PDG5 COMMONLY REPORTED ADVERSE EVENTS ASSOCIATED WITH ANTICOAGULANTS USING FDA ADVERSE EVENT REPORTING SYSTEM DATABASE 2012-2018

Abstract

Newer oral anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Edoxaban (DOACs) have been used for prevention and treatment of deep vein thrombosis and pulmonary embolisms. DOACs use has risen rapidly because Warfarin has a higher risk of major bleeding. The study objectives were to 1) describe the most commonly reported adverse events (AEs) associated with DOACs and Warfarin, and 2) outline patients’ demographics involved in the AE’s reports. This was a retrospective descriptive time-series study. Drug safety data were extracted from the FDA Adverse Event Reporting System (FAERS). Study period was from first quarter 2012 to second quarter 2018. Number of AEs and patient cases were calculated and compared among study DOAC drugs quarterly and annually. Patients’ age and sex were summarized and compared using R program and SAS/STAT software Version 9.4 (Cary, NC, USA). Total number of AE reports for DOACs was 135,333 for Dabigatran, 336,348 for Rivaroxaban, 170,962 for Apixaban, and 1,969 for Edoxaban for study period. Meanwhile, there were 487,244 AE reports for Warfarin . Mean age (SD) of involved patients was 72.5 (3.9) for Dabigatran, 68.5 (5.3) for Rivaroxaban, 70.6 (5.2) for Apixaban, 70.3 (3.7) for Edoxaban, and 62.5 (4.1) for Warfarin. Proportion of female patients was 46% for Dabigatran, 36% for Rivaroxaban, 47% for Apixaban, 41% for Edoxaban, and 47% for Warfarin. The most common DOACs adverse events included several kinds of hemorrhage, such as gastrointestinal and internal, dyspnea, fatigue, nausea, and headache. In this analysis less commonly AE reported in the literature for DOACs were found including spinal cord, ocular, renal, liver, and kidney problems. The unexpected and severe hemorrhage and bleeding are associated with all four anticoagulants, which shows the need for therapeutic risk management in post-marketing surveillance.