Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.

Background: 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.
Methods: For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing.
Results: Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set.
Conclusions: This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.
Competing Interests: T. van Gelder has received lecture fees from Chiesi Pharmaceuticals and Astellas Pharma B.V., and consulting fees from Astellas Pharma B.V., Novartis Pharma B.V., Roche Pharma, Teva Pharma and Sandoz Pharma. D.A. Hesselink has received lecture and consulting fees, as well as grant support from Astellas Pharma B.V., Bristol-Myers Squibb, Chiesi Pharmaceuticals, MSD Pharmaceuticals, Novartis Pharma B.V., and Roche Pharma. The other authors have no conflicts of interest to disclose. The authors declare no conflicts of interest.