cyproterone

Has antiandrogenic and progestogenic/antigonadotropic properties, resulting in blocked binding of the active metabolite of testosterone on the surface of prostatic cancer cells and decreased production of testicular testosterone.

Therapeutic effects:

Decreased spread of prostate cancer.

Pharmacokinetics ⬆ ⬇

Absorption: Completely absorbed following oral administration. Absorption after IM depot injection is delayed and prolonged.

Distribution: Unknown.

Metabolism/Excretion: Metabolized by the CYP3A enzyme system; excreted in feces (60%) and urine (33%), as unchanged drug and metabolites.

Half-Life: PO: 38 hr; IM: 4 days.

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3–4 hr	8–12 hr
IM (depot)	unknown	3–4 days	1–2 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Liver disease/hepatic impairment/liver tumors (not due to prostate cancer);
Dubin Johnson syndrome;
Rotor syndrome;
History of meningioma;
Wasting diseases (not related to prostate cancer);
Severe depression;
Thromboembolism;
OB: Not indicated for use in women;
Pedi: Not recommended for use in children 18 yr.

Use Cautiously in:

History of cardiovascular disease;
Renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: fatigue, weakness, depression, MENINGIOMAS

Resp: cough, dyspnea, pulmonary microembolism

CV: edema, heart failure, hypotension, myocardial infarction, syncope, tachycardia, THROMBOEMBOLISM, vasovagal reactions

GI: anorexia, constipation, diarrhea, HEPATOTOXICITY, LIVER TUMORS, nausea, vomiting

Derm: ↑sweating, dry skin, hot flashes, patchy hair loss

Endo: adrenal suppression, antiandrogen withdrawal syndrome, gynecomastia

F and E: hypercalcemia

GU: impotence, infertility

Hemat: anemia, thrombocytopenia

Metab: glucose intolerance, hyperlipidemia

MS: osteoporosis (long term use)

Misc: allergic reactions

Interactions ⬆ ⬇

Drug-drug:

Antiandrogenic effect may be ↓ by alcohol
Effectiveness/long-term survival may be ↓ by concurrent GnRH agonist treatment.
↑risk of myopathy with HMG CoA reductase inhibitors (statins).
Blood levels and effects may be ↑ by strong inhibitors of CYP3A4 including clotrimazole, itraconazole, ketoconazole and ritonavir.
Blood levels and effectiveness may be ↓ by inducers of CYP3A4 including phenytoin, and rifampicin.
Use cautiously with other drugs that are substrates of the P450 enzymes.

Drug-Natural Products:

Blood levels and effectiveness may be ↓ by St. John's wort.

Route/Dosage ⬆ ⬇

PO (Adults ): 200–300 mg/day in 2–3 divided doses, not to exceed 300 mg/day; After orchiectomy: 100–200 mg/day.
IM (Adults ): 300 mg once weekly; After orchiectomy: 300 mg every 2 wk

Availability ⬆ ⬇

Tablets: 50 mg
In combination with: Ethinyl estradiol (Diane-35, Cyestra-35, Cleo-35)

Assessment ⬆ ⬇

Assess for signs and symptoms of thromboembolism (chest pain, dyspnea, vital signs, level of consciousness). Discontinue therapy if symptoms occur.
Monitor mood changes, especially during first 6–8 wk. Note degree to which these thoughts and behaviors interfere with daily functioning. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.

Lab Test Considerations:

Monitor PSA during therapy. May cause increase in PSA. If PSA increase occurs discontinue therapy and monitor for 6–8 wk for withdrawal response prior to any decision to proceed with other prostate cancer therapy.
May impair carbohydrate metabolism. Monitor fasting blood glucose and glucose tolerance tests periodically during therapy, especially in patients with diabetes. May require dose changes in insulin or oral antidiabetic agents.
Monitor CBC and platelet count periodically during therapy.
Monitor liver function tests prior to and periodically during therapy and if symptoms of hepatotoxicity occur. May develop several wk to mo after therapy starts. Discontinue therapy if hepatotoxicity occurs.
Monitor adrenocortical function tests by serum cortisol assay periodically during therapy.

Implementation ⬆ ⬇

PO: Take by mouth two or three times a day with or just after meals as directed. Dose is usually lower after orchiectomy.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take cyproterone as directed. Take missed doses as soon as remembered, unless almost time for next dose, then skip missed dose and resume usual dosing schedule. Do not double dose.
Inform patient that benign breast lumps may occur; they generally subside 1–3 mo after discontinuation of therapy and/or after dose reduction. Dose reduction should be weighed against the risk of inadequate tumor control.
Advise patient to avoid alcohol during therapy.
May cause fatigue and lassitude during first few wk of therapy; then diminishes. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Inform patient that sperm count and volume of ejaculate decrease with therapy. Infertility is common but is reversible when therapy is discontinued.
Discuss with patient potential for patchy hair loss. Explore methods of coping.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Emphasize the importance of follow-up appointments and blood tests to monitor progression of treatment.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇