Cyproterone

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

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

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.

Benign and malignant hepatic tumors have been observed (rarely) after use; rule out the presence of tumor in patients presenting with severe upper abdominal discomfort, hepatic enlargement or signs of intra-abdominal hemorrhage. Meningioma formation has been reported with chronic therapy (years) at doses ≥25 mg/day. Initiation of therapy in patients with a history or presence of meningioma is contraindicated; discontinue treatment in patients diagnosed with meningioma.

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).

Dry skin and/or transient alopecia may occur.

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.

[Canadian Boxed Warning]: 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. Assess hepatic function prior to treatment initiation and regularly thereafter particularly if signs/symptoms of hepatotoxicity occur; 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.

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.

Shortness of breath was commonly observed in patients receiving doses of 300 mg/day; use caution in patients with existing pulmonary dysfunction (may be more susceptible to effects).

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:

Use with caution in cardiovascular disease; may cause fluid retention

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). Monitor closely in patients with tendency toward depressive episodes.

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. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Solution is oil based and must be injected by slow intramuscular injection only; avoid intravascular injection. Pulmonary microembolism of oily solutions can occur and lead to cough, dyspnea, angina and vasovagal reactions (eg, syncope, malaise, dizziness, hyperhidrosis, paresthesia). Reactions can occur during or immediately after the injection and are reversible; may usually be managed with supportive care (eg, oxygen). Other warnings/precautions:

Although the relevance to the treatment of prostate cancer is unknown, the antiandrogen effects in hypersexuality may be reduced with ethanol. Ethanol should be avoided during treatment.

Retrospective meta-analysis data suggest that 5-year survival rates may be lower when used concomitantly with a GnRH agonist or orchiectomy versus patients treated with castration alone.

[Canadian Boxed Warning]: Should be prescribed and managed by a clinician experienced with hormonal therapy in prostate cancer.