Switching Between Cyclosporin Formulations. What Are the Risks?

The introduction of cyclosporin, refinement in surgical techniques and improvement in allograft preservation have all led to an improvement in graft and ultimately patient survival. Cyclosporin is a lipophilic cyclic polypeptide produced by Trichoderma, a fungus isolated from Norwegian soil. Cyclosporin is a potent, selective and powerful immunosuppressive agent possessing a narrow therapeutic window. Substitution among different formulations of cyclosporin for economic reasons, without close monitoring of pharmacokinetics and pharmacodynamics, can induce undesirable toxic effects. A number of recent reports, largely anecdotal, of adverse drug reactions and acute cellular rejection after conversion from the standard formulation to the microemulsion formulation of cyclosporin have created uncertainty over the therapeutic equivalency of these agents. This leading article reviews the pharmacology, pharmacokinetics and adverse drug reactions of cyclosporin as well as the potential risks associated with switching between cyclosporin formulations in stable renal transplant recipients. Caution should be employed when switching between cyclosporin formulations. Since data are limited, long-term prospective studies are necessary to delineate the role of high peak concentrations obtained from the microemulsion formulation in relation to cyclosporin-induced chronic nephropathy. The significance of the reduction in pharmacokinetic variability with use of the microemulsion formulation in terms of graft and patient survival remains unclear.