LAUSR

Background and ObjectiveBaloxavir marboxil is a prodrug that is metabolized to baloxavir acid, which suppresses viral replication by inhibiting cap-dependent endonuclease with a single oral administration. As the mode of action of baloxavir marboxil is different from that of neuraminidase inhibitors, such as oseltamivir, combination treatment with these drugs can be a treatment option, particularly for severe influenza infection. The aim of this study was to assess the drug–drug interaction between baloxavir marboxil and oseltamivir.MethodsEighteen healthy adult subjects received three treatments in a crossover fashion: single administration of baloxavir marboxil 40 mg alone, repeated twice-daily administration of oseltamivir at 75 mg for 5 days, or single administration of baloxavir marboxil at 40 mg in combination with repeated twice-daily administration of oseltamivir at 75 mg for 5 days.ResultsThe ratios (90% confidence intervals) of maximum plasma concentration and area under the plasma concentration–time curve of baloxavir acid after co-administration compared to baloxavir marboxil alone were 1.03 (0.92–1.15) and 1.01 (0.96–1.06), respectively. The ratios (90% confidence intervals) of maximum plasma concentration and area under the plasma concentration–time curve of oseltamivir carboxylate, the active form of oseltamivir, after co-administration compared to oseltamivir alone were 0.96 (0.93–1.00) and 0.99 (0.96–1.01), respectively, at steady state on day 5. Treatment-emergent adverse events reported were mild and not considered to be related to the study drug.ConclusionThe lack of a clinically meaningful drug–drug interaction between baloxavir marboxil and oseltamivir has been established.