Targeted Therapies for Influenza in Children: Current Evidence and Future Directions

Background: Influenza causes substantial seasonal illness in children, particularly infants and young children. Children with chronic conditions, prematurity, neurologic disorders, or immunocompromise are at increased risk of complications. Although antiviral treatment complements vaccination and supportive care, pediatric evidence remains uneven: randomized trials have largely involved otherwise healthy outpatients, while evidence in hospitalized and medically complex children is mostly observational. Methods: This narrative review synthesizes evidence on the mechanisms, clinical use, and limitations of currently available influenza antivirals in children. It prioritizes pediatric trials, observational studies, and clinical guidance, with adult evidence considered where pediatric data are limited. Results: Oseltamivir remains the most widely recommended treatment, particularly for hospitalized children and those at increased risk. Its benefits in uncomplicated illness are generally modest, and vomiting is a recognized adverse effect. Zanamivir and peramivir are alternatives for selected patients, but their use is constrained by inhaled administration, airway disease, intravenous delivery, and limited evidence in severe illness. Baloxavir offers single-dose oral treatment and rapid suppression of viral replication; however, pediatric trials remain relatively small, reduced susceptibility can emerge during treatment, and evidence in severe disease is insufficient. Novel polymerase inhibitors and host-directed therapies remain investigational or have not established a clear clinical role in children. Conclusions: Future research should prioritize infants, children with comorbidities, and hospitalized patients, while addressing age-specific pharmacokinetics, antiviral resistance, and outcomes that matter to children and families.