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Extended-Release Tacrolimus: A Review of Its Use in De Novo Kidney Transplantation

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Abstract

Extended-release tacrolimus (tacrolimus ER) [Advagraf®; Astagraf XL®; Graceptor®; Prograf XL®] is a once-daily formulation of the immunosuppressive calcineurin inhibitor, which is approved in many countries worldwide for the prophylaxis of transplant rejection in adult de novo kidney transplant recipients. It is absorbed more slowly than the conventional, twice-daily, immediate-release formulation, initially producing lower exposure when administered at the same daily dosage, but providing equivalent exposure upon repeat administration with therapeutic drug monitoring. In randomized, controlled, phase III/IV trials, with extended follow-up to 4 years, the efficacy of tacrolimus ER was similar to that of twice-daily tacrolimus with regard to the prevention of acute rejection or graft dysfunction in adult de novo kidney transplant recipients. Renal function was significantly better with tacrolimus ER, but not tacrolimus, than with ciclosporin. The tolerability profile of tacrolimus ER was descriptively similar to that of the original twice-daily formulation, with no notable differences. Therefore, tacrolimus ER retains the immunosuppressive activity of the original formulation in the prophylaxis of transplant rejection in adult de novo kidney transplant recipients and offers the benefits of once-daily administration.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Paul McCormack is a salaried employee of Adis/Springer.

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    Paul L. McCormack

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Correspondence to Paul L. McCormack.

Additional information

The manuscript was reviewed by: K. A. Andreoni, Department of Surgery, University of Florida, Gainesville, FL, USA; E. M. Billaud, Department of Pharmacology, European G Pompidou Hospital, Paris Descartes University, Paris, France; A. Del Bello, Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France; L. Rostaing, Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

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McCormack, P.L. Extended-Release Tacrolimus: A Review of Its Use in De Novo Kidney Transplantation. Drugs 74, 2053–2064 (2014). https://doi.org/10.1007/s40265-014-0316-3

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