Real-world study of posaconazole tablets for the prophylaxis of invasive fungal disease in patients with end-stage liver disease

BACKGROUND: Data on the pharmacokinetics and tolerability of posaconazole delayed-release tablets in patients with end-stage liver disease (ESLD)(including liver failure and decompensated cirrhosis) remain limited. This study aimed to characterize trough concentrations (Cmin) and describe clinical outcomes during antifungal prophylaxis in this population. METHODS: In this prospective, single-arm study, ESLD patients receiving posaconazole prophylaxis were enrolled between October 2023 and July 2024. Serial Cmin were measured, and hepatic and renal function parameters were monitored. Breakthrough invasive fungal disease (IFD) events were descriptively recorded. RESULTS: Twenty-one patients contributed 79 Cmin measurements. The mean Cmin was 1.60 ± 0.68 mg/L, with 81.0% of samples ≥ 1.0 mg/L; 95.2% of patients achieved at least one target concentration. Substantial interindividual variability was observed, while dose adjustments were infrequent. Breakthrough IFD occurred in 2 patients (9.5%), with no IFD-related deaths. Liver and renal function parameters remained generally stable during follow-up. Reductions in total bilirubin were observed in patients with more advanced liver dysfunction (Model for End-Stage Liver Disease (MELD) > 18 or Child-Pugh C), although these changes were not attributable to posaconazole. CONCLUSION: Posaconazole exposure in patients with ESLD showed considerable interindividual variability, despite most Cmin measurements were within the predefined reference range of 0.5-2.5 mg/L. The drug was generally well tolerated in this cohort. These findings support the role of therapeutic drug monitoring (TDM) in characterizing exposure variability in ESLD. Given the small sample size and observational design, the results are descriptive, and further studies are needed to define optimal dosing and monitoring strategies in this high-risk population. TRIAL REGISTRATION: ChiCTR2200063000. Registration on 27 August 2022.