Androkur - instructions for use, doses, side effects, contraindications

lactose monohydrate - 110,50 mg, corn starch - 59,50 mg, povidone 25,000 -2,50 mg, silicon dioxide colloid, anhydrous - 2,00 mg, magnesium stearate - 0,50 mg.

Description:

Oblong from white to light yellow tablets, with a risk on one side, risks are squeezed out from both sides "LA". On the other side of the tablet a hexagon is squeezed out.

Pharmacotherapeutic group:Antiandrogen

ATX: & nbsp

G.03.H.A.01 Cyproterone

Pharmacodynamics:

The drug Androkur® is an antiandrogenic hormone drug.

Cyproterone, by a competitive mechanism, inhibits the action of androgens on their target organs, for example, protects the prostate gland from the action of androgens of the sex glands and / or the adrenal cortex. Cyproterone has a central antigonadotropic effect, leading to a decrease in the synthesis of testosterone in the testicles, and its content in the serum.As a result, the androgenic stimulation of prostate tissue is suppressed.

In men with the use of Androkur®, depression of sexual desire, potency and function of the testicles is observed. These effects are completely reversible and pass after discontinuation of treatment.

The antigonadotropic effect of cyproterone also appears in combination with gonadotropin-releasing hormone agonists (GnRH). The temporary increase in serum testosterone concentration, observed at the initial stage of GnRH agonist therapy, decreases with the intake of cyproterone.

Sometimes, when taking high doses of cyproterone, there was an increase in the concentration of prolactin.

Systemic Toxicity

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

Pharmacokinetics:

Absorption. Ciproterone is completely absorbed after ingestion. Absolute bioavailability of cyproterone is about 88%.

Distribution. The maximum concentration of cyproterone (Cmax) in the blood serum after taking a dose of 50 mg reaches 140 ng / ml on average after 3 hours.The decrease in the concentration of cyproterone is biphasic and occurs within 24-120 hours with a final half-life (T1 / 2) of 43.9 ± 12.8 hours. The total clearance of ciproterone from serum is 3.5 ± 1.5 ml / min / kg .

Ciproterone almost completely binds to albumin plasma. About 3.5-4% of cyproterone remains unbound. Since the association with proteins is non-specific, a change in the content of globulin binding the sex hormones does not affect the pharmacokinetics of cyproterone.

Due to the long period of elimination in the final phase of elimination from plasma, as well as daily intake, it is probable that ciproteron cumulation in serum is 3 times greater when repeated doses are used per one treatment cycle.

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

Excretion. It is exposed to biotransformation in the liver, it is excreted mainly as metabolites with bile and kidneys (half-life of 1.9 days) in a ratio of 3: 7, part is excreted unchanged with bile.Metabolism in the blood plasma occurs at the same rate (half-life of 1.7 days).

Indications:

Common inoperable or metastatic prostate cancer when it is necessary to suppress the action of testosterone:

antiandrogen therapy for inoperable prostate cancer;
reduction in the severity of hyperandrogenism observed at the beginning of therapy with gonadotropin-releasing hormone agonists (GnRH);
relief of tides in patients with prostate cancer receiving therapy with GnRH agonists, or in patients undergoing orchiectomy.

Increased sexual desire for sexual disorders.

Contraindications:

In the treatment of common inoperable or metastatic prostate cancer when it is necessary to suppress the action of testosterone:

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

In the treatment of increased sexual desire in sexual disorders:

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

Carefully:

In patients with inoperable prostate cancer in the presence of thrombosis and thromboembolism in history, severe diabetes mellitus with angiopathy, sickle cell anemia, Androkur® is assigned only after assessing the individual benefit-risk ratio in each case.

Patients with diabetes mellitus during treatment should be under the supervision of a doctor.

Patients with rare hereditary diseases of milk sugar intolerance, lactase deficiency, glucose malabsorption syndrome and galactose should apply this medication with caution.

Dosing and Administration:

Tablets should be taken daily, inside after eating, with a small amount of liquid. If signs of disease progression appear, Androcour® should be discontinued.

The maximum daily dose of the drug is 300 mg.

Antiandrogen therapy for inoperable prostate cancer

For 200-300 mg per day (2 tablets 2-3 times a day). If the condition improves or remission is achieved, treatment should not be discontinued or the dose reduced.

Reduction of the severity of hyperandrogenism observed at the beginning of therapy with gonadotropin-releasing hormone agonists (GnRH)

200 mg per day (2 tablets 2 times a day) as monotherapy for 5-7 days, then for 3-4 weeks at the same dose in combination with a GnRH agonist at the dose recommended by the manufacturer.

Coping of "tides" in patients with prostate cancer receiving therapy with GnRH agonists, or patients undergoing orchiectomy

50-150 mg per day (1-3 tablets per day) if necessary, followed by a dose increase of 300 mg per day (2 tablets 3 times a day).

Increased sexual desire for sexual disorders

As a rule, treatment is started with 1 tablet of Androkur® 50 mg twice a day. If necessary, the dose can be increased to 200-300 mg per day (2 tablets 2-3 times a day) for a short period. If you achieve a satisfactory result, you should try to reduce the dose of the drug to a minimum effective. In most cases, it is enough to take 50 mg per day (1/2 tablet 2 times a day). When selecting a maintenance dose or when canceling therapy, the dose should be reduced gradually. For this purpose, the daily dose is recommended to be reduced by one tablet, or better by half a tablet, with an interval of several weeks.

To achieve a sustainable therapeutic effect, Androcour® should be taken for a long time, if possible, with simultaneous psychotherapy.

Application in certain categories of patients:

Children and adolescence

The drug Androkur® is not recommended for use in children and adolescents under 18 years due to insufficient information on efficacy and safety in this category of patients.

Treatment with Androkur® is not recommended until the end of puberty, as it is impossible to exclude the possibility of adverse effects on growth and on a not yet stable endocrine system.

Elderly age

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

Liver failure

The use of the drug Androkur® is contraindicated in patients with liver disease (until the liver is normalized).

Renal insufficiency

There is no data on the need to change the dose in this category of patients.

Side effects:

The most frequently observed side effects: decreased libido, impotence and reversible suppression of spermatogenesis.

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

The adverse events reported in the use of Androkur® are listed below. The frequency is defined as: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely (from ≥ 1/10000 to < 1/1000), very rarely (<1/10000).For undesirable effects revealed in the process of post-marketing observations and for which it is not possible to reliably estimate the frequency, "frequency is unknown" is indicated.

From the hematopoietic system:

frequency unknown - anemia *).

From the immune system:

rarely - hypersensitivity reactions.

Disorders of the psyche:

often - depression, depressed mood, anxiety (temporarily).

From the side of the vessels:

frequency unknown - thrombosis and thromboembolism *) **).

On the part of the respiratory system:

often - shortness of breath *).

From the gastrointestinal tract:

frequency unknown - intra-abdominal hemorrhage *).

From the liver and biliary tract:

often - jaundice, hepatitis, liver failure *).

From the skin and subcutaneous tissues:

infrequent - rash.

From the musculoskeletal system:

frequency is unknown - osteoporosis.

From the genitals and mammary glands:

very often - reversible suppression of spermatogenesis, decreased libido, erectile dysfunction; often - gynecomastia.

Other:

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

Undesirable phenomena for which you can find more detailed information in the section "Special instructions" are marked with an asterisk *). Adverse events for which no proof of a causal relationship to drug intake Androkur® labeled

asterisks **. §) - refer to the section "Contraindications".

Against the background of treatment with the drug Androkur®, sexual desire and potency decrease, in addition, the function of the sexual glands is suppressed. These changes are reversible and pass after the withdrawal of therapy.

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

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

As with the use of other anti-androgenic drugs, the long-term androgen deficiency caused by Androkur® can lead to the development of osteoporosis.The development of meningiomas has been reported due to the long-term (for several years) administration of Androkur® in a dose of 25 mg or more.

Overdose:

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

Interaction:

Despite the lack of clinical studies of interactions, it can be expected that ketoconazole, itraconazole, clotrimazole, ritonavir and other potent inhibitors of the CYP3A4 isoenzyme will suppress the metabolism of cyproterone, which is metabolized by the CYP3A4 isoenzyme. On the other hand, inducers of the isoenzyme CYP3A4, such as rifampicin, phenytoin and preparations containing St. John's wort puffed can reduce the concentration of cyproterone.

In vitro studies have shown that at high therapeutic doses of cyproterone (100 mg 3 times daily) it is possible to inhibit the isoenzymes of the cytochrome P450 system, such as CYP2C8, 2C9, 2C19, 3A4 and 2D6.

When joint use of high doses of cyproterone with HMG-CoA reductase inhibitors (statins), which are also metabolized predominantly by the CYP3A4 isoenzyme, the risk of myopathy and rhabdomyolysis associated with taking statins may increase.

Special instructions:

There are reports of a direct dose-dependent toxic effect of Androkur® on the liver (development of jaundice, hepatitis and liver failure). In addition, when the drug was used at a dose of 100 mg or higher, fatal cases were reported. Most of the fatal cases were observed in men in the late stage of prostate cancer. Toxicity depends on the dose and usually develops a few months after the initiation of therapy. Before the start of treatment, periodically during treatment and when any symptoms or signs of hepatotoxicity appear, it is necessary to perform liver function tests. If hepatotoxicity is confirmed, Androcour® should be discontinued unless hepatotoxicity is caused by other causes, such as a metastatic process.In the latter case, treatment should be continued only if the expected positive effect exceeds the risk.

In very rare cases, after taking Androkur®, benign and, more rarely, malignant liver tumors were noted that can lead to life-threatening intra-abdominal bleeding. In cases of complaints of acute pain in the upper abdomen, liver enlargement or in the presence of signs of acute intra-abdominal hemorrhage, a differential diagnosis should be made taking into account a possible liver tumor.

The development of meningiomas (single and multiple) has been reported in connection with the long-term (for several years) administration of Androkur® in a dose of 25 mg or more. In the case of detection of meningioma in a patient receiving treatment with Androkur®, the drug should be discontinued.

There have been reports of thromboembolic complications in patients taking Androcour®, although there was no causal relationship. In patients with previous thrombotic / thromboembolic diseases of the arteries or veins (eg, deep vein thrombosis, pulmonary embolism, myocardial infarction),with disturbances of cerebral circulation in the anamnesis or at the late stages of malignant diseases the risk of occurrence of thromboembolic complications is increased.

During treatment with Androkur®, the development of anemia was reported. Therefore, during treatment with Androkur®, regular examination of peripheral blood should be performed.

In patients with diabetes mellitus, the need for oral hypoglycemic agents or insulin may change. Patients with diabetes mellitus during treatment with Androkur® should be supervised by a doctor.

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

During treatment with Androkur® it is necessary to regularly check the function of the cortical layer of the adrenal glands,since, based on preclinical data, possible suppression of adrenal function is suggested in connection with the corticoid-like effect of Androkur® in high doses.

When treatment with Androcur® in patients with increased sexual desire in sexual disorders, alcohol intake may lead to a decrease in the effect of the drug.

The drug Androkur® contains 110,50 mg of lactose in 1 tablet. Patients with rare hereditary diseases of milk sugar intolerance, lactase deficiency, glucose malabsorption syndrome and galactose should apply this medication with caution.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment with Androkur®, caution should be exercised when driving a car and engaging in other potentially hazardous activities requiring increased concentration of attention, as taking the drug can lead to fatigue, reduced vitality and decreased ability to concentrate.

Form release / dosage:

Tablets 50 mg.

Packaging:

For 10 tablets per blister Al / PVC. For 2 or 5 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N008697

Date of registration:17.05.2010 / 16.11.2016

Expiration Date:Unlimited

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER WEIMAR, GmbH & Co. KG. KG Germany

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp05.09.2017

Illustrated instructions

Instructions

Androkur® (Androcur®)