Real World Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels

Abstract

Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with sub-therapeutic concentrations with the newer delayed-release tablet formulation. In this retrospective, single center cohort study at a national comprehensive cancer center all oncology patients receiving delayed-release posaconazole at standard dosing of 300mg orally per day from 06/2021–07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors associated with sub-therapeutic drug legs at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Of 110 patients identified, 98 met criteria for inclusion into the study. Median time from initiation of posaconazole to drug level assessment was 13 days and median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis 5 (22.7%) failed to achieve concentrations ≥ 0.7 µg/mL and of 76 patients receiving posaconazole for treatment 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multi-variable analysis albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with sub-therapeutic levels. For a higher target of ≥1.8 µg/mL only albumin ≤3 g/dL was associated with sub-therapeutic levels for variables evaluated. A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole particularly for the treatment of invasive fungal infection could be considered.