Consumer medicine information

Anterone 100

Cyproterone acetate

BRAND INFORMATION

Brand name

Anterone 100

Active ingredient

Cyproterone acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Anterone 100.

SUMMARY CMI

Anterone 100

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 100?

Anterone 100 contains the active ingredient cyproterone acetate. Anterone 100 may slow or stop the growth of cancer. Anterone 100 tablets may 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.

For more information, see Section 1. Why am I using Anterone 100? in the full CMI.

2. What should I know before I use Anterone 100?

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 use Anterone 100? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Anterone 100 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 100?

Your doctor will tell you the dose that you should take. The usual daily dose is 50‐300 mg (one half to three tablets) of Anterone 100. Your doctor may request you take Anterone 100 with other medicines and/or change your dose during treatment. More instructions can be found in Section 4. How do I use Anterone 100? in the full CMI.

5. What should I know while using Anterone 100?

Things you should do
  • Remind any doctor, dentist or pharmacist when you visit that you are using Anterone 100.
  • Your doctor will check your liver function and red blood cell count during treatment with Anterone 100 and whenever any symptoms or signs suggesting liver problems are observed and to ensure you do not become anaemic during treatment.
Things you should not do
  • 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 driving or operating machinery until you know how Anterone 100 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.
Looking after your medicine
  • Keep your tablets in a cool dry place, protected from light, where the temperature stays below 25°C.

For more information, see Section 5. What should I know while using Anterone 100? in the full CMI.

6. Are there any side effects?

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.

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 100

Active ingredient(s): Cyproterone acetate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Anterone 100. 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 100.

Where to find information in this leaflet:

1. Why am I using Anterone 100?
2. What should I know before I use Anterone 100?
3. What if I am taking other medicines?
4. How do I use Anterone 100?
5. What should I know while using Anterone 100?
6. Are there any side effects?
7. Product details

1. Why am I using Anterone 100?

Anterone 100 contains the active ingredient cyproterone acetate. Anterone 100 tablets are an anti‐androgen medicine. Androgens such as testosterone are natural male sex hormones. In some types of prostate cancer, androgens may help the cancer cells to grow. By blocking these hormones, Anterone 100 may slow or stop the growth of cancer

Anterone 100 tablets may 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.

2. What should I know before I use Anterone 100?

Warnings

Do not use Anterone 100 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.
  • 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
  • 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 syndrome or Rotor syndrome (your doctor would have told you if you have either of these conditions).
  • 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 existing conditions relating to formation of blood clots.

Anterone 100 tablets should only be taken by men. It should not be taken by women or children and adolescents below 18 years of age.

Anterone 100 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 100.

Check with your doctor if you:

  • diabetes
  • history of blood clotting or sickle cell anaemia
  • osteoporosis, a family history of osteoporosis or risk factors for developing osteoporosis (such as smoking, a diet low in calcium, poor mobility, a slight build or treatment with steroid medicines)

Tell your doctor if fertility after treatment is important. It is recommended that a sperm count is taken to establish fertility before commencing Anterone 100. It can take 3‐20 months for fertile sperm production to be re‐established after stopping this medicine.

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.

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 Anterone 100 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 Anterone 100.

4. How do I use Anterone 100?

How much to take

  • Follow the instructions provided and use Anterone 100 until your doctor tells you to stop.
  • Your doctor will tell you the dose that you should take. The usual daily dose is 50‐300 mg (one half to three tablets) of Anterone 100. Your doctor may request you take Anterone 100 with other medicines and/or change your dose during treatment.
  • Do not alter the dose yourself.
  • Your doctor will advise you if changing the dose is necessary.
  • Shortness of breath may occur at high doses.

When to take Anterone 100

  • 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 100 tablets may diminish the effectiveness of treatment.
  • 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.

How to take it

  • Swallow the tablets whole with some liquid after meals.

If you forget to use Anterone 100

Anterone 100 should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember.

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 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 100

If you think that you have used too much Anterone 100, 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 100?

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 100.

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 100 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 100.

Your doctor will also check your red‐blood cell count to ensure you do not become anaemic during treatment with Anterone 100.

Remind any doctor, dentist or pharmacist when you visit that you are using Anterone 100.

Things you should not do

  • Do not take Anterone 100 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 100 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. The effectiveness of Anterone 100 to reduce abnormal sex drive can also be diminished under the influence of alcohol. Alcohol may prevent Anterone 100 from working as well as it should in reducing abnormal sex drive.

Looking after your medicine

  • Keep your tablets in a cool dry place, protected from light, where the temperature stays below 25°C.
  • Keep the tablets in the foil blister until it is time to take them.
  • If you take the tablets out of the foil blister, they may not keep as well.
  • 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.

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.

Return any unused medicine to your pharmacist.

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 100 will normally prevent sperm production. Fertility is usually regained within a few months of discontinuing therapy.

Anterone 100 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
  • 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 Anterone100 contains

Active ingredient
(main ingredient)		Cyproterone acetate.
Other ingredients
(inactive ingredients)		Lactose monohydrate
Starch maize
Povidone
Starch‐pregelatinised maize
Magnesium stearate,
Silica‐colloidal anhydrous.

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

What Anterone 100 looks like

Anterone 100 are white, capsule shaped, biconvex tablets with ‘CPA 100’ marked on one side and scored on the other. (Aust R 278778).

Available in packs of 20 and 50 tablets.

Who distributes Anterone 100

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

This leaflet was prepared in December 2020.

Published by MIMS May 2021

BRAND INFORMATION

Brand name

Anterone 100

Active ingredient

Cyproterone acetate

Schedule

S4

 

1 Name of Medicine

Cyproterone acetate.

2 Qualitative and Quantitative Composition

Anterone 100 tablets.

Each tablet contains 100 mg cyproterone acetate.

Excipient with known effect.

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

3 Pharmaceutical Form

Capsule shaped, biconvex white tablets with 'CPA 100' marked on one side and scored on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Inoperable prostatic carcinoma.

To suppress 'flare' with initial luteinising hormone releasing hormone (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

The maximum daily dose is 300 mg.

Inoperable prostatic carcinoma.

Anterone 100 should be taken with some liquid after a meal.

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

Initially 1 Anterone 100 tablet twice daily (i.e. 200 mg a day) alone for 5-7 days, followed by 1 Anterone 100 tablet twice daily (i.e. 200 mg a day) 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 (1 Anterone 100 tablet) 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 LHRH analogues or who have had orchiectomy.

50 to 150 mg (half to one and a half tablets) per day with upward titration up to 1 tablet three times daily (300 mg) if necessary.

Paediatric use.

Anterone 100 tablets 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.

Use in the elderly.

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

Patients with hepatic impairment.

The use of Anterone 100 tablets is contraindicated in patients with liver diseases.

Patients with renal impairment.

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

4.3 Contraindications

Liver diseases.
Dubin-Johnson syndrome, Rotor syndrome.
Previous or existing liver tumours (only if these are not due to metastases from carcinoma of the prostate).
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 100.

4.4 Special Warnings and Precautions for Use

Anterone 100 is for use only in men.
During treatment, liver function, adrenocortical function and red blood cell count should be checked regularly.
As with other anti-androgenic treatments, in male patients long-term androgen deprivation with Anterone 100 may lead to osteoporosis.
In men of procreative age, for whom fertility could be important after conclusion of the medication, it is advisable to make at least one control spermatogram as a precaution before the start of treatment in order to counter any unjustified claims of later infertility as a result of the antiandrogen therapy. Spermatogenesis has taken 3-20 months to return to normal after discontinuing therapy.

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 pre-treatment, at regular intervals during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, cyproterone 100 mg should be withdrawn, unless hepatotoxicity can be explained by another cause, e.g. metastatic disease, in which case cyproterone 100 mg should be continued only if the perceived benefit outweighs the risk.
Cases of benign and malignant liver tumors, which may lead to life-threatening intra-abdominal hemorrhage, have been observed after the use of cyproterone 100 mg. 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 cyproterone 100 mg is diagnosed with meningioma, treatment with cyproterone containing products, including cyproterone 100 mg 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 cyproterone 100 mg treatment (see Section 4.3 Contraindications).

Shortness of breath.

A sensation of shortness of breath may occur under high dosed treatment with cyproterone 100 mg. The differential diagnosis in such cases must include the stimulating effect on breathing known for progesterone and synthetic progestogens which is accompanied by hypocapnia and compensatory alkalosis and which is not considered to require treatment.

Thromboembolic events.

The occurrence of thromboembolic events has been reported in patients using cyproterone 100 mg although a causal relationship has not been established. Patients with previous arterial or venous thrombotic/ thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or with a history of cerebrovascular accidents or with advanced malignancies are at increased risk of further thromboembolic events.
In patients with a history of thromboembolic processes or suffering from sickle cell anaemia or from severe diabetes with vascular changes, a careful risk/ benefit evaluation must be carried out in each individual case before cyproterone 100 mg is prescribed.

Adrenocortical function.

During treatment adrenocortical function should be checked regularly, as preclinical data suggest a possible suppression due to the corticoid-like effect of cyproterone 100 mg with high doses.

Anaemia.

Anaemia has been reported during treatment with cyproterone 100 mg. Therefore, the red-blood cell count should be checked regularly during treatment.

Other conditions.

Anterone 100 contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose mal-absorption should not take this medicine.
The sexual drive-reducing effect of Anterone 100 can be diminished under the influence of alcohol.

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 anti-diabetics 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 co-administered with high therapeutic cyproterone acetate doses since they share the same metabolic pathway.
Based on in vitro CYP450 studies, the recommended clinical doses are likely to inhibit CYP2C8, and an inhibition of the CYP 2C9, 2C19, 3A4 and 2D6 is also possible at high therapeutic cyproterone acetate doses of 3 times 100 mg per day.

4.6 Fertility, Pregnancy and Lactation

Anterone 100 is for use only in men.

Effects on fertility.

See Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties.
No available data.
 No available data.

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 cyproterone 100 mg 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 greater than or equal to 1/10; common greater than or equal to 1/100 and < 1/10; uncommon greater than or equal to 1/1,000 and < 1/100; rare greater than or equal to 1/10,000 and < 1/1,000; very rare < 1/10,000.

General.

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.

Skin.

Rare: rash.
The most frequently observed adverse drug reactions (ADRs) in patients receiving cyproterone 100 mg are decreased libido, erectile dysfunction and reversible inhibition of spermatogenesis.
The most serious ADRs in patients receiving cyproterone 100 mg are hepatic toxicity, benign and malignant liver tumours which may lead to intra-abdominal haemorrhage, and thromboembolic events.
Over the course of several weeks cyproterone 100 mg gradually impairs spermatogenesis as a result of the antiandrogenic and antigonadotropic actions. Spermatogenesis recovers gradually within several months of discontinuing therapy.
Cyproterone 100 mg may lead 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 patient's long-term androgen deprivation with cyproterone 100 mg may lead to osteoporosis.
In individual cases, disturbances of liver function, some of them severe, have been reported with high dosed cyproterone 100 mg treatment.
Changes in bodyweight are possible.
Other adverse events reported at a low incidence are: skin discolouration and 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 cyproterone 100 mg. 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. See Table 1.
* For further information see Section 4.4 Special Warnings and Precautions for Use.
+ A causal relationship with cyproterone 100 mg has not been established.
The ADRs identified only during post-marketing surveillance and for which a frequency could not be estimated are: anaemia*, meningioma, intra-abdominal haemorrhage*, thromboembolic events*+.
Under treatment with Anterone 100, 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 cyproterone 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 Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Anterone 100 is an anti-androgenic 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, cyproterone acetate therefore exerts a direct anti-androgenic 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.
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 100 mg of cyproterone acetate gives maximum serum levels of 239.2 ± 114.2 nanogram/mL at 2.8 ± 1.1 hours. Thereafter, drug serum levels declined during a time interval of typically 24 to 120 hours, with a terminal half-life of 42.8 ± 9.7 hours. The total clearance of cyproterone acetate from serum was determined to be 3.8 ± 2.2 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 I metabolism of cyproterone acetate is mainly catalysed by the CYP450 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.
In a study comparing cyproterone 50 mg tablets with the reference (Androcur 50 mg) tablets, the two products were shown to be bioequivalent. The geometric mean ratio and 90% confidence intervals for cyproterone AUC0-∞ were found to be 1.019, and 0.963 to 1.079, respectively, while those for Cmax were 0.958, and 0.880 to 1.044, respectively.

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 cyproterone 100 mg. 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.

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

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. Protect from light.

6.5 Nature and Contents of Container

Anterone 100 tablets presented in pvc/pcdc/aluminium foil blisters. Each pack contains 20* or 50 tablets.
* Currently not marketed.

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

Description.

Cyproterone acetate is a white to pale yellow crystalline powder. Cyproterone acetate is very soluble in chloroform and dioxane, freely soluble in acetone and benzene, soluble in ethanol, methanol and ethyl acetate, sparingly soluble in hexane, and almost insoluble in water.

Chemical structure.

6-chloro-3,20-dioxo-1beta,2beta-dihydro-3 H-cyclopropa [1,2] pregna-1,4,6-trien, 17-yl acetate.
Molecular Formula: C24H29ClO4.
MW: 416.9.

CAS number.

427-51-0.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine: S4.

Summary Table of Changes