Tacrolimus XR Dosing Strategies by Race

By Victoria Socha - Last Updated: February 5, 2024

In May 2008, the Medical University of South Carolina, Charleston, dealt with the nationwide shortage of tacrolimus IR, requiring implementation of a de novo tacrolimus XR protocol. In a virtual presentation at the 2021 American Transplant Congress, N. Patel and colleagues at the center, reported on two different strategies of dosing tacrolimus XR in African American and non-African American de novo kidney transplant recipients. The presentation was titled Racial Differences in Tacrolimus XR Dosing in De Novo Kidney Transplant Recipients.

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The retrospective study included adult kidney transplant recipients between May 2020 and September 2020. The cohort was divided into two groups across two dosing strategies: non-African American and African American, and then further stratified based on initial dosing.  The initial dosing strategy called for treating all patients between 0.12 mg/kg and 0.17 mg/kg tacrolimus XR, regardless of race. The second strategy called for treating non-African American patients with 0.12 mg/kg and African American patients with 0.15 mg/kg tacrolimus XR.

The primary end point was days to a therapeutic tacrolimus trough (>7 ng/mL). Other end points were dose at steady state, number of doses held, dose at post-operative day 30, time in therapeutic range in the first month, and adverse effects.

The study included 122 patients: 57 in the African American group and 27 in the non-African American group. In the African American cohort, there was a statistically higher number of deceased donor kidney transplants and donation-after-cardiac death transplants. Recipients in the African American cohort also had significantly higher estimated post-transplant survival score, higher human leukocyte antigen mismatches, longer duration of dialysis, and were more likely to receive induction with anti-thymocyte globulin.

In the initial analyses, there was a significant interaction between race and dosing strategy for the outcome of time to therapeutic level. During the initial dosing strategy, time to achieving a therapeutic trough was significantly longer among African Americans than among non-African Americans (6.2 days vs 4.4 days; P=.03). Also, during the initial dosing strategy, the incidence of neurotoxicity was significantly higher in the non-African American group than in the African American group.

After the dosing strategy was changed for African American recipients, the time to a therapeutic level decreased to 4 days, with no significant difference between the two groups. The higher level of neurotoxicity in the non-African American recipients remained higher than in the African American recipients.

“The results demonstrate that African Americans can achieve a similar time to therapeutic tacrolimus trough concentrations with tacrolimus XR, as compared to non-African Americans, using a race stratified dosing strategy. Future analyses are underway to assess the impact of CYP 3A5 genotype on dose requirements and time to achieve therapeutic levels,” the researchers said.

Source: Patel N, Carcella T, Bartlett F, Rohan V, Taber D. Racial differences in tacrolimus XR dosing in de novo kidney transplant recipients. Abstract of a presentation at the virtual 2021 American Transplant Congress (Abstract #1273), June 5, 2021.

Post Tags:Nephrology
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