PI-064 - DRUG-DRUG INTERACTIONS BETWEEN ANDROGEN RECEPTOR SIGNALING INHIBITORS AND DIRECT-ACTING ORAL ANTICOAGULANTS IN PATIENTS WITH PROSTATE CANCER: LIMITED AGREEMENT BETWEEN VARIOUS DRUG-DRUG INTERACTION INFORMATION SOURCES

D. Burger^1,2, L. Nijboer³, B. van de Steeg⁴, E. Boerrigter³, M. Benoist⁵, F. Jansman⁵, L. Van der Linden⁶, I. Van oort³, K. Kramers³, n. Mehra³, N. van Erp³; ¹Radboud University Medical Center, Nijmegen, The Netherlands, ²Global DDI Solutions, Utrecht, The Netherlands, ³RadboudUMC, Nijmegen, The Netherlands, ⁴Van Poppel Pharmacy, Wijchen, The Netherlands, ⁵Deventer Hospital, Deventer, The Netherlands, ⁶Leuven Hospital, Leuven, Belgium.

Background: Androgen receptor signaling inhibitors (ARSIs) are frequently used in prostate cancer treatment. These patients have an increased risk of venous thromboembolism and are candidates to receive direct-acting oral anticoagulants (DOACs). These two drug classes may interact with each other with clinically relevant outcomes (i.e.: clotting or bleeding), making drug-drug interaction (DDI) management essential when co-prescribed. Unfortunately, product labels often provide incomplete DDI recommendations. As a result, many clinicians rely on on-line sources, i.e., ‘Interaction Checkers’, whose quality can vary. Hence, to explore similarities and discrepancies, we compared the recommendations for DDIs between ARSIs and DOACs across four freely available Interaction Checkers.

Methods: On August 5, 2024, we compared the recommendations of the following Interaction Checkers: Lexicomp/UpToDate, Drugs.com, Medscape, and DDIManager.co. DDI recommendations were standardized into three categories: “no or minimal interaction expected; no action” (green); “clinically relevant interaction expected; action needed” (orange); or “severe interaction expected, do not co-administer” (red). Agreement was defined as complete (100%), partial (75%) or minimal (50%).

Results: Four ARSIs (abiraterone, apalutamide, darolutamide, and enzalutamide) were evaluated with four DOACs (apixaban, dabigatran, edoxaban and rivaroxaban), resulting in a total of 16 DDI pairs (see Table 1). Complete agreement in DDI recommendations was observed in 5/16 (31%) DDI pairs and partial agreement in 7/16 (44%). Minimal agreement (i.e., all three categories of DDI recommendations were found) was noted in 4/16 (25%) DDI pairs. Enzalutamide showed the highest agreement among ARSIs, while apixaban had the highest agreement among DOACs. Abiraterone and enzalutamide were listed “red” for all DOACs in the EHRA practical guide (2021); remarkably, for abiraterone this is in complete disagreement with the other Interaction Checkers (all green).

Conclusion: The tested Interaction Checkers provided similar DDI recommendations in only a minority of ARSI – DOAC pairs. An alarming 25% of DDI pairs showed completely opposite DDI recommendations, as was also the case with the EHRA practical guide. Greater effort is needed to improve consistency in DDI information sources.