Effectiveness and safety of once‐daily tacrolimus formulations in de novo liver transplant recipients: The PRETHI study

Abstract

Data comparing long‐term effectiveness and safety of once‐daily tacrolimus formulations in de novo liver transplantation are scarce. We compared the effectiveness, pharmacokinetic profile, and safety of LCPT (Envarsus) and PR‐Tac (Advagraf) for up to 12 months post‐transplant. Adult de novo liver transplant recipients who started IR‐Tac (Prograf) and were converted to LCPT or PR‐Tac 3–5 days post‐transplant were included. Data from 163 patients were analyzed, 87 treated with LCPT and 76 with PR‐Tac. The incidence of treatment failure was 30.5% in the LCPT group versus 23.0% in the PR‐Tac group (p = .291). Biopsy‐proven acute rejection (BPAR) was reported in 26.8% of patients in the LCPT group and 17.6% in the PR‐Tac group (p = .166). Graft loss was experienced in one patient (1.2%) in the LCPT group and three patients (4.1%) in the PR‐Tac group (p = .346). Death was registered in three patients (3.7%) in the LCPT group and three patients (4.1%) in the PR‐Tac group (p > .999). Patients in the LCPT group showed 45.7% higher relative bioavailability (Cmin/total daily dose [TDD]; p < .01) with similar Cmin and 33.3% lower TDD versus PR‐Tac (p < .01). The evolution of renal function, safety profile, and the incidence of post‐transplant renal failure, dyslipidemia, obesity, hypertension, and diabetes mellitus were similar in patients treated with LCPT and PR‐Tac. In de novo liver transplant patients, LCPT and PR‐Tac showed comparable effectiveness with higher relative bioavailability, similar Cmin and lower TDD in the LCPT group. Renal function, safety, and post‐transplant complications were comparable in LCPT and PR‐Tac groups.