Cyproterone-Teva - instructions for use, dose, side effects, contraindications

Excipients: potato starch 55.30 mg, lactose monohydrate 98.43 mg, crospovidone 5.77 mg, sodium lauryl sulfate 0.97 mg, giprolose (hydroxypropylcellulose) 3.83 mg, talc 9.00 mg, magnesium stearate 1.13 mg, silicon dioxide colloidal 0.57 mg.

Description:

white round flat pills with a risk on one side and with engraving CYPROT 50 on the other.

Pharmacotherapeutic group:Antiandrogen.

ATX: & nbsp

G.03.H.A.01 Cyproterone

Pharmacodynamics:

Cyproterone has the ability to competitively bind to androgen receptor tissue in target organs, reducing or completely eliminating the effects of androgens (both endogenous and exogenous origin) in target organs of men and women. In addition to the anti-androgen effect cyproterone has a powerful antigonadotropic and progestogen effect.

In men, with the use of cyproterone, there is a weakening of sexual desire and a decrease in the function of the testes. Cyproterone reduces or completely eliminates the effects of androgens on the prostate gland.

When using cyproterone in women, the symptoms of androgenation decrease regardless of what causes these symptoms - increased androgen formation or sensitiveness of receptors to circulating androgens. Hirsutism, androgenic alopecia decrease, the secretion of secretion by sebaceous glands of the skin decreases. Cyproterone inhibits ovulation, which causes its contraceptive effect.

After stopping the use of cyproterone, all of its effects disappear.

Pharmacokinetics:

Ciproterone in a wide range of doses after oral administration is completely absorbed. Absolute bioavailability of cyproterone after oral administration is about 88%. When 50 mg of cyproterone is taken, its maximum serum concentration in 3 hours is 140 mg / ml. Then there is a two-phase decrease in concentration (within 24-120 h). The final half-life is 43.9 ± 12.8 hours.The total serum clearance of cyproterone is 3.5 ± 1.5 ml / min / kg. Cyproterone is biotransformation in the liver mainly with the participation of cytochrome P450 isoenzyme CYP3A4. Metabolism occurs mainly by hydroxylation and conjugation. 15beta-hydroxy derivative is the main metabolite in human blood plasma.

Cyproterone is excreted mainly in the form of metabolites with bile and kidneys, part of cyproterone is excreted unchanged. The ratio of cyproterone in urine and bile is 3: 7. The half-life (T1 / 2) with bile and kidneys was 1.9 days. Metabolites from the blood plasma are excreted at about the same rate (T1 / 2 -1.7 days).

Ciproterone almost completely binds to albumin plasma. Only 3.5-4% is in the blood in a free form. Since the link (nonspecific) with plasma proteins is more important, changes in the content of globulin binding sex hormones do not affect the pharmacokinetics of cyproterone.

Due to the long-term nature of the elimination of cyproterone from the blood plasma, daily intake of ciproterone should be expected to result in a cumulative 3-fold increase in serum ciproterone when repeated doses are administered per treatment cycle.

Indications:

FOR MEN

Palliative treatment of metastatic or locally advanced inoperable prostate cancer:

with ineffectiveness of treatment and contraindications to treatment with luteinizing hormone releasing hormone analogues (LHRH);
with ineffectiveness of surgical treatment;
with a preference for oral therapy.

Prevention of the development of the "flash" effect associated with the rise in the concentration of testosterone in the blood plasma at the beginning of treatment with LHRH agonists.

Treatment of "hot flashes", which are observed with the use of LHRH agonists or after an orchiectomy.

Reduction of sexual desire in hypersexuality and correction of pathological abnormalities in sexual behavior.

FOR WOMEN

Treatment of androgenation symptoms such as

severe hirsutism after ineffectiveness of other treatment;
severe androgenic alopecia, accompanied by a severe form of acne and / or seborrhea.

Contraindications:

Hypersensitivity to cyproterone or any other component of the drug; liver disease with impaired function, hepatic insufficiency, Dubin-Jones syndrome, Rotor syndrome, benign and malignant liver tumors,including in the anamnesis (except for metastases in the liver of prostate cancer); Malignant tumors (other than prostate cancer); idiopathic jaundice or persistent itching during pregnancy (history); herpes of pregnant women (in the anamnesis); diseases accompanied by exhaustion (except for inoperable prostate cancer); severe chronic depression; thrombosis and thromboembolism, including in the anamnesis; severe diabetes mellitus, complicated by angiopathy, including retinopathy; sickle-cell anemia; meningioma, including in the anamnesis; contraindications for oral contraceptives should be considered (with simultaneous use with cyproterone); congenital galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome; children's age till 18 years; pregnancy; the period of breastfeeding.

Carefully:

Diabetes mild and moderate severity, risk factors for thromboembolism, epilepsy, chorea, otosclerosis, multiple sclerosis, porphyria (for patients with androgenation); severe diabetes mellitus with angiopathy, sickle cell anemia,thrombosis and thromboembolism in the anamnesis (for patients with inoperable prostate cancer).

Pregnancy and lactation:

The drug Cyproteron-Teva is contraindicated for use during pregnancy.

If it is necessary to use cyproterone during lactation, it is necessary to solve the problem of stopping breastfeeding.

It can not be ruled out that men may experience abnormal spermatozoa during treatment with cyproterone, which can lead to fetal anomalies.

Men and women should take effective methods of contraception while taking Citrolone-Teva.

Dosing and Administration:

Inside, after eating, squeezed a small amount of liquid (preferably water).

The drug Cyproterone-Teva should be taken only under the supervision of a doctor.

FOR MEN

Palliative treatment of metastatic or locally advanced inoperable prostate cancer

2 tablets 2-3 times a day (200-300 mg / day). The drug Cyproterone-Teva should be taken for a long period of time. When the patient's condition improves or when a positive effect is achieved, treatment should not be discontinued or the dose reduced.Duration of treatment is set individually. Usually the drug is continued until signs of disease progression appear.

Prevention of the development of the "flash" effect associated with the rise of testosterone concentration in testosterone at the beginning of treatment with LHRH agonists

In the first 5-7 days 2 tablets 3 times a day (300 mg / day) in the form of monotherapy, then in the following 3-4 weeks at the same dose in combination with the LHRH agonist (LHRH agonist is used in the dosing regimen described in the corresponding instructions for medical use). If necessary, the dose can be reduced to 2 tablets 2 times a day (200 mg / day) in combination with an agonist LHRH.

Treatment of "hot flashes", which are observed with the use of LHRH agonists or after an orchiectomy

2 tablets 1-2 times a day (100-200 mg / day).

Duration of treatment is set individually.

Reduction of sexual desire in hypersexuality and correction of pathological abnormalities in sexual behavior

1 tablet 2 times a day (100 mg / day). If necessary, the dose can be increased to 2 tablets 2 times a day (200 mg / day), and temporarily - up to 3 times a day (300 mg / day).Duration of treatment is set individually. To achieve a stable therapeutic effect, the drug Cyproteron-Teva should be taken for a long period of time. The time to achieve a stable effect varies from a few weeks to several months. The administration of the drug Cyproteron-Teva should be combined with psychotherapy and other measures (see section "Special instructions").

When a satisfactory effect is achieved, the dose is reduced to a minimum maintenance dose. In most cases 1/2 tablet is enough for this purpose 2 times a day (50 mg / day). At the same time, a reduction in dose or cancellation of treatment should occur gradually with a daily dose change of 1 or better 1/2 of the pill within a week. It should be noted that very often when the treatment with Ciproterone-Teva is discontinued, a relapse of the disease occurs. In these cases, the course of treatment can be repeated.

FOR WOMEN

Treatment of symptoms of androgenization such as severe hirsutism after the ineffectiveness of another treatment and severe androgenic alopecia accompanied by severe form of acne and / or seborrhea

For women of reproductive age with a regular menstrual cycle

Treatment begins on the 1st day of the cycle (from the 1st day of menstrual bleeding).

From the 1st to the 10th day of the cycle (within 10 days) 2 tablets once a day (100 mg / day) daily.

For the purpose of reliable contraception and for the stabilization of the menstrual cycle, the preparation of Cyproteron-Teva is used simultaneously with oral contraceptive (PC) (see section "Special instructions"),

From the 1st to the 21st day of the cycle (for 21 days) daily for 1 tablet of PC. Between the 22nd and the 28th day of the cycle (within 7 days), a break in taking the PC takes place, during which menstrual bleeding usually occurs.

Exactly after 4 weeks (28 days) after the beginning of the first course, i.е. on the same day of the week, begin the next course of combined treatment, regardless of whether bleeding has stopped or not. If there was no bleeding during the break in taking medication, treatment should be interrupted until the pregnancy is completely excluded.

If clinical improvement is observed, the daily dose of the drug Cyproteron-Teva (from the 1st to the 10th day of combined therapy with PC) can be reduced to 1 or 1/2 tablets per day (25-50 mg / day).

For women of reproductive age with an irregular menstrual cycle or amenorrhea

In women of this category, ovulation and conception can occur even before the start of the PC. Therefore, treatment begins immediately after the exclusion of pregnancy. Unlike women with a regular menstrual cycle, the onset of pregnancy is possible starting from the first day of treatment. If the PC is not taken daily for the first 14 days, barrier methods of contraception (condoms) should be used. In this case, the first day of taking the drug Cyproteron-Teva is considered as the 1 st day of the cycle. Further treatment is carried out in the same way as in women with a regular menstrual cycle. During a break in treatment, menstrual bleeding is possible.

The PC taken concomitantly with cyproterone should be taken at a strictly defined time (for example, after an evening meal). The interval between two PC receptions should never exceed 36 hours.

If a woman missed a PC, but is sure that she is not pregnant, since there were no sexual contacts, the next PC reception should take place at the usual time. In order to prevent early menstrual bleeding in this cycle, the remaining PC tablets from the 1st package are taken as usual for the next 7 days, using additional barrier methods of contraception (condoms).If the PC tablet in the 1st package is finished before the 7 days have elapsed, then it is necessary to immediately start taking the PC tablets from the 2nd package, not observing the proper interruption in the PC reception. If after a proper break after taking pills from the 2nd package menstrual bleeding does not occur, then before starting taking pills from the next package, you must exclude pregnancy.

If a woman misses taking a pill of the PC and does not rule out the possibility of pregnancy, you should stop the treatment and consult with a doctor about the advisability of using a postcoital contraceptive. Treatment can be resumed only after the exclusion of pregnancy.

The duration of treatment depends on the severity of the symptoms of androgenation and their changes under the influence of ongoing therapy. Usually the course of application of the drug Cyproteron-Teva is several months. Acne and seborrhea are more likely to be treated than symptoms of hirsutism and alopecia. If necessary, after achieving clinical improvement, cyproterone is discontinued and treatment of PC is continued.

Side effects:

The most frequent adverse reactions in patients taking cyproterone, are decreased sexual desire, erectile dysfunction and suppression of spermatogenesis.

The most serious adverse reactions are hepatotoxicity, the appearance of benign and malignant tumors that can lead to intra-abdominal bleeding, and vascular thromboembolism.

Such adverse reactions, such as abdominal pain, nausea, attacks of general apathy and anxiety, most often occur at 2-6 weeks of treatment. Usually these symptoms quickly pass.

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

On the part of the respiratory, thorax and mediastinal organs: very rarely - dyspnea.

From the side of the organ of hearing and balance: very often - vertigo.

On the part of the blood and lymphatic system: isolated cases - anemia.

From the cardiovascular system: isolated cases - thromboembolism.

From the skin and subcutaneous tissues: infrequent skin rash; single cases - dry skin, changing hair growth.

From the side of skeletal muscles, bones and connective tissue: rarely - muscle weakness; single cases - osteoporosis.

From the digestive system: often - abdominal pain, nausea; very rarely - jaundice, hepatitis, liver failure; isolated cases - intra-abdominal bleeding associated with a benign or malignant liver tumor.

From the nervous system: very often - a feeling of anxiety, headache, dizziness, depression, apathy, depressed mood; isolated cases - meningioma.

On the part of the reproductive system and mammary glands: very often - a decrease in the number of spermatozoa, a decrease in ejaculate volume, male infertility, azoospermia, erectile dysfunction, gynecomastia, tenderness or feeling of mammary gland tension or their increase, menstrual bleeding irregularities or amenorrhea; often - a decrease in sexual desire.

Allergic reactions: rarely - reactions of hypersensitivity.

Other: very often - an increase or decrease in body weight, a sense of fatigue, fatigue, sweating, "hot flashes".

Overdose:

Cases of overdose are not described.

If necessary, symptomatic treatment should be performed.

Interaction:

The anti-androgenic effect of cyproterone is enhanced by its simultaneous use with gonadotropin-releasing hormone agonists (GnRH).

Under the action of cyproterone, the initial increase in testosterone production by GnRH agonists decreases.

With simultaneous use with PCs, the risk of thrombosis and thromboembolism of blood vessels increases.

With the simultaneous use of cyproterone with thiazolidinediones, including pioglitazone and rosiglitazone, there may be a need to correct the dose of these hypoglycemic drugs due to an increase in their concentration in the blood plasma.

With simultaneous application with insulin, it is possible to change its clinical effectiveness, which may cause the need for dose adjustment.

Ethanol reduces the clinical efficacy of cyproterone in patients with alcoholism.

It can be expected that ketoconazole. itraconazole. clotrimazole. ritonavir and other strong inhibitors of the CYP3A4 isoenzyme can suppress the metabolism of cyproterone. 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.

Research in vitro showed that at high therapeutic doses of cyproterone (300 mg / day) it is possible to inhibit the isoenzymes CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP2D6 cytochrome P450

Associated with the use of inhibitors of HMG CoA reductase (statins), the risk of myopathy and rhabdomyolysis may increase with simultaneous application of high therapeutic doses of cyproterone. Statins are metabolized predominantly by the isoenzyme CYP3A4 (have the same metabolic pathway as cyproterone).

Special instructions:

Use strictly according to the doctor's prescription!

The patient should be informed of the need to tell the doctor about the use of any other medication.

Before starting treatment with cyproterone, the patient is recommended to undergo a general medical examination, including determination of the peripheral blood formula, urine analysis, glucose concentrations in blood plasma and urine, blood coagulation, blood pressure, body weight, determination of the functional state of the liver and adrenal glands. Women should undergo comprehensive endocrinological and gynecological examinations, including breast examination, ovarian function,cytological examination of cervical mucus, and also it is necessary to exclude pregnancy. With prolonged use of cyproterone, these diagnostic measures are recommended to be performed every 6 months.

Patients with overweight are recommended to consult a dietitian.

Patients with diabetes mellitus are treated under constant medical supervision, may need to adjust the dose of insulin and other hypoglycemic drugs. Monitoring of liver function in patients with diabetes should be performed approximately every 8 weeks.

There are rare cases after the application of cyproterone, when patients with benign and malignant liver tumors experienced life-threatening intra-abdominal bleeding. It is necessary to stop treatment with cyproterone at signs of hepatoma - an increase in the liver, pain and a feeling of heaviness in the epigastric region of the stomach. With long-term use of cyproterone in a dose of 200-300 mg / day, its hepatotoxic effect (jaundice, hepatitis and liver failure) may appear, which in several cases led to a fatal outcome.Most of the cases described were for elderly patients with prostate cancer. The hepatotoxic effect of cyproterone is dose dependent and usually develops after several months of treatment. If there is a suspicion of developing hepatotoxicity, a liver function test should be performed. When confirming the toxic damage of the liver, the use of cyproterone should be discontinued, except when hepatotoxicity is due to another cause, for example, liver metastasis of prostate cancer. In this case, continuation of treatment is possible provided that the expected benefit from the application exceeds the possible risk.

Ciproterone is not recommended for diseases accompanied by depletion (cachexia), due to the fact that catabolic reactions in the body may increase.

Single cases of vascular thromboembolism have been described against the background of treatment with cyproterone. However, a causal relationship with cyproterone has not been established. However, in patients with a history of deep vein thrombosis, pulmonary artery thromboembolism, myocardial infarction,impaired cerebral circulation or a common malignant neoplasm, there is a high risk of recurrence of thromboembolism during the administration of cyproterone.

Several reports contained information on the occurrence of meningioma with long-term use of cyproterone at a dose of more than 25 mg / day. If a patient has a meningioma, the use of cyproterone should be discontinued.

Very rarely, when using the drug in high doses, dyspnea may appear. This may be due to the stimulating effect of progesterone and synthetic progestogens on respiration, which is accompanied by hypocapnia and compensatory respiratory alkalosis. Symptoms occur after the withdrawal of cyproterone without special treatment.

During the application of cyproterone, the status of adrenocorticosteroid function should be regularly assessed due to the fact that during the experimental studies using high doses of cyproterone, its decrease was noted due to the manifestation of corticoid-like action of cyproterone.

Patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency, glucose-galactose malabsorption, should not take the drug.

When using cyproterone in men for several weeks, spermatogenesis is often suppressed due to the antiandrogenic and antigonadotropic effect of cyproterone - the amount of spermatozoa decreases and the ejaculate volume decreases. Sexual desire and potency are also very often reduced. Spermatogenesis is gradually restored within 3-5 months. after the abolition of cyproterone, in some patients recovery of spermatogenesis can take place within 20 months. It is not yet known whether spermatogenesis can be restored after a very long period of treatment. In 10-20% of cases, gynecomastia is observed in men, which usually decreases with the cancellation or reduction of the dose of the drug.

In men of reproductive age, before starting treatment with cyproterone, it is necessary to evaluate the spermatogram. During treatment with the drug, the reduction of spermatogenesis occurs gradually, so it is impossible to apply cyproterone as a male contraceptive.

In patients with inoperable prostate cancer and with a history of thromboembolic complications or sickle-cell anemia, or severe diabetes with angiopathy,the question of the use of cyproterone should be addressed individually for each patient after a thorough assessment of the expected benefits and possible risks of using cyproterone.

With simultaneous use of alcohol in patients with pathologically increased sexual desire, a decrease in the effect of cyproterone therapy can be observed. In patients with alcoholism, ciproterone treatment of hypersexuality and pathological abnormalities in sexual behavior is usually ineffective.

Because sexual and androgenic activities are not identical, suppression of androgenic activity is not always accompanied by suppression of sexual desire. It requires complex treatment using psychotherapeutic and socio-therapeutic methods in close cooperation with the patient's spouse. When taking appropriate measures, the use of cyproterone to suppress sexual activity can give a positive result.

In patients with organic brain lesions or mental illnesses that have abnormalities in sexual behavior, cyproterone has no clinical efficacy.

In women, the use of cyproterone should only be carried out under the supervision of an experienced doctor, a specialist in the field of hormone therapy.

You can not use cyproterone in young women who have not yet completed the formation of a normal menstrual cycle.

Before starting treatment, pregnancy should be completely ruled out. If menstrual bleeding stops during the treatment, the drug should be discontinued until the pregnancy is completely excluded. During the treatment with the drug, pregnancy should not be allowed. In this regard, women of reproductive age when taking cyproterone should always use effective methods of contraception. It is recommended to take a combined estrogen-progestagenic PC in the lowest possible dose of ethinylestradiol 30-35 μg. When taken in combination with a PC, you should read the appropriate instructions for medical use.

The use of cyproterone in women with diseases that can aggravate the course of pregnancy (epilepsy, chorea, otosclerosis, multiple sclerosis, porphyria, diabetes mellitus and hypertension),should be conducted only under the supervision of a physician, regardless of how cyproterone, as a monotherapy or with a PC.

In patients with gastrointestinal disorders accompanied by vomiting and / or diarrhea, it is not always possible to prevent the onset of pregnancy when using a PC. Despite this, do not stop treatment. Before the end of the treatment cycle, it is recommended to use barrier methods of contraception (condoms) as additional contraceptive measures. If there is no menstrual bleeding during the weekly pause, the drug should be canceled before the pregnancy is excluded.

The intake of cyproterone should not be discontinued if spotting is observed outside the period of a weekly pause in the form of "smearing". With abundant and repeated bleeding, a gynecological examination is necessary.

The use of cyproterone in combination with estrogen increases the risk of thrombosis. This fact must be taken into account when using cyproterone in women who need surgical treatment. It is recommended to interrupt treatment with cyproterone 6 weeks before the planned operation.In the period of prolonged bed rest, the administration of cyproterone should be suspended.

In women at the beginning of treatment with cyproterone, soreness or a feeling of tension of the mammary glands or their increase, the irregularity of menstrual bleeding or amenorrhea are very often observed. There is often a decrease in sexual desire.

In connection with the decrease in the function of the sebaceous glands, dry skin can be noted. The negative impact of cyproterone on the fertility of patients after discontinuation of treatment was not noted.

Patients who have not reached puberty (can not exclude the adverse effects of cyproterone on the growth of the patient and the formation of his endocrine system) should not take cyproterone.

Given the medico-social significance of the manifestation of the effects of cyproterone, it is recommended that patients receive informed consent before starting treatment.

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

During the application of cyproterone, care must be taken when driving vehicles and performing activities that require increased concentration and speed of psychomotor reactions, due to the fact that cyproterone can cause a feeling of fatigue, rapid fatigue, dizziness (especially in the first weeks of treatment).

Form release / dosage:

Tablets 50 mg.

Packaging:

For 10 tablets in PVC / aluminum foil blisters.

5 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store in a dry place protected from light at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014367 / 01

Date of registration:15.08.2008

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

Teva Czech Companies sr.o. Czech Republic

Representation: & nbspTeva Teva Israel

Information update date: & nbsp08.10.2015

Illustrated instructions

Instructions

Cyproterone-Teva (Cyproterone-Teva)