Antiandrogen therapies: Management of drug interactions with anticoagulation

Background Second-generation antiandrogens have significantly improved outcomes in patients with prostate cancer; however, their complex pharmacokinetic profiles can result in significant drug-drug interactions (DDIs) in patients with comorbid conditions which require chronic anticoagulation. Objective This review aims to describe the DDIs between antiandrogens and commonly used anticoagulants, with a focus on understanding the clinical implications of pharmacokinetics and drug metabolism. Methods A comprehensive literature review of pharmacokinetic data, clinical trials, and prescribing information was performed. Drug metabolism of antiandrogens and anticoagulants was examined, including the effects of CYP450 enzyme and/or P-glycoprotein (P-gp) inhibition and induction on anticoagulant efficacy and safety. Results Enzalutamide and apalutamide are strong inducers of CYP3A4, which may reduce exposure to warfarin, apixaban, and rivaroxaban. Apalutamide induces P-gp, and therefore has DDIs with all direct oral anticoagulants (DOACs). Darolutamide and abiraterone exhibit minimal CYP450 induction and inhibition, and do not interact with warfarin or DOACs. Conclusion Drug-drug interactions between antiandrogens and anticoagulants are common and can affect therapeutic efficacy and safety. Clinical decision-making surrounding drug selection requires an interprofessional approach grounded in pharmacokinetic knowledge to ensure safe and effective care in patients with prostate cancer.