Association of H1-antihistamines with torsade de pointes: a pharmacovigilance study of the food and drug administration adverse event reporting system

ABSTRACT

Background: This study aimed to measure the association of various H1-antihistamines (H1A) with Torsade de Pointes (TdP), and present a comprehensive overview of H1A-induced TdP cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: All H1A-induced TdP cases (n = 406) were retrieved from the FAERS database using the preferred term ‘Torsade de Pointes’ of MedDRA version-22 from 1990 to 2019. Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR); Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). H1A with >3 TdP cases were included.

Results: A total of 12 signals (Astemizole, cetirizine, chlorpheniramine, clemastine, desloratadine, diphenhydramine, hydroxyzine, loratadine, meclizine, promethazine, terfenadine, and trimeprazine) were identified including six new signals (cetirizine, chlorpheniramine, clemastine, desloratadine, loratadine, and meclizine). The number of risk factors (p = 0.031) and concomitant QT-prolonging drugs (p = <0.001) were significantly lower among new signals vs old signals. Moreover, new signals were strongly associated with QT-prolongation, cardiac reactions, and electrolyte abnormalities as compared with old signals.

Conclusions: Our study found the increased torsadogenic potential of new signals compared with previously known old signals, hence necessitating clinical studies to determine the actual torsadogenic potential of newly identified signals.

KEYWORDS:

• Torsade de Pointes
• H1-antihistamines
• pharmacovigilance
• FAERS
• disproportionality analysis
• new signal

Author contributions

All authors contributed to the study conception and design. Material preparation and data analysis were performed by Z Ali and M Ismail. Z Ali wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. All authors read and approved the final version.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2021.1846717.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.