Cholinesterase inhibitors-associated torsade de pointes/QT prolongation: a real-world pharmacovigilance study

Ni Zhang; Lanlan Gan; Guiyuan Xiang; Jing Xu; Tingting Jiang; Yanping Li; Yuanlin Wu; Rui Ni; Yao Liu

doi:10.3389/fphar.2023.1343650

Cholinesterase inhibitors-associated torsade de pointes/QT prolongation: a real-world pharmacovigilance study

Front Pharmacol. 2024 Jan 11:14:1343650. doi: 10.3389/fphar.2023.1343650. eCollection 2023.

Authors

Ni Zhang¹, Lanlan Gan¹, Guiyuan Xiang¹, Jing Xu¹, Tingting Jiang¹, Yanping Li¹, Yuanlin Wu¹, Rui Ni¹, Yao Liu¹

Affiliation

¹ Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, China.

Abstract

Objective: Cholinesterase inhibitor (ChEIs) is the first-line drug for Alzheimer's disease (AD). Understanding torsade de pointes (TdP)/QT prolongation with different ChEIs is essential for its safe and rational administration. This study aimed to evaluate the correlation between different ChEIs and TdP/QT prolongation. Methods: All ChEIs related TdP/QT prolongation cases were retrieved from the FAERS database using standard MedDRA query (SMQ) from the first quarter of 2004 to the third quarter of 2022. Disproportionality and sensitivity analysis were used to determine the signal of TdP/QT prolongation related to ChEIs. Results: 557 cases of TdP/QT prolongation related to 3 ChEIs were searched by SMQ. The patients were mostly elderly people, with markedly more female than male. The signals of TdP/QT prolongation for ChEIs were detected by disproportionality analysis, and the signal of Donepezil was the strongest. The sensitivity analysis results indicate a robust and stable correlation between these signals with ChEIs. TdP/QT prolongation usually occurs within 1 month after taking ChEIs. The drug with the highest frequency of combination with donepezil and galantamine is citalopram, and the drug with the highest frequency of combination with rivastigmine is atorvastatin. Conclusion: The signals of TdP/QT prolongation related to ChEIs were strong and stable. It is necessary to be vigilant about the TdP/QT prolongation of various ChEIs, especially in elderly women, the initial stage after taking ChEIs, and when ChEIs combining with drugs that could prolong the QT interval.

Keywords: FAERS; cholinesterase inhibitors; drug safety; pharmacovigilance study; torsade de pointes/QT prolongation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the (Chongqing Clinical Pharmacy Key Specialties Construction Project) and Chongqing Traditional Chinese Medicine Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) under Grant (China 2023ZDXM032).