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

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.

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.

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.

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.