Subtherapeutic posaconazole exposure during delayed-release tablet prophylaxis in high-risk patients with haematological malignancies: rationale for routine therapeutic drug monitoring

Urbancic, KF; Yong, MK; Yong, K; Page, H; Stewart, M; Ritchie, D; Bajel, A; Wong, E; Fong, C; Trubiano, JA; Kong, DCM; Slavin, MA

Author(s): Urbancic, KF; Yong, MK; Yong, K; Page, H; Stewart, M; Ritchie, D; Bajel, A; Wong, E; Fong, C; Trubiano, JA; Kong, DCM; Slavin, MA;
Details: Publication Year 2026-07-02,Volume 81,Issue #8,Page dkag233
Journal Title: Journal of Antimicrobial Chemotherapy
Publication Type: Research article
Abstract: BACKGROUND: Posaconazole prophylaxis is indicated in high-risk patients with haematological malignancies to prevent invasive fungal diseases (IFDs) with guidelines advising steady-state posaconazole plasma concentrations (PPCs) above 0.5-0.7 mg/L. Therapeutic drug monitoring (TDM), however, is not routinely recommended for posaconazole delayed-release tablet (DRT) prophylaxis. OBJECTIVES: To describe PPCs in hospitalized high-risk patients with haematological malignancies treated for AML or undergoing allogeneic haematopoietic cell transplantation receiving posaconazole prophylaxis with posaconazole DRT and factors influencing exposure. PATIENTS AND METHODS: This prospective, two-centre cohort study measured serial PPCs at Days 7, 14 and 21, and during diarrhoea episodes in adult high-risk patients receiving prophylaxis with posaconazole DRT between August 2019 and May 2023. Patients were followed during hospital admission and for 7 days after the last dose of posaconazole or hospital discharge. RESULTS: Ninety-two patients contributed 223 PPCs. Subtherapeutic PPCs (<0.7 mg/L) occurred in 77 (34.5%) samples and 49 (53.3%) patients recorded ≥1 subtherapeutic PPC. The median Day 7 PPC was 0.84 (IQR: 0.47-1.16) mg/L, with no significant changes over time. In patients with diarrhoea compared with no diarrhoea, the median PPC was significantly lower [0.74 (IQR: 0.48-1.00) mg/L versus 0.92 (IQR: 0.64-1.40) mg/L, P = 0.007]. Multivariate analysis identified older age (>60 years) was protective against subtherapeutic PPCs. Six IFDs developed in five patients (5.4%) during follow-up and posaconazole-attributed hepatotoxicity resulted in cessation for one patient (1.1%). CONCLUSIONS: Subtherapeutic PPCs are common during posaconazole DRT prophylaxis, suggesting the need for routine TDM to optimize dosing in those receiving this posaconazole formulation.
Publisher: Oxford University Press
Keywords: Humans; *Antifungal Agents/administration & dosage/blood/therapeutic use/pharmacokinetics; *Triazoles/administration & dosage/blood/therapeutic use/pharmacokinetics; *Hematologic Neoplasms/complications; *Drug Monitoring; Female; Prospective Studies; Middle Aged; Adult; *Invasive Fungal Infections/prevention & control; Male; Aged; Delayed-Action Preparations/administration & dosage; Tablets
Department(s): Infectious Diseases; Haematology
Publisher's Version: https://doi.org/10.1093/jac/dkag233
Open Access at Publisher's Site: https://doi.org/10.1093/jac/dkag233
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-08-13 12:12:35

Last Modified: 2026-08-13 12:12:40