Efficacy and Safety of Conversion from Tacrolimus Twice-Daily (Prograf (R)) to Tacrolimus Once-Daily Prolonged-Released (Advagraf (R)) in Liver Transplantation. An Italian Single-Center Experience

Lifelong immunosuppression is mandatory to sustain graft function following solid organ transplantation. This can place a significant burden on transplant recipients, with regard to the organization of their daily medication intake. In liver transplant patients, adherence to immunosuppressive therapy, and to medical indications in general, is crucial for short- and long-term outcomes. Non-adherence to immunosuppression carries a risk of graft rejection and potential graft loss, and is responsible for a high incidence of post-transplant complications. Prograf® is an immediate-release formulation of the immunosuppressive agent tacrolimus and is administered twice daily (BID) for the prevention and treatment of allograft rejection in liver transplantation. Since simpler dosing regimens, such as once-daily dosing, might help to improve adherence, a prolonged-release formulation of tacrolimus (Advagraf®) has been developed to provide once-daily (QD) dosing, with the aim of guarantee similar efficacy and safety to tacrolimus BID, but with the added benefit of once-daily morning dosing. Therefore, 186 liver transplant patients treated with tacrolimus monotherapy in our Center were switched starting on October 2011 from tacrolimus twice-daily to once-daily prolonged-released. All pts were in stable clinical conditions and with unmodified tacrolimus dosages during the previous year (the average time from the transplant was 5 yrs, with the median time of 3 yrs). The mean total daily doses of tacrolimus QD slightly decreased throughout the study period, and at months 12-24 the mean total daily dose was 4.4 mg. In those 166 out 186 patients, in whom at least one control after conversion was available at the time of the present preliminary evaluation, the median blood level of tacrolimus was 6.3 before, and 4.5 after conversion to once-daily tacrolimus. No major adverse effects were registrered in all 186 pts after conversion, and all patients have been successfully maintained up today on tacrolimus QD monotherapy. Our preliminary data confirm that tacrolimus QD offers a convenient alternative to standard tacrolimus BID for stable liver transplant recipients. Moreover, our data provide evidence that liver transplant patients can be maintained on once-daily tacrolimus dosing monotherapy, providing similar efficacy and safety to the well-established twice-daily formulation, and offering patients a more convenient and simple dosing regimen. Over time, the potential adherence benefits of once-daily dosing may also yield improvements in long-term graft survival. In the future, data from longer-term studies will contribute to the growing clinical experience with this once-daily formulation of tacrolimus.