Gale Special Precautions

Liver: Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure, which has been fatal in some cases, has been reported in patients treated with 200-300 mg/day 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, regularly during 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 If hepatotoxicity is confirmed, cyproterone acetate should normally be withdrawn, unless the hepatotoxicity can be attributed to another cause, e.g. metastatic disease, in which case cyproterone acetate should be continued only if the perceived benefit outweighs the risk.
Very rarely liver tumours, leading in isolated cases to life-threatening intra-abdominal haemorrhage, have been observed after the use of sex steroids, to which class cyproterone acetate belongs. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, hepatic tumour should be considered in the differential diagnosis and, if necessary, cyproterone acetate should be withdrawn.
Thromboembolism: The occurrence of thromboembolic events has been reported in patients using cyproterone acetate, although a causal relationship has not been established. Patients with a history of arterial or venous thrombotic/thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, myocardial infraction), with a history of cerebrovascular accidents or with advanced malignancies are at increased risk of further thromboembolic events, and may be at risk of recurrence of the disease during cyproterone acetate therapy. In patients with a history of thromboembolic disorders or suffering from sickle-cell anaemia or severe diabetes with vascular changes, the risk benefit ratio must be considered carefully in each individual case before cyproterone acetate is prescribed.
In very rare cases, the occurrence of thromboembolic events has been reported in temporal association with the use of cyproterone acetate; a causal relationship seems however questionable.
Chronic depression: It has been found that some patients with severe chronic depression deteriorate during cyproterone acetate therapy. Such patients should be closely monitored for signs of deterioration and warned to contact their doctor immediately if their depression worsens.
Breathlessness: Shortness of breath may occur. Possibly due to the known stimulatory effect of progesterone and synthetic progestogens on breathing, which is accompanied by hypocapnia and compensatory alkalosis, but it is not considered that treatment is required.
Adrenocortical function: During treatment adrenocortical function should be monitored regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of Cyproterone Acetate.
Diabetes mellitus: Strict medical supervision is necessary if the patient suffers from diabetes as cyproterone acetate can influence carbohydrate metabolism. Parameters of carbohydrate metabolism should be examined carefully in all diabetics before and regularly during treatment because the requirement for oral antidiabetics or insulin can change.
Haemoglobin: Hypochromic anaemia has been found rarely during long term treatment, and blood counts before and at regular intervals during treatment are advisable.
Nitrogen balance: A negative nitrogen balance is usual at the start of treatment, but usually does not persist.
Spermatogenesis: A spermatogram should be recorded before starting treatment in patients of procreative age, as a guard against attribution of pre-existing infertility to cyproterone acetate at a later stage.
It should be noted that decline in spermatogenesis is slow and cyproterone acetate should not be regarded as a male contraceptive.
Medico-legal consideration: Doctors are advised to ensure that the fully informed consent of the patient to cyproterone acetate treatment is obtained, witnessed and can be verified.
Lactose: The tablets also contain lactose (see Description). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Patients who are on a lactose-free diet should take this amount into consideration.
Meningiomas: The occurrence of meningiomas (single and multiple) has been reported in association with use of cyproterone acetate primarily at doses of 25 mg and above. The risk of meningioma increases with increasing cumulative doses of cyproterone acetate (see Pharmacology: Pharmacodynamics under Actions). High cumulative doses can be reached with prolonged use (several years) or shorter duration with high daily doses. Patients should be monitored for meningiomas in accordance with clinical practice. If a patient treated Cyproterone Acetate is diagnosed with meningioma, treatment with Cyproterone Acetate and other cyproterone containing products must be permanently stopped (see 'Contraindications').
There is some evidence that the meningioma risk may decrease after treatment discontinuation of cyproterone.
Anaemia: Anaemia has been reported during long-term treatment. Therefore, the red blood count should be checked regularly during treatment.
Effects on ability to drive and use machines: Fatigue and lassitude are common in the first few weeks of therapy but usually become much less marked from the third month - patients should be warned about this and if affected should not drive or operate machinery.
The marked lassitude and asthenia necessitate special care when driving or operating machinery.