To extract severe cutaneous adverse reactions (SCAR) associated with commonly used anti-influenza virus drugs from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) database, analyze the epidemiological characteristics of SCAR to provide a reference for safe clinical medication, and explore the underlying molecular mechanisms using network pharmacology.

Reports from January 2004 to December 2024 in FAERS database were collected, in which oseltamivir, peramivir, zanamivir and baloxavir marboxil were the primary suspected drugs and SCAR was the preferred term (PT). The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were used to mine and analyze adverse drug event (ADE) signals. Targets of commonly used anti-influenza virus drugs and SCAR were extracted, a protein-protein interaction network was constructed, and enrichment analysis was performed.

A total of 263 cases (1.90%) of SCAR related to commonly used anti-influenza virus drugs were collected. Females (55.13%) accounted for a higher proportion than males (35.36%). Positive signals were detected for all drugs except peramivir, with the association strength in descending order, baloxavir marboxil [n=42, ROR 1.75, information component(IC)0.8], zanamivir (n=53, ROR 1.61, IC 0.68) and oseltamivir (n=208, ROR 1.34, IC 0.42). The top 5 PT by frequency were blister, erythema multiforme, drug eruption, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. Network pharmacology analysis showed that the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway may be a key pathway underlying SCAR induced by commonly used anti-influenza virus drugs.

Baloxavir marboxil, oseltamivir and zanamivir carry a risk of SCAR, with baloxavir marboxil and zanamivir showing higher signal intensity, while oseltamivir had the highest number of reports. Close monitoring of skin symptoms in female patients is recommended from 3 days after administration to guard against the occurrence of SCAR. Anti-influenza virus drugs may induce SCAR by regulating the JAK-STAT signaling pathway, which provides insights for further research.