Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
- In postmarketing experience, there have been ZYTIGA-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths. Permanently discontinue ZYTIGA for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.
- Hepatobiliary Disorders: fulminant hepatitis, including acute hepatic failure and death.
ZYTIGA may cause serious side effects including:
- Liver problems. Liver failure may occur, which can lead to death. Tell your healthcare provider if you notice any of the following changes:
- yellowing of the skin or eyes
- darkening of the urine
- severe nausea or vomiting
Post Marketing Experience
- addition of... Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis.
Effects of Abiraterone on Drug Metabolizing Enzymes
- In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA.
6 ADVERSE REACTIONS
6.2 Post Marketing Experience...addition of non-infectious pneumonitis
- Zytiga can cause fetal harm when administered to a pregnant woman. Zytiga is not indicated for use in women…
WARNINGS AND PRECAUTIONS
Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess:
- Zytiga may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition…
- Adrenal insufficiency occurred in the two randomized clinical studies in 0.5% of patients taking Zytiga and in 0.2% of patients taking placebo…
- In the two randomized clinical trials, grade 3 or 4 ALT or AST increases (at least 5X ULN) were reported in 4% of patients who received Zytiga, typically during the first 3 months after starting treatment…
7 ADVERSE REACTIONS
7.1 Drug Interaction, Effects of Abiraterone on Drug Metabolizing Enzymes
- ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid coadministration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3)].