Comparative Analysis of Serious Outcomes From Influenza Antiviral Use

Introduction: The FDA Adverse Event Reporting System (FAERS) collects post-marketing reports of adverse drug events (ADEs). The database is a critical tool for detecting safety signals after drug approval, including serious outcomes that may require intensive care. The neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, & peramivir, & the endonuclease inhibitor baloxavir are prescribed for influenza. Differences in pharmaceutical properties & patient characteristics influence response but little is known about the potential for serious outcomes outside of clinical trials. The objective of this study was to evaluate serious outcomes from NAIs and baloxavir with real-world use.


Methods: ADE reports for oseltamivir, zanamivir, peramivir, and baloxavir were retrieved from the FAERS database from inception through March 2025 using proprietary & generic drug names in all available dosage forms. Cases were excluded if the reported indication was not influenza or if the documented reaction was misuse, incorrect dosing, off-label use, product shortage, dose omission, or entirely lacked an ADE. Duplicate cases were removed. The primary outcome was serious outcomes with antiviral use. Demographic & frequency data were analyzed using descriptive statistics. Serious outcomes, including death, life-threatening outcomes, & hospitalization were compared using the chi-square test & odds of outcomes were determined using the Wald test for logistic regression.


Results: 19,159 cases met inclusion criteria. Oseltamivir had the most cases (n=14,142), followed by zanamivir (n=2,485), baloxavir (n=1,906), & peramivir (n=626). Compared to oseltamivir, odds of serious outcomes were higher with peramivir (OR=9.77, p< 0.001) & zanamivir (OR=1.12, p< 0.0102) & 29% lower with baloxavir (OR=0.71, p< 0.0001). Baloxavir had 34% lower odds of serious outcomes vs. NAIs combined (OR=0.66, p< 0.0001). Compared to oseltamivir, peramivir had a higher incidence of death, life-threatening outcomes, & hospitalizations (p < 0.00001 for all) while zanamivir had fewer hospitalizations (P < 0.0001) & baloxavir had fewer deaths (p < 0.001).


Conclusions: With real-world use, baloxavir resulted in lower odds of serious outcomes than oseltamivir & NAIs combined. Peramivir & zanamivir use was associated with more serious outcomes overall than oseltamivir.