Purpose: To assess the relationship between the time to achieve consecutive therapeutic tacrolimus levels and the incidence of rejection to optimize tacrolimus dosing in cardiac allograft recipients.

Methods: This was a retrospective observational study in heart transplant recipients from January 2010 – August 2012. Goal tacrolimus whole blood trough concentrations were 10 – 15 mcg/mL during the first 90 days post-transplantation. Patients were stratified according to the time to reach four consecutive therapeutic tacrolimus levels by the following time periods post-transplantation: less than or equal to 14 days, greater than 14 days, or never. The time to achieve consecutive therapeutic tacrolimus levels was correlated with the timing, type, and severity of rejection as evidenced on endomyocardial biopsy reports.

Results: Following standard basiliximab induction in 90 patients, tacrolimus was initiated at day 1 (0 – 4), median (range), post-transplantation. Achieving four consecutive therapeutic levels within 14 days post-cardiac transplantation was associated with the lowest incidence of grade 2R and 3R acute cellular rejection (1/8 versus 16/46 versus 13/36) and antibody-mediated rejection (1/8 versus 10/46 versus 4/36), respectively. All therapeutic four levels were equivalent to weight-based dosing recommendations at a median value of 0.07mg/kg/day.

Conclusions: Study results support weight-based tacrolimus dosing to achieve four consecutive therapeutic tacrolimus levels within 14 days post-cardiac transplantation to decrease the incidence of acute allograft rejection. This study is limited by observational design.

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