Drugs List

Therapeutic Indications

Uses

Management of patients with prostatic cancer:
- Suppress "flare" with initial LHRH analogue therapy.
- Long-term palliative treatment where LHRH analogues or surgery are contraindicated, not tolerated, or
where oral therapy is preferred.
- Treatment of hot flushes in patients under treatment with LHRH analogues or who have had
orchidectomy.

Administration

For oral administration with liquid after food.

Contraindications

Hepatic disorder including Dubin-Johnson syndrome/Rotor syndrome
Thromboembolic disorder
Galactosaemia
Wasting disease (except prostate cancer)
Malignant neoplasm (except prostate cancer)
Meningioma or a history of meningioma
Liver tumour or a history of liver tumour
Children under 18 years

Precautions and Warnings

Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure has been reported in patients treated with 200 - 300mg cyproterone acetate daily. Most cases are in men with prostatic cancer. Hepatic toxicity is dose related and develops, usually, several months after treatment has begun. Liver function should be monitored and tests should be performed before starting and during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, cyproterone acetate should normally be withdrawn, unless it can be explained by another cause.

Patients with a history of thrombosis (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction), advanced malignancies or a history of cerebrovascular accidents may be at risk of recurrence of the disease or further thromboembolic events during cyproterone acetate therapy. In patients with a history of thromboembolic processes or suffering from sickle-cell anaemia or severe diabetes with vascular changes, the risk: benefit ratio must be considered carefully in each case before cyproterone acetate therapy is initiated.

Benign and malignant liver changes have been reported. Liver tumours may lead to life-threatening intra-abdominal haemorrhage. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be considered in the differential diagnosis.

Meningiomas have been reported after long term use at doses of 25mg/day and above. Treatment must be stopped if the patient is diagnosed with meningioma.

A spermatogram should be recorded before starting treatment in patients of procreative age, as a guard against attribution of pre-existing infertility to cyproterone acetate at a later stage. The sperm count and the volume of ejaculate are reduced, infertility is usual, and there may be azoospermia after 8 weeks. Note that spermatogenesis is slow, and cyproterone acetate should therefore not be regarded as a male contraceptive. There is evidence that abnormal spermatozoa are produced during treatment with cyproterone, which might give rise to malformed embryos.

Adrenocortical function should be monitored during treatment, since suppression has been observed due to the corticoid-like effect of high dose cyproterone acetate.

Shortness of breath may occur and be accompanied by hypocapnia and compensatory alkalosis. No treatment is normally required.

Blood-counts before and at regular intervals during treatment are advisable. Anaemia has been reported during long term therapy.

Diabetic patients should have parameters of carbohydrate metabolism examined carefully before and regularly during treatment. Dose requirements for oral antidiabetics or insulin can change.

It has been found that some patients with severe chronic depression deteriorate whilst taking cyproterone. Patients should be closely monitored. Advise them to contact their doctor deterioration is noticed.

Contains lactose and is therefore unsuitable for patients with glucose-galactose malabsorption or lactose intolerance.

St John's wort is an inducer of CYP3A4 and may reduce the levels of cyproterone acetate. Advise patients to avoid taking St John's wort products during treatment.

Note: The effect of cyproterone has been found to be reduced by alcohol to the extent that it is of no value when used in the control of libido/sexual deviation in chronic alcoholics. The relevance of this in the treatment of prostate cancer is not known.

Pregnancy and Lactation

Pregnancy

Not indicated for use in women.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Not indicated for use in women.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Fatigue
Lassitude
Breathlessness
Hypocapnia
Alkalosis
Weight changes
Changes in hair pattern
Gynaecomastia
Spermatogenesis suppression
Abnormal sperm
Hepatotoxicity
Benign and malignant liver changes
Jaundice
Hepatitis
Hepatic failure
Changes in scalp or body hair
Discolouration of hair
Female type hair growth
Galactorrhoea
Breast nodules (benign)
Reduction in sperm count and volume
Atrophy of seminiferous tubules
Benign and malignant liver changes
Osteoporosis
Dry skin
Thromboembolism
Hypersensitivity reactions
Rash
Sebum production decreased
Adrenal suppression
Changes in glucose metabolism
Worsening depression
Reduced libido
Infertility
Erectile dysfunction
Anaemia
Restlessness
Hot flushes
Sweating
Meningioma

Presentation

Tablets containing 100mg of cyproterone acetate

Drugs List

Therapeutic Indications

Uses

Management of patients with prostatic cancer:
- Suppress "flare" with initial LHRH analogue therapy.
- Long-term palliative treatment where LHRH analogues or surgery are contraindicated, not tolerated, or
where oral therapy is preferred.
- Treatment of hot flushes in patients under treatment with LHRH analogues or who have had
orchidectomy.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For oral administration with liquid after food.

Contraindications

Hepatic disorder including Dubin-Johnson syndrome/Rotor syndrome
Thromboembolic disorder
Galactosaemia
Wasting disease (except prostate cancer)
Malignant neoplasm (except prostate cancer)
Meningioma or a history of meningioma
Liver tumour or a history of liver tumour
Children under 18 years

Precautions and Warnings

Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure has been reported in patients treated with 200 - 300mg cyproterone acetate daily. Most cases are in men with prostatic cancer. Hepatic toxicity is dose related and develops, usually, several months after treatment has begun. Liver function should be monitored and tests should be performed before starting and during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, cyproterone acetate should normally be withdrawn, unless it can be explained by another cause.

Patients with a history of thrombosis (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction), advanced malignancies or a history of cerebrovascular accidents may be at risk of recurrence of the disease or further thromboembolic events during cyproterone acetate therapy. In patients with a history of thromboembolic processes or suffering from sickle-cell anaemia or severe diabetes with vascular changes, the risk: benefit ratio must be considered carefully in each case before cyproterone acetate therapy is initiated.

Benign and malignant liver changes have been reported. Liver tumours may lead to life-threatening intra-abdominal haemorrhage. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be considered in the differential diagnosis.

Meningiomas have been reported after long term use at doses of 25mg/day and above. Treatment must be stopped if the patient is diagnosed with meningioma.

A spermatogram should be recorded before starting treatment in patients of procreative age, as a guard against attribution of pre-existing infertility to cyproterone acetate at a later stage. The sperm count and the volume of ejaculate are reduced, infertility is usual, and there may be azoospermia after 8 weeks. Note that spermatogenesis is slow, and cyproterone acetate should therefore not be regarded as a male contraceptive. There is evidence that abnormal spermatozoa are produced during treatment with cyproterone, which might give rise to malformed embryos.

Adrenocortical function should be monitored during treatment, since suppression has been observed due to the corticoid-like effect of high dose cyproterone acetate.

Shortness of breath may occur and be accompanied by hypocapnia and compensatory alkalosis. No treatment is normally required.

Blood-counts before and at regular intervals during treatment are advisable. Anaemia has been reported during long term therapy.

Diabetic patients should have parameters of carbohydrate metabolism examined carefully before and regularly during treatment. Dose requirements for oral antidiabetics or insulin can change.

It has been found that some patients with severe chronic depression deteriorate whilst taking cyproterone. Patients should be closely monitored. Advise them to contact their doctor deterioration is noticed.

Contains lactose and is therefore unsuitable for patients with glucose-galactose malabsorption or lactose intolerance.

St John's wort is an inducer of CYP3A4 and may reduce the levels of cyproterone acetate. Advise patients to avoid taking St John's wort products during treatment.

Note: The effect of cyproterone has been found to be reduced by alcohol to the extent that it is of no value when used in the control of libido/sexual deviation in chronic alcoholics. The relevance of this in the treatment of prostate cancer is not known.

Pregnancy and Lactation

Pregnancy

Not indicated for use in women.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Not indicated for use in women.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Fatigue and lassitude are common. Advise patients that the ability to drive or operate machinery may be affected by side effects.

Counselling

Advise patients not to drive or operate machinery if affected by side effects such as lassitude or fatigue.

Advise patient to avoid St John's wort.

Advise patient to contact their doctor if depression worsens.

Side Effects

Fatigue
Lassitude
Breathlessness
Hypocapnia
Alkalosis
Weight changes
Changes in hair pattern
Gynaecomastia
Spermatogenesis suppression
Abnormal sperm
Hepatotoxicity
Benign and malignant liver changes
Jaundice
Hepatitis
Hepatic failure
Changes in scalp or body hair
Discolouration of hair
Female type hair growth
Galactorrhoea
Breast nodules (benign)
Reduction in sperm count and volume
Atrophy of seminiferous tubules
Benign and malignant liver changes
Osteoporosis
Dry skin
Thromboembolism
Hypersensitivity reactions
Rash
Sebum production decreased
Adrenal suppression
Changes in glucose metabolism
Worsening depression
Reduced libido
Infertility
Erectile dysfunction
Anaemia
Restlessness
Hot flushes
Sweating
Meningioma

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

No special requirements

Further Information

Last Full Review Date: April 2011

Reference Sources

British National Formulary, 61st Edition (2011) Pharmaceutical Press, London.

BNF for Children (2010-2011) Pharmaceutical Press, London.

Martindale: The Complete Drug Reference, 36th edition (2009) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Cyprostat 50mg. Bayer plc. Revised January 2011

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.