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Logo ANDROCUR 100 mg TABLETS

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ANDROCUR 100 mg TABLETS

Oral antiandrogen

COMPOSITION
1 Androcur 100 mg tablet contains
cyproterone acetate (6-chloro-17-hydroxy-1alpha,2alpha-methylene-pregna-4,6-diene-3,20-dione-acetate) 100 mg.

PHARMACOLOGICAL CLASSIFICATION
A. 21.12 Hormone inhibitors.

PHARMACOLOGICAL ACTION
Cyproterone acetate has an antiandrogenic, progestational and antigonadotropic effect.
Cyproterone acetate inhibits competitively the effect of androgens at their target organs. The following associated effects, among others, have been described in men: inhibition of sexual drive, reduction of sebaceous gland activity, influence on hair growth, prevention of androgenic growth impulses to the prostatic tissue.
Cyproterone acetate has a central inhibiting effect. The antigonadotropic effect leads to a reduction of testosterone synthesis in the testes and, hence, to a reduction of the serum concentration of testosterone.
The antigonadotropic effect of cyproterone acetate is also exerted when the substance is combined with LH-RH agonists. The initial increase of testosterone provoked by this substance group is decreased by cyproterone acetate.
Prolactin levels may increase with higher doses of cyproterone acetate.

INDICATIONS
Inoperable carcinoma of the prostate.

CONTRA-INDICATIONS
Liver diseases, Dubin-Johnson syndrome, Rotor syndrome, previous or existing liver tumours (if these are not due to metastases), wasting diseases (with the exception of inoperable carcinoma of the prostate), severe chronic depression, existing thromboembolic processes.
In patients with a history of thromboembolic processes or suffering from sickle-cell anaemia or from severe diabetes with vascular changes, the risk:benefit ratio must be considered carefully in each individual case before Androcur is prescribed.

DOSAGE AND DIRECTIONS FOR USE
The tablets are to be taken with some liquid after meals.
To eliminate the effect of adrenocortical androgens after orchidectomy:
  1 tablet once to twice daily (= 100 to 200 mg).
Without orchidectomy:
  1 tablet twice to three times daily (= 200 to 300 mg).
For both recommendations:
  The therapy should not be discontinued nor the dose reduced once improvement or remission occurs.
To reduce the initial increase of androgens in treatment with LH-RH agonists:
  Initially 1 tablet Androcur twice daily (= 200 mg) alone for 5 to 7 days, followed by 1 tablet Androcur twice daily (= 200 mg) for 3 to 4 weeks together with an LH-RH agonist in the dosage recommended by the manufacturer.
To eliminate the effect of adrenocortical androgens in treatment with LH-RH agonists:
  Continuation of the antiandrogen therapy with 1 tablet Androcur once to twice daily (= 100 to 200 mg).

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Experimental investigations produced corticoid-like effects on the adrenal glands in rats and dogs following higher dosages, which could indicate similar effects in humans at the highest given dose (300 mg/day).
Recognised first-line tests of genotoxicity gave negative results when conducted with cyproterone acetate. However, there is some evidence of genotoxicity as further tests showed that cyproterone acetate was capable of producing adducts with DNA (and an increase in DNA repair activity) in liver cells from rats and monkeys and also in freshly isolated human hepatocytes. This DNA-adduct formation occurred at exposures that might be expected to occur in the recommended dose regimens for cyproterone acetate. One in vivo consequence of cyproterone acetate treatment was the increased incidence of focal, possibly pre-neoplastic, liver lesions in which cellular enzymes were altered in female rats.
The clinical relevance of these findings and how these findings related to the risk of developing benign and malignant liver tumours in humans is presently unknown. Clinical experience to date would not support an increased incidence of hepatic tumours in man. Nor did investigations into the tumorigenicity of cyproterone acetate in rodents reveal any indication of a specific tumorigenic potential. However, it must be borne in mind that sexual steroids can promote the growth of certain hormone-dependent tissues and tumours.
Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure, which has been fatal in some cases, has been reported in patients treated with 200 to 300 mg cyproterone acetate. Most reported cases are in men with prostatic cancer. Toxicity is dose-related and develops usually several months after treatment has begun. Liver function tests should be performed pre-treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, cyproterone acetate should normally be withdrawn, unless the hepatotoxicity can be explained by another cause, eg metastatic disease, in which case cyproterone acetate should be continued only if the perceived benefit outweighs the risk.
In rare cases benign, and in even rarer cases malignant, liver tumours leading in isolated cases to life-threatening intraabdominal haemorrhage have been reported after the use of sex steroids to which the substance contained in Androcur 100 mg also belongs. If severe upper abdominal complaints, liver enlargement or signs of intraabdominal haemorrhage occur, a liver tumour should be included in the differential-diagnostic considerations.
Under treatment with Androcur, sexual drive and potency are reduced and spermatogenesis is impaired. These changes are reversible after discontinuation of therapy.
Over the course of several weeks, Androcur gradually restricts the ability to procreate.
The use of Androcur may lead to gynaecomastia (sometimes combined with tenderness to touch of the mamillae). Permanent enlargement of the mammary glands may occur. Galactorrhoea and benign nodules have been reported.
Tiredness and diminished vitality and occasionally temporary inner restlessness or depressive moods can occur.
Changes in body weight are possible.
A sensation of shortness of breath may occur in individual cases under high-dosed treatment with Androcur. The differential diagnosis in such cases must include the stimulating effect on breathing known for progesterone and synthetic progestogens which is accompanied by hypocapnia and compensatory alkalosis and which is not considered to require treatment.
During treatment liver function, adrenocortical function and the red blood-cell count should be checked regularly. In diabetics, carbohydrate metabolism should also be monitored particularly carefully.
In extremely rare cases, the occurrence of thromboembolic events has been reported in temporal association with the use of Androcur. However, a causal relationship seems to be questionable.
Haemoglobin and red cell count may change on therapy with Androcur.
It should be pointed out to patients whose occupation demands great concentration (eg road users, machine operators) that Androcur can lead to tiredness and diminished vitality and can impair the ability to concentrate.
The requirement for oral antidiabetics or insulin can change.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See side effects. Treatment is supportive and symptomatic.

IDENTIFICATION
White to faintly yellowish capsule-shaped tablets. Upper surface: imprinted with "LA" on both sides of the score; lower surface: imprinted with an equilateral hexagon.

PRESENTATION
Cartons containing 60 and 120 tablets.

STORAGE INSTRUCTIONS
Store below 30°C. Keep out of reach of children.

REGISTRATION NUMBER
29/21.12/0515

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Schering (Pty) Ltd
(Reg No: 1964/009072/07)
106 Sixteenth Road
Randjespark
Midrand        1685
P O Box 5278
Halfway House        1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT
6 August 1996

SCHERING (PTY) LTD
(Reg No: 1964/009072/07)
Subsidiary of
Schering AG        Germany

Updated on this site: April 2003
Current: January 2005
Source: Pharmaceutical Industry

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