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. Methods: A retrospective, multicenter study was performed in patients with Child-Pugh class C cirrhosis who received a voriconazole maintenance dose of 100 mg twice daily (group A) or 200 mg 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. Results and discussion: A total of 51 voriconazole C_min were monitored from 34 patients. The C_min of voriconazole was 4.42 ± 2.08 and 5.42 ± 1.96 mg/L in groups A and B, respectively. The proportion of voriconazole C_min over the upper limit of therapeutic level (5 mg/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 4.5 mg/L was associated with a 20% probability of adverse events. What is new and conclusion: The voriconazole maintenance dose of 100 mg twice daily or 200 mg 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.