Efficacy and Safety Evaluation After Conversion From Twice-Daily to Once-Daily Tacrolimus in Stable Liver Transplant Recipients: A Phase 4, Open-Label, Single-Center Study

Background. Simplifying immunosuppressive therapy after liver transplant may improve patient compliance, thereby preventing acute rejection and graft loss. This phase 4, open-label, single-center study was conducted to evaluate the efficacy and safety of twice-daily to once-daily tacrolimus conversion in stable liver transplant recipients. Methods. Between May 2017 and January 2019, twice-daily tacrolimus was converted to once-daily tacrolimus in 101 stable recipients at least 12 months post-liver transplant in Asan Medical Center. The doses of both drugs was converted to 1:1, and the target trough level was 5 to 10 ng/mL. We prospectively analyzed graft function, drug compliance, and adverse reactions after switching regimen for 24 weeks. Results. There was no acute rejection confirmed histologically within 24 weeks, which was the primary endpoint, and there was no chronic rejection, fatal deterioration of liver function, or death in any patient during this period. After conversion, the trough level of tacrolimus decreased, and the mean +/- standard deviation differences between the trough level and baseline level were 1.46 (+/- 2.41) ng/mL, 0.43 (+/- 2.08) ng/mL, and 0.07 (+/- 2.73) ng/mL at 3, 12, and 24 weeks after conversion, respectively. Despite transient fluctuations of the trough level, there was no evidence of rejection or graft dysfunction. There were 37 adverse reactions after conversion; most of them were mild, and thrombocytopenia developed in 1 patient as an adverse drug response. Drug compliance improved after conversion according to questionnaire responses. Conclusions. The conversion to once-daily tacrolimus in stable liver transplant recipients is an effective and safe therapeutic strategy improving drug compliance.