A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients.
Bloom RD, Trofe-Clark J, et al.Clinical Transplantation 2013;27(6):E685-93
Aims
This investigation is a post hoc analysis of a study that compared the steady state pharmacokinetics of a generic tacrolimus formulation (Sandoz) versus the reference drug (Prograf) in stable kidney recipients. The post hoc analysis aims to compare the pharmacokinetic parameters in subpopulations according to patient gender, African American ethnicity, the presence or absence of diabetes and the use of steroids.
Interventions
Patients received either tacrolimus Prograf or generic tacrolimus Sandoz. The patients crossed over and received the alternative drug in the second study period.
Participants
71patients who had undergone a first or second kidney transplant at least six months prior to study entry and were receiving either generic tacrolimus or reference tacrolimus.
Outcomes
The outcomes included the comparison of bioequivalence between the two formulations by measuring the Tacrolimus exposure (AUC ₀₋â‚â‚‚, Cmax, and Tmax) in males and females, between non African Americans and African Americans, and in diabetics and non diabetics.
Follow-up
28 days.
CET Conclusions
This is a post hoc analysis of data from a randomised crossover study comparing the pharmacokinetics of the Novartis generic form of tacrolimus in comparison with the standard form of tacrolimus (Prograf). The initial study showed bioequivalence of the two forms and this adhoc study was directed at looking at sub groups, namely African American’s compared with Caucasians, diabetics with non-diabetics and the use of concomitant steroids. The generic form of tacrolimus showed comparable bioavailabilty to the standard tacrolimus regardless of patient characteristics. However as the authors point out confirmation of the bioequivalence in the individual sub populations of kidney transplant patients would require a larger and adequately powered study. For final proof of bioequivalence of course a head to head randomised clinical trial is required to demonstrate clinical non inferiority. However the key information required by the potential clinical users would be the price compared with the standard form of tacrolimus, Prograf. But of course now the introduction of Advagraf is another complicating factor in this battle between the immunosuppression giants of industry.
Data analysis
Available case analysis
Quality notes
Previously assessed in Alloway et al. A Randomized Pharmacokinetic Study of Generic Tacrolimus Versus Reference Tacrolimus in Kidney Transplant Recipients. American Journal of Transplantation 2012. 12(10): 2825-2831
Trial registration
Not reported.