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

Abstract

The calcineurin inhibitor tacrolimus is included in most immunosuppressive protocols after liver transplantation. This retrospective, observational 24-month study investigated the tolerability of once-daily MeltDose® prolonged-release tacrolimus (LCPT) after switching from twice-daily immediate-release tacrolimus (IR-Tac) in a real-world cohort of 150 patients with previous liver transplantation. No graft rejection or new safety signals were observed. Only 7.3% of patients discontinued LCPT due to side effects. In the overall patient population, median liver transaminases, total cholesterol, triglycerides, glucose, and HbA1c remained constant after switching to LCPT. Total cholesterol significantly decreased (p ≤ 0.002) in patients with initially elevated levels (>200 mg/dL). A total of 71.8% of 96 patients maintained a glomerular filtration rate > 60 mL/min/1.73 m2 throughout the study, while 44.7% of patients were classified as fast metabolizers and 55.3% as slow metabolizers. Median daily tacrolimus dose could be reduced by 50% in fast metabolizers and by 30% in slow metabolizers, while trough levels were maintained in the target range (4–6 ng/mL). In conclusion, our observational study confirmed previous evidence of good overall tolerability and a favorable outcome for the patients after switching from IR-Tac to LCPT after liver transplantation.

Effectiveness and safety of once‐daily tacrolimus formulations in de novo liver transplant recipients: The PRETHI study

“…To our knowledge, this study, including 163 patients, is one of the largest in liver transplant recipients receiving tacrolimus‐based immunosuppression and the largest assessing LCPT in de novo liver transplant patients. Other de novo studies evaluating LCPT included substantially fewer patients, 18,19 whereas the sample size in conversion studies from IR‐Tac to LCPT was similar, although slightly lower 15,17 . Baseline characteristics were in line with those previously observed in de novo and conversion studies 11,15,17,18,26 .…”

“…In stable liver transplant recipients, conversion from IR‐Tac to LCPT resulted in a consistent exposure with a 30% lower total daily dose (TDD) and an expected safety profile 14 . These results were confirmed in a retrospective observational study showing a TDD reduction of 50% in fast metabolizers and of 30% in slow metabolizers with good overall tolerability in patients switching from IR‐Tac to LCPT 15 . The conversion from PR‐Tac to LCPT was also proven safe and cost‐effective in two observational studies, 16,17 resulting in higher tacrolimus bioavailability and improved renal function 17 .…”

“…14 These results were confirmed in a retrospective observational study showing a TDD reduction of 50% in fast metabolizers and of 30% in slow metabolizers with good overall tolerability in patients switching from IR-Tac to LCPT. 15 The conversion from PR-Tac to LCPT was also proven safe and cost-effective in two observational studies, 16,17 resulting in higher tacrolimus bioavailability and improved renal function. 17 In a phase II study assessing the early post-transplant period in de novo liver transplant patients, LCPT and IR-Tac showed similar efficacy and safety.…”

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation

“…Overall AUC was similar to IR‐TAC at a 30% lower TDD with no new safety concerns occurred within 1 year of follow‐up 77 . An additional retrospective, observational study of 150 patients converted from IR‐TAC to LCPT at a ratio of 1:0.7 found maintained target tacrolimus trough levels with a reduced median TDD 78 . No episodes of rejection were seen at 24 months.…”

“…77 An additional retrospective, observational study of 150 patients converted from IR-TAC to LCPT at a ratio of 1:0.7 found maintained target tacrolimus trough levels with a reduced median TDD. 78 No episodes of rejection were seen at 24 months.…”