Therapeutic drug monitoring and safety of voriconazole therapy in patients with Child-Pugh class B and C cirrhosis: A multicenter study

Objectives: The purpose of this study was to investigate the pharmacokinetic profile and safety of voriconazole treatment in patients with Child-Pugh class B and C cirrhosis. Methods: Liver cirrhosis patients who had received the recommended voriconazole maintenance dose (group A) or halved maintenance dose (group B), orally or intravenously, were included. Voriconazolerelated adverse events (AEs) were defined according to the Common Terminology Criteria for Adverse Events. Results: A total of 110 trough plasma concentrations of voriconazole (C-min) were measured in 78 patients. There was a significant difference in voriconazole C-min between group A and group B (C-min, 6.95 +/- 3.42 mg/l vs. 4.02 +/- 2.00 mg/l; p < 0.001). No significant difference in voriconazole C-min between Child-Pugh class B and C cirrhosis patients was observed in either of the two groups. The international normalized ratio and co-medication with a CYP2C19 inhibitor had a significant effect on voriconazole C-min in group B. The incidence of AEs in group A was 26.5% and in group B was 15.9%, and 87.5% of AEs developed within 7 days after starting voriconazole treatment. Conclusions: These results suggest that the recommended dose and halved maintenance dose may be inappropriate in patients with Child-Pugh class B and C cirrhosis due to the high C-min, and that voriconazole C-min should be monitored earlier to avoid AEs. (C) 2018 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license.