Update on the clinical utility of once-daily tacrolimus in the management of transplantation

Abstract

Adherence to immunosuppression and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may confer potential benefit by simplifying immunosuppressive regimens, thereby improving medication adherence among transplant recipients. Pharmacokinetic studies in healthy normal volunteers and stable transplant recipients suggest that once-daily tacrolimus is bioequivalent to twice-daily tacrolimus. Efficacy studies suggest that once-daily tacrolimus is noninferior to twice-daily tacrolimus with a concentration-dependent rejection risk. The incidence of biopsy-proven acute rejection, graft survival, and patient survival are more or less comparable between the two tacrolimus formulations. Once-daily tacrolimus has also been reported to have favorable effects on blood pressure, lipid profile, and glucose tolerance. Once-daily tacrolimus may be a viable option to consider for de novo immunosuppression or for conversion from conventional tacrolimus.

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

“…Data on the clinical utility of once-daily tacrolimus were recently evaluated in a comprehensive review [68]. The authors of that review examined 17 efficacy and safety studies of once-daily tacrolimus (six in de novo kidney transplant recipients, five in stable kidney transplant recipients, one in both de novo and stable kidney transplant recipients, and five in liver transplant recipients).…”

“…The vast majority of studies compared Advagraf Ò and Prograf Ò treatment. The authors of that review concluded that efficacy studies indicate that once-daily tacrolimus is non-inferior to twice-daily tacrolimus, with a concentration-dependent rejection risk [68]. The biopsy-proven acute rejection rates, though often higher with once-daily tacrolimus, were not statistically higher than those with twicedaily tacrolimus.…”

“…Some smaller studies included in that review suggested that once-daily tacrolimus may have favourable effects on blood pressure, the lipid profile and glucose tolerance [68]. For the most part, studies that showed improvement in glucose metabolism with once-daily tacrolimus attributed this to lower C max values achieved with the once-daily formulation [68].…”

“…For the most part, studies that showed improvement in glucose metabolism with once-daily tacrolimus attributed this to lower C max values achieved with the once-daily formulation [68]. Few studies examined in that review had drug safety as a primary end point.…”

“…Non-Caucasians and recipients with elevated immunological risk have been under-represented in studies to date. As once-daily tacrolimus becomes more frequently utilized in clinical practice, more studies on efficacy and drug safety with long-term use need to be conducted in order to better understand drug effects and refine drug administration among transplant patients [68].…”