Use of Generic Tacrolimus in Elderly Renal Transplant Recipients Precaution Is Needed

作者:Robertsen Ida*; A**erg Anders; Ingero Aleksander Olsen; Vethe Nils Tore; Bremer Sara; Bergan Stein; Midtvedt Karsten
来源:Transplantation, 2015, 99(3): 528-532.
DOI:10.1097/TP.0000000000000384

摘要

Background. Proper bioequivalence studies comparing original with generic immunosuppressive drugs in patients are limited, especially in the increasing population of elderly renal transplant recipients. We performed an open-label, single-center, prospective, randomized, cross-over study and compared steady-state pharmacokinetics (PK) of a generic tacrolimus (Tacni) formulation with the original (Prograf) in renal transplant recipients older than 60 years. Methods. Twenty-eight patients, with a median age of 69 years (range, 60 to 78), were randomized at time of transplantation to receive original or generic tacrolimus, and 25 (21 men, 4 women) provided two evaluable 12-hr PK profiles. The PK investigations were performed in a stable phase approximately 6 and 8 weeks postengraftment. After the first PK investigation, tacrolimus formulations were switched (1: 1 dose ratio). Results. Generic tacrolimus did not meet the bioequivalence criteria; the area under the curve(0-12) ratio of generic-original tacrolimus formulation was 1.17 (90% confidence interval, 1.10-1.23) and the C-max ratio was 1.49 (90% confidence interval, 1.35-1.65). The generic formulation also showed a shorter time to C-max (T-max) (P=0.04). Importantly, the lack of bioequivalence was not reflected in the standard monitoring parameter, trough concentrations (P=0.80). Conclusion. Generic tacrolimus (Tacni) was not found to be bioequivalent to the original formulation in elderly renal transplant recipients. The significantly higher systemic exposure of tacrolimus, despite similar trough concentrations, may in the long run increase the risk of adverse effects.

  • 出版日期2015-3