Usage
Cyproterone acetate is primarily prescribed for the treatment of:
- Prostate cancer: It acts as an antiandrogen, reducing the effects of testosterone and inhibiting prostate cancer growth.
- Hirsutism (excessive hair growth in women): It helps reduce the growth of unwanted hair by blocking androgen effects.
- Acne (severe): In combination with ethinylestradiol, it can treat severe acne in women.
- Hypersexuality (in men): It can lower libido and reduce sexual urges.
Pharmacological Classification: Antiandrogen, steroidal.
Mechanism of Action: Cyproterone competitively inhibits the binding of androgens like testosterone and dihydrotestosterone (DHT) to their receptors. This reduces the effects of these hormones, which are responsible for stimulating the growth of prostate cancer cells, promoting hair growth, and influencing sebum production in acne.
Alternate Names
Cyproterone acetate (CPA) is the most common alternate name. Androcur, Cyprostat, and Cyprone are some brand names under which cyproterone is marketed.
How It Works
Pharmacodynamics: Cyproterone competitively blocks androgen receptors, leading to reduced androgenic effects. In prostate cancer, this inhibits tumor growth. In hirsutism and acne, it decreases hair growth and sebum production.
Pharmacokinetics:
- Absorption: Cyproterone is well-absorbed orally.
- Metabolism: Extensively metabolized in the liver, primarily by CYP3A4.
- Elimination: Excreted in both urine and feces.
Mode of Action: Cyproterone acts as a competitive antagonist at androgen receptors. It binds to the receptors, preventing androgens from binding and exerting their effects.
Receptor Binding/Enzyme Inhibition: Cyproterone primarily binds to androgen receptors. At high doses, in vitro studies suggest potential inhibition of CYP enzymes (CYP2C8, 2C9, 2C19, 3A4, and 2D6), and induction of CYP1A2 and CYP2E1.
Dosage
Standard Dosage
Adults:
- Prostate Cancer: 200-300 mg daily, divided into 2-3 doses, taken orally after meals. Alternatively, 300 mg intramuscularly once a week.
- Hirsutism: 50-100 mg daily for 10 days per menstrual cycle (days 1-10 or 5-14), often combined with an estrogen. Maintenance doses can be as low as 10mg daily for 10 days per month.
- Hypersexuality: Starting dose of 50 mg twice daily, titrated up to 100 mg twice or thrice daily.
Children:
Cyproterone is generally not recommended for use in children and adolescents, especially before puberty. In cases where it is prescribed for conditions like precocious puberty, the dose is carefully individualized under strict specialist supervision.
Special Cases:
- Elderly Patients: No specific dosage adjustment is typically required, but caution is advised due to potential age-related decrease in hepatic and renal function.
- Patients with Renal Impairment: Caution is recommended as 33% of the drug is excreted renally. Dosage adjustments may be needed.
- Patients with Hepatic Dysfunction: Contraindicated in patients with liver disease.
- Patients with Comorbid Conditions: Close monitoring required, particularly in patients with diabetes or cardiovascular disease.
Clinical Use Cases
Cyproterone is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary indications are prostate cancer, hirsutism, and severe acne resistant to other therapies.
Dosage Adjustments
Dosage adjustments should be made gradually to minimize side effects and maintain therapeutic efficacy. Careful titration is crucial, especially when initiating or discontinuing treatment.
Side Effects
Common Side Effects
- Fatigue
- Decreased libido
- Gynecomastia (breast enlargement in men)
- Breast tenderness or pain
- Weight changes
- Hot flushes or sweats
Rare but Serious Side Effects
- Liver toxicity (jaundice, hepatitis)
- Blood clots (thromboembolic events)
- Meningioma (brain tumor)
- Depression
Long-Term Effects
- Osteoporosis (with long-term use)
- Infertility (reversible in men, long-term effects in women unknown)
Adverse Drug Reactions (ADR)
Severe liver toxicity, thromboembolic events, and signs of meningioma require urgent medical attention.
Contraindications
- Hypersensitivity to cyproterone
- Liver disease
- Meningioma (current or history)
- Pregnancy and breastfeeding
- Severe chronic depression
- History of thromboembolic events
Drug Interactions
- CYP3A4 Inhibitors (ketoconazole, itraconazole): May increase cyproterone levels.
- CYP3A4 Inducers (rifampicin, phenytoin): May decrease cyproterone levels.
- Alcohol: May reduce antiandrogenic effect.
- Anticoagulants: Increased risk of bleeding.
- Antidiabetic medications: May require dose adjustment.
Pregnancy and Breastfeeding
Pregnancy Safety Category: X (Contraindicated). Cyproterone can cause feminization of male fetuses.
Breastfeeding: Contraindicated as cyproterone is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Competitive androgen receptor antagonist.
- Side Effects: Fatigue, decreased libido, gynecomastia, breast tenderness, weight changes, liver toxicity, blood clots, meningioma, depression.
- Contraindications: Liver disease, meningioma, pregnancy, breastfeeding, severe chronic depression, thromboembolic events.
- Drug Interactions: CYP3A4 inhibitors/inducers, alcohol, anticoagulants, antidiabetic medications.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies depending on indication and individual patient factors (25 mg/day to 300 mg/day).
- Monitoring Parameters: Liver function tests, complete blood count, hormonal levels.
Popular Combinations
- Ethinylestradiol: Combined with cyproterone for severe acne and hirsutism in women.
- LHRH agonists: Used to mitigate tumor flare at the start of LHRH agonist therapy for prostate cancer.
Precautions
- General Precautions: Monitor liver function, blood counts, and hormone levels regularly. Assess for signs of depression, thromboembolic events, and meningioma.
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Use with caution and consider age-related physiological changes.
- Menstruating Individuals: Closely monitor for cycle changes and breakthrough bleeding. Ensure appropriate contraceptive measures are in place.
- Lifestyle Considerations: Limit alcohol intake. Driving may be impaired due to fatigue.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cyproterone?
A: Dosage depends on indication. For prostate cancer, it’s typically 200-300 mg daily in divided doses; for hirsutism, it’s 50-100 mg daily for 10 days per cycle; for hypersexuality, the starting dose is usually 50 mg twice daily.
Q2: What are the common side effects of Cyproterone?
A: Common side effects include fatigue, decreased libido, gynecomastia, breast tenderness, weight changes, and hot flushes.
Q3: What are the serious side effects of Cyproterone?
A: Serious side effects include liver toxicity, blood clots, meningioma, and depression.
Q4: What are the contraindications for using Cyproterone?
A: Cyproterone is contraindicated in patients with liver disease, meningioma, during pregnancy and breastfeeding, and in those with a history of severe chronic depression or thromboembolic events.
Q5: How does Cyproterone interact with other medications?
A: Cyproterone can interact with CYP3A4 inhibitors and inducers, alcohol, anticoagulants, and antidiabetic drugs.
Q6: Can Cyproterone be used during pregnancy or breastfeeding?
A: No, cyproterone is contraindicated during pregnancy and breastfeeding.
Q7: What monitoring is necessary for patients taking Cyproterone?
A: Regular monitoring of liver function tests, complete blood count, and hormone levels is essential. Patients should also be assessed for signs of depression, thromboembolic events, and meningioma.
Q8: How does Cyproterone affect fertility?
A: Cyproterone can impair fertility in both men and women. Fertility in men is usually regained after discontinuation of treatment, while the long-term effects on female fertility are not fully known.
Q9: Should the dose be adjusted in elderly patients?
A: While no specific dose adjustment is routinely recommended, caution should be exercised in elderly patients due to potential age-related declines in hepatic and renal function.
Q10: What are the long-term potential complications of Cyproterone?
A: Long-term use of Cyproterone is associated with an increased risk of osteoporosis.
