Conversion from Twice (Prograf) to Once Daily Administration of Tacrolimus (Advagraf) Regimen in Renal or Liver Transplant Recipients; An Open Multicenter Trial

Abstract

Introduction: “Non-adherence” is an important factor for both acute and chronic rejection and later graft-loss. A new formulation of tacrolimus (Tac) is available that is dosed once daily (OD). OD dosing has been shown to increase adherence. The aims were to assess the change in total Tac dose and trough level at baseline and after conversion from BID to OD dosing in kidney (ktx) and liver recipients (ltx) and how this affected patient self reported adherence. Methods: 241 recipients (mean age 51 y) were included from 23 centres. 224 (205 ktx, 14 ltx and 5 ltx+ktx) completed the study. The patients had stable graft function and were at least 6 months after transplantation. Mean time to conversion was 5.3 and 8.0 years for ktx and ltx. The patients were converted from Tac BID to OD on a 1:1 mg ratio. The patients also filled out a questionnaire at 3 months. Results: 2 patients died, 6 were changed back to Prograf and 9 were withdrawn. No patient had a rejection episode after the conversion. The mean Tac daily dose remained unchanged from visit 1 and after 3 months (3.9±2.0 and 3.9±2.1mg). In 140 patients (62%) the dose was unchanged, 35 (16%) had a lower dose, and 49 (22%) had a higher dose at 3 months. The mean Tac level was significantly lower after conversion. The through level decreased from 6.33±1.8 to 5.60±1.7 ng/ml, p< 0.0001. 141 (63%) of patients had a lower and 83 (37%) had a higher level. The questionnaire showed that 31% “sometimes” forgot their immunosuppressive medication and 19% stated that the conversion helped to improve their compliance. 55% experienced the conversion “for the better”. Conclusions: Conversion from Prograf to Advagraf was safe and well tolerated. Mean daily Tac dose remained the same but trough level was significantly lower after conversion