Identification of bleeding adverse events associated with the concurrent administration of Dabigatran and Dronedarone: Investigation of case reports from the FDA adverse event reporting system database

Purpose: An increased risk of bleeding has been noted when Pradaxa^® (Dabigatran) is co-administered with Multaq^® (Dronedarone). To date, no post-marketing data analysis has identified bleeding adverse events associated with the co-administration of Dabigatran and Dronedarone. The study objective was to investigate potential case reports of bleeding associated with the concurrent administration of Dabigatran-Dronedarone in the United States (US) using the Food and Drug Administration adverse event reporting system (AERS) database.

Methods: Reports listing the concurrent administration of Pradaxa, Dabigatran, or Dabigatran Etexilate with Multaq or Dronedarone as the suspect drug, and bleeding events (combined in a single term based on adverse event reports of haemorrhage, rectal haemorrhage, among others) as the adverse event were extracted from the drug’s approval date (Dabigatran, October 19^th, 2010) through the fourth quarter of 2011; data subsequent to fourth quarter of 2011 were not available at the time of this study. Bayesian statistics within the neural network architecture were implemented to identify potential signals of Dabigatran-Dronedarone-associated bleeding events. A potential signal for the co-administration of two drugs-associated adverse event is generated when the lower limit of the 95% two-sided confidence interval of the information component (IC), denoted by IC₀₂₅ is greater than zero.

Results: A total of 89 Dabigatran-Dronedarone combination reports and 11,810 reports concerning bleeding events were extracted. Forty-five out of 89 combination case reports were identified to be associated with reports of bleeding. Potential signal (IC₀₂₅ = 3.80) was generated for bleeding events associated with the co-administration of Dabigatran and Dronedarone.

Conclusion: The extracted case reports and IC values indicate potential signal of bleeding events associated with the co-administration of Dabigatran-Dronedarone. AERS is not capable of establishing the causal link and detecting the true frequency of an adverse event associated with the concurrent administration of two drugs.