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ANDROCUR DEPOT

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ANDROCUR DEPOT

Antiandrogen injection

COMPOSITION
One 3 mL ampoule Androcur Depot contains cyproterone acetate (6-chloro-17-hydroxy-1alpha,2alpha-methylene-pregna-4,6-diene-3,20-dione-acetate) 300 mg in oily solution.

PHARMACOLOGICAL CLASSIFICATION
A. 21.12 Hormone inhibitors.

PHARMACOLOGICAL ACTION
Androcur is an antiandrogenic hormone preparation.
The active substance, cyproterone acetate, has three partial effects:
an antiandrogenic effect, a progestational effect and an antigonadotropic effect.
Cyproterone acetate blocks the effect of endogenously produced and exogenously administered androgens at the target organs by means of competitive inhibition.
The stimulating effect of male sex hormones on androgen dependent structures and functions is weakened or abolished by cyproterone acetate.
The inherent progestational activity exerts a negative feedback on the hypothalamic receptors so leading to a reduction in gonadotropin release, and hence to diminished production of androgens.

INDICATIONS
Reduction of drive in sexual deviations in the male; inoperable prostatic carcinoma.

CONTRA-INDICATIONS
Androcur Depot is contra-indicated in patients with liver diseases; Dubin-Johnson syndrome; Rotor syndrome; previous or existing liver tumours (in carcinoma of the prostate only if these are not due to metastases); wasting diseases (with the exception of prostatic carcinoma); depression; previous or existing thromboembolic processes; diabetes with vascular changes; sickle-cell anaemia.
As regards patients with prostatic carcinoma who have a history of thromboembolic processes and/or an existing sickle-cell anaemia, or diabetes with vascular changes, the risk:benefit ratio must be considered carefully in each individual case before the use of Androcur Depot.

DOSAGE AND DIRECTIONS FOR USE
Androcur Depot must be injected deep intramuscularly.

•	Reduction of drive in sexual deviations in the male
	1 ampoule of Androcur Depot is given as a deep intramuscular injection. If, in exceptional cases, the effect is inadequate, 2 ampoules can be given, preferably as 1 ampoule each in the right and left gluteal muscles. Efficacy can be maintained by injection intervals ranging from 10 to 21 days.

When the therapeutic result is considered to be satisfactory, an attempt should be made to reduce the dosage by gradually increasing the intervals between injections.
To stabilise the therapeutic effect it is necessary to administer Androcur Depot over a protracted period of time, if possible with the simultaneous use of psychotherapeutic measures.

•	Inoperable prostatic carcinoma
O	After orchidectomy: 300 mg (1 ampoule) every 2 weeks as a deep im injection.
O	Without orchidectomy: 300 mg (1 ampoule) weekly as a deep im injection.

In both cases, treatment should not be interrupted nor the dosage reduced after improvement or remissions have occurred.

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 relate 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 Depot 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.
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.
Over the course of several weeks, Androcur Depot gradually restricts the ability to procreate. This ability is usually regained within a few months of discontinuing the therapy. In rare cases recovery may be possible under dose reduction.
Androcur Depot may lead to gynaecomastia (sometimes combined with tenderness to touch of the mamillae) which may regress after withdrawal of the preparation.
Tiredness and diminished vitality and inner restlessness or depressive moods may occur. Changes in body-weight are possible.
It should be pointed out to patients whose occupation demands great concentration (eg road users, machine operators) that Androcur Depot can lead to tiredness and diminished vitality and can impair the ability to concentrate.
The sexual drive-reducing effect of Androcur Depot can be diminished under the disinhibitory influence of alcohol.
Androcur Depot should not be given before the conclusion of puberty, since an unfavourable influence on longitudinal growth and the still unstabilised axes of endocrine function cannot be ruled out.
During treatment, liver function, adrenocortical function and the red blood-cell count should be checked regularly. In diabetics, carbohydrate metabolism as well should be monitored particularly carefully as hyperglycaemia may occur.
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.
A high dosed treatment may reduce the function of the adrenal cortex, particularly the adrenocortical response to stress.
Androcur should be used with caution in cardiovascular disease, ischemic heart disease, cerebrovascular disease and hypertension.
Haemoglobin and red cell counts may decrease on therapy with Androcur.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Unknown till now.

IDENTIFICATION
Clear, colourless to faintly yellowish oily solution in 3 mL glass ampoules.

PRESENTATION
Ampoules of 3 mL.

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

REGISTRATION NUMBER
R/21.12/184

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
2 December 1991

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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