Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients.
Min SI, Ha J, et al.Nephrology Dialysis Transplantation 2013 Dec;28(12):3110-9.
Aims
To compare the efficacy, safety and pharmacokinetic profiles between general (GEN) tacrolimus and reference (REF) tacrolimus in a cross over study.
Interventions
Patients were administered either GEN tacrolimus (TacroBell) or REF tacrolimus (Prograf).
Participants
126 de novo renal transplant recipients.
Outcomes
The primary outcomes included a comparison of systemic exposure between the GEN tacrolimus and the REF tacrolimus groups on day 10 and 6 months after transplantation in the PK evaluation set. Secondary endpoints included glomerular filtration rate patient survival, allograft survival, biopsy-proven acute rejection, the incidence of adverse events including biochemical and haematological assessments.
Follow-up
9 months
CET Conclusions
This study from Korea in de novo transplant patients compares standard tacrolimus (Prograf) with a generic tacrolimus produced in Korea (TacroBell). Tacrobell had higher Cmax and AUC0-12 than the patients receiving standard tacrolimus. At 6 months a crossover between Prograf and TacroBell was performed with similar pharmacokinetic profiles. There was no difference in therapeutic outcomes in the short term but as the authors point out a much larger study is required, but initial experience suggests that TacroBell can be used safely as a replacement for Prograf. One major factor in the decision to use TacroBell will be its cost in comparison with Prograf and also whether the once a day administration of tacrolimus (Advagraf) proves to be equivalent to twice daily tacrolimus, which seems likely.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01055964