Subtherapeutic posaconazole exposure during delayed-release tablet prophylaxis in high-risk patients with haematological malignancies: rationale for routine therapeutic drug monitoring.
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.
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.
Authors
Urbancic Urbancic, Yong Yong, Yong Yong, Page Page, Stewart Stewart, Ritchie Ritchie, Bajel Bajel, Wong Wong, Fong Fong, Trubiano Trubiano, Kong Kong, Slavin Slavin
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