Generic cyclosporine formulations: more open questions than answers

The introduction of cyclosporine (CsA) in clinical practice has significantly improved patient and allograft survival after organ transplantation. The new microemulsion CsA formulation, Neoral, has been associated with a more reproducible absorption and a better patient outcome as compared to the old formulation Sandimmune. Recently, several generic CsA formulations have been tested as bioequivalent to Neoral. Bioequivalence tests have been performed in selected groups of young, healthy male volunteers usually in single-dose studies, and then extended to completely different population, such as transplant recipients. However, growing body of evidence shows that CsA pharmacokinetics in healthy subjects is different from that of transplant patients, treated chronically with CsA. Therefore, converting patients from Neoral to the new generic formulations could be detrimental, exposing patients to increased risk of graft function deterioration and graft loss. Thus, more research and more accurate bioequivalence tests are required to address the unanswered problems dealing with the generic CsA formulations.