Summary of Product Characteristics Updated 12-Apr-2018 | Bayer plc
Excipient with known effectlactose 184.3 mg.For the full list of excipients, see section 6.1.
AdultsThe maximum daily dose is 300 mg.For long-term palliative treatment where LHRH analogues or surgery are contraindicated, not tolerated, or where oral therapy is preferred the dosage is 200-300 mg/day. Dosage for suppression of "flare" with initial LHRH analogue therapy: Initially 1 tablet of Cyprostat 100 mg twice daily (200 mg) alone for 5 - 7 days, followed by 1 tablet of Cyprostat 100 mg twice daily (200 mg) for 3 4 weeks together with the LHRH analogue therapy in the dosage recommended by the marketing authorisation holder (see SmPC of LHRH analogue).For the above two indications the dosage should be divided into 2 - 3 doses per day and taken with some liquid after meals.For the treatment of hot flushes in patients under treatment with LHRH analogues or who have had orchidectomy a 50 mg starting dose, with upward titration if necessary within the range 50-150 mg/day, is recommended. For this indication the dosage should be divided into 1 - 3 doses per day and taken with some liquid after meals.
Additional information on special populationsPaediatric population: Cyprostat is not recommended for use in male children and adolescents below 18 years of age due to a lack of data on safety and efficacy.Cyprostat must 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.
ElderlyThere are no data suggesting the need for a dosage adjustment in elderly patients.
Patients with hepatic impairmentThe use of Cyprostat is contraindicated in patients with liver diseases (see section 4.4 and 4.8).
Renal impairmentThe use of Cyprostat in patients with renal impairment has not been investigated. There are no data suggesting the need for dosage adjustment in patients with renal impairment (see section 5.2).
Method of administrationFor oral administration.
Meningiomas:The occurrence of (multiple) meningiomas has been reported in association with longer term use (years) of cyproterone acetate at doses of 25 mg/day and above. If a patient treated with Cyprostat is diagnosed with meningioma, treatment with Cyprostat must be stopped (see section 4.3).Chronic depression: It has been found that some patients with severe chronic depression deteriorate whilst taking Cyprostat therapy. Such patients should be closely monitored for signs of deterioration and warned to contact their doctor immediately if their depression worsens.Shortness of breath: Shortness of breath may occur under high-dosed treatment with Cyprostat. This may be due to the stimulatory effect of progesterone and synthetic progestogens on breathing, which is accompanied by hypocapnia and compensatory alkalosis, and which is not considered to require treatment.Adrenocortical function: During treatment, adrenocortical function should be checked regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of Cyprostat with high doses (see section 5.3).Diabetes mellitus: Strict medical supervision is necessary if the patient suffers from diabetes as Cyprostat 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. See also section 4.5.Anaemia: Anaemia has been reported during long-term treatment. Therefore, the red blood cell count should be checked regularly during treatment.Lactose: Cyprostat contains 184.3 mg lactose per tablet. 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.
|Neoplasms benign, malignant and unspecified (incl cysts and polyps)|
|Very rare:||Benign and malignant liver tumours which may lead to life-threatening intra-abdominal haemorrhage (see section 4.4).|
|Not known:||The occurrence of (multiple) meningiomas has been reported in association with longer term use (years) of cyproterone acetate at doses of 25 mg/day and above.|
|Blood and the lymphatic system disorders|
|Not known:||Anaemia during long-term treatment (see section 4.4).|
|Immune system disorders|
|Not known:||Suppression of adrenocortical function.|
|Metabolism and nutrition disorders|
|Common:||Changes in bodyweight during long term treatment (chiefly weight gains in association with fluid retention).|
|Common:||Depressive moods and restlessness (temporary).|
|Not known:||Thromboembolic events, although a causal relationship has not been established (see section 4.4).|
|Respiratory, thoracic and mediastinal disorders|
|Common:||Dyspnoea (see section 4.4).|
|Common:||Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure has been observed in patients treated with Cyprostat. At dosages of 100 mg and above, cases with fatal outcome have also been reported. Most reported fatal cases were in men with advanced carcinoma of the prostate. Toxicity is dose related and develops, usually, several months after treatment has begun.|
|Skin and subcutaneous tissue disorders|
|Not known:||Reduction of sebum production leading to dryness of the skin and improvement of existing acne vulgaris has been reported as well as; transient patchy loss and reduced growth of body hair, increased growth of scalp hair, lightening of hair colour and female type of pubic hair growth.|
|Musculoskeletal and connective tissue disorders|
|Not known:||Osteoporosis (due to long-term androgen deprivation).|
|Reproductive system disorders|
|Very common:||Decreased libido, erectile dysfunction, reduced sexual drive and inhibition of gonadal function. These changes are reversible after discontinuation of therapy.|
|Inhibition of spermatogenesis:|
|Very common:||Sperm count and the volume of ejaculate are reduced.|
|Infertility is usual, and there may be azoospermia after 8 weeks. There is usually slight atrophy of the seminiferous tubules. Follow-up examinations have shown these changes to be reversible, spermatogenesis usually reverting to its previous state about 3-5 months after stopping Cyprostat, or in some users, up to 20 months. That spermatogenesis can recover even after very long treatment is not yet known. There is evidence that abnormal sperms which might give rise to malformed embryos are produced during treatment with Cyprostat. Gynaecomastia:|
|Common:||Gynaecomastia (sometimes combined with tenderness to touch of the mamillae) which usually regresses after withdrawal of the preparation.|
|Rare:||Galactorrhoea and tender benign nodules.|
|Symptoms mostly subside after discontinuation of treatment or reduction of dosage. General disorders and administration site conditions|
|Common:||Hot flushes, sweating, fatigue and lassitude.|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Systemic toxicityPreclinical data reveal no specific risk for humans based on conventional studies of repeated dose toxicity beyond those discussed in other sections of the SPC.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).
Genotoxicity and carcinogenicityRecognised first-line tests of genotoxicity gave negative results when conducted with cyproterone acetate. However, 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, the DNA-adduct level in the dog liver cells was extremely low. This DNA-adduct formation occurred at exposures that might be expected to occur in the recommended dose regimens for cyproterone acetate. In vivo consequences of cyproterone acetate treatment were the increased incidence of focal, possibly preneoplastic, liver lesions in which cellular enzymes were altered in female rats, and an increase of mutation frequency in transgenic rats carrying a bacterial gene as target for mutation. The clinical relevance of these findings is presently uncertain. In long-term carcinogenicity studies in rats cyproterone acetate increased the incidence of liver tumours including carcinomas at high doses which concomitantly caused liver toxicity and exceeded the maximum human dose. Further investigations into rodents at lower, non-hepatotoxic doses revealed benign liver proliferations similar to effects described for other steroid hormones. However, it must be borne in mind that sex steroids can promote the growth of certain hormone dependent tissues and tumours.