Efficacy and Safety of Once-Daily LCP-Tacrolimus Versus Twice-Daily Immediate-Release Tacrolimus in Adult Hispanic Stable Kidney Transplant Recipients: Sub-Group Analysis from a Phase 3 Trial

Abstract

Background The pharmacokinetics and metabolism of tacrolimus, an immunosuppressant commonly used to prevent transplant rejection, can differ in specific subpopulations. This analysis examined treatment outcomes and safety of immediate-release tacrolimus (IR-Tac) and LCP-tacrolimus (LCPT) in stable Hispanic kidney transplant recipients. Material/Methods This was a post hoc analysis of clinical trial data from Hispanic adult stable kidney transplant recipients randomized to remain on IR-Tac or convert from IR-Tac to a reduced dose of LCPT (NCT00817206). Composite treatment failure was evaluated at 12 months. Estimated glomerular filtration rate and tacrolimus trough concentrations were evaluated over 12 months. Results Fifty-five stable (LCPT n=26, IR-Tac n=29) kidney transplant recipients who self-identified as Hispanic or Latino were included in this analysis. Composite treatment failure occurred in 1 patient (4%) who converted to LCPT and 1 (3%) who remained on IR-Tac. The estimated glomerular filtration rate was stable over time and similar in the 2 treatment groups ( P =0.08). Tacrolimus trough levels for both groups were similar over time in the 2 treatment groups ( P =0.98). Treatment-emergent adverse events were similar in patients who converted to LCPT and in those who remained on IR-Tac. Conclusions Efficacy and safety were similar in Hispanic kidney transplant recipients who converted from IR-Tac to LCPT and in those remaining on IR-Tac.

Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac

“…Overall, it seems logical that the treatment with LCPT increases the C/D ratio when compared to IR-Tac calculated C/D ratios ( Figure 3 ). This is in line with the literature [ 31 , 32 ].…”

Extended‐release tacrolimus dosing and outcomes in pediatric and young adult transplant recipients – A single‐center experience

“…2,3 The safety and efficacy of LCPT compared to IR-Tac have been increasingly examined, especially since the 2019 U.S. manufacturing shortage of generic IR-Tac. [4][5][6] IR-Tac has been the mainstay for maintenance immunosuppression in pediatric patients receiving kidney or liver transplants, though LCPT has gained emerging popularity during the IR-Tac shortage. Published data on the use of LCPT in the pediatric population are limited to case reports.…”

“…In adults, once‐daily LCPT has shown improved bioavailability and less intra‐patient drug level variability compared to twice‐daily IR‐Tac 2,3 . The safety and efficacy of LCPT compared to IR‐Tac have been increasingly examined, especially since the 2019 U.S. manufacturing shortage of generic IR‐Tac 4–6 . IR‐Tac has been the mainstay for maintenance immunosuppression in pediatric patients receiving kidney or liver transplants, though LCPT has gained emerging popularity during the IR‐Tac shortage.…”

The effect of tacrolimus conversion from immediate- to extended-release formulation on renal function in renal transplant patients: a meta-analysis

“…There are two once-daily formulations of tacrolimus, namely, standard prolonged-release tacrolimus (such as Advagraf ® ) and extended-release tacrolimus (such as Envarsus ® ), which enhance the convenience for renal transplant patients and assist in improving the medical adherence of these patients ( McCormack, 2014 ; Garnock-Jones, 2015 ; Tremblay and Alloway, 2017 ; Faravardeh et al, 2021 ; Budde et al, 2022 ). The difference between these two formulations is that extended-release tacrolimus uses MeltDose ® Technology, which improves the solubility of tacrolimus by dispersing it in a polymer matrix, thereby increasing its bioavailability ( McCormack, 2014 ; Stifft et al, 2014 ; Garnock-Jones, 2015 ; Oberbauer et al, 2020 ).…”