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

Area of Science:

• Oncology
• Pharmacology
• Clinical Pharmacy

Background:

• Androgen receptor axis-targeted therapies (ARATs) like abiraterone acetate, apalutamide, darolutamide, and enzalutamide are crucial in prostate cancer management.
• Concomitant use of ARATs with oral antithrombotic therapies (anticoagulants/antiplatelets) is common, raising concerns about drug-drug interactions (DDIs).
• Limited literature exists on the clinical consequences and management guidance for these specific ARAT-antithrombotic DDIs.

Purpose of the Study:

• To establish expert consensus on clinically significant drug-drug interactions between ARATs and antithrombotic therapies.
• To provide guidance for managing potential DDIs in prostate cancer patients receiving both drug classes.

Main Methods:

• A three-stage modified electronic Delphi process involving a multidisciplinary expert panel.
• Comprehensive literature review to inform panel discussions on ARAT/antithrombotic DDIs.
• Consensus-building through multiple voting rounds on drug pairs, clinical consequences, and management strategies.

Main Results:

• Consensus reached to avoid 11 specific ARAT/antithrombotic therapy drug pairs.
• Consensus reached to modify therapy for eight ARAT/antithrombotic therapy drug pairs.
• Assessments primarily utilized pharmacokinetic data and extrapolation from similar drug metabolism studies.

Conclusions:

• The e-Delphi process identified critical ARAT/antithrombotic drug interactions requiring clinical attention.
• The study underscores the need for further research into the clinical impact of these DDIs.
• Suggested management actions offer a practical framework for clinicians managing prostate cancer patients on these concomitant therapies.