APO-CYPROTERONE

What it is

Anterone 50 contains 50 mg cyproterone acetate per tablet. Cyproterone acetate is an antiandrogenic hormone preparation. Cyproterone acetate prevents the effect of endogenously produced and exogenously administered androgens at the target organs by means of competitive inhibition. Cyproterone acetate also exerts a progestational and antigonadotropic effect.

Approved indications

— Moderately severe to severe hirsutism in women — Moderately severe to severe androgen-dependent loss of scalp hair (moderately severe to severe androgenic alopecia) in women — Moderately severe to severe acne and/or seborrhoea associated with other features of androgeni­sation in women — Reduction of drive in sexual deviations in men — Inoperable prostatic carcinoma: to suppress flare with initial LHRH analogue therapy, in long-term palliative treatment where LHRH analogues or surgery are ineffective, not tolerated, contraindicated or where oral therapy is preferred, and in the treatment of hot flushes in patients treated with LHRH analogues or who have had orchidectomy

Dosing overview

For hirsutism secondary to female androgenization, the usual starting dose is one tablet of 50 mg taken daily for 10 days per month (from the 5th to the 14th day of the cycle). Once a satisfactory response has been attained it is usually possible to reduce the dose further, with doses as low as 10 mg a day for 10 days per month shown to be adequate for maintenance therapy in this condition. For other severe signs of androgeni­sation, two tablets of 50 mg are to be taken daily from the 5th to the 14th day of the cycle (10 days). These women should also receive ethinyloestradiol 50 micrograms daily from the 5th to the 25th day of the cycle to provide necessary contraceptive protection and to stabilise the cycle. In postmenopausal or hysterectomised patients, Anterone 50 may be administered alone at an average dose of ½ to 1 tablet of 50 mg once daily for 21 days, followed by a 7-day tablet-free interval. For reduction of drive in sexual deviations in men, the maximum daily dose is 300 mg. Treatment is generally started with one 50 mg tablet twice daily. For inoperable prostatic carcinoma to suppress LHRH analogue flare, 300 mg per day may be reduced to 200 mg per day.

Key safety warnings

Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure has been observed in patients treated with cyproterone acetate. At dosages of 100 mg and above, cases with fatal outcome have been reported. Most reported fatal 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, at regular intervals during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. Benign and malignant liver tumours, which may lead to life-threatening intra-abdominal haemorrhage, have been observed after the use of cyproterone. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be included in the differential diagnostic considerations. The occurrence of meningiomas (single and multiple) has been reported in association with long-term use (years) of cyproterone acetate at doses of 25 mg per day and above. The risk of meningioma increases with increasing cumulative doses of cyproterone acetate. The occurrence of thromboembolic events has been reported in patients using cyproterone although a causal relationship has not been established. Patients with previous arterial or venous thrombotic or thromboembolic events or with advanced malignancies are at increased risk of further thromboembolic events. In male patients, long-term androgen deprivation with cyproterone may lead to osteoporosis.

Contraindications

Contraindications in women include pregnancy, lactation, liver diseases, history of jaundice or persistent pruritus during a previous pregnancy, history of herpes of pregnancy, previous or existing liver tumours, Dubin-Johnson syndrome, Rotor syndrome, presence or history of meningioma, wasting diseases, severe chronic depression, previous or existing thromboembolic processes, severe diabetes with vascular changes, sickle-cell anaemia, and hypersensitivity to any of the components of Anterone 50. Contraindications in men for reduction of drive in sexual deviations include liver diseases, Dubin-Johnson syndrome, Rotor syndrome, previous or existing liver tumours, presence or history of meningioma, wasting diseases, severe chronic depression, previous or existing thromboembolic processes, severe diabetes with vascular changes, sickle-cell anaemia, and hypersensitivity to any of the components of Anterone 50. For inoperable carcinoma of the prostate, contraindications include liver diseases, Dubin-Johnson syndrome, Rotor syndrome, previous or existing liver tumours (only if these are not due to metastases from carcinoma of the prostate), presence or history of meningioma, wasting diseases (with the exception of inoperable carcinoma of the prostate), severe chronic depression, existing thromboembolic processes, and hypersensitivity to any of the components of Anterone 50.

Regulatory history

Anterone 50 tablet (cyproterone acetate 50 mg tablets) received initial ARTG approval on 07 October 2016 under registration number AUSTR 278777.