BACKGROUND:
We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza.
METHODS:
This open-label study administered one weigth-adjusted dose of baloxavir to 107 children aged 1-11 years with laboratory-confirmed, febrile influenza virus infection of <48 hours duration.
RESULTS:
Adverse events (AEs) were reported in 34.6% of patients, most commonly vomiting (7.5%); no serious AEs or AEs causing discontinuation occurred. The median time to alleviation of influenza illness was 44.6 hours (95% confidence interval 38.9, 62.5 hours), to resolution of fever 21.4 hours, and to sustained cessation of infectious viral shedding was 24.0 hours. However, viruses with amino acid substitutions in the viral polymerase acidic protein at position I38 (PA/I38T/M) emerged in 18 of 77 (23.4%) patients. Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses). Among patients with PA/I38T/M-substituted virus emergence, those with baseline HAI antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer).
CONCLUSION:
A single, oral dose of baloxavir marboxil was well-tolerated, and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children.