Title:STABIL-study: The Course of Therapy, Safety and Pharmacokinetic Parameters of Conversion of Prograf® to Tacrolimus HEXAL®/Crilomus® in Renal Transplant Recipients – an Observational Study in Germany
Volume: 16
Issue: 4
Author(s): Lukas J. Lehner*, Klaus Kalb, Karl Weigand, Ulrich Pein, Peter Schenker, Wolfgang Seeger, Robert Roehle, Kerstin Dienes, Fabian Halleck and Klemens Budde
Affiliation:
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin,Germany
Keywords:
Renal transplant, immunosuppression, generic, tacrolimus, trough levels, conversion.
Abstract:
Background/Objective: Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant
for the prevention and treatment of rejection following renal transplantation. For
safe and socioeconomically efficient conversion of the innovator into a generic formulation, high-
-quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics
in kidney transplant recipients.
Patients and Methods: From 2014 to 2017, we enrolled 32 kidney transplant recipients, receiving
newly prescribed Tacrolimus HEXAL®/Crilomus® in 5 German centers. Efficacy and safety data
were collected over 6-8 months and retrospectively compared to the period prior to conversion.
Results: The mean tacrolimus trough level was 4.91 ng/mL Standard Deviation (SD) (SD ±1.7) before
and 5.06 ng/mL (SD ±1.97) after conversion. Mean tacrolimus trough concentration-dose-ratio
(+/- SD) was 187.1 ng/mL/mg/kg/day (SD 99.2) for the reference and 205.1 ng/mL/mg/kg/day (SD
133) for the generic product, resulting in a non-significant difference of 18.0 ng/mL/mg/kg/day
(SD 71.8) (p=0.84, Wilcoxon V=180). Overall, dosing had to be changed in 4 (14.8%) patients.
Graft function remained stable and no rejections occurred.
Conclusion: In conclusion, conversion to the generic tacrolimus formulation can be considered
safe and feasible in long-term kidney transplant recipients in Germany. As suggested by guidelines,
vigilant therapeutic drug monitoring is recommended to account for possible tacrolimus concentration
variability on the individual patient level.
