abiraterone

TOP 100

a-bir-a-ter-one (Yonsa, Zytiga)

Do not confuse Zytiga with Zetia or ZyrTEC.

• PHARMACOTHERAPEUTIC: Anti-androgen. CLINICAL: Antineoplastic.

Treatment of metastatic castration-resistant prostate cancer in combination with prednisone (Zytiga) or methylprednisolone (Yousa). Zytiga: Treatment of metastatic, high-risk castration-sensitive prostate cancer (in combination with prednisone).

Contraindications: Hypersensitivity to abiraterone. Use in women who are pregnant or may become pregnant. Cautions: History of cardiovascular disease (especially HF, recent MI, or ventricular arrhythmia) due to potential for hypertension, hypokalemia, fluid retention; moderate hepatic impairment; adrenal insufficiency. Avoid use with strong CYP3A4 inducers.

Selectively and irreversibly inhibits CYP17, an enzyme needed for androgen biosynthesis (expressed in testicular, adrenal, or prostatic tumor tissue). Inhibits formation of testosterone precursors DHEA and androstenedione. Therapeutic Effect: Lowers serum testosterone to castrate levels.

Widely distributed. Protein binding: 99%. Primarily excreted in feces. Peak plasma concentration: 2 hrs. Half-life: 12 hrs (up to 19 hrs with hepatic impairment).

Pregnancy/Lactation: Contraindicated in women who are or may become pregnant. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

DRUG: May increase concentration/effects of doxorubicin (conventional), thioridazine. May decrease concentration/effect of tamoxifen. Strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin), dabrafenib, enzalutamide, lorlatinib may decrease concentration/effect. HERBAL: None significant. FOOD: Do not give with food (no food should be consumed for at least 2 hrs before or 1 hr after dose). LAB VALUES: May increase serum ALT, AST, bilirubin, triglycerides. May decrease serum potassium, phosphate.

Tablets: (Yonsa): 125 mg. (Zytiga): 250 mg, 500 mg.

PO

(Yonsa):

• May give without regard to food. · Do not break, crush, dissolve, or divide tablets. Give whole with water. · (Zytiga): Give on empty stomach only (at least 1 hr before or 2 hrs after food). · Give with water. · Administer whole. Do not break, crush, dissolve, or divide tablets. Women who are or may become pregnant should wear gloves if handling the tablets.

■ALERT ■ Consider increased dosage of predniSONE during unusual stress or infection. Interrupting predniSONE therapy may induce adreno-corticoid insufficiency. Note: Pts should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Metastatic Castration-Resistant Prostate Cancer

PO: ADULTS, ELDERLY: (Yonsa): 500 mg once daily (with methylPREDNISolone 4 mg 2 times/day). (Zytiga): 1,000 mg once daily (with predniSONE 5 mg 2 times/day).

Metastatic Castration-Sensitive Prostate Cancer

PO: ADULTS, ELDERLY: (Zytiga): 1,000 mg once daily (with prednisone 5 mg once daily).

Dosage Modification

Hepatic Enzymes Greater Than Upper

Limit of Normal (ULN) (During Treatment)

If hepatotoxicity occurs at reduced dose of 500 mg daily, discontinue treatment.

Dosage Adjustment for Concomitant Strong CYP3A4 Inducers

Increase abiraterone dose to 1,000 mg twice daily.

Dosage in Renal Impairment

No dose adjustment.

Dosage in Hepatic Impairment

Mild impairment: No dosage adjustment necessary. Moderate impairment: Reduce dose to 250 mg daily. Discontinue if serum ALT, AST greater than 5 times ULN or serum bilirubin greater than 3 times ULN. Severe impairment: Avoid use.

Frequent (30%–26%): Joint swelling/discomfort, peripheral edema, muscle spasm, musculoskeletal pain, hypokalemia. Occasional (19%–6%): Hot flashes, diarrhea, UTI, cough, hypertension, urinary frequency, nocturia. Rare (less than 6%): Heartburn, upper respiratory tract infection.

Mineralocorticoid excess (severe fluid retention, hypokalemia, hypertension) may compromise pts with prior cardiovascular history. Safety not established in pts with left ventricular ejection fraction less than 50%. Tachycardia, atrial fibrillation, supraventricular tachycardia, atrial flutter, complete AV block, bradyarrhythmia reported in 7% of pts. Chest pain, unstable angina, HF reported in less than 4% of pts. Stress, infection, or interruption of daily steroids may cause adrenocortical insufficiency. Hepatotoxicity (serum ALT, AST greater than 5 times ULN) reported in 2% of pts. Pts with hepatic impairment are more likely to develop hepatotoxicity

• BASELINE ASSESSMENTObtain BMP, LFT. Question history of HF, myocardial infarction, arrhythmias, angina pectoris, peripheral edema, hepatic impairment, adrenal or pituitary abnormalities, left ventricular ejection fraction (if applicable). Question history of corticosteroid intolerance if applicable.INTERVENTION/EVALUATIONMonitor BMP as clinically indicated. Monitor for mineralocorticoid excess (hypokalemia, hypertension, fluid retention) at least once monthly. Assess for cardiac arrhythmia if hypokalemia occurs. Obtain ECG for palpitations, dyspnea, dizziness. Monitor for symptoms of adrenocortical insufficiency during predniSONE interruption, periods of stress, infection. Measure serum ALT, AST, alkaline phosphatase, bilirubin every 2 wks for 3 mos, then monthly. If hepatotoxicity occurs, dosage modification will be necessary. Pts with moderate hepatic impairment must have LFT every wk for first month, then every 2 wks for 2 mos, then monthly. If serum ALT, AST above 5 times ULN or serum bilirubin above 3 times ULN, treatment should be discontinued.PATIENT/FAMILY TEACHING
• Must be taken on empty stomach (no food 2 hrs before and 1 hr after dose). · If taken with food, toxic levels may result. · Sexually active men must wear condoms during treatment and for 1 wk after treatment. · Women who are pregnant or are planning pregnancy may not touch medication without gloves. · Dizziness, palpitations, headache, confusion, muscle weakness, leg swelling/discomfort may become more apparent during periods of unusual stress, infection, or interruption of predniSONE therapy. · Report liver problems (yellowing of skin, bruising, light-colored stool, right upper quadrant pain), chest pain, palpitations. · An increase in urinary frequency or nocturia is expected as treatment becomes therapeutic. · Do not chew, crush, dissolve, or divide tablets.