Consumer medicine information

Cyprocur 100 Tablets

Cyproterone acetate

BRAND INFORMATION

Brand name

Cyprocur 100 Tablets

Active ingredient

Cyproterone acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cyprocur 100 Tablets.

What is in this leaflet

This leaflet answers some common questions about Cyprocur 100.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Cyprocur 100 against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What CYPROCUR 100 is used for

Cyprocur 100 tablets contain cyproterone acetate as the active ingredient. Cyproterone acetate belongs to a group of medicines called anti-androgens. It blocks the actions of male sex hormones (androgens) which are released naturally in the body. It also reduces the production of androgens.

It has been shown that the growth of tumours of the prostate gland may be dependent on male hormones. Since cyproterone acetate blocks the action of androgens and reduces the amount of androgens produced by the body, it can be used to help treat cancer of the prostate gland.

It can also be used in conjunction with other medications or following surgical removal of the testes to treat side effects such as “sweats” or “hot flushes” and to prevent any initial worsening of the disease.

Cyprocur 100 is for use only in men.

This medicine is available only with a doctor's prescription.

There is no evidence that Cyprocur 100 tablets are addictive.

Before you take it

When you must not take it

Do not take Cyprocur 100 if you are allergic to:

  • cyproterone acetate
  • any other ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.

Do not take Cyprocur 100 if you suffer from:

  • liver disease, previous or existing liver tumours unless they are caused by metastases from prostate cancer (your doctor would have told you if you have this)
  • existing blood clots
  • previous or existing benign brain tumour (meningioma)
  • severe chronic depression
  • Dubin-Johnson syndrome or Rotor syndrome (your doctor would have told you if you have either of these conditions)
  • wasting diseases (with the exception of cancer of the prostate)
  • a rare hereditary problem associated with lactose e.g. galactose intolerance and Lapp lactase deficiency.

Do not take Cyprocur 100 if you are under 18 years of age.

It is not recommended for use in male children and adolescents below 18 years of age as the safety and effectiveness in this age group has not been established.

Do not take Cyprocur 100 after the expiry date printed on the pack has passed.

If you take this medicine after the expiry date, it may not work as well.

Do not take it if the packaging shows signs of tampering or the tablets do not look quite right.

Talk to your doctor if you are not sure whether you should start taking this medicine.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • diabetes
  • history of blood clotting or sickle cell anaemia
  • osteoporosis, a family history of osteoporosis or risk factors for developing osteoporosis (such as smoking, a diet low in calcium, poor mobility, a slight build or treatment with steroid medicines).

Tell your doctor if fertility after treatment is important.

In this case it is advisable to have a spermatogram before taking Cyprocur 100 to establish your fertility before commencing therapy. It can take 3-20 months for fertile sperm production to be re-established after stopping this medicine.

If you have not told your doctor about any of the above, tell them before you start taking Cyprocur 100.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines reduce the contraceptive effectiveness of Cyprocur 100.

These include:

  • phenytoin, a medicine used to treat epilepsy
  • medicines used to treat fungal infections, including ketoconazole, itraconazole, clotrimazole
  • ritonavir, a medicine used in the treatment of HIV
  • rifampicin, a bactericidal antibiotic used to treat infections such as tuberculosis and leprosy
  • St John's wort, a herbal remedy used to treat mood disorders
  • statins (HMGCoA inhibitors), medicines used to lower cholesterol levels in people with or at risk of cardiovascular disease
  • medicines used to treat diabetes.

These medicines may be affected by Cyprocur 100 or may affect how well it works. You may need different amounts of your medicine or you may need to take different medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Cyprocur 100.

How to take it

Follow all directions given to you by your doctor.

They may differ from the information contained in this leaflet.

How much to take

Your doctor will tell you the dose that you should take and whether your need to take it with other medicines.

The usual daily dose is 50-300 mg (one half to three tablets) of Cyprocur 100.

Do not alter the dose yourself.

Your doctor will advise you if changing the dose is necessary.

How to take it

Swallow the tablets with some liquid after meals.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too many Cyprocur 100 tablets. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

While you are taking it

Things you must do

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Cyprocur 100, especially if you are starting any new medicines.

Keep all of your doctor’s appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Your doctor will check your liver function during treatment with Cyprocur 100 and whenever any signs or symptoms suggesting liver problems are observed.

If you have diabetes, your doctor will monitor you to ensure that you receive the appropriate dose of oral antidiabetic or insulin.

Your doctor will also check your red blood cell count to ensure you do not become anaemic during treatment with this medicine.

Things you must not do

Do not take Cyprocur 100 to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

If you stop taking it suddenly, your condition may worsen or you may have unwanted side effects.

Things to be careful of

Be careful driving or operating machinery until you know how this medicine affects you.

Cyprocur 100 may cause drowsiness and loss of concentration in some people.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking this medicine.

All medicines have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • tiredness
  • weight increase
  • decreased sexual drive
  • headache
  • depressive mood
  • fast heart beat
  • nausea and other gastrointestinal complaints
  • breast pain, change in breast size, breast swelling and/or tenderness
  • osteoporosis
  • hot flushes, sweating.

These side effects are common.

If you were fertile before treatment, Cyprocur 100 may also result in your inability to produce sperm (infertility). Fertility is usually regained within a few months of discontinuing therapy.

Cyprocur 100 may also result in the inability to get or maintain an erection (impotence). This ability is usually also regained within a few months of discontinuing therapy.

Tell your doctor as soon as possible if you notice any of the following side effects:

  • yellowing of the skin and/or eyes
  • severe upper abdominal pain.

These serious side effects are rare and may require medical attention.

If the following happens, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • sudden severe headache, loss of vision, loss of coordination, slurred speech, shortness of breath, chest pain, numbness heat or swelling.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Other side effects not listed above may happen in some people.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After taking it

Storage

Keep your tablets in a cool dry place, protected from light, where the temperature stays below 25°C.

Keep the tablets in the foil blister until it is time to take them.

If you take the tablets out of the foil blister, they may not keep as well.

Do not store Cyprocur 100 or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach them.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Cyprocur 100 or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Cyprocur 100 are white, capsule shaped, biconvex tablets with ‘CPA 100’ marked on one side and scored on the other.

Available in packs of 50 tablets.

Ingredients

Active ingredient:
Each Cyprocur 100 tablet contains 100 mg of cyproterone acetate.

Inactive ingredients:

  • lactose
  • starch-maize
  • starch pregelatinised maize
  • povidone
  • magnesium stearate
  • silica-colloidal anhydrous.

Cyprocur 100 tablets do not contain gluten, sucrose, tartrazine or any other azo dyes.

BRAND INFORMATION

Brand name

Cyprocur 100 Tablets

Active ingredient

Cyproterone acetate

Schedule

S4

 

Name of the medicine

Cyproterone acetate.

Excipients.

Lactose, maize starch, povidone, pregelatinised maize starch, magnesium stearate, colloidal silica.

Description

Chemical name: 6-chloro-17αhydroxy-1α, 2α-methylene-pregna-4, 6-diene-3, 20-dione acetate. Molecular formula: C24H29ClO4. MW: 416.96. CAS: 427-51-0. Cyproterone acetate is a white to pale yellow crystalline powder. Cyproterone acetate is very soluble in chloroform and dioxane, freely soluble in acetone and benzene, soluble in ethanol, methanol and ethyl acetate, sparingly soluble in hexane, and almost insoluble in water.

Actions

Anti-androgenic hormone preparation.

Pharmacology

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 anti-androgenic 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 luteinising hormone releasing hormone (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 cyproterone acetate. Studies showed increased prolactin levels up to 20 nanogram/mL (normal range 5 to 15 nanogram/mL). There are no data for periods longer than six months.

Pharmacokinetics.

Absorption.

Following oral administration, cyproterone acetate is completely absorbed over a wide dose range.
The ingestion of cyproterone acetate 100 mg 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 hours. The total clearance of cyproterone acetate from serum was determined to be 3.8 ± 2.2 mL/minute/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 to 119%).

Distribution.

The major part of circulating cyproterone acetate is bound to serum albumin. In a study in 15 women receiving cyproterone acetate 2 mg in combination with ethinyloestradiol 35 microgram, the free fraction of cyproterone acetate was about 3.5 to 4%. Because protein binding is nonspecific, 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 conjugations. The main metabolite in human plasma is the 15 beta-hydroxy derivative. Some dose parts are excreted unchanged with bile fluid. Phase I metabolism of CPA is mainly catalysed by the CYP450 enzyme CYP3A4.

Elimination.

In a study in six women administered a 14C labelled dose of cyproterone acetate (CPA) 2 mg in combination with oestrogen 50 microgram, 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 by a factor of about three can be expected in the serum during repeated daily administration.
In a study comparing Cyproterone 50 mg tablets with the reference (Androcur 50 mg) tablets, the two products were shown to be bioequivalent. The geometric mean ratio and 90% confidence intervals for cyproterone AUC0-∞ were found to be 1.019, and 0.963 to 1.079, respectively, while those for Cmax were 0.958, and 0.880 to 1.044,respectively.

Indications

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

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).
Wasting diseases (with the exception of inoperable carcinoma of the prostate).
Severe chronic depression.
Existing thromboembolic processes.
Hypersensitivity to any of the components of Cyprocur 100.

Precautions

Cyprocur 100 is for use only in men.
During treatment, liver function, adrenocortical function and red blood cell count should be checked regularly.
As with other anti-androgenic treatments, in male patients long-term androgen deprivation with Cyprocur 100 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 to 20 months to return to normal after discontinuing therapy.
Direct hepatic toxicity, including jaundice, hepatitis and liver failure, which has been fatal in some cases, has been reported in patients treated with cyproterone acetate. At dosages of 100 mg and above, cases with fatal outcome have been reported. Most reported cases are in men with carcinoma of the prostate. Toxicity is dose related and usually develops several months after treatment has begun. Liver function tests should be performed pretreatment, at regular intervals during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, Cyprocur should normally be withdrawn unless hepatotoxicity can be explained by another cause, e.g. metastatic disease, in which case Cyprocur should be continued only if the perceived benefit outweighs the risk.
Cases of benign and malignant liver tumors, which may lead to life threatening intra-abdominal hemorrhage, have been observed after the use of Cyprocur. 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/day and above. If a patient treated with Cyprocur is diagnosed with meningioma, treatment with Cyprocur must be stopped (see Contraindications).
Strict medical supervision is necessary if the patient suffers from diabetes, because the requirement for oral antidiabetics or insulin can change during Cyprocur treatment (see Contraindications).
A sensation of shortness of breath may occur in individual cases under high dosed treatment with Cyprocur. 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.
The occurrence of thromboembolic events has been reported in patients using Cyprocur 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 Cyprocur 100 is prescribed.
During treatment adrenocortical function should be checked regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of Cyprocur with high doses.
Anaemia has been reported during treatment with Cyprocur. Therefore, the red-blood cell count should be checked regularly during treatment.
Cyprocur tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine.

Carcinogenesis, mutagenesis, impairment of fertility.

Cyproterone acetate 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 Cyprocur. 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.
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 CPA 50 mg/kg 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.

Effect on ability to drive or operate machinery.

It should be pointed out to patients whose occupation demands great concentration (e.g. road users, machine operators) that Cyprocur 100 can lead to tiredness and diminished vitality and can impair the ability to concentrate.

Interactions

The requirement for oral antidiabetics or insulin can change.
Although clinical interaction studies have not been performed, since this drug is metabolised 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, e.g. rifampicin, phenytoin and products containing St John's wort (Hypericum perforatum) may reduce the levels of cyproterone acetate.
The risk of statin associated myopathy or rhabdomyolysis may be increased when those HMGCoA 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 CYP 2C9, 2C19, 3A4 and 2D6 is also possible at high therapeutic cyproterone acetate doses of 100 mg three times daily.

Adverse Effects

Adverse reactions reported in clinical trials. The following adverse reactions have been reported at the approximate frequencies (not necessarily implicating a causal relationship) indicated below.
Very common: greater than or equal to 1/10; common: greater than or equal to 1/100 and < 1/10; uncommon: greater than or equal to 1/1,000 and < 1/100; rare: greater than or equal to 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 adverse drug reactions (ADRs) in patients receiving Cyprocur are decreased libido, erectile dysfunction and reversible inhibition of spermatogenesis.
The most serious ADRs in patients receiving Cyprocur are hepatic toxicity, benign and malignant liver tumours which may lead to intra-abdominal haemorrhage and thromboembolic events.
Over the course of several weeks Cyprocur 100 gradually impairs spermatogenesis as a result of the antiandrogenic and antigonadotropic actions. Spermatogenesis recovers gradually within several months of discontinuing therapy.
Cyprocur 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 Cyprocur may lead to osteoporosis.
In individual cases, disturbances of liver function, some of them severe, have been reported with high dosed Cyprocur treatment.
Changes in bodyweight are possible.
Other adverse events reported at a low incidence are skin discolouration and striae.

Postmarketing information.

The following adverse effects have been reported in users of cyproterone acetate (postmarketing data) but for which the association to Cyprocur has neither been confirmed nor refuted.
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.
**A causal relationship with Cyprocur has not been established.
The ADRs identified only during postmarketing surveillance and for which a frequency could not be estimated are: anaemia*, meningioma, intra-abdominal haemorrhage*, thromboembolic events**.
Meningiomas have been reported in association with long-term use (several years) of Cyprocur doses of 25 mg and above (see Contraindications and Precautions).
Under treatment with Cyprocur 100, sexual drive and potency are reduced and gonadal function is inhibited. These changes are reversible after discontinuation of therapy.

Dosage and Administration

The maximum daily dose is 300 mg.

Inoperable prostatic carcinoma.

Cyprocur 100 tablets should be taken with some liquid after a meal.

To reduce the initial increase of male sex hormones ('flare') in treatment with luteinising hormone releasing hormone (LHRH) agonists.

Initially 1 Cyprocur 100 tablet twice daily (i.e. 200 mg a day) alone for five to seven days, followed by 1 Cyprocur 100 tablet twice daily (i.e. 200 mg a day) for three to four weeks together with an LHRH agonist in the dosage recommended by the manufacturer.

In long-term palliative treatment of advanced prostate cancer in patients who have not had an orchiectomy.

100 mg (1 Cyprocur 100 tablet) two to three times daily. Treatment should not be interrupted nor the dosage reduced after improvement or remissions have occurred.

To treat hot flushes in patients under treatment with luteinising hormone releasing hormone analogues or who have had orchiectomy.

50 to 150 mg (½ to 1½ tablets) per day with upward titration up to 1 tablet three times daily (300 mg) if necessary.

Children and adolescents.

Cyprocur 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.

Use in the elderly.

There is no data suggesting the need for dosage adjustment in elderly patients.

Patients with hepatic impairment.

The use of Cyprocur is contraindicated in patients with liver diseases.

Patients with renal impairment.

There is no data suggesting the need for dosage adjustment in patients with renal impairment.

Overdosage

There is no clinical experience in overdose. Assessment and symptomatic treatment should be initiated as required.
In cases of overdose, it is advisable to contact the Poisons Information Centre (131 126) for recommendations on the management and treatment of overdose.

Presentation

Tablets (white, capsule shaped, biconvex, marked CPA 100 on one side, scored on reverse: 20's*, 50's (blister pack).
*Not currently marketed in Australia.

Storage

Store below 25°C. Protect from light.

Poison Schedule

S4.