Linezolid-related Optic Nerve Disorders: Insight from a Pharmacovigilance Analysis of the U.S. FDA Adverse Event Reporting System

Objective Linezolid is a crucial oxazolidinone used to treat multidrug-resistant gram-positive infections; however, it is associated with optic neuropathy and other adverse events. Data regarding the usage and toxicity features of linezolid and those of tedizolid, a related agent with a potentially improved safety profile, are limited. Therefore, this study aimed to investigate the signals and characterize the clinical features of optic nerve disorders related to oxazolidinones using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods This retrospective pharmacovigilance study examined FAERS data from July 2014 to April 2024. Disproportionality analyses (reporting odds ratio [ROR] and information component [IC]) were conducted to detect signals of oxazolidinone-related optic nerve disorders. Firth-type penalized logistic regression was used to further characterize the features of optic nerve disorders by comparing them with other adverse events (AEs). Results In total, 15,350,730 reports were retrieved from the FAERS database, from which signals (defined as ROR > 1 and IC > 0) were detected only for linezolid, consistent with sensitivity analyses. Compared with other linezolid-related AEs, linezolid-related optic nerve disorders were characterized by younger age (<60 years; adjusted odds ratio [OR]: 6.86, 95% confidence interval [CI]: 2.36–26.51, p < 0.001) and high cumulative doses (≥720 mg/kg; adjusted OR: 7.96, 95% CI: 2.93–20.62, p < 0.001). Conclusion Among oxazolidinones, a signal for optic nerve disorders was detected exclusively for linezolid. Clinicians should ensure regular ophthalmologic monitoring during linezolid treatment, particularly in younger patients and those receiving high cumulative doses.