Valproic acid and prolonged QT: highlights from the FDA Adverse Event Reporting System (FAERS) database

Several drugs can induce QT prolongation; however, the role of valproic acid played on the onset of this side effect has not been elucidated yet. Moreover, epilepsy itself represents a risk factor for the development of cardiovascular diseases; therefore, it is crucial to characterize the potential correlation between valproic acid and the occurrence of this cardiovascular complication.
We performed a descriptive analysis on the U.S. Food and Drug Administration Adverse Event Reporting System database, retrieving all adverse event reports involving valproic acid as suspect drug. After deduplication and data cleaning, we selected all cases reporting valproic acid as unique suspect and we analyzed those reporting the adverse event of interest, identified through the Standardized MedDRA Query “Torsade de pointes/QT prolongation”. Finally, we evaluated each case presenting other concomitant medications to explore potential drug-drug-interactions.
Of 52,080 reports included in the analysis, 540 cases were referred to “Torsade de pointes/QT prolongation”. Loss of consciousness and syncope were the most reported events, included, respectively, in 241 (44.63%) and in 118 (21.85%) Individual Case Safety Reports. QT elongation and abnormal electrocardiogram QT interval are reported only in 26 (0.1%) cases, ventricular arrhythmia only in 2 cases and the development of torsade de pointes has been recorded just in 1 case. Sudden death has been reported in 20 (0.1%) cases.
Our analysis revealed a very low number of cases reporting the adverse event of interest. The adverse event seems to be the consequence of multifactorial coexisting causes rather than imputable to the valproate alone.

Impact statement

Our analysis evidences that valproic acid does not significantly influence QT elongation, which is the result of several coexisting factors.