Subtherapeutic concentrations of posaconazole tablet: determining risk factors and effectiveness of a standardized dose adjustment in hematology inpatients

Posaconazole is indicated for antifungal prophylaxis in hematology patients at high-risk of invasive fungal infections (IFI). Consensus guidelines recommend maintaining steady-state trough concentrations above 0.7 mg/L; however, upto one-third of patients return subtherapeutic concentrations which is associated with breakthrough IFI. This retrospective observational study of 496 concentrations from 90 hematology inpatients prescribed posaconazole tablet (PCZ-tab) between May 2017 and May 2019 identified 24% (n = 121) of posaconazole concentrations were subtherapeutic after the dosage of 300 mg daily. On multivariable analyses, diarrhea (p = 0.002), male gender (p = 0.018), and concurrent regular metoclopramide (p = 0.002) were significantly associated with subtherapeutic posaconazole concentrations. Eighty-nine percent of patients (n = 16) who underwent dose adjustment to 200 mg twice daily successfully achieved target posaconazole concentrations at first steady-state measurement. This study confirms that therapeutic drug monitoring of posaconazole remains necessary as subtherapeutic posaconazole concentrations are relatively common, and that dose adjustment of 200 mg twice daily, safely enabled achievement of therapeutic concentrations.