Drug-drug interactions between abiraterone (ABI) or enzalutamide (ENZ) and concomitant medications in patients with metastatic castration resistant prostate cancer (mCRPC)

Abstract

Introduction: Patients with mCRPC are generally elderly with several comorbidities requiring concomitant medications. ABI and ENZ are two oral drugs approved for treatment of mCRPC that target androgen signaling. Since these drugs have comparable results, the therapeutic choice might be driven by patient's comorbidities and concomitant therapies. ABI is metabolized by the enzyme sulfotransferase 2A1 and by CYP3A4. ENZ is metabolized by enzyme CYP2C8, with minor CYP3A4/5 involvement. Our aim was to evaluate the most frequent concomitant medications in patients with mCRPC and their possible interaction with ABI and ENZ. Patients and Methods: Patients with mCRPC treated at our Institution were assessed, concomitant medications were registered and those with hepatic metabolism were examined for possible interaction with ABI and ENZ. Descriptive statistics were used. Results: Forty-five patients with mCRPC were included: the median age was 67.8 years. The most frequent comorbidities were hypertension in 55%, hypercholesterolemia in 13%, ischemic heart disease in 11%, and diabetes mellitus in 9%. The most frequently medications taken by patients were: lansoprazole in 47%, oxycodone in 27%, paracetamol in 22%, statins in 13%, codeine in 13%, and warfarin in 4%. Lansoprazole is metabolized by CYP2C19 and CYP3A4, which are both moderately inhibited by ABI, whereas ENZ is a strong CYP3A4 inducer and moderate CYP2C19 inducer. Statins are metabolized by CYP3A4. Oxycodone, codeine and paracetamol are metabolized by CYP2D, which is strongly inhibited by ABI, while ENZ is a weakly inducer. Warfarin is metabolized by CYP2C9, which is induced by ENZ. Conclusion: ABI and ENZ differently affect the metabolism of some common concomitant medications in patients with mCRPC with possible reduced efficacy or increased toxicity. The different pharmacokinetic profile should be accounted in the choice of treatment for mCRPC.