Indications for use

Inoperable prostate cancer.

Increased sex drive with sexual deviations in men.

Contraindications for use

When treating inoperable prostate cancer:

• hypersensitivity to cyproterone or to other components of the drug;
• liver diseases, accompanied by a violation of its function;
• Dubin-Johnson syndrome, Rotor syndrome;
• a history of liver tumors or currently (with the exception of metastases of prostate cancer to the liver);
• cachexia (with the exception of cachexia in prostate cancer);
• severe chronic depression;
• thrombosis and thromboembolism at the present time;
• the presence of a meningioma at the present time or in anamnesis;
• children and adolescents under 18 years of age.

In the treatment of increased sex drive in sexual deviations in men:

• hypersensitivity to cyproterone or to other components of the drug;
• liver diseases, accompanied by a violation of its function;
• Dubin-Johnson syndrome, Rotor syndrome;
• history of liver tumors or current;
• cachexia;
• severe chronic depression;
• history of thrombosis and thromboembolism;
• severe diabetes mellitus with angiopathy;
• sickle cell anemia;
• the presence of a meningioma at the present time or in anamnesis;
• children and adolescents under 18 years of age.

Carefully:

In patients with inoperable prostate cancer with a history of thromboembolic processes, severe diabetes mellitus with angiopathy, sickle cell anemia, Androkur® Depo is prescribed only after assessing the individual balance of benefits and risks in each case.

Patients with diabetes mellitus should be under medical supervision during treatment.

Side effects

The most commonly observed side effects are decreased libido, impotence and reversible suppression of spermatogenesis.

The most serious side effects: hepatotoxicity, benign and malignant liver tumors, which can lead to intra-abdominal bleeding and the development of thromboembolic processes.

The adverse events reported with Androkur® Depo are listed below. Frequency is defined as: very often (? 1/10), often (? 1/100 to

From the hematopoietic system: the frequency is unknown - anemia *).

From the immune system: rarely - hypersensitivity reactions.

Mental disorders: often - depression, depressed mood, anxiety (temporarily).

From the side of the vessels: the frequency is unknown - oily microembolism of the pulmonary artery *), vasovagal reactions *), thrombosis and thromboembolism *) **).

From the respiratory system: often - shortness of breath *).

From the gastrointestinal tract: frequency unknown - intra-abdominal bleeding *).

From the liver and biliary tract: often - jaundice, hepatitis, liver failure *).

On the part of the skin and subcutaneous tissues: infrequently - rash.

From the musculoskeletal system: the frequency is unknown - osteoporosis.

On the part of the genitals and mammary glands: very often - reversible suppression of spermatogenesis, decreased libido, erectile dysfunction; often - gynecomastia.

Others: often - an increase or decrease in body weight, increased fatigue, hot flashes, increased sweating; very rarely - the development of benign or malignant liver tumors *); frequency unknown - meningioma *) §)

Adverse events for which a causal relationship with the intake of Androkur® Depo has not been proven are marked with asterisks **. §).

The most appropriate term from MedDRA - The Medical Dictionary for Regulatory Activities (version 8.0) is provided to denote a specific adverse reaction. Synonyms or related conditions are not listed, but they should also be taken into account.

In men, on the background of treatment with Androkur® Depo, libido and potency decrease, in addition, the function of the sex glands is suppressed. These changes are reversible and disappear after discontinuation of therapy.

Within a few weeks, as a result of the antiandrogenic and antigonadotropic action of Androkur® Depo, spermatogenesis is suppressed, which is gradually restored several months after discontinuation of therapy.

In men, taking Androkur® Depo can lead to the development of gynecomastia (which is sometimes accompanied by increased tactile sensitivity and soreness of the nipples), which usually disappears after drug withdrawal or dose reduction.

As with the use of other antiandrogenic drugs, prolonged androgen deficiency caused by Androkur® Depo can lead to the development of osteoporosis. It has been reported about the development of meningiomas due to prolonged (over several years)

Taking Androkur® drugs (in other dosage forms) at a dose of 25 mg or more.

Drug interactions

Despite the absence of clinical studies of interactions, it can be expected that ketoconazole, itraconazole, clotrimazole, ritonavir and other strong inhibitors of CYP3A4 will suppress the metabolism of cyproterone acetate, which is metabolized by the isoenzyme CYP3A4. On the other hand, inducers of CYP3A4, such as rifampicin, phenytoin, and preparations 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 a day), inhibition of isoenzymes of the cytochrome P450 system, such as CYP2C8, 2C9, 2C19, 3A4 and 2D6, is possible.

The risk of myopathy and rhabdomyolysis associated with the use of statins may increase with the simultaneous administration of high therapeutic doses of cyproterone acetate with HMG-CoA reductase inhibitors (statins), which are metabolized predominantly by the CYP3A4 isoenzyme, since they share the same metabolic pathway.

The need for oral antidiabetic drugs or insulin may change.

Method of administration and dosage

Androkur® Depot, like all other oil solutions, should be administered strictly intramuscularly and very slowly. In some cases, pulmonary embolism with oil can cause signs and symptoms such as coughing, shortness of breath, and chest pain. Other signs and symptoms may also occur, including vasovagal reactions (eg, malaise, increased sweating, dizziness, paresthesia, or fainting). These reactions can occur during or immediately after injection and are reversible. In such cases, supportive therapy (eg, oxygen inhalation) is usually used.

It is necessary to avoid intravascular administration of the drug.

Antiandrogen therapy for inoperable prostate cancer

300 mg (1 ampoule) deep intramuscularly every 7 days. When the condition improves or remission is achieved, it is not recommended to interrupt treatment or reduce the dose.

To reduce increased sex drive in sexual deviations in men

Usually every 10-14 days, 300 mg (1 ampoule) is injected deeply intramuscularly. In exceptional cases, when this dose is not enough, you can enter 600 mg (2 ampoules) every 10-14 days (preferably 3 ml in the right and left buttock). When a satisfactory result of treatment is achieved, you should try to reduce the dose, gradually increasing the intervals between injections.

To achieve a stable therapeutic effect, Androkur® Depo should be used for a long time, if possible, with simultaneous psychotherapy.

Application in certain categories of patients

Children and adolescence

The drug Androkur® Depo is not recommended for use in children and adolescents under 18 years of age due to insufficient information on the efficacy and safety in this category of patients. Treatment with Androkur® Depot is not recommended until the end of puberty, since the likelihood of an adverse effect on growth and on the still unstable endocrine system cannot be ruled out.

Elderly age

There is no evidence of the need to change the dose of the drug in elderly patients.

Liver failure

The use of Androkur® Depo is contraindicated in patients with liver diseases (as long as the liver parameters are not normalized).

Renal failure

There is no evidence of the need to change the dose of the drug in this category of patients.

Overdose

Acute toxicity studies after a single use of the drug have shown that cyproterone can be considered a practically non-toxic substance. Also, the risk of acute intoxication after a single single accidental use of a dose several times higher than the therapeutic dose is unlikely. There is no specific antidote. If necessary, symptomatic therapy is recommended.

Precautions and special instructions

During treatment with Androkur® Depo, the function of the liver, adrenal cortex and the study of peripheral blood should be regularly assessed.

In patients taking Androkur®, there have been cases of hepatotoxicity (development of jaundice, hepatitis and liver failure). When using the drug at a dose of 100 mg and above, fatal cases have been reported. Most fatalities have been reported in men with advanced prostate cancer. Toxicity is dose dependent and usually develops several months after initiation of therapy. Before starting treatment, regularly during treatment and if any symptoms or signs of hepatotoxicity appear, liver function tests should be performed. With confirmed hepatotoxicity, cyproterone therapy is recommended to be canceled, unless the hepatotoxicity is due to other reasons, for example, a metastatic process. In the latter case, treatment should be continued only if

In very rare cases, after the use of Androkur® Depo, benign and even less often malignant liver tumors were noted, which in some cases could lead to life-threatening intra-abdominal bleeding. In case of complaints of acute pain in the upper abdomen, enlarged liver, or in the presence of signs of acute intra-abdominal bleeding, the differential diagnosis should be carried out taking into account a possible liver tumor.

Thromboembolic complications have been reported in patients using Androkur® Depo, although no causal relationship has been identified. In patients with previous thrombotic / thromboembolic diseases of the arteries or veins (eg, deep vein thrombosis, pulmonary embolism, myocardial infarction), with a history of cerebral circulation disorders, or in advanced stages of malignant diseases, the risk of thromboembolic complications is increased.

During treatment with Androkur® Depo, anemia was reported. Therefore, during treatment with Androkur® Depo, the peripheral blood should be examined regularly.

Patients with diabetes mellitus need close medical supervision, as the need for oral hypoglycemic agents or insulin may change.

The use of Androkur® Depot in high doses can sometimes be accompanied by shortness of breath. In such cases, when carrying out a differential diagnosis, the known stimulating effect of progesterone and synthetic gestagens on respiration, accompanied by hypocapnia and compensatory respiratory alkalosis, should be taken into account. Special treatment for this symptom complex is not required.

During treatment with Androkur® Depo, it is necessary to regularly check the function of the adrenal cortex, since, based on preclinical data, it is assumed that the function of the adrenal glands may be suppressed due to the corticoid-like effect of Androkur® Depo in high doses.

Androkur® Depot, like all other oil solutions, should be administered strictly intramuscularly and very slowly. In some cases, pulmonary embolism with oil can cause signs and symptoms such as coughing, shortness of breath, and chest pain. Other signs and symptoms may also occur, including vasovagal reactions (eg, malaise, increased sweating, dizziness, paresthesia, or fainting). These reactions can occur during or immediately after injection and are reversible. In such cases, supportive therapy (eg, oxygen inhalation) is usually used.

When treating with Androkur® Depot, patients with increased sex drive in sexual dysfunctions, alcohol intake can lead to a decrease in the effect of the drug.

Influence on the ability to drive vehicles and use mechanisms

During the period of treatment with Androkur® Depo, care must be taken when driving a car and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions, since when taking Androkur® Depo, you may experience increased fatigue, which worsens these indicators.

Conditions of dispensing from pharmacies

On prescription