Posaconazole is commonly administered as antifungal prophylaxis in individuals with hematologic malignancies. Nevertheless, considerable interindividual variability in its pharmacokinetic profile can result in insufficient plasma exposure and subsequent prophylaxis failure. Evidence from real-world settings regarding the pharmacokinetics of posaconazole tablets and intravenous formulations in East Asian populations is still scarce. This study was conducted to assess plasma posaconazole concentrations and to identify factors associated with subtherapeutic exposure in Taiwanese patients. This analysis used a nested case-control design based on records from the National Taiwan University Hospital database. Adult individuals with hematologic malignancies who received posaconazole in either delayed-release oral tablet form or intravenous form and had therapeutic drug monitoring performed were eligible for inclusion. To explore determinants of low drug exposure, multivariate logistic regression modeling was conducted, defining subtherapeutic plasma concentrations as values below 0.7 μg/mL. Levels above 1.83 μg/mL were considered supratherapeutic. In the cohort of 221 patients, 24.9% had drug concentrations below the therapeutic range, whereas 24.0% exceeded the upper therapeutic limit (supratherapeutic). The multivariate logistic regression analysis identified several factors independently associated with insufficient posaconazole exposure. Being male was associated with increased odds of low concentrations (OR = 2.31). The occurrence of diarrhea also significantly contributed (OR = 2.18). Moreover, concomitant therapy with proton pump inhibitors (OR = 2.00) and prokinetic agents (OR = 2.17) was independently associated with decreased plasma posaconazole levels. Even with standard dosing regimens, both subtherapeutic and supratherapeutic posaconazole exposures continue to pose clinical challenges. Implementing therapeutic drug monitoring alongside individualized risk assessment is crucial to improving the effectiveness of antifungal prophylaxis in patients with hematologic malignancies.
