Cyproterone-Teva 50 mg 50 pcs

ATX code: G03HA01

Pharmacotherapeutic group: antiandrogen

Pharmacological properties

Pharmacodynamics. Cyproterone has the ability to compete with
tissue androgen receptors 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 antiandrogenic effect,
cyproterone has a powerful antigonadotropic and progestogenic effect.
In men, while taking cyproterone, there is a weakening of sexual desire and
a decrease in testicular function. Cyproterone reduces or completely eliminates the effects
of androgens on the prostate gland.
The use of cyproterone in women reduces the symptoms of androgenization
regardless of what causes these symptoms - increased
production of androgens or increased sensitivity of receptors to circulating
androgens. Reduces hirsutism, androgenetic alopecia, reduces the secretion of
the secretion of the sebaceous glands of the skin. Cyproterone inhibits ovulation, which causes its
contraceptive effect.

After you stop taking cyproterone, all of its effects disappear.

Pharmacokinetics.

Cyproterone in a wide range of doses after oral administration
is completely absorbed. The absolute bioavailability of cyproterone after
oral administration is about 88%. When taking 50 mg of cyproterone, its maximum
concentration in blood serum after 3 hours is 140 mg / ml. Then there is
a two-phase decrease in concentration (within 24-120 hours). 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 undergoes biotransformation in the liver, mainly with the
participation of the CYP3A4 isoenzyme of cytochrome P450. Metabolism occurs mainly
by hydroxylation and conjugation. 15beta-hydroxy derivative is the main
metabolite in human 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 is 1.9 days. Metabolites
are excreted from blood plasma at approximately the same rate (T1 / 2 - 1.7 days).
Cyproterone is almost completely bound to plasma albumin. Only 3.5-4%
is in the blood in a free form. Since the connection (non-specific) with
plasma proteins is more important, changes in the content of
sex hormone-binding globulin do not affect the pharmacokinetics of cyproterone.
Due to the long-term nature of the elimination of cyproterone from blood plasma during its
daily intake should be expected to accumulate cyproterone in serum 3 times
greater when using repeated doses in one cycle of treatment

FOR MEN

Palliative treatment of metastatic or locally advanced inoperable
prostate cancer:
with treatment failure and contraindications to treatment with analogues
of luteinizing hormone releasing hormone (LHRH);
with the ineffectiveness of surgical treatment;
when oral therapy is preferred.
Prevention of the development of the "flare" effect associated with an increase in the concentration
of testosterone in the blood plasma at the beginning of treatment with LHRH agonists.
Treatment of "hot flashes" that occur with the use of LHRH agonists or after orchiectomy.

Decreased sexual desire in hypersexuality and correction of pathological
deviations in the field of sexual behavior.

FOR WOMEN
Treatment of symptoms of androgenization such as:
severe hirsutism after failure of other treatments;
severe androgenetic alopecia, accompanied by severe acne and / or seborrhea.

Hypersensitivity to cyproterone or any other component of the drug;
liver disease with impaired function, liver failure,
Dubin-Jones syndrome, Rotor syndrome, benign and malignant liver tumors,
including a history (except for liver metastases of prostate cancer);
malignant tumors (except prostate cancer); idiopathic jaundice
or persistent itching during pregnancy (history); herpes of pregnant women (in history);
cachexia (except for inoperable prostate cancer); severe chronic
depression; thrombosis and thromboembolism, including history; severe form of sugar
diabetes complicated by angiopathy, including retinopathy; sickle cell
anemia; meningioma, including history; it is necessary to take into account contraindications
for oral contraceptives (with simultaneous use with cyproterone);
congenital galactose intolerance, lactase deficiency,
glucose-galactose malabsorption syndrome; children's age up to 18 years; pregnancy;
breastfeeding period .

With caution
Mild to moderate diabetes mellitus, risk factors for
thromboembolism, epilepsy, chorea, otosclerosis, multiple sclerosis, porphyria (for
patients with manifestation of androgenization).

The most common adverse reactions in patients taking cyproterone
are decreased libido, erectile dysfunction, and inhibition 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 as abdominal pain, nausea, bouts of general apathy and anxiety, most often appear on the 2nd-6th week of treatment. Usually these symptoms pass quickly.
The incidence of side effects is classified according to the recommendations
World Health Organization: very often - at least 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; frequency unknown (cannot estimate frequency from available sources).
On the part of the respiratory system, chest and mediastinum: very rarely - shortness of breath.
On the part of the organ of hearing and balance: very often - vertigo.
On the part of the blood and lymphatic system: isolated cases - anemia.
From the side of the cardiovascular system: isolated cases - thromboembolism, the frequency is unknown - thrombosis, pulmonary embolism, myocardial infarction, increased blood pressure.
From the skin and subcutaneous tissues: infrequently - skin rash; isolated cases -
dry skin, changes in hair growth.
From the side of skeletal muscles, bones and connective tissue: rarely - muscle weakness; isolated 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 tumor of the liver.
From the nervous system: very often - a feeling of anxiety, headache, dizziness, depression, apathy, depressed mood; isolated cases - meningioma, the frequency is unknown - cerebrovascular accident.
From the endocrine system: the frequency is unknown - suppression of the function of the adrenal cortex.
On the part of the reproductive system and mammary glands: very often - a decrease in the number of spermatozoa, a decrease in the volume of ejaculate, male infertility, azoospermia, erectile dysfunction, gynecomastia, soreness or a feeling of tension in the mammary glands or their increase, irregular menstrual bleeding or amenorrhea; often - a decrease in sexual desire.
Allergic reactions: rarely - hypersensitivity reactions.
Other: very often - increase or decrease in body weight, feeling tired, fatigue, sweating, "hot flashes"

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

Under the action of cyproterone, the initial increase in testosterone production by GnRH agonists is reduced.
With simultaneous use with PC, the risk of developing thrombosis and vascular thromboembolism increases.
With the simultaneous use of cyproterone with thiazolidinediones, including
pioglitazone and rosiglitazone, it may be necessary to adjust the dose of these hypoglycemic drugs due to an increase in their concentration in
blood plasma.
With simultaneous use with insulin, its clinical efficacy may change, which may necessitate 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 CYP3A4 isoenzyme, such as rifampicin, phenytoin, and
preparations containing St. John's wort, can reduce the concentration of cyproterone.
In vitro studies have shown that at high therapeutic doses of cyproterone (300
mg / day), inhibition of cytochrome P450 isoenzymes CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP2D6
Associated with the use of inhibitors of HMG CoA reductase (statins), the risk of developing myopathy and rhabdomyolysis may increase with simultaneous use of high
therapeutic doses of cyproterone. Statins are metabolized predominantly by the CYP3A4 isoenzyme (they have the same metabolic pathway as cyproterone).

Inside, after eating, drinking a small amount of liquid (preferably water).
The drug Cyproterone-Teva should be taken only under the supervision of a physician.

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 interrupted or the dose should be reduced. The duration of treatment is set individually. Usually, the use of the drug is continued until signs of disease progression appear.
Prevention of the "flare" effect associated with the rise in plasma testosterone concentration at the beginning of treatment with LHRH agonists
For the first 5-7 days, 2 tablets 3 times a day (300 mg / day) as monotherapy, then for the next 3-4 weeks at the same dose in combination with an 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 LHRH agonist.
Treatment of "hot flashes" that occur with the use of LHRH agonists or after orchiectomy
The initial dose is 50 mg, followed by an increase (50-150 mg / day).
The duration of treatment is set individually.
Decreased sexual desire in hypersexuality and correction of pathological deviations in the field of 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).
The duration of treatment is set individually. To achieve a stable therapeutic effect, Cyproterone-Teva should be taken for a long
period of time. The time to achieve a stable effect varies from several weeks to several months. Taking the drug Cyproterone-Teva should be combined with
psychotherapy and other measures (see section "Special Instructions").
When a satisfactory effect is achieved, the dose is reduced to the minimum maintenance dose. In most cases, 1/2 tablet 2 times is enough for this.
per day (50 mg / day). In this case, the dose reduction or withdrawal of treatment should occur
gradually with a change in the daily dose by 1 or better 1/2 tablets during the week.

It should be noted that very often, when treatment with Cyproterone-Teva is stopped, a relapse of the disease is observed. In these cases, the course of treatment can be
repeated.

FOR WOMEN
Treatment of symptoms of androgenization such as: severe hirsutism after failure of other treatments and severe androgenetic alopecia accompanied by severe
acne and/or seborrhea
For women of reproductive age with regular menstrual
cycles menstrual bleeding).
From the 1st to the 10th day of the cycle (within 10 days), 2 tablets 1 time per day (100 mg / day)
daily.
For the purpose of reliable contraception and to stabilize the menstrual cycle, Cyproterone-Teva is used simultaneously with an oral contraceptive (PC)
(see section "Special Instructions").
From the 1st to the 21st day of the cycle (within 21 days), 1 PC tablet daily. Between the 22nd and 28th day of the cycle (within 7 days) they take a break in taking PC, during which menstrual-like bleeding usually occurs.
Exactly 4 weeks (28 days) after the start of the first course, i.e. on the same day
of the week, start the next course of combined treatment, regardless of whether the bleeding has stopped or not. If there was no bleeding during the break in taking the drugs, treatment should be interrupted until
pregnancy is completely excluded.
If clinical improvement is observed, the daily dose of Cyproterone-Teva (from the 1st to the 10th day of combination therapy with PC) can be reduced to 1 or
1/2 tablets per day (25-50 mg / day).
For women of reproductive age with irregular menstrual cycles or amenorrhea
In women in this category, ovulation and conception may occur even before the start of PC administration.
Therefore, treatment begins immediately after the exclusion of pregnancy. Unlike women with regular menstrual cycles, pregnancy is possible
from the first day of treatment. If PC is not taken daily for the first 14 days, barrier methods of contraception (condoms) should be used. In this
case, the 1st day of taking the drug Cyproterone-Teva is considered as the 1st 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-like bleeding is possible.

PC, taken simultaneously with cyproterone, should be taken at a strictly defined time (for example, after an evening meal). The interval between two
PC doses should never exceed 36 hours.
If a woman missed taking a PC, but is sure that she is not pregnant because there was no
sexual intercourse, then the next PC intake should occur 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 over the next 7 days, using additional barrier methods of contraception (condoms). If
the PC tablets in the 1st package are over before 7 days have elapsed, then you must immediately start taking the PC tablets from the 2nd package, without observing the prescribed
interruption in PC reception. If, after the prescribed break after taking the PC tablets from the 2nd package, menstrual bleeding does not occur, then pregnancy must be excluded before starting the PC tablets from the next package.
If a woman misses taking a PC pill and does not exclude the possibility of pregnancy, treatment should be suspended and a doctor should be consulted 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 androgenization and their changes under the influence of the therapy. Usually the course of using the drug Cyproterone-Teva is several months. Acne and seborrhea phenomena faster
are more treatable than the symptoms of hirsutism and alopecia. If necessary, after
achieving clinical improvement, cyproterone is discontinued and treatment with PC alone is continued.

In case of overdose, if the patient is conscious and without spontaneous vomiting, vomiting should be induced.

It is necessary to apply symptomatic therapy with constant monitoring of the patient and vital functions.

Use strictly according to the doctor's prescription!
The patient should be informed about the need to inform the doctor about the use of any other medicinal product.
Before starting treatment with cyproterone, the patient is recommended to undergo a general medical examination, including determination of the peripheral blood count, urinalysis,
glucose concentration in blood plasma and urine, indicators of the blood coagulation system, blood pressure, body weight, determination of the functional state of the liver and
adrenal glands. Women should undergo a comprehensive endocrinological and gynecological examination, including examination of the mammary glands, function
ovaries, cytological examination of cervical mucus, and it is also necessary to exclude pregnancy. With prolonged use of cyproterone, these diagnostic
measures are recommended every 6 months.

Patients with overweight are advised to consult a dietitian.
In patients with diabetes, treatment is carried out under constant medical supervision, because. dose adjustment of insulin and other
hypoglycemic drugs may be required. Monitoring of liver function in patients with diabetes
mellitus should be carried out approximately every 8 weeks.
Rare cases have been described after the use of cyproterone, when life-threatening intra-abdominal bleeding occurred in patients with benign and malignant liver tumors. Treatment with cyproterone should be discontinued with
signs of hepatoma - liver enlargement, pain and a feeling of heaviness in the epigastric region of the abdomen. With prolonged use of cyproterone at a dose of 200-300 mg / day,
manifest its hepatotoxic effect (jaundice, hepatitis and liver failure), which in several cases led to death.
Most of the reported cases concerned elderly patients with prostate cancer. The hepatotoxic effect of cyproterone is dose-dependent and usually develops
after several months of treatment. If hepatotoxicity is suspected,
a liver function test should be performed. If
liver toxicity is confirmed, cyproterone should be discontinued unless hepatotoxicity is due to another cause, such as liver
metastasis from prostate cancer. In this case, the continuation
treatment is possible provided that the expected benefit from the application outweighs
the possible risk.
Cyproterone is not recommended for use in diseases accompanied by depletion (cachexia), due to the fact that catabolic reactions in
the body may increase.
Isolated cases of vascular thromboembolism during treatment with cyproterone have been described.
However, a causal relationship with cyproterone has not been established. However, in patients with a history of deep vein thrombosis, pulmonary embolism
, myocardial infarction, cerebrovascular accident or advanced
malignancy, there is a high risk of recurrent thromboembolism during
the use of cyproterone.

Several reports contained information about 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, cyproterone should be discontinued.
Very rarely, when using the drug in high doses, shortness of breath may occur. This may be due to the stimulatory effect of progesterone and synthetic
progestogens on respiration, which is accompanied by hypocapnia and compensatory
respiratory alkalosis. Symptoms resolve after discontinuation of cyproterone without special treatment.
During the use of cyproterone, it is necessary to regularly assess the state of adrenocorticosteroid function due to the fact that during experimental
studies with the use of high doses of cyproterone, its decrease was noted due to the manifestation of the cortico-like action of cyproterone.
Patients with rare hereditary diseases such as galactose intolerance, lactase deficiency, malabsorption of glucose-galactose
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 number of spermatozoa decreases and the volume of ejaculate decreases.
Sexual desire and potency are also very often reduced. Spermatogenesis is gradually restored within 3-5 months. after discontinuation of cyproterone, in some patients
restoration 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 abolition 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 decrease in spermatogenesis occurs gradually, therefore, cyproterone should not be used as a male
contraceptive.
With the simultaneous use of alcohol in patients with a pathologically increased sexual desire, a decrease in the effect of cyproterone therapy may be observed. In
patients with alcoholism, treatment with cyproterone for hypersexuality and pathological
deviations in the field of sexual behavior is usually ineffective.
Since sexual and androgenic activity are not identical, the suppression of androgenic activity is not always accompanied by the suppression of sexual desire.
Comprehensive treatment is required using psychotherapeutic and socio-therapeutic methods in close cooperation with the patient's spouse. When
appropriate measures are taken, the use of cyproterone to suppress sexual activity can give a positive result.
In patients with organic brain damage or mental illness
with deviations in the field of sexual behavior, cyproterone has no clinical efficacy.
In women, the use of cyproterone should be carried out only under the supervision of an experienced
doctor - a specialist in the field of hormonal therapy.
Do 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 excluded. If menstrual bleeding stops during treatment, the drug should be discontinued until pregnancy is completely excluded. During the period of drug treatment, pregnancy should not be allowed. In this regard, women of reproductive age when taking cyproterone should definitely use effective methods of contraception. It is recommended to take a combined estrogen-progestogen PC at the lowest possible dose of ethinyl estradiol 30-35 mcg.
When taken in combination with a PC, you should read the appropriate instructions for use.
medical application.
The use of cyproterone in women suffering from diseases that can aggravate the course of pregnancy (epilepsy, chorea, otosclerosis, multiple sclerosis, porphyria, diabetes mellitus and arterial hypertension) should be carried out only under the supervision of a physician, regardless of how cyproterone is used, as
monotherapy or from a PC.
In patients with gastrointestinal disorders accompanied by vomiting
and / or diarrhea, it is not always possible to prevent pregnancy with the use of PC. Despite this, treatment should not be stopped. Until the end of the
treatment cycle, it is recommended to use barrier methods of contraception (condoms) as additional contraceptive measures. If during a week-long pause in admission
drug menstrual bleeding is absent, the drug should be discontinued until the exclusion of pregnancy.
Cyproterone should not be discontinued if spotting occurs outside of the weekly pause. With heavy and recurring
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 requiring surgical treatment. It is recommended to interrupt treatment with cyproterone 6 weeks before the planned operation. During prolonged bed rest, cyproterone should be discontinued.
Women at the beginning of treatment with cyproterone very often experience soreness or a feeling of tension in the mammary glands or their enlargement, irregular menstrual bleeding or amenorrhea. Often there is a decrease in sexual desire.
Due to the decrease in the function of the sebaceous glands, dry skin may occur.
There was no negative effect of cyproterone on the fertility of patients after discontinuation of treatment.
Patients who have not reached puberty (an adverse effect of cyproterone on the g