Improvement in Attaining Tacrolimus Trough Concentrations via the Implementation of a Strict Weight-Based Dosing Guideline Following Heart Transplantation

Introduction Initial tacrolimus dosing is often chosen based on patient's weight, but the extent to which body weight affects tacrolimus requirements post-orthotopic heart transplantation (OHT) is uncertain. We hypothesized that a weight-based tacrolimus dosing approach would aid more timely achievement of target tacrolimus concentrations early post-OHT. Methods In phase 1 (1/1/15-12/31/16), all adult OHT recipients at a single center were retrospectively reviewed. Exclusion criteria were death within 2 months of OHT or follow-up care outside the transplant center. Baseline demographics were collected, including age, sex, race, body weight (kg), tacrolimus starting dose, and serum creatinine (Scr). For the first 14 days post-OHT, or until the patient reached the target tacrolimus concentration, the following were recorded: daily dose of tacrolimus (mg/day), concomitantly administered medications known to interact with tacrolimus, Scr, whole blood tacrolimus concentrations, and weight. The time (in days) to desired tacrolimus concentration (generally 10-12 ng/mL, but individualized) and the dose required for target concentration were recorded. The relationship between body weight and tacrolimus daily dose at the time of achieving the target concentration was also determined using linear regression. During phase 2 (1/1/17-12/31/18), recommended initial dosing of tacrolimus 0.05 mg/kg/day (in 2 split doses) titrated to a proposed daily dose of 0.1 mg/kg/day was implemented, and the same variables collected as described for phase 1. Unpaired T-testing and Chi square test were used to compare time to and percentage with therapeutic concentration at discharge, respectively, between the 2 phases. Results Amonsgt 157 patients (68 in phase 1; 89 in phase 2), the majority were male (72%) and white (80%). The time to therapeutic tacrolimus concentration was 16±11 days in phase 1 and 13±7 days in phase 2 (p=0.03). The percentage of patients with therapeutic tacrolimus concentrations at time of discharge was 59% in phase 1 and 78% in phase 2 (p =0.02). Doses ≥2 mg/day were initiated in 31% of phase 1 and 52% of phase 2 patients; however, the initial starting dose (in mg/day and mg/kg/day) was not observed to influence the time to therapeutic concentration. There was a modest relationship between body weight and final tacrolimus dose (mg/day) of r=0.34, p Conclusions Implementing a weight-based tacrolimus dosing guideline allowed for a higher percentage of patients with therapeutic tacrolimus concentrations at discharge and a modest reduction in the time to therapeutic concentration. The mean weight-based tacrolimus requirement for OHT recipients was 0.1 mg/kg/day. Although positively correlated with initial tacrolimus dose requirement, body weight alone was not a strong determinant of tacrolimus dosing.