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

Ana Sánchez Fructuoso, Juan Carlos Ruiz, Antonio Franco, Fritz Diekmann, Dolores Redondo, Jesús Calviño, Nuria Serra, María José Aladrén, Secundino Cigarrán, Ana Manonelles, Ana Ramos, Gonzalo Gómez, José Manuel González Posada, Amado Andrés, Isabel Beneyto, Andrés López Muñiz, Manel Perelló, Ricardo Lauzurica, Ana Sánchez Fructuoso, Juan Carlos Ruiz, Antonio Franco, Fritz Diekmann, Dolores Redondo, Jesús Calviño, Nuria Serra, María José Aladrén, Secundino Cigarrán, Ana Manonelles, Ana Ramos, Gonzalo Gómez, José Manuel González Posada, Amado Andrés, Isabel Beneyto, Andrés López Muñiz, Manel Perelló, Ricardo Lauzurica

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 (LCP-Tac) in 365 stable kidney transplant recipients. We compared kidney function three months before and three months after the conversion. Three months after conversion, the total daily dose was reduced ~35% (P < .0001), and improved bioavailability and stable serum LCP-Tac concentrations were observed. There was no increase in the number of patients requiring tacrolimus dose adjustments after conversion. Renal function was unaltered, and no cases of BPAR were reported. Reports of tremors, as collected in the clinical histories for each patient, decreased from pre-conversion (20.8%) to post-conversion (11.8%, P < .0001). LCP-Tac generated a cost reduction of 63% compared with PR-Tac. In conclusion, the conversion strategy to LCP-Tac from other tacrolimus formulations in stable kidney transplant patients showed safety and effectiveness in a real-world setting, confirming the data from RCTs. The specific pharmacokinetic properties of LCP-Tac could be potentially advantageous in patients with tacrolimus-related adverse events.

Keywords: LCPT; extended-release tacrolimus; immediate-release tacrolimus; kidney transplant; prolonged-release tacrolimus; tacrolimus.

Conflict of interest statement

The authors declare no conflicts of interest.

© 2019 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Patient disposition
Figure 2
Figure 2
Evolution of Cmin and TDD in the conversion from IR‐Tac to LCP‐Tac (A) and from PR‐Tac to LCP‐Tac (B). The plots show values at 3 months pre‐conversion (t = −3), at conversion (T = 0), in early post‐conversion (t = 1), and at 3 months post‐conversion (t = 3). Cmin (blue lines) is shown as mean ± CI95, and TDD (red lines) is shown as median ± P25‐P75
Figure 3
Figure 3
Bioavailability of Tac 3 months before and 3 months after conversion to LCP‐Tac. For IR‐Tac to LCP‐Tac, P = .0250; for PR‐Tac to LCP‐Tac, P < .0001 (Wilcoxon test)

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