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

Abstract

ObjectivesThe 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. MethodsLiver 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. ResultsA total of 110 trough plasma concentrations of voriconazole (Cmin) were measured in 78 patients. There was a significant difference in voriconazole Cmin between group A and group B (Cmin, 6.95±3.42mg/l vs. 4.02±2.00mg/l; p<0.001). No significant difference in voriconazole Cmin 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 Cmin 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. ConclusionsThese 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 Cmin, and that voriconazole Cmin should be monitored earlier to avoid AEs.