Zytiga Drug Interactions

Effect of food on abiraterone: Administration of ZYTIGA with food significantly increases the absorption of abiraterone. The efficacy and safety of ZYTIGA given with food has not been established. ZYTIGA must not be taken with food (see Dosage & Administration, Precautions and Pharmacology: Pharmacokinetics under Actions).
Interactions with other drugs: Potential for other drugs to affect abiraterone exposures: In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer (rifampicin, 600 mg daily for 6 days) followed by a single dose of abiraterone acetate 1,000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55%.
Strong inducers of CYP3A4 (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital) during treatment with ZYTIGA are to be avoided, or used with careful evaluation of clinical efficacy.
In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.
Potential for ZYTIGA to affect exposures to other drugs: Abiraterone is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a clinical study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the CYP2D6 substrate dextromethorphan, the systemic exposure (AUC) of dextromethorphan was increased by approximately 200%. The AUC₂₄ for dextrorphan, the active metabolite of dextromethorphan, increased approximately 33%.
Caution is advised when ZYTIGA is administered with drugs activated by or metabolized by CYP2D6, particularly with drugs that have a narrow therapeutic index. Dose reduction of narrow therapeutic index drugs metabolized by CYP2D6 should be considered.
In the same study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the CYP1A2 substrate theophylline, no increase in systemic exposure of theophylline was observed.
In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone was increased by 46% and the AUCs for M-III and M-IV, the active metabolites of pioglitazone, each decreased by 10% when pioglitazone was given together with a single dose of 1000 mg abiraterone acetate. Patients should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA. Examples of medicinal products metabolized by CYP2C8 include pioglitazone and repaglinide.