Modeling of Alternative Weight-Based Dosing Strategies of LCP-Tacrolimus in De Novo Kidney Transplant Patients

J. D. Momper¹, S. J. Patel², M. A. Moten², D. R. Stevens², U. Meier-Kriesche²

¹Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, ²Medical Affairs, Veloxis Pharmaceuticals, Cary, NC

Meeting: 2021 American Transplant Congress

Abstract number: 939

Keywords: Dosage, FK506, N/A, Weight

Topic: Clinical Science » Kidney » Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Information

Session Name: Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: LCP-tacrolimus (LCPT; Envarsus XR^®) is a modified-release once-daily formulation approved for prophylaxis of organ rejection in de novo kidney transplant patients in combination with other immunosuppressants. A phase 3 study of LCPT initiated at a dose of 0.17 mg/kg/day resulted in trough concentrations >12ng/mL in 36.5% of recipients after the first dose. The objective of this study was to simulate alternative weight-based dosing strategies of LCPT in this population, using the recommended starting dose per product labelling: (i) 0.14 mg/kg actual body weight (ABW), (ii) 0.14 mg/kg ideal body weight (IBW), (iii) 0.14 mg/kg ABW with a dose cap of 12 mg.

*Methods: The initial dose of LCPT was given within 48 hours of transplantation. First dose trough concentrations for each alternative dosing scenario were simulated by proportional scaling of actual dose received and observed trough concentration, as follows:

For each dosing scenario, the proportion of subjects with a predicted first tacrolimus trough concentration <3, 3 - 6, 6 - 9, 9 - 12, 12 - 15, and >15 ng/mL was determined.

*Results: A total of 266 de-novo kidney transplant patients were included. The median (interquartile range; IQR) age, actual body weight, ideal body weight, and actual dose received were 46 years (35 – 55 years), 73.0 kg (62.5 – 87.0 kg), 63.5 kg (55.4 – 71.4 kg), and 13 mg (10 – 15 mg). The proportion of subjects with a predicted trough concentration within each bin are shown in the Table.

Proportion of subjects (n=266) with a predicted trough conc based on dose modeling strategies.
First trough concentration (ng/mL)	0.17 mg/kg ABW (observed)	0.14 mg/kg ABW	0.14 mg/kg IBW	0.14 mg/kg ABW with dose cap of 12 mg
<3	5.3%	9.3%	12.0%	9.3%
3 to 6	20.5%	22.0%	29.7%	23.2%
6 to 9	19.4%	27.4%	22.4%	27.4%
9 to 12	18.3%	12.4%	15.1%	12.4%
12 to 15	9.1%	11.6%	8.1%	10.4%
>15	27.4%	17.4%	12.7%	17.0%

*Conclusions: Alternative LCPT dosing strategies may result in a greater proportion of therapeutic first-dose trough concentrations in de-novo kidney transplant patients. In particular, dosing LCPT based upon IBW is predicted to reduce the likelihood of supratherapeutic first-dose trough concentrations.

To cite this abstract in AMA style:

Momper JD, Patel SJ, Moten MA, Stevens DR, Meier-Kriesche U. Modeling of Alternative Weight-Based Dosing Strategies of LCP-Tacrolimus in De Novo Kidney Transplant Patients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/modeling-of-alternative-weight-based-dosing-strategies-of-lcp-tacrolimus-in-de-novo-kidney-transplant-patients/. Accessed May 30, 2025.

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