Real-world safety analysis of deutetrabenazine post-marketing: a disproportionality study leveraging the FDA Adverse Event Reporting System (FAERS) database.

Abstract

Background: Deutetrabenazine, a selective vesicular monoamine transporter type 2 (VMAT2) inhibitor, has been demonstrated efficacy in treating refractory neurologic disorders such as Tardive Dyskinesia (TD) and Huntington's disease but have potential adverse events (AEs) that require detailed pharmacovigilance. This study aimed to comprehensively assess the safety profile of deutetrabenazine in real-world settings by analyzing AEs reported from the FDA Adverse Event Reporting System (FAERS) database.

Methods: We conducted a retrospective pharmacovigilance study using FAERS data from Q3 2017 to Q3 2024, focusing on deutetrabenazine-related AEs. We applied four disproportionality analysis methods-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multinomial Gamma Poisson Shrinkage (MGPS)--to identify potential safety signals. Furthermore, we utilized the Weibull distribution model to analyze the temporal risk of AEs.

Results: Among the 10,571,578 reports obtained from the FAERS database, 4,337 AE reports were associated with deutetrabenazine. Using four independent computational methods at the preferred term (PT) level, we identified 1,131 PTs that indicated noteworthy adverse reactions. The drug's label-listed adverse reactions, including depression, somnolence, suicidal ideation, and fatigue, showed remarkable signals. Furthermore, we detected potential adverse reactions that were not specified on the label, such as drug ineffectiveness, dyskinesia, death, falls, and insomnia. The majority of these AEs were reported within the initial month of deutetrabenazine treatment, with a median time to onset of 40.5 days.

Conclusion: This research has yielded initial safety insights into the practical use of deutetrabenazine, validating established adverse reactions and uncovering further possible risks. These findings present essential safety considerations for physicians when prescribing deutetrabenazine for the clinical treatment.