Consumer medicine information

Androcur

Cyproterone acetate

BRAND INFORMATION

Brand name

Androcur

Active ingredient

Cyproterone acetate

Schedule

SUMMARY CMI

ANDROCUR^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Androcur?

Androcur contains the active ingredient cyproterone acetate. In men, Androcur is used for reduction of sex drive in cases of sexual deviations in men, as well as for antiandrogen treatment in inoperable prostate cancer. In women, Androcur is used to slow or stop moderately severe to severe signs of androgenisation such as excessive hairiness, loss of scalp hair, acne, oily skin and dandruff.

For more information, see Section 1. Why am I using Androcur? in the full CMI.

2. What should I know before I take Androcur?

Do not use if you have ever had an allergic reaction to cyproterone acetate or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I take Androcur? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Androcur and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take Androcur?

In men, for prostate cancer, the usual daily dose is 50-300 mg of Androcur. In women, the dose is 50-100 mg of Androcur daily from the 1^st to the 10^th day of the cycle. Your doctor will advise of the most suitable dose for you to take. Follow all directions given to you by your doctor or pharmacist carefully.

More instructions can be found in Section 4. How do I take Androcur? in the full CMI.

5. What should I know while taking Androcur?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using Androcur. Your doctor may do liver function tests and red-blood cell count to make sure the medicine is working and to prevent unwanted side effects. Tell your doctor if you have diabetes
Things you should not do	Do not stop using this medicine suddenly or lower the dosage without checking with your doctor. Do not take Androcur to treat any other complaints unless your doctor tells you to
Driving or using machines	Be careful driving or operating machinery until you know how Androcur affects you. This medicine may cause tiredness and can impair the ability to concentrate.
Drinking alcohol	Be careful when drinking alcohol while you are taking this medicine. If you drink alcohol, tiredness and the ability to concentrate may be worse. Alcohol may prevent Androcur from working as well as it should in reducing abnormal sex drive.
Looking after your medicine	Keep your tablets in a cool dry place where the temperature stays below 30°C. Do not store Androcur or any other medicine in the bathroom, near a sink, or on a window-sill. Keep your tablets in the pack until it is time to take them

For more information, see Section 5. What should I know while taking Androcur? in the full CMI.

6. Are there any side effects?

The serious side effects include 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, hearing loss, memory loss, seizures and weakness in the arms or legs.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

ANDROCUR^® (ANNE-dro-cur)

Active ingredient(s): cyproterone acetate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Androcur. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Androcur.

Where to find information in this leaflet:

1. Why am I using Androcur?
2. What should I know before I take Androcur?
3. What if I am taking other medicines?
4. How do I take Androcur?
5. What should I know while taking Androcur?
6. Are there any side effects?
7. Product details

1. Why am I using Androcur?

Androcur contains the active ingredient cyproterone acetate. Androcur is an antiandrogen medicine. It works by blocking the effect of androgens, which are natural sex hormones produced mainly in males but are also produced, to a slight extent, in females.

In men, androgens may help cancer cells to grow in some types of prostate cancer. By blocking these hormones, Androcur may slow or stop the growth of cancer. Androcur 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.

Androcur is also used to reduce abnormal sex drive in men.

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

2. What should I know before I take Androcur?

Warnings

Do not take Androcur if:

you are allergic to cyproterone acetate, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
Do not use Androcur 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 (your doctor would have told you if you have this)
- sickle-cell anaemia (your doctor would have told you if you have this)

Check with your doctor if you:

have any other 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)
take any medicines for any condition
have an intolerance to some sugars, Androcur tablets contains lactose monohydrate
have any allergies to any other medicines, foods, preservative or dyes

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

If taken during pregnancy, Androcur may lead to signs of feminisation in the male foetus. Therefore, your doctor will check that you are not pregnant before you start taking Androcur. Women should use a reliable form of contraception while taking Androcur.

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 Androcur passes into breast milk and there is a possibility that your baby may be affected.

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 Androcur. It can take 3-20 months for fertile sperm production to be re-established after stopping this medicine.
The long-term effects of Androcur on female fertility are not known.

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

3. What if I am taking other medicines?

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

Some medicines may interfere with Androcur and affect how it works.

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

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Androcur.

4. How do I take Androcur?

How much to take

Follow the instructions provided and take Androcur until your doctor tells you to stop.

MEN:

For Prostate cancer, the dose is 50-300 mg of Androcur. Your doctor may request you take Androcur with other medicines and/or change your dose during treatment.
For Reduction of abnormal sex drive, generally treatment is started with 50 mg of Androcur 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 1^st day of your cycle (= 1^st 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 1^st day of the cycle.
Starting from day 1 take 50-100 mg (as advised by your doctor) of Androcur daily from the 1^st to the 10^th 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.
Your doctor will re-evaluate your treatment when you reach menopause. Long-term use (years) of Androcur should be avoided.
If you are postmenopausal or have had a hysterectomy, Androcur may be administered alone. The usual dose is 25-50 mg of Androcur once daily for 21 days, followed by a 7-day tablet-free interval.
Shortness of breath may occur at high doses.

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

When to take Androcur

Androcur should be taken whole, with some liquid after meals.
Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

Missed Androcur tablets may diminish the effectiveness of treatment and may lead to breakthrough bleeding in women.

If you forget to take Androcur

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 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 Androcur 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 take too much Androcur

If you think that you have used too much Androcur, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking Androcur?

Things you should do

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 Androcur 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 Androcur.
Your doctor will also check your red-blood cell count to ensure you do not become anaemic during treatment with Androcur.
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 Androcur to reduce abnormal sex drive, you should consider undertaking 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.

Remind any doctor, dentist or pharmacist you visit that you are using Androcur.

Things you should not do

Do not stop using this medicine suddenly or lower the dosage without checking with your doctor.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Androcur affects you.

Androcur 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.

Drinking alcohol

Tell your doctor if you drink alcohol.

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

Alcohol may prevent Androcur from working as well as it should in reducing abnormal sex drive.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects	What to do
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	Speak to your doctor if you have any of these less serious side effects and they worry you.

If you were fertile before treatment, Androcur 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 Androcur 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.

Serious side effects

Serious side effects

What to do

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

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Use of cyproterone acetate has been linked to the development of meningioma (generally benign tumour). The risk increases when used for several years, or with high doses (25 mg per day and above).

Serious side effects	What to do
changes in vision (e.g. seeing double or blurriness), hearing loss or ringing in the ears, loss of smell, headaches that worsen with time, memory loss, seizures, weakness in your arms or legs	Call your doctor straight away, if you notice any of these serious side effects.

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

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Androcur contains

Active ingredient (main ingredient)	cyproterone acetate
Other ingredients (inactive ingredients)	corn starch povidone magnesium stearate aerosil
Potential allergens	lactose monohydrate

Do not take this medicine if you are allergic to any of these ingredients.

What Androcur looks like

Androcur 50 mg tablets are white, round tablets, scored on one side with “BV” marking in a hexagon on the other side, presented in blisters containing 50 tablets.

Australian registration number

AUST R 156920

Who distributes Androcur

Amdipharm Mercury (Australia) Pty Ltd
Level 9, 76 Berry Street
North Sydney NSW 2060

Ph: 1800 627 680

Amdipharm Mercury (Australia) Pty Ltd is an ADVANZ PHARMA company

This leaflet was prepared in November 2024.

Published by MIMS February 2025

BRAND INFORMATION

Brand name

Androcur

Active ingredient

Cyproterone acetate

Schedule

1 Name of Medicine

Cyproterone acetate.

2 Qualitative and Quantitative Composition

Androcur 50 mg tablets.

Each Androcur 50 mg tablet contains 50 mg cyproterone acetate.

Excipients with known effect.

Sugars as lactose monohydrate.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Androcur 50 mg tablets.

Round, white, scored tablets marked with "bv" inside a hexagon.

4 Clinical Particulars

4.1 Therapeutic Indications

Women.

Moderately severe to severe signs of androgenisation.

Moderately severe/ severe forms of hirsutism;
moderately severe/ severe androgen dependent loss of scalp hair (moderately severe/ severe androgenic alopecia);
moderately severe/ severe forms of acne and/or seborrhoea associated with other features of androgenisation.
Cyproterone acetate inhibits the influence of male sex hormones which are also produced by the female. It is thus possible to treat diseases in women caused either by increased production of androgens or a particular sensitivity to these hormones. Hirsutism and alopecia may be expected to recur over a period of time after cessation of treatment.
If Androcur is taken during pregnancy, the properties of the preparation may lead to signs of feminisation in the male foetus. Therefore, in women of childbearing potential, pregnancy must be excluded at the commencement of treatment and ethinyloestradiol taken as well to ensure contraception. This also promotes regular menstruation.

Men.

Reduction of drive in sexual deviations.

Androcur reduces the force of the sexual urge in men with sexual deviations. Whilst under treatment the man can control himself better in a predisposing stimulatory situation, but there is no influence on any deviating direction of sexual drive. Abnormal patterns of sexual behaviour require treatment when they are distressing to the patient. A prerequisite for therapy is the desire by the patient for treatment.
Androcur therapy should be supplemented by psychotherapeutic and sociotherapeutic measures in order to exploit the period of reduced drive for personal and social reorientation.

Inoperable prostatic carcinoma.

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

4.2 Dose and Method of Administration

Androcur tablets should be taken with some liquid after a meal.

Women.

Pregnant women must not take Androcur. Therefore, pregnancy must be excluded before the start of therapy.
In women of childbearing potential, the treatment is commenced on the 1st day of the cycle (= 1st day of bleeding). Only women with amenorrhoea or menstrual bleeding at very irregular intervals can start treatment immediately. In this case the first day of treatment is to be regarded as the 1st day of the cycle and the following recommendations then observed as normal.
For hirsutism secondary to female androgenisation; the usual starting dose should be 1 tablet of Androcur 50 mg taken daily for 10 days per month (from the 1st to the 10th day of the cycle). Once a satisfactory response has been attained it is usually possible to reduce the dose further. Doses as low as 10 mg a day for 10 days per month have been shown to be adequate for maintenance therapy in this condition.
For other severe signs of androgenisation; 2 tablets of Androcur 50 mg are to be taken daily, from the 1st to the 10th day of the cycle (= for 10 days).
In addition, these women should receive a progestogen/ oestrogen containing preparation to provide the necessary contraceptive protection and to stabilise the cycle. An appropriate combined oral contraceptive preparation should be commenced on day 1 of the cycle as directed.
Women receiving the cyclical combined therapy should keep to a particular time of the day for tablet taking. If more than 12 hours elapse from this time, contraceptive protection in this cycle may be reduced. Attention is drawn to the special notes (especially on contraceptive reliability and to the missed tablet recommendations) in the product information for the combined oral contraceptive preparation being taken in conjunction with Androcur. If bleeding fails to occur after this cycle, pregnancy must be excluded before tablet taking is resumed.
Missed Androcur tablets may diminish the therapeutic efficacy and may lead to intermenstrual bleeding. The missed Androcur tablet should be disregarded (no double dose should be taken to make up for the missed tablet) and tablet taking resumed at the regular time together with the combined oral contraceptive preparation.
A withdrawal bleeding usually occurs during the tablet free interval or whilst taking the 7 day placebo tablets. Exactly 4 weeks after the first course of treatment was started, i.e. on the same day of the week, the next cyclical course of combined treatment is started, regardless of whether bleeding has stopped or not. If no bleeding occurs during the tablet free or 7 day placebo tablet interval, the possibility of pregnancy must be excluded before restarting tablet taking.
Following clinical improvement, the daily dose of Androcur 50 mg may be reduced to 1 or 1/2 tablet during the 10 days on which it is given in each treatment cycle. The dose regimen for the combined oral contraceptive preparation remains unchanged. Re-evaluate the treatment with Androcur 50 mg at the start of the menopause. Long-term use (years) of Androcur 50 mg should be avoided (see Section 4.4 Special Warnings and Precautions for Use, Meningioma).
In postmenopausal or hysterectomised patients, Androcur may be administered alone. According to the severity of the complaints, the average dose should be 1/2 to 1 tablet Androcur 50 mg once daily for 21 days, followed by a 7 day tablet free interval.
The length of treatment depends on the severity of the pathological signs of androgenisation and response to treatment. Treatment is usually carried out over several months initially. Acne and seborrhoea usually respond sooner than hirsutism or alopecia. Hirsutism and alopecia are likely to recur when treatment is stopped.

Men.

The maximum daily dose is 300 mg.
Reduction of drive in sexual deviations. The individual dose will be determined by the response. Generally, treatment is started with one 50 mg tablet twice daily. It may be necessary to increase the dose to two 50 mg tablets twice daily, or even two 50 mg tablets three times daily for a short period of time. The duration of cyproterone acetate treatment should be defined on an individual basis. If a satisfactory result is achieved, the therapeutic effect should be maintained with the lowest possible dose. Quite often 1/2 tablet twice daily is sufficient. When establishing the maintenance dose or when discontinuing the preparation, the dosage should not be reduced abruptly, but gradually.
To this end, the daily dose should be reduced by 1 tablet, or better 1/2 tablet, at intervals of several weeks.
To stabilise the therapeutic effect it is necessary to take Androcur over a protracted period of time, if possible with the simultaneous use of psychotherapeutic measures.
Inoperable prostatic carcinoma.

To reduce the initial increase of male sex hormones ('flare') in treatment with LH-RH agonists.

Initially 100 mg (2 tablets Androcur 50 mg) twice daily alone for 5-7 days, then 100 mg (2 tablets Androcur 50 mg) twice daily for 3-4 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 (2 tablets Androcur 50 mg) 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 LH-RH analogues or who have had orchiectomy.

50 mg once to three times daily with upward titration to 100 mg three times daily if necessary.

Paediatric use.

Androcur is not recommended for use in female patients before conclusion of puberty. There are no data suggesting the need for dosage adjustment in female patients who have completed puberty.
Androcur 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.
Androcur must not be given before the conclusion of puberty since an unfavourable influence on longitudinal growth and the still unstabilised axes of endrocine function cannot be ruled out.

Use in the elderly.

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

Patients with hepatic impairment.

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

Patients with renal impairment.

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

4.3 Contraindications

Contraindications in women.

Pregnancy.
Lactation.
Liver diseases.
Dubin-Johnson syndrome, Rotor syndrome.
History of jaundice or persistent pruritus during a previous pregnancy.
History of herpes of pregnancy.
Previous or existing liver tumours.
Presence or history of meningioma.
Wasting diseases.
Severe chronic depression.
Previous or existing thromboembolic processes.
Severe diabetes with vascular changes.
Sickle cell anaemia.
Hypersensitivity to any of the components of Androcur.
With regard to the cyclical combined therapy of severe signs of androgenisation, attention is also drawn to the data on contraindications contained in the product information for the progestogen-oestrogen containing preparation used in addition to Androcur.

Contraindications in men.

Reduction of drive in sexual deviations.

Liver diseases.
Dubin-Johnson syndrome, Rotor syndrome.
Previous or existing liver tumours.
Presence or history of meningioma.
Wasting diseases.
Severe chronic depression.
Previous or existing thromboembolic processes.
Severe diabetes with vascular changes.
Sickle cell anaemia.
Hypersensitivity to any of the components of Androcur.

Inoperable carcinoma of the prostate.

Liver diseases.
Dubin-Johnson syndrome, Rotor syndrome.
Previous or existing liver tumours (only if these are not due to metastases from carcinoma of the prostate).
Presence or history of meningioma.
Wasting diseases (with the exception of inoperable carcinoma of the prostate).
Severe chronic depression.
Existing thromboembolic processes.
Hypersensitivity to any of the components of Androcur.
Androcur 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.

4.4 Special Warnings and Precautions for Use

During treatment liver function, adrenocortical function and red blood cell count should be checked regularly.
The long-term effects on female fertility are not known with certainty.
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.
As with other antiandrogenic treatments, in male patients long-term androgen deprivation with Androcur may lead to osteoporosis.

Use in hepatic impairment.

Liver.

Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure has been observed in patients treated with cyproterone acetate. At dosages of 100 mg and above, cases with fatal outcome have been reported. Most reported fatal cases were in men with advanced carcinoma of the prostate. Toxicity is dose related and develops, usually, several months after treatment has begun. Liver function tests should be performed pretreatment, at regular intervals during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, Androcur should be withdrawn, unless hepatotoxicity can be explained by another cause, e.g. metastatic disease, in which case Androcur should be continued only if the perceived benefit outweighs the risk.
Cases of benign and malignant liver tumours which may lead to life threatening intra-abdominal haemorrhage have been observed after the use of Androcur. 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.

Meningioma.

The occurrence of meningiomas (single and multiple) has been reported in association with long-term use (years) of cyproterone acetate at doses of 25 mg/day and above. The risk of meningioma increases with increasing cumulative doses of cyproterone acetate. If a patient treated with Androcur is diagnosed with meningioma, treatment with cyproterone containing products, including Androcur must be permanently stopped (see Section 4.3 Contraindications).

Diabetes.

Strict medical supervision is necessary if the patient suffers from diabetes because the requirement for oral antidiabetics or insulin can change during Androcur treatment (see Section 4.3 Contraindications).

Shortness of breath.

A sensation of shortness of breath may occur under high dosed treatment with Androcur. 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.

Thromboembolic events.

The occurrence of thromboembolic events has been reported in patients using Androcur 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.

Adrenocortical function.

During treatment adrenocortical function should be checked regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of Androcur with high doses.

Anaemia.

Anaemia has been reported during treatment with Androcur. Therefore, the red blood cell count should be checked regularly during treatment.

Other conditions.

Androcur tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Specifically to be observed in women.

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. 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 treatment in women of childbearing potential. If, during the combined treatment, spotting occurs during the 3 weeks in which the tablets are being taken, tablet taking should not be interrupted. However, if persistent or recurrent bleeding occurs at irregular intervals, a gynaecological examination must be carried out to exclude organic diseases.
With regard to the additional use of a combined oral contraceptive preparation, attention is drawn to all the data contained in the product information for this product.

Specifically to be observed in men.

The sexual drive reducing effect of Androcur can be diminished under the influence of alcohol.
In patients with inoperable carcinoma of the prostate presenting 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 Androcur is prescribed.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The requirement for oral antidiabetics or insulin can change.
Although clinical interaction studies have not been performed, since this drug is 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 may reduce the levels of cyproterone acetate.
The risk of statin associated myopathy or rhabdomyolysis may be increased when those HMG-CoA inhibitors (statins), which are primarily metabolised by CYP3A4, are coadministered with high therapeutic cyproterone acetate doses since they share the same metabolic pathway.
Based on in vitro CYP450 studies, the recommended clinical doses are likely to inhibit CYP2C8, and an inhibition of the CYP2C9, 2C19, 3A4, and 2D6 is also possible at high therapeutic cyproterone acetate doses of 3 times 100 mg per day.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties.
(Category D)
The use of Androcur is contraindicated during pregnancy (also see Section 4.3 Contraindications).
Administration of cyproterone acetate during the hormone sensitive differentiation phase of the genital organs (after approx. day 45 of pregnancy) could lead to signs of feminisation in male fetuses.
The use of Androcur is contraindicated during lactation, as small amounts of cyproterone acetate are excreted in human milk (see Section 4.3 Contraindications).

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Adverse 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 ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000.

General.

Very common: tiredness, weight increase.
Common: headache, depressive moods.

Cardiovascular.

Common: thrombotic phenomena.

Gastrointestinal.

Common: nausea and other gastrointestinal complaints.

Reproductive.

Very common: diminished libido.
Common: mastodynia, irregular menstrual cycles.

Skin.

Rare: rash.
The most commonly reported adverse drug reactions (ADRs) in female patients receiving Androcur are spotting, weight increase and depressed mood.
The most frequently observed ADRs in male patients receiving Androcur are decreased libido, erectile dysfunction and reversible inhibition of spermatogenesis.
The most serious ADRs in patients receiving Androcur are hepatic toxicity, benign and malignant liver tumours which may lead to intra-abdominal haemorrhage, and thromboembolic events.
Over the course of several weeks, Androcur gradually impairs spermatogenesis as a result of the antiandrogenic and antigonadotropic actions. Spermatogenesis recovers gradually within several months of discontinuing therapy.
In male patients, Androcur 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.
As with other antiandrogenic treatments, in male patients long-term androgen deprivation with Androcur may lead to osteoporosis.
In women, ovulation is inhibited under the combined treatment so that a state of infertility exists.
A feeling of tension in the breasts may occur.
In individual cases, disturbances of liver function, some of them severe, have been reported with high dosed Androcur treatment.
Changes in bodyweight are possible.
Other adverse events reported at a low incidence were dysmenorrhoea, vaginal discharge, skin discolouration, striae.

Postmarketing information.

The following adverse effects have been reported in users of cyproterone acetate and are based on postmarketing data and cumulative experience with Androcur (see Table 1). 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.

In male patients under treatment with Androcur, sexual drive and potency are reduced and gonadal function is inhibited. These changes are reversible after discontinuation of therapy.
Meningiomas have been reported in association with long-term use (several years) of Androcur doses of 25 mg and above (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems (Australia).

4.9 Overdose

There is no clinical experience in overdose. Assessment and symptomatic treatment should be initiated as required.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, cyproterone acetate is completely absorbed over a wide dose range.
The ingestion of 50 mg of cyproterone acetate gives maximum serum levels of about 140 nanogram/mL at about 3 hours. Thereafter, drug serum levels declined during a time interval of typically 24 to 120 hours, with a terminal half-life of 43.9 ± 12.8 h. The total clearance of cyproterone acetate from serum was determined to be 3.5 ± 1.5 mL/min/kg. The absolute bioavailability of cyproterone acetate is unknown. Relative bioavailability was calculated, in a study of eight young women, from a dose corrected comparison of area under the curves of serum levels after 100 mg oral and 300 mg intramuscular depot administration and was found to be 80 ± 30% when averaged over all volunteers (range 23%-119%).

Distribution.

The major part of circulating cyproterone acetate is bound to serum albumin. In a study in 15 women receiving 2 mg cyproterone acetate in combination with 35 microgram ethinyloestradiol, the free fraction of cyproterone acetate was about 3.5-4%. Because protein binding is 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 15β-hydroxy derivative. Some dose parts are excreted unchanged with bile fluid. Phase 1 metabolism of cyproterone acetate is mainly catalysed by the cytochrome P450 enzyme CYP3A4.

Excretion.

In a study in 6 women administered a ¹⁴C labelled dose of 2 mg cyproterone acetate in combination with 50 microgram oestrogen, approximately 30% of the label was found in the urine and 58% in the faeces. The renal and biliary excretion was determined to proceed with a half-life of 1.9 days. Metabolites from plasma were eliminated at a similar rate (half-life of 1.7 days).

Steady-state conditions.

According to the long half-life of the terminal disposition phase from plasma (serum) and the daily intake, an accumulation of cyproterone acetate by a factor of about 3 can be expected in the serum during repeated daily administration.

5.3 Preclinical Safety Data

Genotoxicity.

Cyproterone acetate was negative in a standard battery of genotoxicity studies. However, further tests showed that cyproterone acetate 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 Androcur. In vivo consequences of cyproterone acetate treatment were the increased incidence of focal, possibly preneoplastic, liver lesions in which cellular enzymes were altered in female rats, and an increase of mutation frequency in transgenic rats carrying a bacterial gene as target for mutation. The clinical relevance of these findings presently remains uncertain.

Carcinogenicity.

Long-term animal carcinogenicity studies were performed in rats and mice. In one rat study, an increased incidence of hepatomas was reported at oral dose levels of 50 mg/kg cyproterone acetate 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 cyproterone acetate in animals could not be determined.
Clinical experience and limited epidemiological data available to date do not appear to have supported an increased incidence of hepatic tumours in humans. However, it must be borne in mind that steroidal sex hormones can promote the growth of certain hormone dependent tissues and tumours.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, maize starch, povidone, colloidal anhydrous silica and magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Androcur 50 mg tablets are supplied in bottles* or (PVC/Al) blister pack of 20 and 50 tablets.
Presentations marked * are not marketed in Australia.
PBS availability (Authority Required):
Tablets 50 mg - Qty. 20 Rpts. 5.
Tablets 50 mg - Qty. 50 Rpts. 5.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Cyproterone acetate is a white to pale yellow crystalline powder. M.P. 206-213°C. 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 solvent hexane and almost insoluble in water.

Chemical structure.

Chemical name: 6-chloro-17α- hydroxy-1α,2α- methylene-pregna-4,6- diene-3,20-dione acetate.
Molecular formula: C₂₄H₂₉ClO₄.
Molecular mass: 416.96.

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Androcur 50 mg Tablets