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. Voriconazole-related 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±3.42mg/l vs. 4.02±2.00mg/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 7days 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.