Avoiding Tacrolimus Underexposure and Overexposure with a Dosing Algorithm for Renal Transplant Recipients: A Single Arm Prospective Intervention Trial

Bodyweight‐based tacrolimus dosing followed by therapeutic drug monitoring is standard clinical care after renal transplantation. However, after transplantation, a meager 38% of patients are on target at first steady‐state and it can take up to 3 weeks to reach the target tacrolimus predose concentration (C 0 ). Tacrolimus underexposure and overexposure is associated with an increased risk of rejection and drug‐related toxicity, respectively. To minimize subtherapeutic and supratherapeutic tacrolimus exposure in the immediate post‐transplant phase, a previously developed dosing algorithm to predict an individual’s tacrolimus starting dose was tested prospectively. 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 CYP3A5 genotype, body surface area, and age as covariates. The target tacrolimus C 0 , measured for the first time at day 3, was 7.5–12.5 ng/mL. Between February 23, 2019, and July 7, 2020, 60 patients were included. One patient was excluded because of a protocol violation. On day 3 post‐transplantation, 34 of 59 patients (58%, 90% CI 47–68%) had a tacrolimus C 0 within the therapeutic range. Markedly subtherapeutic (< 5.0 ng/mL) and supratherapeutic (> 20 ng/mL) tacrolimus concentrations were observed in 7% and 3% of the patients, respectively. Biopsy‐proven acute rejection occurred in three patients (5%). In conclusion, algorithm‐based tacrolimus dosing leads to the achievement of the tacrolimus target C 0 in as many as 58% of the patients on day 3 after kidney transplantation.