Co‐administration of proton pump inhibitors and/or of steroids may be a risk factor for low trough concentrations of posaconazole delayed‐released tablets in adult patients with haematological malignancies

Abstract

Posaconazole exposure during treatment with delayed-released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.

Evaluation of posaconazole plasma concentrations achieved with the delayed‐release tablets in Korean high‐risk patients with haematologic malignancy

“…17 However, in real-world patients, co-administration of PPIs has been reported to be a risk factor for low-trough PCZ concentrations in patients receiving PCZ-DRT for prophylaxis. 14,16,18 Findings of this study are in agreement with these previous reports.…”

“…The percentages were higher than reported rates (10% and 5%, respectively) from a phase 3 clinical trial of PCZ‐DRT . However, real‐world studies of neutropenic AML/MDS patients and HSCT recipients with GVHD have shown higher prevalence of patients failing to achieve 700 ng/mL target concentration with PCZ‐DRT formulation at steady state, ranging from 15% to 33.3% …”

“…11 However, real-world studies of neutropenic AML/ MDS patients and HSCT recipients with GVHD have shown higher prevalence of patients failing to achieve 700 ng/mL target concentration with PCZ-DRT formulation at steady state, ranging from 15% to 33.3%. [13][14][15][16] In comparison, the historical cohort of adult patients with AML/ MDS undergoing remission induction chemotherapy and receiving PCZ-OS formulation showed a median PCZ concentration of 713 ng/ mL. 3 In this historical cohort, 48% failed to achieve target concentration of 700 ng/mL and 27% failed to achieve target concentration of 500 ng/mL.…”

Initial posaconazole dosing to achieve therapeutic serum posaconazole concentrations among children, adolescents, and young adults receiving delayed‐release tablet and intravenous posaconazole

“…Some recent studies reported that concomitant administration of medications that increase the pH of the stomach may also affect the exposure of the DRT 5,6 . In our study, 41 patients received either a PPI and/or a H 2 RA; however, only 13 (31%) of these patients had subtherapeutic levels.…”

“…The bioavailability and systemic exposure of the posaconazole suspension have been reported to be impacted by food intake, mucositis, diarrhea, and an increase in gastric pH and/or motility 3,4 . Although the bioavailability of the DRT is not markedly affected by food intake, two recent studies suggested that PPI may affect the exposure of the delayed‐release tablet 5,6 …”