Effectiveness and safety of the conversion to MeltDose^® extended‐release tacrolimus from other formulations of tacrolimus in stable kidney transplant patients: A retrospective study

Abstract

Tacrolimus is the cornerstone of immunosuppressive therapy after kidney transplantation. Its narrow therapeutic window mandates serum level strict monitoring and dose adjustments to ensure the optimal risk-benefit balance. This observational retrospective study analyzed the effectiveness and safety of conversion from twice-daily immediate-release tacrolimus (IR-Tac) or once-daily prolonged-release tacrolimus (PR-Tac) to the recent formulation once-daily MeltDose ® extended-release tacrolimus 2 of 9 | SÁNCHEZ FRUCTUOSO ET al.

Real-World Administration of Once-Daily MeltDose® Prolonged-Release Tacrolimus (LCPT) Allows for Dose Reduction of Tacrolimus and Stabilizes Graft Function Following Liver Transplantation

“…Lower tacrolimus dosing may also have contributed to the good overall long-term tolerability of LCPT. In accordance with previous observations, median trough levels of tacrolimus remained within the target range in both fast and slow metabolizers despite dose reductions [ 25 , 37 ]. Identification of fast metabolizers and optimization of tacrolimus formulation could therefore provide a strategy to improve graft survival [ 38 ].…”

“…Thus, we confirm previous findings of good overall tolerability of LCPT in patients after solid organ transplantation [ 17 , 23 ], which is likely due to its smooth pharmacokinetic profile and fewer peak-to-trough fluctuations [ 19 , 24 ]. Accordingly, switching immunosuppressive therapy from IR-Tac or ER-Tac to LCPT has been shown to be associated with significantly lower peak-related toxicity such as tremors, concentration difficulties, headache, and insomnia [ 23 , 25 ].…”

“…The small effect size indicates that the difference between baseline is negligible over time, despite its statistical significance. In previous studies investigating conversion from IR-Tac to LCPT, no renal function data were presented in a 53-week study in liver transplant recipients [ 18 ], and in kidney transplant patients a slight but significant increase of mean serum creatinine from 1.56 to 1.61 mg/dL ( p < 0.05) was observed in a retrospective cohort study in kidney transplant recipients with no changes of GFR [ 25 ]. Furthermore, a randomized trial in kidney transplant recipients showed similar estimated GFR (eGFR) between LCPT and IR-Tac patients [ 26 , 27 ], and a systematic review of 10 observational studies did not show differences between IR-Tac and extended-release (ER-)Tac in renal function in adult kidney de novo transplantations [ 28 ].…”

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

“…Due to differences in bioavailability, dosing recommendations also differ between tacrolimus formulations, which include twice-daily immediate-release tacrolimus (IR-Tac), a once-daily extended-release capsule formulation, and a once-daily MeltDose ® (LCPT) formulation [ 1 ]. For example, owing to the approximately 30% greater bioavailability of LCPT than IR-Tac [ 4 , 5 ], the total daily dose (TDD) must be reduced in patients who switch from IR-Tac to LCPT.…”

Immunosuppression-related neurological disorders in kidney transplantation

“…Dose reduction of CNIs may lead to significant improvement in symptoms, and some patients may also respond to beta-blockers. Extended-release formulations of tacrolimus may provide some benefit over conventional forms, but randomized controlled trials in this context are still lacking [86,87].…”