Evaluation of Different Initial Doses of Envarsus in De Novo Kidney Transplant Recipients

Background/Objectives: Envarsus is a novel prolonged-release formulation of tacrolimus with enhanced bioavailability. The summary of product characteristics recommends an initial dose of 0.17 mg/kg/day for the prophylaxis of rejection in kidney transplant recipients, which may be excessive. This study aimed to compare the pharmacokinetics of four different initial doses of Envarsus: 0.15 mg/kg/day (group 1), 0.12 mg/kg/day (group 2), 0.10 mg/kg/day (group 3), and 0.08 mg/kg/day (group 4). Induction therapy included thymoglobulin, sirolimus, and prednisone, with Envarsus initiated once serum creatinine levels fell below 3 mg/dL. Methods: A comprehensive pharmacokinetic sampling strategy was implemented between 48 and 72 h post-transplant, allowing for the calculation of AUC using the trapezoidal method. Additionally, trough levels at 72 h were assessed, with the therapeutic range defined as 5-8 ng/mL. Patients with trough concentrations above 8 ng/mL either had their tacrolimus dose reduced or their treatment temporarily discontinued for 24 h. Kidney function was evaluated three months post-transplant. Results: A total of 167 patients completed the study (39 in group 1, 43 in group 2, 42 in group 3, and 43 in group 4). The groups were balanced in baseline characteristics. Compared with groups 1 and 2, groups 3 and 4 had significantly lower mean trough concentrations (7.9 ng/mL and 6.5 ng/mL vs. 11.3 ng/mL and 10.8 ng/mL, respectively) and lower AUC values (310 ng·h/mL and 271 ng·h/mL vs. 458 ng·h/mL and 390 ng·h/mL, respectively). Additionally, the proportion of patients with supratherapeutic drug levels was lower in groups 3 and 4 (47.6% and 37.2% vs. 76.9% and 67.4%, respectively), as was the proportion of patients requiring a skipped dose (14.3% and 14.0% vs. 30.8% and 27.9%, respectively). Importantly, the percentage of patients within the therapeutic range was higher in the 0.08 mg/kg/day group (41.9%), demonstrating improved drug level stability at this dose. Despite these differences, kidney function remained similar in all groups at three months, and no significant differences in the incidence of adverse events were observed among the four dosing groups. Conclusions: An initial dose of 0.08 mg/kg/day resulted in adequate tacrolimus exposure, improved the proportion of patients within the therapeutic range, and minimized unnecessary drug accumulation. These findings suggest that a lower initial dose of Envarsus may be preferable to optimize drug exposure while improving therapeutic precision.