*Purpose: Bodyweight-based tacrolimus dosing followed by therapeutic drug monitoring is standard clinical care after renal transplantation. However, after transplantation, a meagre 38% of patients is on target at first steady state and it can take up to three weeks to reach the target tacrolimus pre-dose concentration (C₀). Tacrolimus under- and overexposure is associated with an increased risk of rejection and drug-related toxicity, respectively. To minimize sub- and supra-therapeutic tacrolimus exposure in the immediate post-transplant phase, a previously-developed dosing algorithm to predict an individual’s tacrolimus starting dose was tested prospectively.

*Methods: In this single-arm, prospective, therapeutic intervention trial, 60 de novo kidney transplant recipients received a tacrolimus starting dose based on a dosing algorithm instead of a standard, bodyweight-based dose. The algorithm included cytochrome P450 (CYP) 3A4 and 3A5 genotype, body surface area and age as covariates. The target tacrolimus C₀, measured for the first time at day 3, was 7.5-12.5 ng/mL.

*Results: Between 23 February 2019 and 07 July 2020, 60 patients were included. One patient was excluded because of a protocol violation. On day three post-transplantation, 34 out of 59 patients (58%; 90%-CI 47% to 68%) had a tacrolimus C₀ within the therapeutic range. Markedly sub-therapeutic (<5.0 ng/mL) and supra-therapeutic (>20 ng/mL) tacrolimus concentrations were observed in 7% and 3% of the patients, respectively. Biopsy-proven acute rejection occurred in three patients (5%).

*Conclusions: Algorithm-based tacrolimus dosing leads to the achievement of the tacrolimus target C₀ in as many as 58% of the patients on day three after kidney transplantation.

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