Quantifying the Interaction Between Posaconazole and Tacrolimus in Liver Transplant Recipients: A Practical Approach

B. Lane¹, U. Kaszubski¹, A. Freeman¹, B. Wise¹, L. Hutchinson¹, M. Janusek¹, G. Therapondos², H. Bohorquez³, S. Anders¹

¹Pharmacy, Ochsner Medical Center, New Orleans, LA, ²Hepatology, Ochsner Medical Center, New Orleans, LA, ³Transplant Surgery, Ochsner Medical Center, New Orleans, LA

Meeting: 2021 American Transplant Congress

Abstract number: 1097

Keywords: Calcineurin, Drug interaction, Liver transplantation, Pharmacokinetics

Topic: Clinical Science » Liver » Liver: Immunosuppression and Rejection

Session Information

Session Name: Liver: Immunosuppression and Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: The interaction between tacrolimus (FK) and posaconazole (POSA) is well documented, however the extent of this interaction and the practical management has yet to be fully described post-liver transplant. Literature evaluating this interaction has been hindered by small sample sizes, limited patient populations, use of various POSA formulations and little evidence describing the timing of the interaction. Recent construction at this institution prompted the use of POSA due to its coverage of mold species. The goal of this study is to quantify the interaction between FK and delayed release POSA tablets.

*Methods: This was a single-center, retrospective study that included adult liver transplant recipients between 8/1/17 – 9/1/20. The primary endpoint was the difference in the day 5 FK C/D in the POSA group compared to a control. Secondary endpoints included the incidence of acute kidney injury (AKI), biopsy proven acute rejection (BPAR) within one month of azole discontinuation, length of stay, frequency of a patient having one or more supra- or subtherapeutic FK trough, and therapeutic troughs by day 2 & 5.

*Results: A total of 217 patients were included. Baseline demographics were similar between groups. Day 5 FK C/D with POSA was approximately three-fold that of the control group. The effects of this interaction impacted the day 2 FK C/D but had a more pronounced effect on the day 5 FK C/D. The POSA group was more likely to have a therapeutic trough (5-15 ng/mL) by day 2 & 5 and at time of hospital discharge. This group was also more likely to have a supratherapeutic trough, however this did not result in a higher incidence of AKI. Upon discontinuation of POSA, this group was highly likely to experience a subtherapeutic level, however this did not lead to more BPAR.

*Conclusions: This study is the first to evaluate this interaction in post-liver transplant recipients utilizing delayed release POSA tablets in combination with FK. Concomitant therapy resulted in a three-fold increase in FK C/D compared to a control, supporting the empiric dose reduction per the package insert to maintain similar FK trough concentrations. Impacts of this interaction were observed as early as day 2 however the effects continued upwards of day 5, requiring a significantly lower weight-based FK dose.

To cite this abstract in AMA style:

Lane B, Kaszubski U, Freeman A, Wise B, Hutchinson L, Janusek M, Therapondos G, Bohorquez H, Anders S. Quantifying the Interaction Between Posaconazole and Tacrolimus in Liver Transplant Recipients: A Practical Approach [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/quantifying-the-interaction-between-posaconazole-and-tacrolimus-in-liver-transplant-recipients-a-practical-approach/. Accessed November 21, 2024.

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