Factors Influencing Blood Concentration of Voriconazole and Therapeutic Drug Monitoring in Patients with Child-Pugh Class C Cirrhosis

What Is Known and Objective. CYP2C19 is an important influencing factor for voriconazole trough plasma concentration (C-min); however, it is not verified in Child-Pugh C (CP-C) cirrhosis patients, and no voriconazole dosage regimen is recommended for these patients in the package insert. This retrospective study identified CYP2C19 and other factors influencing voriconazole C-min for CP-C cirrhosis, and obtained an appropriate method of application of voriconazole for them. Methods. A total of 66 patients with CP-C cirrhosis who accepted voriconazole therapy were involved. The voriconazole C-min, clinical characteristics, CYP2C19 genotype, and adverse effects (AEs) were recorded and analyzed. Results. Unlike other research studies, voriconazole C-min was not different among normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs) of the CYP2C19 enzyme in CP-C cirrhosis (P > 0.05). The maintenance dose regimen for voriconazole was the only independent influencing factor for C-min (P = 0.045; OR = 3.753; 95% CI, 1.029-13.694). At about 1/3 of the recommended maintenance dose, only 16.7% (8/48) had C-min > 5.5 mu g/mL, 4.5% (3/48) had C-min mu g/mL, and only one AE happened. There were four voriconazole-related AEs that happened in this study, and three AEs occurred (3/4, 75%) when the maintenance dose was not adjusted with therapeutic drug monitoring (TDM). What Is New and Conclusion. Voriconazole C-min did not significantly vary according to CYP2C19 enzyme metabolization status (being an NM, IM, or PM) in CP-C cirrhosis. Reducing the maintenance dose of voriconazole to approximately 1/3 the standard maintenance dose and administering in combination with TDM in patients with CP-C cirrhosis are recommended.