Crushed Posaconazole Delayed-Release Tablets Have Reduced Bioavailability and Interaction With Tacrolimus Relative to Other Administration Routes

Abstract

Background:

Prior studies suggest that posaconazole delayed-release tablet (DRT) may be crushed for feeding tube administration. It is unknown whether this decreases posaconazole absorption, subsequently impacting its interaction with tacrolimus relative to oral (PO) or intravenous (IV) administration.

Objective:

This study aimed to assess the impact of posaconazole administration route on posaconazole and tacrolimus trough concentration-to-dose ratio (C/D) in lung transplant recipients (LTR).

Methods:

Single-center retrospective study of adult LTR transplanted between December 2021 and August 2024 who received tacrolimus-based immunosuppression and posaconazole prophylaxis. The primary outcome was posaconazole C/D across posaconazole administration routes (noncrushed PO DRT, IV, and crushed DRT). Secondary outcomes included tacrolimus C/D, achievement of initial therapeutic posaconazole level, and a paired analysis of tacrolimus C/D in LTR converting from crushed to noncrushed PO posaconazole DRT.

Results:

Sixty-one posaconazole levels were analyzed for 42 LTR. Median posaconazole C/D were 4.2 for IV, 4.1 for noncrushed PO DRT, and 2.1 for crushed DRT (P < 0.01) with 40% of LTR having initial therapeutic posaconazole levels on crushed DRT regimens versus 94% for IV and 86% for noncrushed PO DRT(P < 0.01). Median tacrolimus C/D for IV, noncrushed PO DRT, and crushed DRT posaconazole regimens were 4.0, 5.0, and 6.8, respectively (P = 0.72). Seven LTR were switched from crushed posaconazole DRT to noncrushed PO DRT and median tacrolimus C/D increased following route change (7.8 vs 9.5; P = 0.04).

Conclusion and Relevance:

Posaconazole C/D was lower in LTR receiving crushed posaconazole DRT versus other routes. LTR switching from crushed to noncrushed posaconazole DRT had increased tacrolimus C/D. Clinicians using crushed posaconazole DRT via feeding tubes should be aware that 1:1 conversion with other routes may result in subtherapeutic posaconazole and tacrolimus levels.