Literature-based case analysis of serious adverse drug events associated with edoxaban

Abstract

Background: Edoxaban, a direct oral factor Xa inhibitor, is widely used for stroke prevention in non-valvular atrial fibrillation and for the treatment of deep vein thrombosis and pulmonary embolism. Compared with warfarin, edoxaban offers non-inferior thromboembolic protection with a lower risk of major bleeding. However, with the increasing clinical use of edoxaban, reports of serious adverse events (AEs) have emerged, necessitating a comprehensive safety assessment.

Methods: A comprehensive systematic literature search of 6 databases was conducted until December 2024. Case reports of serious AEs were included. Data extraction was performed using a structured Excel-based data collection form. Descriptive statistical analyses were performed to summarize the characteristics of the cases.

Results: 41 cases of serious AEs met the inclusion criteria. 26 involved severe bleeding events, whereas 2 cases involved thrombotic events. 7 patients had medication errors. P-glycoprotein inhibitors were co-administered in 9 cases, contributing to increased bleeding risk, while P-gp inducers were used in 2 cases, potentially reducing edoxaban efficacy. The median time to AE onset was within one month in 18 cases, but 1 case occurred after four years of therapy. 6 patients died, of whom 4 deaths were attributed to AEs.

Conclusion: This study highlights the clinical risks associated with edoxaban, particularly in elderly patients, those with impaired renal function, and those receiving concomitant P-gp inhibitors. In addition to confirming previously known risk factors, this study provides practical prescribing insights by synthesizing real-world evidence on medication errors, inappropriate co-administration, and off-label use. These findings are of direct relevance to prescribers and underscore the importance of individualized risk assessment and continuous pharmacovigilance.

Keywords: Bleeding; Drug interactions; Edoxaban; Pharmacovigilance; Serious adverse events.