Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about CYPROTERONE AN.

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 CYPROTERONE AN against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine.

You may need to read it again.

What CYPROTERONE AN is used for

CYPROTERONE AN is an antiandrogenic hormone medication.

Androgens such as testosterone are natural male sex hormones. In men, androgens may help cancer cells to grow in some types of prostate cancer. By blocking these hormones, CYPROTERONE AN may slow or stop the growth of cancer.

CYPROTERONE AN may also be used in combination with other medicines or following surgical removal of the testes to treat side effects such as “hot flushes” or “sweats” and to prevent any initial worsening of the disease.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

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

Before You Take CYPROTERONE AN

When you must not take it

Do not take CYPROTERONE AN if you have an allergy to:

• cyproterone acetate, the active ingredient in CYPROTERONE AN
• any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin

Do not take CYPROTERONE AN if you have any of the following medical conditions:

• 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)
• Dubin-Johnson or Rotor syndrome (your doctor would have told you if you have either of these conditions)
• previous or existing benign brain tumour (meningioma)
• wasting disease (a disease causing muscle loss or loss of strength, with the exception of prostate cancer)
• severe and persistent depression
• previous or existing conditions relating to formation of blood clots

CYPROTERONE AN should only be taken by men. It should not be taken by women or children and adolescents below 18 years of age.

CYPROTERONE AN tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking CYPROTERONE AN.

Do not take this medicine after the expiry date printed on the pack and blister.

If it has expired return it to your pharmacist for disposal.

Do not take this medicine if the packaging is torn or shows signs of tampering.

If the packaging is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

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.

For men it is recommended that a sperm count is taken to establish fertility before commencing CYPROTERONE AN. It can take 3-20 months for fertile sperm production to be re-established after stopping this medicine.

The long-term effects of CYPROTERONE AN on female fertility are not known.

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

Taking other medicines

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

Some medicines and CYPROTERONE AN may interfere with each other.

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, an 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 CYPROTERONE AN, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking this medicine.

How to take CYPROTERONE AN

Follow all directions given to you by your doctor and pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

Your doctor will advise of the most suitable dose for you to take. The usual daily dose is 50-300 mg of CYPROTERONE AN. Your doctor may request you take CYPROTERONE AN with other medicines and/or change your dose during treatment.

Do not alter the dose yourself.

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

Shortness of breath may occur at high doses.

How to take it

Swallow the tablets whole with some liquid after meals.

When to take it

Take your medicine after meals at about the same time each day.

Taking it at the same time each day will have the best effect. It will also help you remember when to take it. Missed CYPROTERONE AN tablets may diminish the effectiveness of treatment.

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 have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much CYPROTERONE AN.

Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Keep telephone numbers of these places/services handy.

While you are taking CYPROTERONE AN

Things you must do

If you are about to start taking any new medicines, tell your doctor and pharmacist that you are taking CYPROTERONE AN tablets.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

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 CYPROTERONE AN and whenever any symptoms or signs 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 whilst taking CYPROTERONE AN.

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

Things you must not do

Do not take CYPROTERONE AN 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 CYPROTERONE AN tablets affects you.

This medicine may cause tiredness and can impair the ability to concentrate. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, tiredness and the ability to concentrate may be worse.

Side Effects

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

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

Do not be alarmed by the following lists of side effects.

You may not experience any of them.

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

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

• tiredness, fatigue
• weight change
• headache
• depressive mood
• nausea and other gastrointestinal complaints
• breast pain, change in breast size, breast swelling and/or tenderness
• breast enlargement in men
• hot flushes, sweating
• shortness of breath
• osteoporosis

If you were fertile before treatment, CYPROTERONE AN will normally prevent sperm production in men. In men, fertility is usually regained within a few months of discontinuing therapy.

CYPROTERONE AN will also normally result in the inability to get or maintain an erection (impotence). This ability is usually also regained within a few months of discontinuing therapy.

The above includes the more common side effects of your medicine.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

• yellowing of the skin and/or eyes, light coloured bowel motions, dark coloured urine
• severe upper abdominal pain
• vomiting blood or material that looks like coffee grounds, bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea
• sudden severe headache, loss of vision, loss of coordination, slurred speech, shortness of breath, chest pain, numbness, heat or swelling in the arms and legs

The above list includes serious side effects that may require medical attention or hospitalisation. Serious side effects are rare.

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

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

After taking CYPROTERONE AN

Storage

Keep your tablets in the pack until it is time to take them.

If you take the tablets out of the pack, they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30 °C.

Do not store CYPROTERONE AN or any other medicine in the bathroom, near a sink, or on a window-sill.

Do not leave it in the car.

Heat and damp can destroy some medicines.

Keep it where children cannot reach it.

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 CYPROTERONE AN, or your tablets have passed their expiry date, ask your Pharmacist what to do with any that are left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

CYPROTERONE AN capsule shaped tablets with ‘100’ engraved on one face and a break line on the other face.

CYPROTERONE AN is presented in bottles (AUST R 184234) or blisters (AUST R 184233) containing 50 tablets.

Ingredients

Active Ingredient:
Cyproterone acetate

Other Ingredients:

• Lactose monohydrate,
• Croscarmellose sodium
• Microcrystalline cellulose
• Povidone
• Magnesium stearate.

Name and Address of the Sponsor

Amneal Pharma Australia Pty Ltd
12 River Street
South Yarra 3141
Australia

Date of Preparation
September 2016

Name of the medicine

Cyproterone acetate.

Excipients.

Description

Chemical name: 6-chloro-17-hydroxy-1α, 2 α- methylene-pregna-4,6- diene- 3,20-dione acetate. Molecular formula: C₂₄H₂₉ClO₄. Molecular weight: 416.95. 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.
Each Cyproterone AN 100 mg tablet contains cyproterone acetate 100 mg.
Excipients: lactose monohydrate, povidone, microcrystalline cellulose, croscarmellose sodium and magnesium stearate.
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 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 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.

Distribution.

Metabolism.

Elimination.

Steady-state conditions.

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 Cyproterone AN.

Precautions

Cyproterone AN 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 Cyproterone AN 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, Cyproterone AN should normally be withdrawn unless hepatotoxicity can be explained by another cause, e.g. metastatic disease, in which case Cyproterone AN 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 Cyproterone AN. 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 Cyproterone AN is diagnosed with meningioma, treatment with Cyproterone AN 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 Cyproterone AN treatment (see Contraindications).
A sensation of shortness of breath may occur in individual cases under high dosed treatment with Cyproterone AN. 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 Cyproterone AN 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 AN is prescribed.
During treatment adrenocortical function should be checked regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of Cyproterone AN with high doses.
Anaemia has been reported during treatment with Cyproterone AN. Therefore, the red blood cell count should be checked regularly during treatment.
Cyproterone 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.

Effect on ability to drive or operate machinery.

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.

Cardiovascular.

Gastrointestinal.

Reproductive.

Skin.

Postmarketing information.

Neoplasms benign and malignant.

Blood and lymphatic system disorders.

Immune system disorders.

Metabolism and nutrition disorders.

Psychiatric disorders.

Skin and subcutaneous tissue disorders.

Musculoskeletal and connective tissue disorders.

Hepatobiliary disorders.

Gastrointestinal disorders.

Respiratory, thoracic and mediastinal disorders.

Cardiovascular disorders.

Reproductive system and breast disorders.

General disorders and administration site conditions.

Dosage and Administration

The maximum daily dose is 300 mg.

Inoperable prostatic carcinoma.

Children and adolescents.

Use in the elderly.

Patients with hepatic impairment.

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 100, scored on reverse), 100 mg: 50's (PVC/ PVDC/ aluminium blister pack, AUST R 184233; HDPE bottle with low density PP closures, AUST R 184234).

Storage

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

Poison Schedule

S4.