Cyproterone Acetate

Registered South African indications:

• Prostatic carcinoma
• Suppression of sex drive in males
• Androgenisation in females

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Hepatic impairment
• Porphyria
• Meningioma or history thereof
• Malignant tumours (except for carcinoma of the prostate)
• Liver tumours or history thereof (unless due to metastases from carcinoma of the prostate)
• Liver diseases, including Dubin-Johnson syndrome
• Rotor syndrome
• Wasting diseases (except for inoperable carcinoma of the prostate)
• Thromboembolic disorders or history thereof
• Males below 18 years whose bone or testicular maturity is incomplete
• Severe diabetes with vascular changes
• Sickle cell anaemia
• Severe chronic depression
• Patients whose bone maturation and testicular development are incomplete

Cautions

• Renal impairment
• Males of reproductive potential
• High cumulative doses
• Prolonged duration of therapy
• Chronic alcohol abuse
• Diabetes mellitus
• Previous arterial or venous thrombotic/ thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction)
• History of cerebrovascular accidents
• Advanced malignancies
• Galactose intolerance
• Lapp lactose deficiency
• Glucose-galactose malabsorption
• Lactose-free diet
• May impair ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: tab, inj

Palliative management of prostatic cancer

• Consult specialist for dosages

Severe androgenisation in females - women of childbearing potential

• Oral (tab): Initial: 100mg, dly for 10 days cyclically starting on the 5th-14th day of the menstrual cycle; Maintenance: 25-50mg, dly for 10 days cyclically

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Initiate on day 5 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

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Cyclical treatment: 10 days of treatment from day 5-14 of the menstrual cycle repeated every 28 days (with each menstrual cycle)

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One complete cycle of combined oral contraceptive (COC) tablets should be taken before initiation of treatment. Ensure COC given for duration of treatment

Exclude pregnancy before starting treatment

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If no bleeding occurs during inactive tablet phase, interrupt treatment and exclude pregnancy before treatment can resume

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Missed dose: The missed tablet should be disregarded (no double dose should be taken to make up for the missed tablet) and tablet taking resumed at the regular time together with the combined oral contraceptive

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Severe androgenisation in females - postmenopausal women/ hysterectomised females

• Oral (tab): 25-50mg, dly for 21 days cyclically

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Cyclical treatment: daily cyproterone for 21 days followed by a 7 day treatment free interval after which cyproterone should be continued

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Suppression of sex drive

• Oral (tab): Initial: 50mg, 12hrly Increased to 50-100mg, 8-12hrly for short period of time; Maintenance: 25-50mg, 12hrly

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Downtitrate gradually by 25-50mg at intervals of several weeks

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• IM: 300-600mg, every 10-21 days

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If giving dose of 600mg IM, it is preferred to give 300mg in each buttock

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To reduce the initial increase in male sex hormones associated with initiation of gonadotropin-releasing hormone (GnRH) agonists

• Oral (tab): 100mg, 12hrly  

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Cyroterone should be started 5-7 days before GnRH agonist and continued for 3-4 weeks with GnRH agonist

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Treatment of hot flushes in patient on GnRH agonist or who have had orchidectomy

• Oral (tab): 100mg, 12-24hrly

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The tablets are to be taken with some liquid after meals  

Not indicated for use in children 

Pregnancy

• Contraindicated
• Not indicated for use in pregnancy

Breastfeeding

• Contraindicated
• Not indicated for use by breastfeeding women

Fertility

• 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 the decline in spermatogenesis is slow, and cyproterone acetate should therefore, not be regarded as a male contraceptive
• 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 cyproterone acetate, 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 sperm which might give rise to malformed embryos are produced during treatment with cyproterone acetate

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Restlessness
• Fatigue
• Meningiomas

Cardiovascular Disorders

• Thromboembolic events

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Intra-abdominal haemorrhage

Hepatobiliary Disorders

• Jaundice
• Hepatitis
• Hepatic failure
• Benign and malignant liver tumours

Genitourinary Disorders

• Tender benign breast nodules
• Gynaecomastia
• Galactorrhoea
• Decreased sperm count
• Decreased volume of ejaculate
• Abnormal spermatazoa
• Infertility
• Decreased libido
• Erectile dysfunction
• Decreased sexual drive
• Inhibition of gonadal function

Endocrine and Metabolic Disorders

• Suppression of adrenocortical function
• Changes in weight
• Hot flushes

Musculoskeletal Disorders

• Osteoporosis

Skin and Subcutaneous Tissue Disorders

• Rash
• Dry skin
• Transient patchy loss and reduced growth of body hair
• Increased growth of scalp hair
• Lightening of hair colour
• Female pattern pubic hair growth
• Sweating

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Hypersensitivity reactions

• Alcohol
• CYP2C8 substrates
• Thiazolidinediones
• Pioglitazone
• Rosiglitazone
• CYP3A4 inducers
• Rifampicin
• Phenytoin
• CYP3A4 inhibitors
• Ketoconazole
• Itraconazole
• Clotrimazole
• Ritonavir
• HMG-CoA inhibitors (statins)
• St. John's wort

• Full blood count
• Hepatic function
• Adrenocortical functioning

Specific cases may require

• Blood glucose
• Electrolytes

Tablet 10mg, Tablet 50mg - EML (Tertiary)

Cyproterone acetate acts as an antiandrogen by blocking androgen receptors. It also has progestogenic activity, which exerts a negative feedback effect on hypothalamic receptors, so leading to a reduction in gonadotrophin release, and hence to diminished production of testicular androgens. Sexual drive and potency are reduced and gonadal function is inhibited. An occasional tendency for the prolactin levels to increase slightly has been observed under higher doses of cyproterone acetate. 

Tablet 10mg

• Androcur (Bayer) originator

Tablet 50mg

• Androcur (Bayer) originator
• Cipla-Cyproterone acetate (Cipla)

Tablet 100mg

• Androcur (Bayer) originator

Injection (per 3ml) 300mg

• Androcur Depot (Bayer) originator

COMBINATION PREPARATIONS

Cyproterone Acetate/ Ethinyloestradiol

Tablet 2mg/0.035mg

• Claro 35 (Sandoz)
• Diane-35 (Bayer)
• Ginette (Cipla)
• Minerva-35 (Bayer) originator

Cyproterone Acetate/ Estradiol

Tablet 2mg/0.035mg

• Diva 35 (Unicorn)