Drug information of Cyproterone acetate

Mechanism of effect

Cyproterone is a steroid with antiandrogenic, antigonadotropic, and progestin-like activity. Blocks binding of dihydrotestosterone (DHT) to prostatic cancer cells and exerts negative feedback on hypothalamic-pituitary axis by inhibiting luteinizing hormone (LH) secretion leading to decreased testosterone production.

Pharmacodynamic

Cyproterone is an antiandrogen . It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. 

Pharmacokinetics

• Absorption: Oral: Complete
• Protein binding: 96%
• Metabolism: Hepatic; primary metabolite is 15beta-hydroxy-cyproterone acetate
• Distribution: V_d: IM: 20.6 L/kg
• Bioavailability: Oral: 88%
• Half-life elimination: Oral: 38 ± 5 hours; Depot injection: 4 days
• Time to peak, plasma: Oral: 3 to 4 hours; Depot injection: 3.4 days

Dosage

• Prostate cancer: 

Males:

• Oral: 200 to 300 mg daily in 2 to 3 divided doses (maximum: 300 mg daily); following orchiectomy, reduce dose to 100 to 200 mg daily
• IM: 300 mg (3 mL) once weekly; reduce dose in orchiectomized patients to 300 mg (3 mL) every 2 weeks
• Note: May interchange between oral and IM administration during chronic therapy; dosages should remain within usual ranges

Geriatric 

Refer to adult dosing.

Renal Impairment 

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution

Hepatic Impairment 

Use is contraindicated with hepatic impairment or liver disease.

Interactions

Alerts

• Concerns related to adverse effects:

Adrenalcortical function suppression: Has been reported with use; monitor adrenal function periodically during therapy.

Anemia: Hypochromic anemia has been observed (rarely); monitor CBC regularly.

Antiandrogen withdrawal syndrome: Antiandrogens may promote prostate cancer growth in some patients with metastatic prostate cancer; discontinue therapy immediately with increasing prostate specific antigen (PSA) levels and monitor 6 to 8 weeks for withdrawal response prior to initiating alternative treatment. Decreased PSA levels and/or clinical improvement have been reported following therapy discontinuation.

CNS depression: Lassitude, weakness, and fatigue are common during first few weeks of treatment; symptoms usually lessen ~about 3 months after therapy initiation. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Gynecomastia: Hyperplasia of the breast has been reported; subsides usually within 1 to 3 months after therapy discontinuation and/or dose reduction. Risk of treatment failure should be considered prior to discontinuation or dose reduction.

Hepatotoxicity: Use of cyproterone is associated with dose-dependent hepatotoxicity (jaundice, hepatitis, acute hepatic failure) including fatal case reports with doses ≥100 mg/day.Most reported fatalities were in males treated for prostate cancer. Hepatotoxicity typically develops a few weeks to several months after treatment initiation. Discontinue in patients with evidence of hepatic injury. Use in patients with prior or existing hepatic disease is contraindicated. Use caution with concurrent use of other hepatotoxic drugs.

Metabolic effects: Changes in lipid profile, hypercalcemia, and/or fluid retention may occur; a negative nitrogen balance is usual at therapy initiation but typically corrects itself within 3 months of ongoing therapy.

Respiratory effects: Shortness of breath was commonly observed in patients receiving doses of 300 mg/day; use caution in patients with existing pulmonary dysfunction.

Thromboembolism: May increase the risk of thromboembolism (particularly when used in combination with ethinyl estradiol); discontinue use immediately with signs/symptoms of thrombophlebitis or thromboembolism. Use with caution in patients with an inoperable prostate tumor, history of thromboembolic processes, sickle cell anemia or severe diabetes with vascular changes.

• Disease-related concerns:

Cardiovascular disease: Use with caution in cardiovascular disease; may cause fluid retention

Depression: Use with caution in patients with a history of depression (contraindicated in severe chronic depression); has been associated with an increased incidence of depression, particularly early in the course of therapy (initial 6t o 8 weeks).

Diabetes: Use with caution in patients with diabetes or impaired glucose tolerance, may cause alterations in glucose metabolism. Monitor for loss of glucose control; may require adjustments in diabetes medications.

Points of recommendation

Cyproterone may cause some people to become drowsy, dizzy, or less alert than they are normally. Make sure you know how you react to cyproterone before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

Cyproterone may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn.

 When you begin taking cyproterone:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.
• Wear protective clothing, including a hat. Also, wear sunglasses.
• Apply a sun block product that has a skin protection factor (SPF) of at least 15.
• Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.
• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

While you are taking cyproterone, be careful to limit the amount of alcohol you drink.

Pregnancy level

Breast feeding warning