Plasma Concentrations of Prophylactic Posaconazole and Risk Factors for Subtherapeutic Exposure in Taiwanese Patients with Hematologic Malignancies

Hsing-Yu Lin,1,* Shu-Chen Hu,2,* Tsung-Yu Pai,1 Fang-Ju Lin,1,3,4 Chien-Chih Wu1,3 1Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 3School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 4Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Chih Wu, Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, 7 Chung Shan S. Road, Taipei, Taiwan, Email [email protected]: Posaconazole is widely used for antifungal prophylaxis in patients with hematologic malignancies. However, interindividual pharmacokinetic variability may lead to subtherapeutic exposure and treatment failure. Real-world data on the pharmacokinetics of posaconazole tablets and infusion in East Asian populations remain limited. This study aims to evaluate the plasma concentration of posaconazole and risk factors for subtherapeutic exposure in Taiwanese patients.Methods: This nested case-control study was conducted using data from the National Taiwan University Hospital database. The study cohort comprised adult patients with hematologic malignancies receiving delayed-release tablets or intravenous formulations of posaconazole and undergoing therapeutic drug monitoring. Factors associated with subtherapeutic posaconazole exposure (< 0.7 μg/mL) were identified through multivariate logistic regression. Supratherapeutic concentration was defined as a level > 1.83 μg/mL.Results: Of a total of 221 patients, 24.9% and 24.0% exhibited subtherapeutic and supratherapeutic posaconazole concentrations, respectively. Multivariate logistic regression indicated that male sex (odds ratio [OR] = 2.31), diarrhea (OR = 2.18), and concurrent use of proton pump inhibitors (OR = 2.00) or prokinetic agents (OR = 2.17) were independently associated with subtherapeutic exposure to posaconazole.Conclusion: Subtherapeutic and supratherapeutic exposures to posaconazole remain a concern despite standard dosing. Therapeutic drug monitoring and personalized risk assessment are essential for optimizing antifungal prophylaxis in patients with hematologic malignancies.Keywords: posaconazole, therapeutic drug monitoring, antifungal prophylaxis, hematologic malignancies