A retrospective, multicenter study of voriconazole trough concentrations and safety in patients with Child-Pugh class C cirrhosis.

Abstract

Voriconazole is a broad-spectrum antifungal agent and is mainly metabolized by the liver, yet there have been no reports about voriconazole treatment in patients with Child-Pugh class C cirrhosis. The objective of this study was to investigate the pharmacokinetic profile and safety of voriconazole treatment in this cohort of patients. A retrospective, multicenter study was performed in patients with Child-Pugh class C cirrhosis who received a voriconazole maintenance dose of 100mg twice daily (group A) or 200mg daily (group B) orally or intravenously. All voriconazole Cmin were measured by high-performance liquid chromatography, and voriconazole-related adverse events were defined according to Common Terminology Criteria for Adverse Events. The relationship between voriconazole Cmin and adverse events was explored using logistic regression model. A total of 51 voriconazole Cmin were monitored from 34 patients. The Cmin of voriconazole was 4.42±2.08 and 5.42±1.96mg/L in groups A and B, respectively. The proportion of voriconazole Cmin over the upper limit of therapeutic level (5mg/L) in groups A and B was 34.48% and 47.62%, respectively. Additionally, 23.5% (8/34) of patients exhibited signs of voriconazole-related adverse events, and 87.5% (7/8) of adverse events occurred within the first week after voriconazole treatment. Logistic regression model showed that there was a positive correlation between voriconazole Cmin and the incidence of adverse reactions. Voriconazole Cmin value of 4.5mg/L was associated with a 20% probability of adverse events. The voriconazole maintenance dose of 100mg twice daily or 200mg daily orally or intravenously may be inappropriate in patients with Child-Pugh class C cirrhosis because of the higher voriconazole Cmin and higher incidence of adverse events. Monitoring voriconazole Cmin earlier is extremely important to prevent the occurrence of voriconazole-related adverse reactions.