Cyproterone Sandoz^®

MIMS Revision Date: 01 May 2026

1 Name of Medicine

Cyproterone acetate.

2 Qualitative and Quantitative Composition

Each Cyproterone Sandoz 100 mg tablet contains 100 mg cyproterone acetate.
Excipient with known effect. Sugars as lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Cyproterone Sandoz 100 mg tablets are white to off white, capsule shaped tablet with '100' engraved on one face, and a break line on the other face.

4 Clinical Particulars

4.1 Therapeutic Indications

Inoperable prostatic carcinoma. To suppress flare with initial luteinising hormone releasing hormone (LHRH) analogue therapy; in long-term palliative treatment where LHRH analogues or surgery are ineffective, not tolerated, contraindicated or where oral therapy is preferred; in the treatment of hot flushes in patients treated with LHRH analogues or who have had orchidectomy.

4.2 Dose and Method of Administration

Dosage. Cyproterone Sandoz 100 mg tablets are to be taken with some liquid after meals.
Inoperable prostatic carcinoma. Suppression of flare with initial LHRH analogue therapy. Initially 100 mg twice daily alone for 5-7 days, then 100 mg twice daily for 3-4 weeks together with an LHRH agonist at the dosage recommended by the manufacturer.
Long-term palliative treatment without orchidectomy. 100 mg two or three times daily. Treatment should not be interrupted, nor the dosage reduced, after improvement or remissions have occurred.
Treatment of hot flushes (in patients treated with LHRH analogues or postorchidectomy). Low initial dose of 50 mg once to three times daily, with upward titration to 100 mg three times daily if necessary.
See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose.
Dosage adjustment. Renal impairment. There are no data suggesting the need for dosage adjustment in patients with renal impairment.
Hepatic impairment. The use of cyproterone acetate is contraindicated in patients with liver diseases.
Paediatric use. Cyproterone acetate 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.
Elderly. There are no data suggesting the need for dosage adjustment in elderly patients.

4.3 Contraindications

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.
Hypersensitivity to any of the components of Cyproterone Sandoz 100 mg.

4.4 Special Warnings and Precautions for Use

Cyproterone Sandoz 100 mg is for use only in men.
During treatment, liver function, adrenocortical function and red blood cell count should be checked regularly.
As with other antiandrogenic treatments, in male patients long-term androgen deprivation with cyproterone acetate may lead to osteoporosis.
In men of procreative age, for whom fertility could be important after conclusion of the medication, it is advisable to make at least one control spermatogram as a precaution before the start of treatment in order to counter any unjustified claims of later infertility as a result of the antiandrogen therapy. Spermatogenesis has taken 3-20 months to return to normal after discontinuing therapy.
Meningioma. 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/day and above. The risk of meningioma increases with increasing cumulative doses of cyproterone acetate. If a patient treated with cyproterone is diagnosed with meningioma, treatment with cyproterone containing products, including Cyproterone Sandoz must be permanently stopped (see Section 4.3 Contraindications).
Diabetes. Strict medical supervision is necessary if the patient suffers from diabetes, because the requirement for oral antidiabetics or insulin can change during cyproterone acetate treatment (see Section 4.3 Contraindications).
Shortness of breath. A sensation of shortness of breath may occur under high-dosed treatment with cyproterone acetate. 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.
Thromboembolic events. The occurrence of thromboembolic events has been reported in patients using cyproterone acetate although a causal relationship has not been established. Patients with previous arterial or venous thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or with a history of cerebrovascular accidents or with advanced malignancies are at increased risk of further thromboembolic events.
In patients with a history of thromboembolic processes or suffering from sickle-cell anaemia or from severe diabetes with vascular changes, a careful risk:benefit evaluation must be carried out in each individual case before cyproterone acetate is prescribed.
Adrenocortical function. During treatment, adrenocortical function should be checked regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of cyproterone acetate with high doses.
Anaemia. Anaemia has been reported during treatment with cyproterone acetate. Therefore, the red-blood cell count should be checked regularly during treatment.
Other conditions. Cyproterone Sandoz tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose mal-absorption should not take this medicine.
The sexual drive-reducing effect of cyproterone acetate can be diminished under the influence of alcohol.
Use in hepatic impairment. 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 were in men with advanced carcinoma of the prostate. 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. If hepatotoxicity is confirmed, cyproterone acetate should be withdrawn, unless hepatotoxicity can be explained by another cause, e.g. metastatic disease, in which case cyproterone acetate should be continued only if the perceived benefit outweighs the risk.
Cases of benign and malignant liver tumours, which may lead to life-threatening intra-abdominal haemorrhage, have been observed after the cyproterone acetate use. 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 and, if necessary, discontinuation of the preparation considered.
Use in the elderly. See Section 4.2 Dose and Method of Administration.
Paediatric use. See Section 4.2 Dose and Method of Administration, Paediatric use.
Effects on laboratory tests. No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The requirement for oral antidiabetics or insulin can change.
Although clinical interaction studies have not been performed, since this drug is metabolized by CYP3A4, it is expected that ketoconazole, itraconazole, clotrimazole, ritonavir and other strong inhibitors of CYP3A4 inhibit the metabolism of cyproterone acetate. On the other hand, inducers of CYP3A4 such as e.g. rifampicin, phenytoin and products containing St. John's wort (Hypericum perforatum) may reduce levels of cyproterone acetate.
The risk of statin associated myopathy or rhabdomyolysis may be increased when those HMG-CoA inhibitors (statins), which are primarily metabolised by CYP3A4, are coadministered with high therapeutic cyproterone acetate doses since they share the same metabolic pathway.
Based on in vitro CYP450 studies, the recommended clinical doses are likely to inhibit CYP2C8, and an inhibition of the CYP2C9, 2C19, 3A4, and 2D6 is also possible at high therapeutic cyproterone acetate doses of 3 times 100 mg per day.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. See Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties.
Use in pregnancy. (Category D)
Cyproterone Sandoz 100 mg is for use only in men.
Use in lactation. No data available.

4.7 Effects on Ability to Drive and Use Machines

It should be pointed out to patients whose occupation demands great concentration (e.g. road users, machine operators) that Cyproterone Sandoz 100 mg can lead to tiredness and diminished vitality and can impair the ability to concentrate (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Adverse effects reported in clinical trials. The following adverse effects have been reported at the approximate frequencies (not necessarily implicating a causal relationship) indicated below.
Very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000.
General. Very common: tiredness, weight increase. Common: headache, depressive moods.
Cardiovascular. Common: thrombotic phenomena.
Gastrointestinal. Common: nausea and other gastrointestinal complaints.
Reproductive. Very common: diminished libido. Common: mastodynia.
Skin. Rare: rash.
The most frequently observed ADRs in patients receiving cyproterone acetate are decreased libido, erectile dysfunction and reversible inhibition of spermatogenesis.
The most serious ADRs in patients receiving cyproterone acetate are hepatic toxicity, benign and malignant liver tumours which may lead to intra-abdominal haemorrhage, and thromboembolic events.
Over the course of several weeks, cyproterone acetate 100 mg gradually impairs spermatogenesis as a result of the antiandrogenic and antigonadotropic actions. Spermatogenesis recovers gradually within several months of discontinuing therapy.
Cyproterone acetate may lead to gynaecomastia (sometimes combined with tenderness to touch of the breast) which usually regresses after withdrawal of the preparation or reduction of the dose.
As with other antiandrogenic treatments, in male patients long-term androgen deprivation with cyproterone acetate may lead to osteoporosis.
In individual cases, disturbances of liver function, some of them severe, have been reported with high dosed cyproterone acetate treatment.
Changes in body weight are possible.
Other adverse events reported at a low incidence are skin discolouration and striae.
Post-marketing information. The following adverse effects have been reported in users of cyproterone acetate (post-marketing data) and are based on post-marketing data and cumulative experience with cyproterone acetate. The most appropriate MedDRA term to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well.
Very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000.
General disorders and administration site conditions. Common: fatigue, hot flushes, sweating. Very rare: tiredness, sleep disturbances.
Cardiovascular. Very rare: thrombotic phenomena, tachycardia.
Gastrointestinal. Very rare: nausea, gastrointestinal complaints.
Hepatobiliary. Common: hepatic toxicity, including jaundice, hepatitis, hepatic failure. Rare: increased liver enzymes. Very rare: liver function disturbance.
Reproductive system and breast disorders. Very common: reversible inhibition of spermatogenesis. Common: gynaecomastia. Very rare: breast tenderness, breast pain.
Skin and subcutaneous tissue disorders. Uncommon: rash.
Musculoskeletal and connective tissue disorders. Very rare: osteoporosis.
Immune system disorders. Rare: hypersensitivity reaction.
Metabolism and nutrition disorders. Common: weight increased or weight decreased.
Psychiatric disorders. Very common: libido decreased, erectile dysfunction. Common: depressed mood, restlessness (temporary).
Neoplasms benign and malignant. Very rare: benign and malignant liver tumours*.
Respiratory, thoracic and mediastinal disorders. Common: shortness of breath*.
The ADRs identified only during postmarketing surveillance and for which a frequency could not be estimated are anaemia*, meningioma, intra-abdominal haemorrhage*, thromboembolic events*⁺.
Under treatment with Cyproterone Sandoz, sexual drive and potency are reduced and gonadal function is inhibited. These changes are reversible after discontinuation of therapy.
Meningiomas have been reported in association with long-term use (several years) of Cyproterone Sandoz doses of 25 mg and above (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
* For further information see Section 4.4 Special Warnings and Precautions for Use.
⁺ A causal relationship with Androcur has not been established.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no clinical experience in overdose. Assessment and symptomatic treatment should be initiated as required.
Use of Cyproterone Sandoz 100 mg at high doses has been associated with hepatic toxicity, particularly in the elderly (see Section 4.8 Adverse Effects (Undesirable Effects)).
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action. Cyproterone acetate is an antiandrogenic hormone preparation.
Cyproterone acetate inhibits competitively the effect of androgens at androgen-dependent target organs, e.g. it shields the prostate from the effect of androgens originating from the gonads and/or the adrenal cortex. Prostatic carcinoma and its metastases are in general androgen dependent, cyproterone acetate therefore exerts a direct antiandrogenic action on the tumour and its metastases.
Cyproterone acetate in addition has a progestogenic action exerting a negative feedback effect centrally on the hypothalamic receptors, so leading to a reduction in gonadotropin release, and hence to diminished production of testicular androgens. Treatment with cyproterone acetate in men results in a reduction of sexual drive and potency and inhibition of gonadal function. These changes are reversible following discontinuation of the therapy.
The antigonadotropic effect of cyproterone acetate is also exerted when the substance is combined with LHRH agonists. The initial increase of testosterone provoked by this substance group is decreased by cyproterone acetate.
Prolactin levels can increase slightly under higher doses of CPA. Studies showed increased prolactin levels increased up to 20 nanogram/mL (normal range 5-15 nanogram/mL). There are no data for periods longer than 6 months.
Clinical trials. No data available.

5.2 Pharmacokinetic Properties

Absorption. Following oral administration, cyproterone acetate is completely absorbed over a wide dose range.
The ingestion of 100 mg of cyproterone acetate gives maximum serum levels of 239.2 ± 114.2 nanogram/mL at 2.8 ± 1.1 hours. Thereafter, drug serum levels declined during a time interval of typically 24 to 120 hours, with a terminal half-life of 42.8 ± 9.7 h. The total clearance of cyproterone acetate from serum was determined to be 3.8 ± 2.2 mL/min/kg. The absolute bioavailability of cyproterone acetate is unknown. Relative bioavailability was calculated, in a study of eight young women, from a dose-corrected comparison of area under the curves of serum levels after 100 mg oral and 300 mg intramuscular depot administration and was found to be 80 ± 30% when averaged over all volunteers (range 23%-119%).
Distribution. The major part of circulating cyproterone acetate is bound to serum albumin. In a study in 15 women receiving 2 mg cyproterone acetate in combination with 35 microgram ethinyloestradiol, the free fraction of cyproterone acetate was about 3.5-4%. Because protein binding is non-specific, changes in SHBG (sex hormone binding globulin) levels do not affect the pharmacokinetics of cyproterone acetate.
Metabolism. Cyproterone acetate is metabolised by various pathways, including hydroxylations and glucuronide conjugations. The main metabolite in human plasma is the 15β-hydroxy derivative. Some dose parts are excreted unchanged with bile fluid. Phase I metabolism of cyproterone acetate is mainly catalysed by the CYP450 enzyme CYP3A4.
Excretion. In a study in 6 women administered a ¹⁴C labelled dose of 2 mg cyproterone acetate in combination with a 50 microgram oestrogen, approximately 30% of the label was found in the urine and 58% in the faeces. The renal and biliary excretion was determined to proceed with a half-life of 1.9 days. Metabolites from plasma were eliminated at a similar rate (half-life of 1.7 days).
Steady state conditions. According to the long half-life of the terminal disposition phase from plasma (serum) and the daily intake, an accumulation of cyproterone acetate in the serum by a factor of about 3 can be expected during repeated daily administration.

5.3 Preclinical Safety Data

Genotoxicity. Cyproterone acetate (CPA) was negative in a standard battery of genotoxicity studies. However, further tests showed that CPA was capable of producing hepatocyte DNA adducts in rats, dogs and monkeys (and an increase in DNA repair activity in rats) in vivo, and also in freshly isolated rat and human liver cells in vitro. This DNA adduct formation occurred at exposures that might be expected to occur in the recommended dose regimens for Cyproterone Sandoz 100 mg. In vivo consequences of CPA 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 presently remains uncertain.
Carcinogenicity. Long-term animal carcinogenicity studies were performed in rats and mice. In one rat study, an increased incidence of hepatomas was reported at oral dose levels of 50 mg/kg CPA and above. In mouse (and a second rat) carcinogenicity studies, increases in benign proliferative changes (nodular hyperplasia) in liver cells of female mice and male and female rats were reported at oral doses of 2 mg/kg. Because of shortcomings in these studies (inadequate pharmacokinetic data and the need to reassess the liver pathology), the carcinogenic potential of CPA in animals could not be determined.
Clinical experience and limited epidemiological data available to date do not appear to have supported an increased incidence of hepatic tumours in humans. However it must be borne in mind that steroidal sex hormones can promote the growth of certain hormone dependent tissues and tumours.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone and magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.
Protect from light and moisture.

6.5 Nature and Contents of Container

Cyproterone Sandoz 100 mg tablets is available in (PVC/PVDC/Al) blister packs of 50 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Cyproterone acetate is a white to pale yellow crystalline powder. Melting point: 206 to 213°C. It is very soluble in chloroform and dioxane, freely soluble in acetone and benzene, soluble in ethanol, methanol and ethyl acetate, sparingly soluble in solvent hexane and almost insoluble in water.
Chemical structure.

Chemical name: 6-chloro-17αhydroxy-1α,2α-methylene-pregna- 4,6-diene-3,20-dione acetate.
Empirical formula: C₂₄H₂₉ClO₄.
Molecular weight: 416.96.
CAS number. 427-51-0.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Date of First Approval

15 November 2004

Date of Revision

23 March 2026

Summary Table of Changes