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) were measured in 78 patients. There was a significant difference in voriconazole C between group A and group B (C, 6.95±3.42mg/l vs. 4.02±2.00mg/l; p<0.001). No significant difference in voriconazole C 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 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, and that voriconazole C should be monitored earlier to avoid AEs.