Abstract

Immunosuppressive drugs are critical dose drugs - small changes in the dose
or systemic exposure can result in changes in both their efficacy and toxicity. The primary immunosuppressive drugs in use today, ciclosporin and tacrolimus, are now available as generic formulations. There are international criteria for testing generic formulations against the innovator drug, designed to guarantee the bioequivalence of the two formulations. Whilst there are many excellent generic formulations, which allow trouble-free switching between brands of the same active drug, there are concerns regarding the criteria used to test generic formulations for indications such as transplantation. These concerns are reected by the recent introduction of more stringent criteria for critical dose drugs in Canada and Denmark, and proposed changes by the EU regulatory body. Generic formulations manufactured in some parts of the world give rise to more serious concerns, both in terms of the amount of drug they contain and the excipients in the formulations. This presentation will focus on some of the issues relating to the quality of generic medicines and the impact they could have on efficacy and toxicity following organ transplantation. It will be concluded that, whilst the use of generic formulations may hold out the prospect of cost savings, the total economic impact of brand switching should be taken into consideration.
Clinicians should be aware that a simple comparison of pharmacokinetic
properties may not necessarily equate to therapeutic equivalence.

Keywords: immunosuppressive drugs, toxicity, Organ Transplantation