(B-139) A comparative evaluation of potential rivaroxaban drug interactions from four database programs

Background: Rivaroxaban, a direct factor Xa inhibitor, is widely prescribed for the prevention or treatment of thrombotic events. Its plasma concentration is influenced by hepatic cytochrome P450-3A4 enzyme and P-glycoprotein transporter, making it susceptible to drug-drug interactions (DDIs). Identifying potential DDIs can facilitate early interventions, protecting patients from bleeding or thrombotic complications. However, the consistency of DDI references is often questioned.

Objectives: To evaluate the consistency of information on drugs potentially interacting with rivaroxaban as reported in four database programs.

Methods: We extracted lists of rivaroxaban DDIs from Micromedex, Lexicomp, Medscape, and Epocrates from December, 2023 to February, 2024. Descriptive analyses were conducted on the scope of drugs listed, severity categories, evidence grading, and sources of conclusions. Additionally, the Fleiss’ kappa coefficient was used to assess consistency among the sources.

Results: A total of 479 rivaroxaban DDIs were identified: 193 (40.3%) from Micromedex, 291 (60.8%) from Lexicomp, 162 (33.8%) from Medscape, and 313 (65.3%) from Epocrates. Only 85 (17.7%) interactions were listed in all four sources, while 227 (47.4%) were unique to a single source, indicating slight agreement for the scope of drugs listed (kappa coefficient 0.102). Among 85 drugs listed in all four sources, severity was categorized as major or above in 82 (96.5%) in Micromedex, 54 (63.5%) in Lexicomp, 20 (23.5%) in Medscape, and 53 (62.3%) in Epocrates, showing poor agreement (kappa coefficient -0.031). Micromedex and Lexicomp provided evidence grading and sources. In Micromedex, only 29 (15.0%) of 193 DDIs rated supporting evidence as good or excellent, while 160 (82.9%) were extrapolated from interactions with similar drugs or pharmacological mechanisms. Similarly, only 54 (18.5%) of 291 DDIs in Lexicomp had good supporting evidence, while 227 (78.0%) were extrapolated.

Conclusions: There is significant variability in rivaroxaban DDIs listings across sources, with most DDIs lacking credible evidence. Harmonization in DDI compendia and further studies on clinical impacts are needed. In clinical practice, healthcare professionals should consult multiple references, rather than rely on a single source.