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

• Published in: International journal of infectious diseases Vol. 72; pp. 49 - 54
• Main Authors: Wang, Taotao, Yan, Miao, Tang, Dan, Xue, Ling, Zhang, Tao, Dong, Yuzhu, Zhu, Li, Wang, Xinggang, Dong, Yalin
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01.07.2018; Elsevier
• Subjects: Adverse events; Liver cirrhosis; Therapeutic drug monitoring; Trough concentration; Voriconazole; Therapeutic drug monitoring; Trough concentration; Adverse events; Liver cirrhosis; Voriconazole; voriconazole; adverse events; liver cirrhosis; therapeutic drug monitoring; trough concentration
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2018.05.009

•This is the first study of voriconazole pharmacokinetics and safety in cirrhosis patients.•Voriconazole Cmin for the standard dose was 6.95±3.42mg/l in cirrhosis patients.•Voriconazole Cmin was 4.02±2.00mg/l in cirrhosis patients receiving the halved dose.•Voriconazole Cmin was related to INR and CYP2C19 inhibitor use in cirrhosis patients.•Most adverse events developed within 7days after starting voriconazole treatment. 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. 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. A 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. 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 Cmin, and that voriconazole Cmin should be monitored earlier to avoid AEs.