Tacrolimus once-daily formulation: in the prophylaxis of transplant rejection in renal or liver allograft recipients

Abstract

Tacrolimus once-daily (OD) is a new oral formulation of the well established immunosuppressant tacrolimus. Tacrolimus OD provided equivalent steady-state systemic tacrolimus exposure to that achieved with standard oral tacrolimus twice daily in stable renal and liver transplant recipients. The two formulations also provided broadly similar steady-state systemic exposure in de novo renal and liver transplant recipients. In a large, randomised, nonblind, multicentre, three-armed, noninferiority trial in de novo renal transplant recipients, the efficacy failure rates (primary endpoint) [any patient who died, experienced graft failure, had a biopsy-confirmed acute rejection or was lost to follow-up] of tacrolimus OD (14.0%) and standard tacrolimus (15.1%) were noninferior to that of ciclosporin (cyclosporine) microemulsion (17.0%) at 1 year, when each was given in conjunction with corticosteroids, mycophenolate mofetil and basiliximab induction. Data from a pharmacokinetic study suggests that tacrolimus OD has similar efficacy to standard tacrolimus in de novo liver transplant recipients over 6 weeks of treatment. In noncomparative 2-year trials, tacrolimus OD was effective in stable renal and liver transplant recipients converted to tacrolimus OD from standard tacrolimus. The overall tolerability profile of tacrolimus OD appears to be similar to that of standard tacrolimus in de novo and stable renal and liver transplant patients.