Tacrolimus XR Dosing Strategies by Race

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.

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.