Drug-induced QT prolongation and torsade de pointes: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database

Abstract

Introduction: Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive landscape of culprit-drug of QT prolongation and TdP is currently lacking.Aim: To identify the top drugs reported in association with QT prolongation and TdP and provide information for clinical practice.Method: We reviewed the reports related to QT prolongation and TdP in the FDA Adverse Event Reporting System (FAERS) database from January 1, 2004 to December 31, 2022, and summarized a potential causative drug list accordingly. Based on this drug list, the most frequently reported causative drugs and drug classes of QT prolongation and TdP were counted, and the disproportionality analysis for all the drugs was conducted to in detect ADR signal. Furthermore, according to the positive–negative distribution of ADR signal, we integrated the risk characteristic of QT prolongation and TdP in different drugs and drug class.Results: A total of 42,713 reports in FAERS database were considered to be associated with QT prolongation and TdP from 2004 to 2022, in which 1,088 drugs were reported as potential culprit-drugs, and the largest number of drugs belonged to antineoplastics. On the whole, furosemide was the most frequently reported drugs followed by acetylsalicylic acid, quetiapine, citalopram, metoprolol. In terms of drug classes, psycholeptics was the most frequently reported drug classes followed by psychoanaleptics, analgesics, beta blocking agents, drugs for acid related disorders. In disproportionality analysis, 612 drugs showed at least one positive ADR signals, while citalopram, ondansetron, escitalopram, loperamide, and promethazine were the drug with the maximum number of positive ADR signals. However, the positive-negative distribution of ADR signals between different drug classes showed great differences, representing the overall risk difference of different drug classes.Conclusion: Our study provided a real-world overview of QT prolongation and TdP to drugs, and the presentation of the potential culprit-drug list, the proportion of reports, the detection results of ADR signals, and the distribution characteristics of ADR signals may help understand the safety profile of drugs and optimize clinical practice.

Evaluating drug withdrawal syndrome risks through food and drug administration adverse event reporting system: a comprehensive disproportionality analysis

“…However, the study has its limitations. Disproportionality analysis only establishes a statistical association between drug usage and AEs and does not confirm a causal relationship between the drug and the adverse drug event (ADE) because the lack of details about patient exposure, reporting biases and confounding biases ( Zhou et al, 2022 ; Li et al, 2023 ; Fusaroli et al, 2024 ). Moreover, there are phenomena such as underreporting, incomplete case information, duration of use and dosage cannot be considered when analyzing the association between drugs and AEs.…”

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

“…The U.S. FDA Adverse Event Reporting System (FAERS) database is a freely accessible database created by the FDA to collect cases of adverse drug reactions (ADRs) from around the world ( Nagai and Ishikawa, 2021 ; Li et al, 2023 ). The database, which includes all AEs and medication errors recorded by the FDA, facilitates the identification and quantitative analysis of signals that indicate disproportionate reporting of ADRs, thus helping to identify correlations between specific drugs and specific AEs.…”