The FDA has directed the manufacturers of several prominent influenza vaccines to update their product labelling with a new notification regarding the risk of fever-induced seizures. The regulatory action, targeting industry leaders Sanofi, AstraZeneca, GSK, and CSL Seqirus, follows post-approval surveillance that highlighted a pattern of heightened seizure risk among young children immediately following immunisation.
BEST study identifies paediatric risk
The mandate stems from two observational studies conducted by the FDA’s Biologics Effectiveness and Safety System (BEST). Analysing data from three commercial insurance sources across the 2023–2025 flu seasons, the study specifically compared the risk within 24 hours of vaccination against a control window of 8 to 63 days post-administration.
The studies identified an increased incidence of febrile seizures in children aged six months to four years. Data indicated an estimated risk of 21 febrile seizure episodes for every ten units of one million quadrivalent vaccinations. For trivalent formulations, the rate was higher, at approximately 44 episodes per one million doses. While it was noted that these seizures are typically brief and generally harmless, the FDA is requesting that manufacturers include specific language noting that an “increased risk of febrile seizures was observed during the first day following vaccination” for the specified paediatric demographic.
Manufacturer response and safety outlook
In response to the directive, pharmaceutical leaders have reaffirmed the long-term safety profiles of their vaccines. A spokesperson for Sanofi emphasised that the company maintains a commitment to robust surveillance, stating: “The existing data continue to support the established safety and efficacy profile of Fluzone SD.”
GSK has also confirmed it is reviewing the label update request. “Our top priority is patient safety,” a representative noted. “We are committed to monitoring and ensuring the safety of all our products… and we are confident in their safety and efficacy profile.”
The FDA’s action underscores its reliance on real-world evidence (RWE) to refine safety profiles for vaccines – and this is not the first time it has prompted a shift. In June 2025, the agency used RWE to update mRNA vaccine labelling to include specific data on myocarditis and pericarditis risks in adolescent males, a signal only detectable once millions of doses had been administered globally.
