For patients with moderate hepatic impairment (Child-Pugh Class B)* monitor serum transaminases (ALT [alanine aminotransferase] and AST [aspartate aminotransferase]) and bilirubin levels:
If elevations in ALT and/or AST >5X ULN (upper limit of normal) or total bilirubin >3X ULN occur, discontinue ZYTIGA® and do not re-treat patients with ZYTIGA®.
*There are no clinical data for ZYTIGA® 250 mg once daily in patients with moderate hepatic impairment, and caution is advised
To determine the Child-Pugh classification of your patient, view the FDA guidelines.
Permanently discontinue ZYTIGA® (abiraterone acetate) for patients who develop a concurrent elevation of ALT greater than 3X ULN and total bilirubin greater than 2X ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.
First occurrence of hepatotoxicity
Recurrence of hepatotoxicity (at 750 mg dose)
* LFT: Liver Function Test
Recurrence of hepatotoxicity (at 500 mg dose)
The safety of ZYTIGA® re-treatment of patients who develop AST or ALT ≥20X ULN and/or bilirubin ≥10X ULN is unknown.
For patients taking strong CYP3A4 inducers
References: 1. Auchus RJ. The genetics, pathophysiology, and management of human deficiencies of P450c17. Endocrinol Metab Clin North Am. 2001;30(1):101-119. 2. Attard G, Reid AHM, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008;26(28):4563-4571. 3. Krasner AS. Glucocorticoid-induced adrenal insufficiency. JAMA. 1999;282(7):671-676. 4. Kraan GPB, Dullaart RPF, Pratt JJ, Wolthers BG, Drayer NM, De Bruin R. The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different. J Clin Endocrinol Metab. 1998;83(4):1247-1252.