1 Adverse Reaction Overview The adverse events associated most frequently with the use of cyproterone acetate are those related to the hormonal effects of the drug. These reactions usually disappear upon discontinuation of therapy or reduction of dose: decreased libido, breast enlargement, breast tenderness, benign nodular hyperplasia of the breast, galactorrhea, gynecomastia, abnormal spermatozoa, impotence, and inhibition of spermatogenesis.
The most serious adverse drug reactions (ADRs) in patients receiving cyproterone acetate are hepatic toxicity, benign and malignant liver tumors which may lead to intra-abdominal hemorrhage, and thromboembolic events. CYPROTERONE (Cyproterone Acetate) Page 11 of 38 As with other antiandrogenic treatments, long-term androgen deprivation with CYPROTERONE may lead to osteoporosis.
Other adverse events which have been reported are listed below:
Cardiovascular System: hypotension, tachycardia, heart failure, syncope, myocardial infarct, hemorrhage, cerebrovascular accident, cardiovascular disorder, retinal vascular disorder, embolus, pulmonary embolism, superficial and deep thrombophlebitis, thrombosis, retinal vein thrombosis, phlebitis, vascular headache, shock, pulmonary oil microembolism, vasovagal reactions.
Gastrointestinal System: constipation, diarrhea, indigestion, anorexia, nausea, vomiting, cholestatic jaundice, cirrhosis of liver, hepatic coma, hepatitis, hepatoma, hepatomegaly, jaundice, liver carcinoma, liver failure (for further information see 7 WARNINGS AND PRECAUTIONS - Hepatic/Biliary/Pancreatic), abnormal liver function test, liver necrosis, pancreatitis, glossitis.
Hematology: increased fibrinogen, decreased prothrombin, thrombocytopenia, anemia (for further information see 7 WARNINGS AND PRECAUTIONS - Hematologic), hemolytic anemia, hypochromic anemia, normocytic anemia, leukopenia, leukocytosis.
Metabolism: negative nitrogen balance, decreased response to ACTH, hyperglycemia, lowered cortisol, hypercalcemia, increased SGOT, increased SGPT, increased creatinine, hypernatremia, edema, weight gain, weight loss, diabetes mellitus.
Musculoskeletal System: myasthenia, osteoporosis. Central Nervous System: fatigue, lassitude, weakness, hot flashes, increased sweating, aphasia, coma, depression, dizziness, encephalopathy, hemiplegia, personality disorder, psychotic depression, abnormal gait, headache, temporary restlessness.
Meningiomas (single and multiple) have been reported in association with long-term use (several years) of cyproterone acetate. In a retrospective cohort study using data from a primary care database, meningiomas were reported very rarely in patients treated with cyproterone acetate for prostate cancer after several months of treatment; in these cases, causality was not established (see 7 WARNINGS AND PRECAUTIONS - Carcinogenesis and Mutagenesis).
Respiratory System: asthma, increased cough, dyspnea, hyperventilation, respiratory disorder, shortness of breath on effort (see 7 WARNINGS AND PRECAUTIONS - Respiratory), lung fibrosis. CYPROTERONE (Cyproterone Acetate) Page 12 of 38 Skin: eczema, urticaria, erythema nodosum, exfoliative dermatitis, rash, maculopapular rash, dryness of the skin, pruritus, alopecia, hirsutism, skin discoloration, photosensitivity reactions, scleroderma.
Sensory System: ear disorder, optic atrophy, optic neuritis, abnormality of accommodation, abnormal vision, blindness, retinal disorder. Urogenital System: enlarged uterine fibroids, uterine hemorrhage, increased urinary frequency, bladder carcinoma, kidney failure, hematuria, urate crystalluria, urine abnormality.
Other: ascites, allergic reaction, asthenia, chills, fetal chromosome abnormality, death, fever, hernia, malaise, injection site reaction. Adverse reactions are rarely of sufficient severity to require dosage reduction or discontinuation of treatment.
If reactions are severe, it may be beneficial to reduce the dosage. 2 Clinical Trial Adverse Reactions The clinical trial data on which the original indication was authorized is not available. 3 Less Common Clinical Trial Adverse Reactions The clinical trial data on which the original indication was authorized is not available.
4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data The clinical trial data on which the original indication was authorized is not available. 5 Post-Market Adverse Reactions Meningioma.