Enzalutamide and apalutamide significantly reduce exposure to warfarin and DOACs due to strong induction of CYP3A4 and P-glycoprotein, affecting anticoagulant effectiveness.
What are the pharmacokinetic drug-drug interactions between second-generation antiandrogens and commonly used anticoagulants in patients with prostate cancer?
Darolutamide and abiraterone are preferred over enzalutamide and apalutamide in prostate cancer patients requiring chronic anticoagulation due to minimal pharmacokinetic interactions.
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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.
Duong et al. (Tue,) reported a other. Enzalutamide and apalutamide significantly reduce exposure to warfarin and DOACs due to strong induction of CYP3A4 and P-glycoprotein, affecting anticoagulant effectiveness.