Overweight kidney transplant recipients are at risk of being overdosed following standard bodyweight-based tacrolimus dosing

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L.M. Andrews, B.C.M. de Winter, J.T. Tang, N.M. Shuker, R. Bouamar, A.J.C. van Schaik, B.C.P. Koch, T. van Gelder, D.A. Hesselink

Chair(s): Drs. F.M. Molenaar

Thursday 9 march 2017

12:45 - 13:00h

Categories: Poster - Klinisch

Parallel session: Postersessie - Klinisch 5

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Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight.

The aim of this study was to investigate whether a Tac starting dose based on bodyweight leads to the achievement of Tac target whole-blood predose concentrations (C₀) in overweight patients on day 3 after transplantation. This was defined as the first steady state concentration attained after five unaltered Tac doses.

This is a post-hoc analysis of a randomized-controlled trial investigating whether adaptation of the Tac starting dose according to CYP3A5 genotype increases the proportion of kidney transplant recipients reaching the target Tac predose concentration. In this trial, patients were randomized to receive Tac in either the standard, bodyweight-based dose of 0.20 mg/kg/day according to the package insert, or to a dose based on their CYP3A5 genotype. For the analysis, the data were divided into three groups: the standard-dose group, the genotype-based group, and all patients scaled to the standard bodyweight dose. The correlation between Tac C₀ and bodyweight (or BMI) was investigated by calculating the goodness of fit. Dosing guidelines were calculated using linear regression lines.

Data was available for 203 kidney transplant recipients with a median BMI of 25.6 (range 17.2-42.2) and bodyweight of 78.9 kg (range 37.6-123.1). More than 50% of the overweight or obese patients had a tacrolimus predose concentration above the target range of 10-15 ng/mL. The CYP3A5 non-expressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. If the BMI is 25-30, only 85% of the standard dose (0.2 mg/kg/day) should be prescribed to reach the target concentration, and if the BMI is 30-35 we propose 75% of the standard dose. The dosing guideline for patients with an unknown genotype was validated using the FDCC dataset.  

This study demonstrates that dosing tacrolimus solely on bodyweight results in overexposure in more than half of overweight or obese patients.