Interactions Between Direct Oral Anticoagulants and Drugs Involving CYP-Enzymes and P-gp Transporters Detected by a Clinical Decision Support System: A Retrospective Cohort Study.

Purpose: Physicians can be supported by electronic clinical decision support systems (CDSS) for drug-drug interaction (DDI) management of DDIs between direct oral anticoagulants (DOACs) and CYP3 A4/P-glycoprotein (P-gp) inhibitors and inducers, to prevent adverse drug events (ADEs).

Methods: A retrospective cohort study was performed studying DDI alerts for DOAC-CYP3 A4/P-gp influencing drug combination prescriptions in patients admitted to a tertiary care hospital. Patient-, DDI-, and ADE-related data were analyzed to explore CDSS performance and real-world DDI management. A multidisciplinary panel conducted an ADE analysis using the Drug Interaction Probability Scale.

Results: Out of 15,201 triggered CDS alerts, 166 individual alerts were included. Primary indication for DOAC therapy was atrial fibrillation (86.1%). The most involved DOAC was dabigatran (63%). DDI exposure was median 3 days (IQR = 2-7 days). CYP3 A4/P-gp inhibitor DDIs were most prevalent (n = 121), with amiodarone being most prevalently prescribed (71%). Inducers were mainly antiepileptic drugs (n = 31). Thirty-four CDS alerts (20%) were actively shown to the physician upon prescribing (acceptance rate 50%). Eighteen ADEs were identified (11%, 14 bleeding; 4 thromboembolic events), 15 having a possible and 3 a probable probability of being DDI associated.

Conclusion: Despite a low number of observed, potentially associated ADEs, CDSS for DDI management aids physicians to optimize DOAC treatment as the described DDIs can cause significant patient harm. Increased ADE monitoring and larger real-world studies are needed to refine CDS tools and further optimize patient safety.