ANDROCUR . 50 mg. 50 tablets

 

CLINICAL DATA

 Indications

  Indications for men

Suppress libido for sexual deviations. Anti-androgen treatment of carcinoma of the prostate.

  Indications for women

 

Severe androgenic phenomena, eg.: Very severe hirsutism, severe androgenetic alopecia, often accompanied by severe acne and / or seborrhea.

 

  Posology and method of administration

 

 Dosage in men

Suppress libido in sexual deviatio

The tablets should be taken with some liquid after meals.

 

Treatment usually begins with I tablet twice daily if needed, the dose is increased two times a day or even two tablets three times daily 2 tablets for a short time. Once a satisfactory result, the treatment effect should be maintained at the lowest possible doza.Chesto enough to take 1/2 tablet twice daily. When switching to maintenance dose or when you need to discontinue use, dose reduction should be gradual. For this purpose, the daily dose should be reduced by one tablet or even better with a 1/2 tablet at intervals of several weeks.

 

Androcur should not be used continuously, possibly in conjunction with psychotherapy to achieve a stable therapeutic effect.

 

Anti-androgen treatment of inoperable prostate cancer

 

2 tablets two to three times a day (200-300 rag). The tablets should be taken with some liquid after yadene.Lechenieto should not be terminated and the dose should not be changed after reaching remisiya.Za reduce initial increased level of male sex hormones during treatment with LH-RH agonists:

 

Initially 2 tablets Androcur twice daily (200 mg) for 5-7 days, then take two tablets Androcur twice daily (200 mg) with LH-RH agonist in the manufacturer's recommended dose for 3 - 4 weeks.

 

For the treatment of hot flushes in patients treated with LH-RH analogues or orchiectomy who underwent one to three tablets daily (50-150 mg) with increasing dose titration to 2 tablets three times daily (300 mg), if necessary.

 

 Dosage in the female

Women of childbearing age

 

Pregnant women should not use Androcur. Before treatment is necessary to exclude pregnancy.

 

In women of childbearing potential treatment begins on the first day of the cycle (first day of bleeding). Only women with amenorrhea can begin treatment vednaga.V then begins the day the treatment is considered the first day of the cycle and is further subject to the following preporaki.Ot 1st to the 10th day of the cycle (10 days) taken with some liquid after eating 2 tablets Androcur daily. Additionally it is a medicine that contains estrogen and progestogen, for example. 1 st to 21 th day of cycle 1 tablet Diane-35 daily to get the necessary contraceptive protection and to stabilize the cycle.

 

Women who are cyclic combined therapy should take the tablet at a certain time of day.

 

After 21 days following 7 day period during which no tablets and bleeding occurs. Just four weeks after the first treatment cycle, ie the same day of the week, starting next cyclical course of combination therapy, whether bleeding has stopped.

 

After the onset of clinical improvement, Androcur daily dose can be reduced to 1 or 1/2 tablet in the first 10 days of combined with Diane-35 treatment. May the monotherapy Diane-35.

 

Missing bleeding

 

If bleeding occurs in free medications from interval treatment should be discontinued and pregnancy excluded before renewed again.

 

Ignore tablets

 

Women who are cyclic combined therapy should take the tablet at a certain time of day. If admission is delayed more than 12 hours, contraceptive effect may be reduced.

 

Special attention is given to the product information on Diane-35 (contraceptive reliability and recommendations for missed tablet). If bleeding occurs in the free cycle of drugs, treatment should be discontinued and pregnancy excluded before renewed again. Missing Androcur tablets can reduce the therapeutic effectiveness and cause breakthrough bleeding. It is necessary to take a double dose missed tablets Androcur and dosing should continue at the usual time with Diane-35.

 

Patients undergone hysterectomy or menopause

 

Patients undergone hysterectomy or menopause Androcur may be administered alone. Depending on the severity of the complaints the average dose should be 1 to 1/2 tablet daily for 21 days followed by a 7 - day free tablet space.

 

  Contraindications

 

Pregnancy, lactation, liver disease, history of jaundice or persistent itching during a previous pregnancy, a history of herpes of pregnancy syndrome, Dubin-Johnson, a Rotor, previous or existing liver tumors (carcinoma of the prostate only if these are not due of metastases), wasting diseases (with the exception of carcinoma of the prostate), severe chronic depression, previous or existing thromboembolic processes, severe diabetes with vascular changes, sickle cell anemia, hypersensitivity to any ingredient of Androcur.

 

In patients with prostate cancer or a history of thromboembolic processes or suffering from sickle cell anemia or severe diabetes with vascular changes should be carefully weigh the benefits and risks of each case before prescribed Androcur.

 

 Special warnings and special precautions for use

 

Libido suppressant effect of Androcur can be reduced by the action of alkohol.Androcur should not be given before the end of puberty because it can not be ruled out its adverse effects on growth, unstable interactions of endocrine glands.

 

During treatment should regularly monitor the liver and adrenal function, and the number of erythrocytes.

 

There are reports of direct hepatic toxicity, including jaundice, hepatitis and hepatic failure with fatal outcome in some cases, patients received 200-300 mg cyproterone acetate. Most reports refer to men with prostate cancer. Toxicity is dose-related and usually occurs several months after initiation of treatment. Need liver function tests before starting treatment as soon as symptoms or signs of hepatotoxicity. If hepatotoxicity is confirmed, cyproterone acetate intake should be discontinued, except in cases where the cause of damage is another example. metastases. In these cases, treatment with cyproterone acetate may continue only if the expected benefit clearly outweighs the risk.

 

As with other sex steroids, "reported isolated cases of benign and malignant liver changes., In rare cases, liver tumors can cause life-threatening intra-abdominal haemorrhage. If symptoms appear in the upper abdominal, liver enlargement or signs of intra-abdominal haemorrhage in the differential diagnosis should include liver tumor.

 

Diabetes patients should be seen by a doctor. In rare cases, it may appear a feeling of shortness of breath during treatment with high doses of Androcur. In the differential diagnosis in these cases should be considered stimulative effect on respiration known for progesterone and synthetic progestogens, accompanied by hypocapnia and compensatory respiratory alkalosis, which does not consider the need for specific treatment.

 

In extremely rare cases of thromboembolic events associated with the use of Androcur. However, the causal relationship is unclear.

Before starting treatment, women should have a full general and gynecological examination (including the breasts and cervical smear). Women of childbearing age should exclude any possibility of pregnancy.

 

If during combination treatment, persistent or recurrent bleeding at irregular intervals to do gynecological examination to exclude possible organic disease.

 

In view of the additional use of Diane-35 should be paid attention to all the data contained in the information for this product.

 

  Interactions

 

You can not change the need for insulin and oral antidiabetics.

 

 Pregnancy and lactation

 

Androcur use during pregnancy and lactation is contraindicated.

 

In a study of 6 women receiving a single oral dose of 50 mg cyproterone acetate0, 2% of the dose is excreted in breast milk.

 

 Effects on ability to drive and use machines

 

Should be given to patients whose occupation requires a higher concentration (eg drivers of motor vehicles, machine operators) that Androcur can lead to tiredness and diminished vitality and can impair the ability to concentrate.

 

  Adverse Reactions

 

For several weeks, Androcur suppress spermatogenesis as a result of antigonadotropic and antiandrogenic action. Spermatogenesis is restored gradually, a few months after cessation of treatment.

 

In men Androcur sometimes cause gynecomastia (combined with the sense of touch to the nipple), usually resolves after discontinuation of mu.Kakto with any other anti-androgen therapy treatment with Androcur can in rare cases lead to osteoporosis.

 

In combination treatment of women suppresses ovulation so that sterility appears. It is possible to show a sense of tension in the chest.

 

Can occur tiredness and diminished vitality and sometimes transient inner restlessness or depressive mood swings.

 

Possible changes in body weight.

 

In rare cases, allergic reactions and rashes.

  Overdose

Tests for acute toxicity following administration of a single dose of cyproterone acetate, a substance lekarstvyaenoto Androcur show that it is practically non-toxic. Not expected risk of acute poisoning after accidental intake of a single dose, multiple doses exceeding the recommended treatment.

 

PHARMACOLOGICAL

 

 Pharmacodynamic properties

 

Androcur is an antiandrogenic hormone product. It inhibits androgens produced in the female body in smaller quantities, and has progestagen and antigonadotropic action.

 

In men treated with Androcur decreased libido and potency and partially inhibit gonadal function. These changes are reversible after discontinuation. Cyproterone acetate inhibits competitively the effect of androgens in target organs, eg. Has a protective effect on the prostate by the action of androgens originating from the gonads and / or the adrenal cortex.

 

Reduces hirsutism in women and androgen-conditioned alopecia and increased function of the sebaceous glands. During treatment suppressed the function of yaychnitsite.Pri administration of high doses of cyproterone acetate, a trend towards a slight increase in the levels of prolactin.

 

 Pharmacokinetic properties

 

After oral administration, cyproterone acetate is completely absorbed in the wider order of doses. After taking 50 mg cyproterone acetate is produced maximal serum concentration of 140 ng / ml for approximately 3 hours. Thereafter, serum concentrations fall within the range typically 24 to 120 hours with a terminal half-life of 43.9 +12.8 h. The total clearance of cyproterone acetate in serum is 3.5 +1.5 ml / min / kg. Cyproterone acetate is metabolized in different ways including hydroxylation and conjugation. The main metabolite in human plasma is 15 p-hydroxy saedinenie.Chast of the dose is excreted unchanged in the bile. The majority is excreted as metabolites in urine and bile, the ratio is 3:7. Half-life of renal and biliary excretion was 1.9 days. Plasma metabolites are eliminated with a similar rate (half-life 1.7 days).

 

Cyproterone acetate is almost exclusively bound to plasma albumin. About 3.5-4% remains unbound. Since protein binding is non-specific, changes in the concentration of SHBG (sex hormone binding globulin) did not affect the pharmacokinetics of cyproterone acetate.

 

Because of the long half-life of the terminal disposition phase plasma (serum) and the daily intake can be expected accumulation of cyproterone acetate and approximately threefold increase in its concentration in serum after repeated daily priem.Absolyutnata bioavailability of cyproterone acetate is almost complete (88% of dose ).

 

  Preclinical safety data

 

Systemic toxicity

 

In animal after multiple oral dosing has not been established signs of systemic intolerance that could impose a ban for people in medical dozi.Ne were performed experimental studies in animals to possible sensitizing effect of cyproterone acetate.

  

Embryotoxicity and teratogenicity

 

There were no embryological and teratogenic after treatment during organogenesis of the fetus before the development of the external genitalia. Administration of high doses of cyproterone acetate during the hormone-sensitive differentiation phase of the genital organs (starting around the 45th day of pregnancy) can cause feminisation of male fetuses. Observations on newborn males who were exposed to cyproterone acetate in the uterus showed no signs of feminisation. However, the use of Androcur in pregnancy is contraindicated.

 

Genotoxicity and carcinogenicity

 

The first recognized genotoxicity tests conducted with cyproterone acetate is negative, but further tests showed that cyproterone acetate can cause branches to DNA (and an increase in the doubling of DNA) in liver cells of rats and monkeys, as well as fresh isolated human hepatocytes. In hepatocytes of dogs are not formed branches in DNK.Obrazuvaneto branches of the DNA occurs at concentrations that are expected at the recommended dose regimen of cyproterone acetate. One consequence of treatment with cyproterone acetate in vivo is increased incidence of focal, possibly preneoplastichni liver lesions with altered cellular enzymes in female rats and increased mutation chestota.Klinichniyat experienced and reliable epidemiological studies conducted in support of increasing the number of hepatic tumors in humans. Tests tumorigenic potential of cyproterone acetate in rodents also showed no evidence of a specific tumorigenic potential. However, it should be noted that sex hormones can cause growth of some hormone-dependent tissues and tumors.

 

Generally available toxicological findings warrant rejection of the use of Androcur in humans if used according to testimony and recommended dozi.Eksperimentalnite tests showed an effect similar to that of adrenal corticoids on rats and dogs after higher doses, suggests the possibility of similar effects in humans treated with a maximum dose of 300 rag day.

 

PHARMACEUTICAL PARTICULARS

 

  List of excipients and their amounts

lactose monohydrate 110.500 mg maize starch 59.500 mg povidone 25,000 2.500 mg colloidal anhydrous silica 2.000 mg magnesium stearate 0.500 mg

 

 Incompatibilities

He is known.

 Shelf Life

5 years.

Special precautions for storage

No special storage requirements.

  Nature and contents of container

tablets, sealed in thick strips made of PVC and aluminum foil hot crimp cover.