Safety and Efficacy of Conversion from Twice-Daily Tacrolimus (Prograf) to Once-Daily Prolonged-Release Tacrolimus (Graceptor) in Stable Kidney Transplant Recipients

Background. Graceptor is a new modified-release once-daily formulation of tacrolimus with an efficacy and safety profile similar to twice-daily tacrolimus (Prograf), as identified by clinical trials, offering a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily Prograf to once-daily Graceptor in stable kidney transplant recipients. Methods. We switched 33 Japanese patients who had undergone kidney transplantation >= 1 years before from twice-daily Prograf to once-daily Graceptor. The dose conversion ratio between Prograf and Graceptor was 1:1. We compared the following parameters: minimum tacrolimus concentration (C-min); concentration dose per weight (CDW); serum creatinine (sCr); blood urea nitrogen (BUN); total cholesterol (TC); high-density lipoprotein cholesterol (HDL-C); uric acid (UA); fasting blood sugar (FBS). Time points for measurements were 1 month before study start and 1 and 2 months afterward. Results. The mean age of the subjects in this study was 46.5 +/- 13.1 years. Mean C-min decreased from 4.55 +/- 1.79 to 3.20 +/- 1.22 ng/dL. The mean CDW also decreased, from 99.8 +/- 69.5 to 75.0 +/- 55.1 mg/dL/kg over the 2 months. There were no significant changes in sCR, BUN, UA, and FBS. Mean TC increased from 187.5 +/- 51.4 to 194.3 +/- 43.4 mg/dL, and mean HDL-C changed from 53.7 +/- 12.0 to 56.1 +/- 11 mg/dL. There were no episodes of rejection or infection. Conclusions. We conclude that switching from Prograf to Graceptor is safe and has the advantage of improving adherence. It could also have a beneficial effect in controlling glycemic levels and the adverse effects of tacrolimus. In many cases (25%-30%), the minimum concentration of tacrolimus decreased after changing tablets. With Graceptor, the ratio of area under trough level to area under the curve (AUC) is low compared with Prograf, resulting in low C-min values of 1-2 ng/mL, and the AUC for Graceptor is very similar to that for Prograf.