Comparative pharmacovigilance analysis of intravenous versus oral linezolid: Insights from the FDA Adverse Event...

This study aimed to compare the safety profiles of intravenous and oral linezolid by analyzing adverse event (AE) reports from the US Food and Drug Administration Adverse Event Reporting System. We extracted linezolid-related AE reports from US Food and Drug Administration Adverse Event Reporting System (2004 Q1-2025 Q2). After de-duplication and exclusion of reports with unknown administration routes, 7591 reports (intravenous: 3445; oral: 4146) were included. Disproportionality analyses using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker were performed to detect AE signals. Time-to-onset analysis was conducted using Weibull distribution. Intravenous administration was associated with acute, severe AEs such as neonatal complications, acute kidney injury, and serotonin syndrome, predominantly occurring within 30 days (median onset: 6 days). Oral administration showed stronger signals for chronic toxicities, including peripheral neuropathy, optic neuropathy, anemia, and metabolic disturbances, with a later median onset of 11 days and prolonged event distribution. Hematologic toxicity patterns also differed: the oral route was linked to anemia and pancytopenia, while the intravenous route was associated with leukopenia and agranulocytosis. The safety profiles of linezolid differ significantly between intravenous and oral routes, largely driven by treatment duration, patient population, and clinical setting. These findings support route-specific monitoring strategies: acute toxicity surveillance for intravenous therapy and long-term neurotoxicity and hematologic monitoring for oral therapy.