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 which has several different uses.

Androgens such as testosterone are natural male sex hormones which are also produced, to a slight extent, in females.

MEN
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.

CYPROTERONE AN is also used to reduce abnormal sex drive in men.

WOMEN
In women, androgens may increase hair growth, loss of scalp hair and secretion of oil from the sweat glands. By blocking these hormones, CYPROTERONE AN may slow or stop excessive hairiness, loss of scalp hair, acne, oily skin and dandruff.

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

CYPROTERONE AN should not be taken by children and adolescents below 18 years of age or girls who have not completed puberty.

Do not take this medicine if you are pregnant or suspect you may be pregnant.

It may affect your developing baby if you take it during pregnancy.

Do not breastfeed if you are taking this medicine.

The active ingredient in CYPROTERONE AN passes into breast milk and there is a possibility that your baby may be affected.

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)
• history of jaundice (yellow skin or eyes), herpes or persistent itching during a previous pregnancy
• 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
• severe diabetes with blood vessel changes
• sickle-cell anaemia (your doctor would have told you if you have this)

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 you are pregnant or plan to become pregnant or are breastfeeding.

If taken during pregnancy, CYPROTERONE AN may lead to signs of feminisation in the male foetus.

Therefore, your doctor will check that you are not pregnant before you start taking CYPROTERONE AN.

Women should use a reliable form of contraception while taking CYPROTERONE AN.

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.

Do not alter the dose yourself.

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

MEN:

Prostate cancer
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.

Reduction of abnormal sex drive
Generally treatment is started with 50 mg of CYPROTERONE AN twice daily and may be increased to 100 mg twice daily or three times daily before reducing gradually to the lowest effective dose. Your doctor may change your dose during treatment.

WOMEN:

If you are of childbearing age, you should commence your tablet taking on the 1st day of your cycle (= 1st day of bleeding). If you have no menstrual periods (amenorrhoea) your treatment can start immediately. In this case, the first day of treatment is to be regarded as the 1st day of the cycle.

Starting from day 1 take 50-100 mg (as advised by your doctor) of CYPROTERONE AN daily from the 1st to the 10th day of the cycle (= for 10 days). Additionally, your doctor will advise the most appropriate contraceptive for you to take to provide the necessary contraceptive protection and to stabilise your cycle.

If you are postmenopausal or have had a hysterectomy, CYPROTERONE AN may be administered alone. The usual dose is 25-50 mg of CYPROTERONE AN once daily for 21 days, followed by a 7-day tablet-free interval.

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 and may lead to breakthrough bleeding in women.

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 also taking an oral contraceptive and more than 12 hours has elapsed from the time CYPROTERONE AN was due to be taken, note that contraceptive protection in this cycle may be reduced and thus there is an increased risk of becoming pregnant.

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.

If you are a female taking an oral contraceptive during treatment, tell your doctor if your period does not occur during the tablet-free/ placebo interval.

Your doctor may need to check whether you are pregnant before you can continue treatment.

If you are a male taking CYPROTERONE AN to reduce abnormal sex drive, you should consider additional measures such as therapy or counselling in order to take advantage of the period of reduced drive.

These measures may assist in achieving personal and social re-orientation.

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. The effectiveness of CYPROTERONE AN to reduce abnormal sex drive can also be diminished under the influence of alcohol.

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
• decreased sexual drive
• breast pain, change in breast size, breast swelling and/or tenderness
• breast enlargement in men
• menstrual cycle irregularity, spotting
• hot flushes, sweating
• shortness of breath
• osteoporosis

If you were fertile before treatment, CYPROTERONE AN will normally prevent sperm production in men and ovulation in women. In men, fertility is usually regained within a few months of discontinuing therapy. The long term effects on female fertility are not known.

In men 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 are white round tablets engraved 50 with a break line on one side, plain on the other side.

CYPROTERONE AN is presented in bottles (AUST R 184227) or blisters (AUST R 184226) containing either 20 tablets or 50 tablets.

Ingredients

Active Ingredient:

Cyproterone acetate

Other Ingredients:

• Lactose monhydrate,
• 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, 2α-methylene-pregna- 4,6- diene-3,20- dione acetate. Molecular formula: C₂₄H₂₉ClO₄. MW: 416.95. CAS: 427-51-0.

Pharmacology

Following oral administration, cyproterone acetate is absorbed slowly. Its bioavailability is unknown. The maximum plasma level is reached 3 to 4 hours after ingestion.
Cyproterone acetate is eliminated with a half-life of 38 ± 5 h. After 10 days, 33 ± 6 of the dose can be demonstrated in the urine and 60 ± 8% in the faeces. Cyproterone acetate is eliminated with the urine mainly in the form of unconjugated metabolites and with the bile in the form of glucuronidized metabolites, the main one being 15 β-hydroxy-cyproterone acetate.
Radioimmunoassays show that about 0.2% of the dose is eliminated with the breast milk. Cyproterone AN is an antiandrogenic hormone preparation. Cyproterone acetate is believed to prevent the effect of endogenously produced and exogenously administered androgens at the target organs by means of competitive inhibition. The stimulating effect of male sex hormones on androgen dependent structures and functions is weakened or counteracted by cyproterone acetate.
Cyproterone acetate also exerts a progestational and antigonadotropic effect. 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 function of androgen dependent target organs, such as the prostate, is restricted.
Prostatic carcinoma and its metastases are in general androgen dependent. Cyproterone AN exerts a direct antiandrogenic action on the tumour and its metastases and in addition it exerts a negative feedback effect on the hypothalamic receptors, so leading to a reduction in gonadotropin release, and hence to diminished production of testicular androgens.
In women, hirsutism is diminished, but also androgen dependent loss of scalp hair and elevated sebaceous gland function are reduced. During the treatment ovarian function is inhibited.

Indications

Women.

Men.

Contraindications

Pregnancy, lactation, liver diseases, a history of existing hepatic tumours (in carcinoma of the prostate only if these are not due to metastases), a history of jaundice or persistent itching during a previous pregnancy, a history of herpes of pregnancy, Dubin-Johnson syndrome, Rotor syndrome, wasting diseases (with the exception of carcinoma of the prostate), severe chronic depression, previous or existing thromboembolic processes, severe diabetes with vascular changes, sickle cell anaemia. Hypersensitivity to the active substance or to any of the excipients.
In patients with prostatic carcinoma presenting with a history of thromboembolic processes or suffering from sickle cell anaemia or from severe diabetes with vascular changes, the risk: benefit ratio must be considered carefully in each individual case before Cyproterone AN is prescribed.
Cyproterone AN should 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.

Precautions

Before the start of therapy, a thorough general medical and gynaecological examination (including the breasts and a cytological smear of the cervix) should be carried out in women. Serious organic causes of androgenisation, e.g. Cushing's syndrome, ovarian tumours, adrenal carcinoma and adrenogenital syndrome should be excluded. Pregnancy must be excluded at the time of commencing in women of child bearing potential. The long-term effects on female fertility are not known with certainty.
If, during the combined treatment, slight ‘unscheduled’ bleeding occurs during the 3 weeks per cycle in which the tablets are being taken; tablet taking should not be interrupted. However, if the bleeding is heavy, the patient should consult her doctor.
It should be pointed out to patients whose occupation demands great concentration (e.g. road users, machine operators) that Cyproterone AN can lead to tiredness and diminished vitality and can impair the ability to concentrate.
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.
The sexual drive reducing effect can be diminished under the disinhibitory influence of alcohol.
During treatment liver function, adrenocortical function and red blood cell count should be checked regularly. In diabetics, carbohydrate metabolism should be monitored carefully. The requirement for oral antidiabetics or insulin can change.
Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure, which have been fatal in some cases, has been reported in patients treated with 200-300 mg cyproterone acetate. Most reported cases are in men with prostatic cancer. Toxicity is dose related and develops, usually, several months after treatment has begun. Liver function tests should be performed pretreatment and when ever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, cyproterone should normally be withdrawn, unless hepatotoxicty 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.
In rare cases benign and even in rarer cases malignant liver tumours leading in isolated cases to life threatening intra-abdominal haemorrhage have been observed after the use of hormonal steroids. 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.
A sensation of shortness of breath may occur in individual cases under high dose 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 compensated respiratory alkalosis and which is not considered to require treatment.
In extremely rare cases, the occurrence of thromboembolic events has been reported in temporal association with the use of Cyproterone AN. However, a casual relationship seems to be questionable.
The following additional information is applicable to use of all cyclic combined oestrogen/ progesterone therapies, including oral contraceptives.
Use of combined oestrogen/ progesterone medication may be associated with an increased risk of thromboembolism, stroke and myocardial infarction, increasing over the age of 30 and further increased by cigarette smoking, hypertension, obesity, diabetes, hypercholesterolaemia, or a history of pre-eclamptic toxaemia. This risk of myocardial infarction is substantially increased in women aged 40 and over. All users of combined oestrogen/ progesterone medications should be encouraged not to smoke.
Therapy should be discontinued if feasible at least 6 weeks prior to elective surgery of a kind associated with increased risk of embolism and during any period of prolonged immobilisation.
Optic neuritis and retinal thrombosis have been reported in association with combined oestrogen/ progestogen treatment. Discontinue medication pending examination if there is unexplained sudden partial or complete loss of vision, sudden onset of protosis, diplopia or migraine. If examination reveals papilloedema or retinal vascular lesions medication should be withdrawn.
Susceptible women may experience a rise in blood pressure. The prevalence of hypertension increases with the duration of use and the age of the patient. Blood pressure should be measured and care should be exercised in prescribing these preparations for patients with hypertension.
Regular monitoring of blood pressure is desirable.
The first spontaneous ovulation after stopping combined oestrogen/ progestogen treatment is sometimes delayed; and there is evidence of temporary impairment of fertility in some women who discontinue combined oestrogen/ progestogen treatment, which appears to be independent of the duration of use. Impairment diminishes with time, but may be evident for up to 30 months after cessation in nulliparous women. It should be suggested to patients who decide to become pregnant that alternative methods of contraception be used until they have their first spontaneous period, so that the estimated date of delivery may be made with more certainty.
Women with a strong family history of breast cancer, or have breast nodules, fibrocystic disease or abnormal mammograms, should be monitored with particular care after they elect to use combined oestrogen/ progestogen treatment.
Epidemiological studies report doubling of the risk of gall bladder disease in combined oestrogen/ progestogen treatment users of two or more years. The onset or exacerbation of migraine or other persistent severe headache requires full discontinuation of combined oestrogen/ progestogen treatment pending full investigation.
Contraceptive efficacy may be impaired by drug interactions especially rifampicin, semisynthetic penicillins and anticonvulsant drugs; and also by severe diarrhoea, or by vomiting shortly after the ingestion of a tablet.
Before prescribing combined oestrogen/ progestogen treatment a complete history and physical examination is desirable, with particular reference to blood pressure, breasts, abdomen and pelvic organs. A Papanicolaou smear and urinalysis should be carried out.
Combined oestrogen/ progestogen treatment may cause some degree of fluid retention. Care is therefore necessary in those who may be aggravated, especially cardiac and renal insufficiency, migraine and asthma. Patients should be warned that vulvovaginal monilial infection may occur or recur, and of the need for appropriate treatment.

Carcinogenicity and mutagenicity.

Use in pregnancy.

Use in lactation.

Effects on laboratory tests.

Adverse Effects

Over the course of several weeks, Cyproterone AN gradually impairs spermatogenesis. In male patients, Cyproterone AN occasionally leads to gynaecomastia (sometimes combined with tenderness to touch of the breast), which usually regresses after withdrawal of the preparation or reduction of the dose.
In women ovulation is inhibited under the combined treatment so that a state of infertility exists.
In individual cases, disturbances of the liver function, some of them severe, have been reported with high dose Cyproterone AN treatment.
The following adverse reactions have been reported in clinical trials: diminished libido 16%, tiredness 13.5%, increase in bodyweight 11%, mastodynia 8%, nausea and other gastrointestinal complaints 7.4%, cycle irregularity 4%, headache 3.3%, depressive moods 3%, thrombotic phenomena 1.2%.
Other adverse reactions reported at low incidence are: galactorrhoea, sleep disturbances, hot flushes, tachycardia, dysmenorrhoea, vaginal discharge, skin discolouration, striae, allergic reactions, increased libido.

Dosage and Administration

Women.

Use of all cyclic combined oestrogen/ progesterone therapies, including oral contraceptives.

Women of childbearing potential.

Postmenopausal or hysterectomised women.

Men.

Reduction in the drive of sexual deviation.

Inoperable prostatic carcinoma.

Presentation

Tablets (white, round, flat, bevelled, marked 50 over a breakline, plain on reverse), 50 mg (PVC/ PVDC/ aluminium blister pack (AUST R 184226), HDPE bottle with a low density PP closure pack (AUST R 184227)).

Storage

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

Poison Schedule

S4.