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

What is known and objective 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. MethodsResults and discussionA 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 C-min 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 C-min and adverse events was explored using logistic regression model. A total of 51 voriconazole C-min were monitored from 34 patients. The C-min of voriconazole was 4.422.08 and 5.42 +/- 1.96mg/L in groups A and B, respectively. The proportion of voriconazole C-min 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 C-min and the incidence of adverse reactions. Voriconazole C-min value of 4.5mg/L was associated with a 20% probability of adverse events. What is new and conclusionThe 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 C-min and higher incidence of adverse events. Monitoring voriconazole C-min earlier is extremely important to prevent the occurrence of voriconazole-related adverse reactions.