Linezolid and the risk of QT interval prolongation: A pharmacovigilance study of the Food and Drug Administration Adverse Event Reporting System

Abstract

Aims: Few studies have investigated linezolid (LZD)-associated cardiotoxicity. This study explored the potential association between LZD and QT interval prolongation.Methods: Adverse event reports of QT interval prolongation associated with LZD from the Food and Drug Administration Adverse Event Reporting System from January 2013 to December 2021 were analysed and the reporting odds ratio (ROR) with 95% confidence intervals were calculated.Results: A total of 6738 adverse event reports of LZD as the primary and secondary suspected drug were obtained from the database, including 192 reports with electrocardiogram QT prolonged (QTp), and the ROR value was 26.1 (95% CI = 22.6-30.2).There were 8 reports of long QT syndrome, ROR 14.2 (95% CI = 7.1-28.5); 5 reports of torsade de pointes, ROR 3.2 (95% CI = 1.3-7.6); and 5 reports of ventricular tachycardia, ROR 1.9 (95% CI = 0.8-4.5). Subgroup analysis revealed that patients with tuberculosis treated with LZD had a higher reporting rate among all QTp reports, exhibiting an odds ratio of 330.0 (95% CI = 223.1-488.1). The odds ratios of QTp associated with LZD treatments in patients with and without tuberculosis were 4.2 (95% CI = 3.4-5.3) and 1.2 (95% CI = 0.8-1.6), respectively. Conclusion:The study showed an association between LZD and QT interval prolongation. In the report on patients with tuberculosis, the incidence of QTp was higher when treated with LZD.

Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database

“…Our data also reported adverse reactions consistent with those specified on the drug label, such as tongue discoloration (n = 70,) and tooth discoloration (n = 42,). A high incidence of vomiting and diarrhea has been reported in several previous studies (Li and Xu, 2018;Shi et al, 2023), but no positive signals were found after our disproportionality analysis. This may be because these adverse reactions are common with the adverse reaction reports for other drugs in the FAERS database, which in turn influences the signal value.…”

“…Gastrointestinal-related symptoms (nausea, vomiting, and diarrhea) were the most common reasons for discontinuation of the drug (Moise et al, 2002;Noel et al, 2012). Nausea (Shorr et al, 2015), gastrointestinal intolerance (Veerman et al, 2023), diarrhea, and vomiting (Shi et al, 2023) were the most common side effects reported in previous studies. A single-center retrospective observational study (Tsutsumi et al, 2022) found that female gender is an independent risk factor for linezolid-induced vomiting, which may be associated with multiple signaling pathways including D2, 5-HT3, and neurokinin-1 receptors (Navari and Aapro, 2016).…”

“…Four cases of rhabdomyolysis associated with linezolid have been reported (Allison et al, 2009;Carroll et al, 2012;Lechner et al, 2017). Moreover, a FAERS-based study identified an association between linezolid and prolongation of the QT interval along with a higher incidence in TB patients (Shao et al, 2023). The causal relationship between linezolid and rhabdomyolysis and QT interval prolongation is unclear, necessitating further clinical studies to comprehend the pathogenesis of these adverse events.…”

“…Other studies have reported associations between linezolid and specific side effects using centralized data (Lee and Caffrey, 2018;Dai et al, 2020;Gatti et al, 2021a;Battini et al, 2022;Ni et al, 2022;Shao et al, 2023). This study, for the first time, comprehensively documented and evaluated the safety of post-marketing administration of linezolid based on the largest sample of realworld data to date.…”

Emergency Management of Electrical Storm: A Practical Overview

“…In the SHIELD trial, a precipitating cause could be identified in only 13% of electrical storms, typically represented by worsening heart failure, which should be treated in favor of better hemodynamic stability, and electrolyte disturbances [ 3 ]. Electrolyte abnormalities should be corrected, especially potassium [ 39 , 40 , 41 ] and magnesium serum levels: their deficiency may be associated with Torsade de Pointes (TdP), and intravenous magnesium might be effective even if magnesium serum levels are within range [ 42 ]. QT prolongation is often associated with recurrence of TdP, and in this setting, bradycardia may become a trigger factor: in fact, increasing cardiac frequency through beta adrenergic receptor stimulation (with isoproterenol) or transvenous pacing has proved to be effective.…”