BACKGROUND AND OBJECTIVE: Baloxavir 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.
METHODS: Eighteen 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.
RESULTS: The 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.
CONCLUSION: The lack of a clinically meaningful drug-drug interaction between 
baloxavir marboxil and oseltamivir has been established.