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 ↓ production of testicular testosterone.

Therapeutic effects:

Decreased spread of prostate cancer.

Pharmacokinetics ⬆ ⬇

Absorption: PO: Completely absorbed. IM: delayed and prolonged absorption after depot injection.

Distribution: Unknown.

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

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

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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.

Use Cautiously in:

Cardiovascular disease;
Renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, HF, hypotension, MI, syncope, tachycardia, THROMBOEMBOLISM, vasovagal reactions

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

Endo: adrenal suppression, antiandrogen withdrawal syndrome, glucose intolerance, gynecomastia

F and E: hypercalcemia

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

GU: impotence, infertility

Hemat: anemia, thrombocytopenia

Metab: hyperlipidemia

MS: osteoporosis

Neuro: fatigue, weakness, depression, MENINGIOMAS

Resp: cough, dyspnea, pulmonary microembolism

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).
Strong CYP3A4 inhibitors, including clotrimazole, itraconazole, ketoconazole and ritonavir, may ↑ levels and risk of toxicity.
Strong CYP3A4 inducers, including phenytoin and rifampin, may ↓ levels and effectiveness.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness.

Route/Dosage ⬆ ⬇

PO (Adults ): 200—300 mg/day in 2—3 divided doses (max dose = 300 mg/day); After orchiectomy: 100—200 mg/day.
IM (Adults ): 300 mg once weekly; After orchiectomy: 300 mg every 2 wk.

Availability ⬆ ⬇

Oil for IM depot injection: 100 mg/mL
Tablets: 50 mg
In combination with:
ethinyl estradiol (Diane-35, Cyestra-35, Cleo-35).

Assessment ⬆ ⬇

Assess for signs/symptoms of thromboembolism (chest pain, dyspnea, vital signs, level of consciousness). If thromboembolism occurs, discontinue cyproterone.
Monitor mood changes, especially during 1st 6—8 wk. Note degree to which these thoughts and behaviors interfere with daily functioning. Inform health care provider if patient demonstrates significant ↑ in anxiety, nervousness, or insomnia.

Lab Test Considerations:

Monitor PSA during therapy. May ↑ PSA. Discontinue cyproterone if PSA ↑ occurs and monitor for 6—8 wk for withdrawal response before 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 other antidiabetic agents.
Monitor CBC periodically during therapy.
Monitor liver function tests before and periodically during therapy and if symptoms of hepatotoxicity occur. Elevated liver enzymes may develop several weeks to months after therapy starts. If hepatotoxicity occurs, discontinue cyproterone.
Monitor adrenocortical function tests by serum cortisol assay periodically during therapy.

Implementation ⬆ ⬇

PO: Administer at the same time each day, after meals and with liquids. Dose is usually lower after orchiectomy.
IM: Administer slowly and avoid IV injection, which can lead to pulmonary microembolism.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take 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.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient that benign breast lumps may occur; they generally subside 1—3 mo after discontinuation of therapy and/or after dose ↓. Dose ↓ should be weighed against the risk of inadequate tumor control.
Advise patient to avoid alcohol during therapy.
May cause fatigue and lassitude during 1st few weeks of therapy; then diminishes. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient that sperm count and volume of ejaculate ↓ with therapy. Infertility is common but reversible when therapy is discontinued (usually within 3—5 mo but may take up to 20 mo).
Discuss with patient potential for patchy hair loss. Explore methods of coping.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇