Dosing &
Monitoring

 

When to Modify Dose

Dosing Modifications

hepatic table

For patients with moderate hepatic impairment (Child-Pugh Class B)* monitor serum transaminases (ALT [alanine aminotransferase] and AST [aspartate aminotransferase]) and bilirubin levels:

  • Prior to the start of treatment
  • For the first month of treatment, monitor every week
  • For the following 2 months of treatment, monitor every 2 weeks
  • Monthly thereafter

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

  • Patient develops hepatotoxicity: ALT (alanine aminotransferase) and/or AST (aspartate aminotransferase)
    >5X ULN (upper limit of normal) or total bilirubin >3X ULN
    • Withhold ZYTIGA® treatment and monitor LFTs*
    • Patient's LFTs return to baseline levels or patient's AST and ALT ≤2.5X ULN and total bilirubin ≤1.5X ULN
      — Resume ZYTIGA® at 750 mg once daily
    • Monitor AST, ALT, and bilirubin at a minimum of every 2 weeks for 3 months and monthly thereafter

Recurrence of hepatotoxicity (at 750 mg dose)

  • If hepatotoxicity recurs at 750 mg once daily:
    • Withhold ZYTIGA® treatment and monitor LFTs*
    • When patient's LFTs return to baseline levels or patient's AST and ALT ≤2.5X ULN and total bilirubin ≤1.5X ULN
      —    Resume ZYTIGA® at 500 mg once daily

* LFT: Liver Function Test

Recurrence of hepatotoxicity (at 500 mg dose)

  • If hepatotoxicity recurs at 500 mg once daily:
            —    Discontinue treatment with ZYTIGA®

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

  • Avoid concomitant strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during ZYTIGA® treatment
  • Although there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers, because of the potential for an interaction, if a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency to twice a day only during the co-administration period (eg, from 1,000 mg once daily to 1,000 mg twice a day)
  • Reduce the dose back to previous dose and frequency if the concomitant strong CYP3A4 inducer is discontinued

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.