Abiraterone

Concurrent infection, stress, or interruption of daily corticosteroids is associated with reports of adrenocortical insufficiency. Monitor closely for signs and symptoms of adrenocorticoid insufficiency, which could be masked by adverse events associated with mineralocorticoid excess. Diagnostic testing for adrenal insufficiency may be clinically indicated. Increased corticosteroid doses may be required before, during, and after stress.

Severe hepatotoxicity (eg, fulminant hepatitis, acute liver failure, and death) has been reported. Significant increases in liver enzymes (including grade 3 and 4 events) have also been observed (higher likelihood in patients with baseline elevations), generally occurring in the first 3 months of treatment. May require dosage reduction, treatment interruption, and/or discontinuation. ALT, AST, and bilirubin should be monitored prior to treatment, every 2 weeks for 3 months and monthly thereafter; patients with hepatic impairment, elevations in liver function tests, or experiencing hepatotoxicity require more frequent monitoring (see dosage adjustment for hepatic impairment and monitoring parameters). Evaluate liver function promptly with signs or symptoms of hepatotoxicity. The safety of retreatment after significant elevations (ALT or AST ≥20 times the upper limit of normal [ULN] and/or total bilirubin ≥10 times ULN) has not been evaluated.

Increased mineralocorticoids due to CYP17 inhibition may result in hypertension, hypokalemia, and fluid retention (including grade 3 and 4 events). Monitor at least monthly for hypertension, hypokalemia, and fluid retention. Concomitant administration with corticosteroids reduces the incidence and severity of these adverse events. Disease-related concerns:

May cause hypertension, hypokalemia, and fluid retention. Control hypertension and correct hypokalemia prior to and during treatment. Use with caution in patients with cardiovascular disease, particularly with heart failure, recent MI, or ventricular arrhythmia. Patients with left ventricular ejection fraction (LVEF) • Hepatic impairment: Do not use in patients with preexisting severe hepatic impairment (Child-Pugh class C); dosage reduction is recommended in patients with baseline moderate impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Abiraterone must be administered on an empty stomach (administer at least 1 hour before and 2 hours after any food); abiraterone AUC (exposure) may be increased up to 10-fold if administered with a meal.