Cardiovascular thromboembolic events associated with use of Febuxostat: Investigation of case reports from the FDA adverse event reporting system database

Purpose: Uloric (Febuxostat) has been linked with cardiovascular thromboembolic events for chronic management of hyperuricemia in gout patients (information from package insert and randomized clinical trials). However, no post-marketing data analysis has investigated these drug-associated adverse event reports. The study objective was to extract Febuxostat-associated cardiovascular thromboembolic event reports in the United States (US) using the Food and Drug Administration adverse event reporting system (AERS) database.

Methods: Reports listing Uloric and Febuxostat as the suspect drug and cardiovascular thromboembolic events (combined in a single term based on adverse event reports of myocardial infarction, stroke, among others) as the adverse event were extracted from the drug’s approval date (February 16^th, 2009) through the fourth quarter of 2011, since at the time when this study was conducted, data after the fourth quarter of 2011 were not available. Bayesian statistics within the neural network architecture were implemented to identify potential signals of Febuxostat-associated cardiovascular thromboembolic events. A potential signal for the drug-adverse event combination reports is generated when the lower limit of the 95% two-sided confidence interval of the information component (IC), denoted by IC₀₂₅is greater than zero.

Results: A total of 86 and 3,460 reports concerning Febuxostat and cardiovascular thromboembolic events, respectively, were extracted. Twenty-one combination reports of Febuxostat-associated cardiovascular thromboembolic events were identified in gout patients. The mean age of case reports for Febuxostat-associated cardiovascular thromboembolic events was 64 years. Potential signal (IC₀₂₅= 4.09) was generated for combination reports of Febuxostat-associated cardiovascular thromboembolic events.

Conclusion: The extracted case reports from AERS indicate potential signals of Febuxostat-associated cardiovascular thromboembolic events. AERS is not capable of establishing the causal link and detecting the true frequency of an adverse event associated with a drug. The higher IC value found merits continued surveillance and assessment of the credibility of the reported adverse events associated with the drug.