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

Authors

Karen F Urbancic, Michelle K Yong, KarYee Yong, Hayley Page, Marcelle Stewart, David Ritchie, Ashish Bajel, Eric Wong, Chun Fong, Jason A Trubiano, David C M Kong, Monica A Slavin

Published in

The Journal of antimicrobial chemotherapy. Volume 81. Issue 8. Jul 02, 2026.

Abstract

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.
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.
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.
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%).
Subtherapeutic PPCs are common during posaconazole DRT prophylaxis, suggesting the need for routine TDM to optimize dosing in those receiving this posaconazole formulation.

PMID:
42455040
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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