Retrospective evaluation of LCP-tacrolimus (Envarsus XR) dosing in de novo kidney transplant.

INTRODUCTION

Tacrolimus is known to exhibit significant inter- and intra-patient pharmacokinetic (PK) and pharmacodynamic (PD) variability regarding therapeutic response. LCP-tacrolimus (LCPT-Envarsus XR) was approved in 2018 for use as a de novo immunosuppressive agent in kidney transplants, but there is limited evidence to guide de novo dosing of LCPT in patients with obesity. The primary objective of this study was to evaluate the impact of different calculated weight-based de novo LCPT dosing on early transplant outcomes.

METHODS

This was a retrospective study of patients with obesity (BMI ≥ 30 kg/m2 ) who received a kidney transplant at the University of Illinois Hospital and Health System (UIH), between March 2019 and March 2021. Subjects were included if were age 18 years or older and received de novo LCPT throughout index hospitalization. The primary endpoint of this study was to compare correlations between the first tacrolimus trough level and dosing weight strategy (e.g., TBW, AdjBW, IBW).

RESULTS

There was a statistically significant, though modest, correlation between all three dosing strategies and the first tacrolimus trough level (TBW correlation coefficient = .431, p < .001; AdjBW correlation coefficient = .455, p < .001; IBW correlation coefficient = .465; p < .001). In regression modeling for supratherapeutic levels each additional .01 mg/kg increase in dose by TBW, AdjBW, and IBW increased the odds of a supratherapeutic level by 1.46, 1.34, and 1.24, respectively (p < .001).

CONCLUSIONS

The use of LCPT in kidney transplant recipients with obesity dosed using TBW demonstrated the strongest correlation with initial supratherapeutic tacrolimus levels. Larger prospective studies are needed to investigate the further impact of body weight on dosing regimens in the obese population.