Tacrolimus Dose Requirements in Lung Transplant Recipients on Systemic Azole Antifungals: The Influence of Race and Transplant Indication

K. S. Walter¹, T. Wert¹, R. Coakley², L. J. Lobo², R. A. Evans¹

¹Department of Pharmacy, University of North Carolina, Chapel Hill, NC, ²Department of Medicine, University of North Carolina, Chapel Hill, NC

Meeting: 2021 American Transplant Congress

Abstract number: 1214

Keywords: African-American, Dosage, FK506, Lung

Topic: Clinical Science » Lung » Lung: All Topics

Session Information

Session Name: Lung: All Topics

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: CYP3A5 polymorphisms, drug interactions, and alterations in gastric absorption impact tacrolimus metabolism. This is important for those at higher risk of expressing these factors, such as African American (AA) and cystic fibrosis (CF) patients. We sought to assess the effect of race and transplant indication on tacrolimus dose requirements (TDRs) and transplant outcomes in lung transplant recipients (LTRs) initiated on a fixed tacrolimus dose and antifungal prophylaxis with a systemic azole after transplant.

*Methods: All adult LTRs transplanted from 1/2015-10/2019 initiated on an equivalent tacrolimus dose posttransplant were included and stratified by race (AA or non-AA) and transplant indication (CF or non-CF). TDRs, tacrolimus levels, tacrolimus time in therapeutic range (TTR), systemic azole use, biopsy proven acute rejection (BPAR), and patient/graft survival for the first year posttransplant were evaluated.

*Results: 68 LTRs were included (10 AA, 16 CF); approximately 90% were on a systemic azole at 1 and 3 months posttransplant. CF LTRs were significantly younger (32 vs 59 years) and had a mean lower body weight (53.4 vs 81.1 kg) at baseline compared to non-CF LTRs. In AAs, TDRs were significantly higher throughout the first year posttransplant, while in CF LTRs, TDRs were only significantly higher throughout the first 3 months posttransplant (Figures 1, 2). There was no difference in time to first therapeutic level or number of dose adjustments to achieve this level between groups. The majority of LTRs did not have a therapeutic tacrolimus level at discharge (55% AA vs 41% non-AA, p=0.1; 63% CF vs 73% non-CF, p=0.4). Tacrolimus TTR was similar between groups (55% AA vs 41% non-AA, p=0.1; 34% CF vs 45% non-CF, p=0.2). No difference in BPAR or patient/graft survival within 12 months was observed.

*Conclusions: While both AA and CF LTRs had significantly higher TDRs to maintain similar trough levels, this did not influence transplantation outcomes. Further research is needed to determine the optimal dosing strategy in these patient populations immediately posttransplant.

To cite this abstract in AMA style:

Walter KS, Wert T, Coakley R, Lobo LJ, Evans RA. Tacrolimus Dose Requirements in Lung Transplant Recipients on Systemic Azole Antifungals: The Influence of Race and Transplant Indication [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/tacrolimus-dose-requirements-in-lung-transplant-recipients-on-systemic-azole-antifungals-the-influence-of-race-and-transplant-indication/. Accessed November 21, 2024.

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