Cyproterone
Pronunciation
(sye PROE ter one)
Synonyms
Cyproterone Acetate
Generic Available
Yes (Canada)
Canadian Brand Names
Alti-CPA; Androcur®; Androcur® Depot; Gen-Cyproterone
Use
Palliative treatment of advanced prostate carcinoma
Restrictions
Not available in U.S.
Pregnancy Risk Factor
Not indicated for use in women
Pregnancy Implications
In males, sperm count and volume of ejaculate will be reduced. After ~2 months of treatment, infertility may be noted.
Contraindications
Hypersensitivity to cyproterone or any component of the formulation; active liver disease or hepatic dysfunction; renal impairment
Warnings/Precautions
Cyproterone has been associated with hepatic toxicity (jaundice, hepatitis, hepatic failure); typically this toxicity develops after several months of therapy. Monitor hepatic function and consider discontinuation of therapy in patients with evidence of hepatic injury.
Use caution in patients with a history of depression. Cyproterone has been associated with an increased incidence of depression, particularly early in the course of therapy (initial 6-8 weeks). Use with caution in patients with diabetes or impaired glucose tolerance, may cause alterations in glucose metabolism. Use with caution in conditions that may be aggravated by fluid retention, or cardiovascular disease. May increase the risk of thromboembolism and/or alter lipid profiles.
Adverse Reactions
Frequency not defined.
Cardiovascular: Heart failure, hemorrhage, hypotension, MI, stroke, shock, stroke, syncope, tachycardia, thrombosis (DVT, pulmonary embolism, retinal vein thrombosis)
Central nervous system: Libido increased, lassitude, fatigue, weakness, dizziness, encephalopathy, depression, headache
Dermatologic: Dry skin (sebum reduction), patchy loss of body hair, eczema, urticaria, erythema nodosum, rash, exfoliative dermatitis, photosensitivity, scleroderma, pruritus, hirsutism, skin discoloration
Endocrine & metabolic: Hyperglycemia, negative nitrogen balance, gynecomastia, hot flashes, benign nodular breast hyperplasia, galactorrhea, inhibition of spermatogenesis, impotence, adrenal suppression (dose related), hypercalcemia, diabetes mellitus, weight gain/loss
Gastrointestinal: Constipation, diarrhea, dyspepsia, nausea, anorexia, pancreatitis, glossitis, vomiting
Genitourinary: Hematuria, urinary frequency, bladder carcinoma
Hematologic: PT decreased, fibrinogen increased, thrombocytopenia, anemia, hemolytic anemia, leukopenia, leukocytosis
Hepatic: Hepatic dysfunction (dose related), hepatitis, transaminases increased, cholestatic jaundice, cirrhosis, hepatic failure, hepatic necrosis, ascites, hepatic coma, hepatomegaly, hepatoma, hepatic carcinoma
Local: Injection site reaction
Neuromuscular and skeletal: Weakness, myasthenia, osteoporosis
Ocular: Optic neuritis, optic atrophy, abnormal accommodation, abnormal vision, retinal disorder, blindness
Renal: Serum creatinine increased, renal failure
Respiratory: Asthma, bronchospasm, cough, dyspnea, pulmonary embolism, pulmonary fibrosis
Miscellaneous: Allergic reaction
Overdosage/Toxicology
Toxicity is unlikely following single exposures of excessive doses. Any treatment following emesis and charcoal administration should be supportive and symptomatic.
Ethanol/Nutrition/Herb Interactions
Ethanol: May reduce the effect of cyproterone (not established in the treatment of prostatic carcinoma); avoid concurrent use.
Stability
Store at controlled room temperature of 25°C (77°F).
Mechanism of Action
Cyproterone is a steroidal compound with anti-androgenic, anti-gonadotropic, and progestin-like activity.
Pharmacodynamics/Kinetics
Absorption: Oral: Rapid and complete
Metabolism: Hepatic, some metabolites have activity
Half-life elimination: Oral: 38 hours; Depot injection: 4 days
Time to peak, plasma: Oral: 3-4 hours; Depot injection: 3 days
Excretion: Urine (35%, as metabolites); feces (60%)
Dosage
Adults: Males: Prostatic carcinoma (palliative treatment):
Oral: 200-300 mg/day in 2-3 divided doses; following orchiectomy, reduce dose to 100-200 mg/day; should be taken with meals
I.M. (depot): 300 mg (3 mL) once weekly; reduce dose in orchiectomized patients to 300 mg every 2 weeks
Dosage adjustment in renal impairment: Use is contraindicated
Dosage adjustment in hepatic impairment: Use is contraindicated with hepatic impairment or active liver disease
Administration
Administer at the same time each day. Take with meals.
Monitoring Parameters
Liver function tests should be performed at baseline and periodically thereafter, or whenever signs or symptoms suggestive of hepatotoxicity are noted. Adrenal function should be monitored periodically.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Glossitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dosage Forms
Injection, solution, as acetate (Androcur® Depot): 100 mg/mL (3 mL) [contains benzyl benzoate and castor oil]
Tablet, as acetate (Androcur®): 50 mg
International Brand Names
Alti-CPA (CA); Androcur® (CA); Androcur® Depot (CA); Gen-Cyproterone (CA)