Generic tacrolimus in renal transplantation — review of the literature and results of a pilot observational trial

Abstract

Kidney transplantation is considered the best option for renal replacement therapy. It also allows the savings to the health care system, as the costs of care for the patient after the transplant is more than 50% lower compared to treatment with hemodialysis or peritoneal dialysis. Success in transplantation depends on immunosuppressive therapy; most often regimens consisting of drugs belonging to different groups are used; the most common are: calcineurin inhibitors (CNI — cyclosporine and tacrolimus), anti-metabolites (mainly derivatives of mycophenolic acid), and steroids. Calineurin inhibitor is the mainstay of long-term immunosupressive therapy and tacrolimus is a first-choice drug in most centers. One of the main costs of treatment after kidney transplantation are the costs of immunosuppressive drugs. Recently, generic tacrolimus formulations became available; their introduction allows for a significant reduction in immunosuppressive treatment costs borne by taxpayers. CNI belong to the so-called drugs with narrow therapeutic range (NTIDs) and require close monitoring of blood levels. Substituting generic formulations of these drugs is controversial, and there are recent guidelines of scientific societies relating to the process of replacing the original NTID preparations with generics. The article presents an overview of the literature concerning the bioequivalence of generic tacrolimus formulations in healthy volunteers and patients after kidney transplantation, treatment outcomes of patients de novo and conversion of the original drug to a generic. The results show that not all generic formulations of tacrolimus meet current European Medicines Agency guidelines and the pharmacokinetic differences compared to the original drug necessitate substantial modification of doses of generic drugs. In the last part we discuss the results of our own experience in treating de novo kidney transplant patients with a generic formulation of tacrolimus (Taliximun, Valeant).