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 ± 3.42 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.