Consumer medicine information

What is in this leaflet

This leaflet answers some of the common questions about CYPROCUR 50 tablets.

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

All medicines have risks and benefits. Your doctor has weighed the risks of you taking CYPROCUR 50 tablets 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 the medicine. You may need to read it again.

What CYPROCUR 50 tablets are used for

CYPROCUR 50 tablets are an anti-androgenic hormone medication containing the active ingredient cyproterone acetate, which is used to 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.

Androgenic hormones are generally required for cancer of the prostate gland to grow.

CYPROCUR 50 tablets work in two ways. Firstly, they stop the androgenic hormones (testosterone) present in your body from being able to attach to the cancer cells. Secondly, they decrease the amount of androgen hormone present in your blood stream by an effect on the hormonal mechanisms that control androgen production by the body.

CYPROCUR 50 tablets can also be used to reduce the sex drive of men with sexual deviations.

It is also used in the treatment of women who have a problem with facial or chest hair, are balding or have severe acne.

CYPROCUR 50 tablets are only available on a doctor's prescription.

There is no evidence that this medicine is addictive.

Before you take it

When you must not take it

Do not take CYPROCUR 50 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 this medicine if you are pregnant. CYPROCUR 50 tablets should not be taken during pregnancy as it may lead to the development of female characteristics in male babies.
Your doctor should carry out a thorough gynaecological and medical examination before starting treatment to exclude pregnancy.

Female patients should be aware that the long term effects of CYPROCUR 50 tablets on fertility are not known.

Do not take this medicine if you are breast feeding.

Do not give CYPROCUR 50 tablets to children.

Do not take CYPROCUR 50 tablets 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:

• are pregnant or breastfeeding
• have a history of herpes of pregnancy
• have liver disease. Your doctor should perform a blood test to check your liver before starting you on CYPROCUR 50 tablets and again if liver disease is suspected
• suffer from or have a history of jaundice or persistent itching during a previous pregnancy
• have ever suffered from blood clots in the leg, stroke or heart attack
• have severe diabetes that has damaged your blood vessels
• have sickle-cell anaemia
• have hypertension
• have suffered from severe chronic depression
• have Dubin-Johnson syndrome or Rotor syndrome.

For males, tell your doctor if fertility after treatment is important. In this case, it is advisable to have a sperm count before taking CYPROCUR 50 to establish your fertility before commencing therapy, as this medicine can cause a decrease in sperm count. It may take between 3 to 20 months for the sperm count to return to normal once therapy has been stopped.

If you have not told your doctor about any of the above, tell them before you start taking CYPROCUR 50 tablets.

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 interfere with CYPROCUR 50 tablets. These include:

• penicillins (antibiotic).
• rifampicin (antibiotic).
• anticonvulsants, medicines used to treat fits.

These medicines may be affected by CYPROCUR 50 tablets or may affect how well it works.

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

How to take it

Follow all directions given to you by your doctor.

How much to take

Your initial dose will depend on the condition being treated and your response to the medicine. Your doctor may gradually reduce the dose for maintenance therapy.

How to take it

Swallow the tablet, with some liquid, after meals.

If you forget to take it

If it is almost time to take your next dose, skip the dose that you have missed and take your next dose when you are meant to. Otherwise take it as soon as you remember, then go back to taking your tablets as usual.

Do not double a dose to make up for a dose that you have missed. This may increase the chance of you getting an unwanted side effect.

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 your nearest hospital, if you think that you or anyone else may have taken too many CYPROCUR 50 tablets.

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

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 50, especially if you are starting any new medicines.

Keep all of your doctor’s appointments so that your progress can be checked. You may be required to have regular tests for liver, blood or other body functions.

Female patients who have a family history of breast cancer and are taking the combined CYPROCUR 50 tablets/ ethinyloestradiol treatment should have regular breast examinations.

Things you must not do

Do not take CYPROCUR 50 tablets to treat any other medical complaints unless your doctor tells you to.

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

Things to be careful of

Be careful driving or operating machinery until you know how it affects you. CYPROCUR 50 tablets may cause drowsiness and loss of concentration in some people.

If you are taking CYPROCUR 50 tablets to reduce your sex drive, alcohol may stop CYPROCUR 50 tablets from working as well as it should.

Female patients should not smoke whilst taking combined CYPROCUR 50 tablets/ ethinyloestradiol treatment.

Female patients should be aware that the contraceptive action of the combined treatment of CYPROCUR 50 tablets and ethinyloestradiol may be reduced by diarrhoea or vomiting shortly after taking a tablet. In these cases, an additional form of contraception such as a diaphragm or condom should be used for the remainder of the cycle.

In women taking combined CYPROCUR 50 tablets/ ethinyloestradiol treatment, if light bleeding or spotting occurs during the 3 weeks in which the tablets are being taken, do not stop taking your tablets.

However, if bleeding is heavy, consult your doctor immediately.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking CYPROCUR 50. All medicines can have side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

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

The most common side effect is tiredness and loss of concentration which may affect your ability to drive or operate machinery.

CYPROCUR 50 tablets may occasionally result in gynaecomastia (swelling of the breast area which is sometimes also associated with tenderness or sensitivity of the breast area to touch), diminished libido, changes in body weight, nausea, allergy, depressive moods, headache, shortness of breath and blood clotting (which may lead to a clot on the lungs, stroke or heart attack) and increase in blood pressure in women.

In males, if you were fertile before treatment, CYPROCUR 50 may also result in your inability to produce sperm (infertility). Fertility is usually regained within a few months of discontinuing therapy. This medicine 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.

Yellowing of the skin/eyes, darkening of the urine and abdominal pain or swelling should be all reported immediately to your doctor.

In very rare cases, liver tumours may lead to life-threatening bleeding into the stomach. You must inform your doctor of the occurrence of unusual upper abdominal complaints which do not disappear spontaneously within a short time.

Tell your doctor 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 CYPROCUR 50 tablets in a cool dry place 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 50 tablets or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. 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 the tablets or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets left over.

Product description

What it looks like

CYPROCUR 50 are white, round tablets with a break line on one side.

Available in packs of 20 or 50 tablets.

Ingredients

Active ingredient:
Each CYPROCUR 50 tablet contains 50 mg of cyproterone acetate.

Inactive ingredients:

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

CYPROCUR 50 tablets do not contain gluten, sucrose, tartrazine or any other azo dyes.

Sponsor

Aspen Pharma Pty Ltd
34-36 Chandos St
St Leonards, NSW 2065

Australian registration number: AUST R 178007.

This leaflet was revised in November 2011.

Published by MIMS July 2014

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: C₂₄H₂₉CIO₄. 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.
Cyprocur 50 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. Cyprocur 50 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 Cyprocur 50 is prescribed.
Cyprocur 50 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 Cyprocur 50 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 Cyprocur 50. 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 Cyprocur 50. However, a causal 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 penicillin's 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, Cyprocur 50 gradually impairs spermatogenesis. In male patients, Cyprocur 50 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 Cyprocur 50 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, circular, flat, bevelled, scored on one side, plain on reverse), 50 mg: 20's, 50's.

Storage

Store below 25°C.

Poison Schedule

S4.