Favipiravir treatment in Thai children with COVID-19: effectiveness, safety, and modeling drug exposure.

Background: Despite widespread favipiravir (FPV) use for coronavirus disease 2019 (COVID-19) in Thailand, pediatric clinical evidence remains limited. Objectives: This study evaluated FPV's effectiveness and safety for treating COVID-19 in children and adolescents. Methods: This multicenter, retrospective, observational cohort study included patients ≤18 years old testing COVID-19 positive between July 2021 and December 2022 across 11 hospitals in Thailand. Patients were divided into those with and without chest X-ray-confirmed pneumonia. Patients who received FPV were treated with 35 mg/kg twice daily on day 1 and 15 mg/kg twice daily on days 2-5. Pharmacokinetic (PK) modeling estimated plasma exposure in children using scaled Thai adult data. Results: Of 2,999 patients, 68.2% had no pneumonia. FPV recipients (n = 1,886) were mostly <5 years old, had a fever, infected during the Omicron wave, had lower mean cycle threshold (Ct) values of SARS-CoV-2 gene at diagnosis, and hospitalized compared to non-recipients. FPV treatment significantly shortened fever duration and hospitalization in both pneumonia and non-pneumonia patients. For non-pneumonia patients, being <5 years old, and receiving FPV were associated with complete recovery at discharge. For pneumonia patients, a history of preterm birth, pulmonary disease, and ICU admission reduced the likelihood of complete recovery at discharge. No serious adverse events were reported. PK models predicted that FPV plasma trough concentrations in children ≥10 kg were above efficacy targets. Conclusions: Early FPV treatment shortened fever duration and hospital stays in children and adolescents with COVID-19, promoting clinical recovery in both pneumonia and non-pneumonia cases.