Modified-release Tacrolimus

Abstract

TAC-MR (TAC-MR) is a new extended release tacrolimus formulation that allows a unique daily dose. In health volunteers and in kidney and liver transplant recipients, tacrolimus exposition (AUC – area under the plasma-concentration curve) and residual concentration were similar after TAC or TAC-MR administration. The switch of TAC to TAC-MR is effective and safe, using the same monitoring strategy and same therapeutic range. Therapeutic equivalence between TAC and TAC-MR was proved in a prospective, randomized open study that included 638 new kidney transplant recipients. The average of tacrolimus doses and residual blood concentration, the ethnical influence and the difficulty to reach the therapeutic range were similar between renal transplant recipients that received TAC and TAC-MR. Differences in patients proportion that presented failure in the efficacy (endpoint composed by acute rejection proven by biopsy, graft loss, death or discontinuation) and in the safety profile. Results of these studies indicate that TAC-MR, administered in a unique dose presents efficacy and safety similar to TAC, allowing the same therapeutic monitoring strategy. Expanded access programs studies are necessary to evaluate the TAC-MR influence in patient adherence to treatment, as well as if the pharmacokinetics differences could result in significantly adverse effects reduction, factor with a recognized impact on the recipient subject survival.