Consumer medicine information

Anterone 50 Tablets

Cyproterone acetate

BRAND INFORMATION

Brand name

Anterone 50

Active ingredient

Cyproterone acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Anterone 50 Tablets.

SUMMARY CMI

Anterone 50

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 Anterone 50?

Anterone 50 contains the active ingredient cyproterone acetate. Anterone 50 may slow or stop the growth of cancer and also used to reduce abnormal sex drive in men. Anterone 50 tablets may slow or stop excessive hairiness, loss of scalp hair, acne, oily skin and dandruff.

For more information, see Section 1. Why am I using Anterone 50? in the full CMI.

2. What should I know before I use Anterone 50?

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. Do not take this medicine if you are pregnant or suspect you may be pregnant. 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 use Anterone 50? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Anterone 50 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 use Anterone 50?

  • The usual daily dose is 50‐300 mg of Anterone 50 tablets. 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 use Anterone 50? in the full CMI.

5. What should I know while using Anterone 50?

Things you should do
  • Remind any doctor, dentist or pharmacist when you visit that you are using Anterone 50.
  • Your doctor will check your red‐blood cell count to ensure you do not become anaemic and will also check liver function during treatment with Anterone 50 tablets.
Things you should not do
  • Anterone 50 tablets should not be taken by children and adolescents below 18 years of age or girls who have not completed puberty.
  • Do not breastfeed if you are taking this medicine.
Driving or using machines
  • Be careful driving or operating machinery until you know how Anterone 50 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.
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 Anterone 50 tablets from working as well as it should in reducing abnormal sex drive.
Looking after your medicine
  • Keep Anterone 50 tablets in a cool dry place where the temperature stays below 25°C.
  • Keep your tablets in the blister in the tablet pack carton until it is time to take them.

For more information, see Section 5. What should I know while using Anterone 50? in the full CMI.

6. Are there any side effects?

The serious side effect includes 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. 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

Anterone 50

Active ingredient(s): Cyproterone acetate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Anterone 50. 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 Anterone 50.

Where to find information in this leaflet:

1. Why am I using Anterone 50?
2. What should I know before I use Anterone 50?
3. What if I am taking other medicines?
4. How do I use Anterone 50?
5. What should I know while using Anterone 50?
6. Are there any side effects?
7. Product details

1. Why am I using Anterone 50?

Anterone 50 contains the active ingredient Cyproterone acetate. Anterone 50 tablets are an anti‐androgen medicine.

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, Anterone 50 tablets may slow or stop the growth of cancer. Anterone 50 tablets 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.

Anterone 50 tablets 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, Anterone 50 tablets may slow or stop excessive hairiness, loss of scalp hair, acne, oily skin and dandruff.

2. What should I know before I use Anterone 50?

Warnings

Do not use Anterone 50 if:

  • you are allergic to cyproterone acetate, or 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
  • Always check the ingredients to make sure you can use this medicine.
  • you are a children and adolescents below 18 years of age or girls who have not completed puberty.
  • you are pregnant or suspect you may be pregnant. It may affect your developing baby if you take it during pregnancy.
  • you are breast‐feeding. The active ingredient in Anterone 50 tablets passes into breast milk and there is a possibility that your baby may be affected.
  • you have 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)
  • you have Dubin‐Johnson or Rotor syndrome (your doctor would have told you if you have either of these conditions)
  • you have history of jaundice (yellow skin or eyes), herpes or persistent itching during a previous pregnancy
  • you have previous or existing benign brain tumour (meningioma)
  • you have wasting disease (a disease causing muscle loss or loss of strength, with the exception of prostate cancer)
  • you have severe and persistent depression
  • you have previous or existing conditions relating to formation of blood clots
  • you have severe diabetes with blood vessel changes (your doctor would have told you if you have this)
  • you have sickle‐cell anaemia (your doctor would have told you if you have this).

Check with your doctor if you:

  • have diabetes
  • have history of blood clotting or sickle cell anaemia
  • have 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)

Anterone 50 tablets tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking Anterone 50 tablets.

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.

If taken during pregnancy, Anterone 50 tablets may lead to signs of feminisation in the male foetus. Therefore, your doctor will check that you are not pregnant before you start taking Anterone 50 tablets. Women should use a reliable form of contraception while taking Anterone 50 tablets.

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

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 Anterone 50 tablets. It can take 3‐20 months for fertile sperm production to be re‐established after stopping this medicine.

The long‐term effects of Anterone 50 tablets on female fertility are not known.

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.

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

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Anterone 50.

4. How do I use Anterone 50?

How much to take

  • Your doctor will advise of the most suitable dose for you to take.
  • Follow the instructions provided and use Anterone 50 until your doctor tells you to stop.
  • 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 Anterone 50 tablets. Your doctor may request you take Anterone 50 tablets with other medicines and/or change your dose during treatment.
  • Reduction of abnormal sex drive
    Generally treatment is started with 50 mg of Anterone 50 tablets 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 5th 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 5th day of the cycle.
  • Starting from day 1 take 50‐100 mg (as advised by your doctor) of Anterone 50 tablets daily from the 5th to the 14th 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, Anterone 50 tablets may be administered alone. The usual dose is 25‐50 mg of Anterone 50 tablets once daily for 21 days, followed by a 7‐day tablet‐free interval.
  • Shortness of breath may occur at high doses.

When to take Anterone 50

  • 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 Anterone 50 tablets tablets may diminish the effectiveness of treatment and may lead to breakthrough bleeding in women.

How to take it

  • Swallow the tablets whole with some liquid after meals.
  • 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 use Anterone 50

Anterone 50 should be used regularly as prescribed. If you miss your dose at the usual time, then take it as soon as you remember, and then go back to taking your medicine as you would normally.

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

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

If you are also taking an oral contraceptive and more than 12 hours has elapsed from the time Anterone 50 tablets 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 use too much Anterone 50

If you think that you have used too much Anterone 50, 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 using Anterone 50?

Things you should do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Anterone 50 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 Anterone 50 tablets 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 Anterone 50 tablets.

Your doctor will also check your red‐blood cell count to ensure you do not become anaemic during treatment with Anterone 50 tablets.

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 Anterone 50 tablets 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.

Things you should not do

  • Do not take Anterone 50 tablets 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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Anterone 50 affects you.

Be careful driving or operating machinery until you know how Anterone 50 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.

Drinking alcohol

Tell your doctor if you drink 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 Anterone 50 tablets from working as well as it should in reducing abnormal sex drive.

Looking after your medicine

  • Keep your tablets in the blister in the tablet pack carton until it is time to take them.
  • If you take the tablets out of the blister they may not keep as well.
  • Keep Anterone 50 tablets in a cool dry place where the temperature stays below 25°C.
  • Heat and damp can destroy some medicines.
  • A locked cupboard at least one‐and‐a‐half metres above the ground is a good place to store medicines.

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.

When to discard your medicine

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Return any unused medicine to your pharmacist.

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.

If you were fertile before treatment, Anterone 50 tablets 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 Anterone 50 tablets 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.

Less serious side effects

Less serious side effectsWhat to do
More broad or affecting different parts of the body
  • 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.

Serious side effects

Serious side effectsWhat to do
More broad or affecting different parts of the body
  • 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
  • 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, or go straight to the Emergency Department at your nearest hospital 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 Anterone 50 contains

Active ingredient
(main ingredient)		cyproterone acetate
Other ingredients
(inactive ingredients)		lactose monohydrate,
starch‐maize,
povidone,
magnesium stearate,
silica‐colloidal anhydrous,
starch‐pregelatinised maize.

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

What Anterone 50 looks like

Anterone 50 tablets are white tablets containing 50 milligrams of the antiandrogenic substance, cyproterone acetate and presented in blister packs containing 20 and 50 tablets (AUST R 278777).

Who distributes Anterone 50

Cipla Australia Pty Ltd
Level 1, 132 – 136 Albert Road
South Melbourne VIC 3205
Phone no: 1 800 569 074
Email id: [email protected]

This leaflet was prepared in December 2020.

Published by MIMS May 2021

BRAND INFORMATION

Brand name

Anterone 50

Active ingredient

Cyproterone acetate

Schedule

S4

 

1 Name of Medicine

Cyproterone acetate.

2 Qualitative and Quantitative Composition

Anterone 50 tablets.

Each tablet contains 50 mg cyproterone acetate.

Excipient with known effects.

Contains lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White circular flat bevelled tablets, with breakline on one side and plain on the other.

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 cyproterone is taken during pregnancy, the properties of the preparation may lead to signs of feminisation in the male foetus. Therefore, in women of child bearing potential, pregnancy must be excluded at the commencement of treatment and ethinyl oestradiol taken as well to ensure contraception. This also promotes regular menstruation.

Men.

Reduction of drive in sexual deviations.

Cyproterone 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.
Cyproterone therapy should be supplemented by psychotherapeutic and sociotherapeutic measures in order to exploit the period of reduced drive for personal and social re-orientation.
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

Women.

Pregnant women must not take Anterone 50. Therefore, pregnancy must be excluded at the time therapy is commenced in women of child bearing potential.

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

See Section 4.4 Special Warnings and Precautions for Use.

Women of child bearing potential.

In women of child bearing potential, the treatment is commenced on the 5th day of the cycle (1st day of bleeding = 1st day of the cycle). 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 5th day of the cycle and the following recommendations then observed.
For hirsutism secondary to female androgenization, the usual starting dose should be one tablet of Anterone 50 taken daily for 10 days per month (from the 5th to the 14th 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 androgenization, 2 tablets of Anterone 50 are to be taken daily with some liquid after a meal from the 5th to the 14th day of the cycle (= for 10 days). In addition, these women should receive ethinyl oestradiol 50 microgram daily from the 5th to the 25th day of the cycle to provide the necessary contraceptive protection and to stabilise the cycle.
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. The use of Anterone 50 and ethinyl oestradiol should nevertheless be continued according to instructions, ignoring the missed tablet or tablets, in order to avoid premature bleeding in this cycle. However, an additional non-hormonal barrier method of contraception (not the rhythm or temperature methods) is to be employed for the rest of the cycle.
A 7-day tablet-free interval is observed after 21 days, during which time a withdrawal bleeding occurs. 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 interval, the possibility of pregnancy must be excluded before restarting tablet taking.
Following clinical improvement, the daily dose of Anterone 50 may be reduced to 1 or ½ tablet during the 10 days on which it is given in each cycle. The dose regimen for ethinyl oestradiol remains unchanged. If improvement is maintained over a further few months, Anterone 50 daily from the 5th to the 19th day of the cycle (= 15 days), may be sufficient.
As the dose of Anterone 50 is reduced, contraceptive efficacy may be impaired.
Therefore a reliable form of contraception (not the rhythm or temperature methods) must be employed during treatment. If a non-hormonal method is adopted, ethinyl oestradiol from day 5 to 25 will need to be continued to stabilise the cycle.
Pyridoxine and folate plasma levels may be depressed by combined oestrogen/progesterone treatment. Folate supplementation may be desirable if a patient becomes pregnant shortly after ceasing tablet taking.

Postmenopausal or hysterectomised women.

In postmenopausal or hysterectomised patients Anterone 50 may be administered alone. According to the severity of the complaints, the average dose should be ½ to 1 tablet Anterone 50 once daily for 21 days, followed by a 7 day tablet-free interval.
The length of the treatment depends on the severity of the pathological signs of androgenization 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 in the drive of sexual deviation. 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 ½ 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 ½ tablet, at intervals of several weeks.
To stabilise the therapeutic effect it is necessary to take Anterone 50 over a protracted period of time, if possible with the simultaneous use of psychotherapeutic measures.
The tablets are to be taken with some liquid after meals.
Inoperable prostatic carcinoma.

To suppress LHRH analogue "flare".

300 mg/day which may be reduced to 200 mg/day.

In long-term palliative treatment.

After orchidectomy, two 50 mg tablets once to twice daily. Without orchidectomy, two 50 mg tablets 2 to 3 times daily.

In the treatment of hot flushes.

Low initial dose with upward titration if necessary.
The tablets are to be taken with some liquid after meals. Treatment should not be interrupted nor the dosage reduced after improvement or remissions have occurred.

4.3 Contraindications

Contraindications in women.

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.
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 Anterone 50.

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 Anterone 50.

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 Anterone 50.
Cyproterone 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

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 Anterone 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.

Use in hepatic impairment.

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. At dosages of 100 mg and above, cases with fatal outcome have been reported. Most reported fatal 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 pre-treatment, at regular intervals during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, cyproterone should normally be withdrawn, unless hepatotoxicity 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 Anterone 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.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

See Section 4.2 Dose and Method of Administration.
In extremely rare cases, the occurrence of thromboembolic events has been reported in temporal association with the use of Anterone 50. 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 penicillin's and anti-convulsant 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 vulvo-vaginal monilial infection may occur or recur, and of the need for appropriate treatment.

Effects on laboratory tests.

Certain changes maybe induced in laboratory data:
a) liver functions; transaminases (SGOT, SGPT) and bromsulphthalein retention are increased.
b) clotting factors; VII, VIII, IX and X, prothrombin, platelet aggregation are in increased. But antithrombin 3 decreased.
c) thyroid functions; thyroid binding globulin (TBG), total thyroxin (T4) and protein bound iodine (PBI) are increased. T3 resin uptake (reflecting TBG) is decreased whilst free T4 and clinical thyroid state remain unaltered.
d) adrenal function; plasma cortisol is increased (due to increase in steroid binding globulins) whilst adrenal function is essentially normal.
e) agglutination reactions; false positive rheumatoid factor and anti-nuclear factor are increased.
f) blood glucose, phospholipids and triglycerides are increased.
These tests usually return to pre-therapy values shortly after discontinuation of oestrogen/progestogen treatment.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No data available.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Also see Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties.
(Category D)
The use of cyproterone is contraindicated during pregnancy as the properties of the pregnancy may lead to signs of feminisation in the male foetus.
 The use of cyproterone 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 Anterone 50 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 Anterone 50 are spotting, weight increase and depressed mood.
The most frequently observed ADRs in male patients receiving Anterone 50 are decreased libido, erectile dysfunction and reversible inhibition of spermatogenesis.
The most serious ADRs in patients receiving Anterone 50 are hepatic toxicity, benign and malignant liver tumours which may lead to intra-abdominal haemorrhage, and thromboembolic events.
Over the course of several weeks Anterone 50 gradually impairs spermatogenesis as a result of the antiandrogenic and antigonadotropic actions. Spermatogenesis recovers gradually within several months of discontinuing therapy.
In male patients Anterone 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.
As with other antiandrogenic treatments, in male patients long-term androgen deprivation with Anterone 50 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 Anterone 50 treatment.
Changes in body weight are possible.
Other adverse events reported at a low incidence were dysmenorrhoea, vaginal discharge, skin discolouration, striae.

Post-marketing information.

The following adverse effects have been reported in users of cyproterone acetate and are based on post-marketing data and cumulative experience with Anterone 50. The most appropriate MedDRA term to describe a certain adverse reaction is listed in Table 1. Synonyms or related conditions are not listed, but should be taken into account as well.
In male patients under treatment with Anterone 50, 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 Anterone 50 doses of 25 mg and above (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
The following adverse reactions have been reported in clinical trials: Diminished libido 16%, tiredness 13.5%, increase in body weight 11%, mastodynia 8%, nausea and other gastrointestinal complaints 7.4%, cycle irregularity 4%, headache 3.3%, depressive moods 3%, thrombotic phenomena 1.2%.

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 Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Cyproterone 50 mg 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. Anterone 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, cyproterone acetate is completely absorbed over a wide dose range slowly. Its bioavailability is unknown. The maximum plasma level is reached 3 to 4 hours after ingestion.

Excretion.

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 15β-hydroxy-cyproterone acetate.
Radioimmunoassays show that about 0.2% of the dose is eliminated with the breast milk.

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 Anterone 50. In vivo consequences of cyproterone acetate treatment were the increased incidence of focal, possibly pre-neoplastic, 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 and mutagenicity.

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 dose 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, starch-maize, povidone, magnesium stearate, silica-colloidal anhydrous, starch-pregelatinised maize.

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 25°C.

6.5 Nature and Contents of Container

Anterone 50 tablets presented in pvc/pvdc/aluminium foil blisters. Each pack contains 20 or 50 tablets.

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

Chemical structure.

Cyproterone acetate. The chemical name is 6-chloro-17 -hydroxy-1 α, 2α-methylene-pregna-4,6- diene-3,20-dione acetate.
Structural formula:
Molecular formula: C24H29ClO4.
Molecular weight: 416.95.

CAS number.

427-51-0.

7 Medicine Schedule (Poisons Standard)

S4 Prescription Only Medicine.

Summary Table of Changes