Tacrolimus prolonged release in kidney transplantation

Abstract

Lack of improvement in long-term post-transplant outcomes in recent times has highlighted nonadherence to immunosuppressive therapy as a major risk factor for poor patient outcomes. A once-daily immunosuppressive dosing regimen has been shown to be associated with improved patient adherence and, possibly, better long-term outcomes. Consequently, tacrolimus prolonged release (Advagraf^®) has been developed to ensure similar efficacy and safety to Prograf^®, with the added benefit of once-daily dosing. Phase II pharmacokinetic studies have demonstrated that patients can be converted from Prograf to Advagraf on a one-to-one total daily-dose basis and that trough levels can be monitored using the systems already in place. Studies investigating de novo use have shown that Advagraf can be initiated within the same dose range as Prograf, and that trough levels should be monitored over time, with the dose adjusted accordingly to maintain exposure within the appropriate therapeutic range. Large multicenter Phase III studies have demonstrated the good long-term efficacy and safety profiles of Advagraf, and suggest that Advagraf also has the potential to provide the added benefits of lower inter- and intrasubject variability compared with Prograf. In one large Phase III study, measures of renal function also favored Advagraf over Prograf. In conclusion, once-daily Advagraf treatment could potentially enhance post-transplantation adherence to medication and, consequently, improve long-term graft protection while maintaining adequate immunosuppression.

Keywords::

• Advagraf^®
• graft survival
• immunosuppression
• kidney transplantation
• nonadherence
• tacrolimus prolonged release

Financial & competing interests disclosure

Bernard Krämer has participated in clinical trials funded by Astellas, Bristol-Myers Squibb, Novartis, Roche and Wyeth; has received lecture fees from Astellas, Novartis, Roche and Wyeth; has served on advisory/safety boards for Astellas, Bristol-Myers Squibb, Novartis and Wyeth; and has received research grants from Astellas and Novartis. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Editorial assistance was provided by Ify Ikelionwu of ACUMED^® (London, UK) and was funded by Astellas Pharma Europe.