Association between high serum favipiravir concentrations and drug-induced liver injury

Kawasuji, H.; Tsuji, Y.; Ogami, C.; Takegoshi, Y.; Kaneda, M.; Murai, Y.; Kimoto, K.; Ueno, A.; Miyajima, Y.; Fukui, Y.; Nagaoka, K.; Sakamaki, I.; Morinaga, Y.; Yamamoto, Y.

Objectives This study aimed to evaluate the incidence and pattern of favipiravir-induced liver injury and the potential association between serum concentrations in hospitalized COVID-19 patients. Patients and methods We retrospectively reviewed laboratory-confirmed patients with COVID-19 for whom serum favipiravir trough concentration (Cmin) was measured under steady-state conditions during treatment. All patients were administered 1800 mg of favipiravir twice daily on the first day and 800 mg twice daily from the second day. Results Thirty observed favipiravir concentrations were collected from nine patients. Of these, favipiravir-induced liver injury developed in three patients after 13 (11-14) days from the initiation of therapy, with two classified as cholestatic and one hepatocellular injury, with a score of four (possible), seven (probable), and three (possible) based on the CIMOS/RUCAM scoring system. Median (range) favipiravir Cmin at steady state was found to be significantly higher in patients with liver injury at 66.4 (47.8-72.4) mg/L than in those without injury at 12.8 (9.4-21.8) mg/L(P = 0.028). Conclusions Higher favipiravir serum concentrations were observed in patients who developed favipiravir-induced liver injury than in those who did not. As the variations in favipiravir concentrations between patients were large, personalized optimal dosing strategies may be needed for safe use.