Drug Interactions between Androgen Receptor Axis-Targeted Therapies and Antithrombotic Therapies in Prostate Cancer: Delphi Consensus.

Simple Summary: Prostate cancer is most commonly diagnosed in males after the age of 55 years. These patients are also at risk for cardiovascular disease and venous thromboembolism requiring antithrombotic therapy. Prostate cancer treatments, such as androgen receptor axis-targeted therapies (ARATs, i.e., abiraterone acetate, apalutamide, darolutamide, and enzalutamide), may interact with common antithrombotic medications like warfarin, clopidogrel, and the direct oral anticoagulants. However, the data detailing the clinical outcomes of patients treated with these combinations are limited. We undertook a comprehensive review of the literature and modified Delphi process to enable development of an evidence-based consensus document for the co-prescribing of ARATs with antithrombotic medications. Our assessments relied heavily on pharmacokinetic data and extrapolation from drug interaction studies of similarly metabolized drugs, highlighting the need for more research into the clinical impact of drug interactions in prostate cancer patients. Nonetheless, we provide a practical framework to support clinicians in day-to-day therapeutic decision making. Background/Objectives: Abiraterone acetate, apalutamide, darolutamide, and enzalutamide, which make up the androgen receptor axis-targeted therapies (ARATs) drug class, are commonly used in the management of prostate cancer. Many patients on ARATs also receive oral antithrombotic therapy (i.e., anticoagulants or antiplatelets). The concomitant use of ARATs and antithrombotic therapies creates the potential for clinically relevant drug–drug interactions, but the literature regarding the actual consequences of these interactions, and guidance for co-prescribing, is limited. We assembled a multidisciplinary panel of experts and provided them with clinical information derived from a comprehensive literature review regarding the drug–drug interactions between ARATs and antithrombotic therapies. Methods: A three-stage modified electronic Delphi process was used to gather and consolidate opinions from the panel. Each stage consisted of up to three rounds of voting to achieve consensus on which ARAT/antithrombotic therapy drug pairs warrant attention, the possible clinical consequences of drug–drug interactions, and suggested actions for management. Results: The panel achieved consensus to avoid 11 ARAT/antithrombotic therapy drug pairs and modify therapy for eight pairs. Assessments relied heavily on pharmacokinetic data and extrapolation from drug–drug interaction studies of similarly metabolized drugs. Conclusions: This e-Delphi process highlights the need for further research into the clinical impact of ARAT/antithrombotic drug interactions. Nonetheless, the suggested actions aim to provide clinicians with a practical framework for therapeutic decision making. [ABSTRACT FROM AUTHOR]