Cyclosporine and tacrolimus (FK506): A comparison of efficacy and safety profiles

Multicenter clinical trials conducted in the United States and Europe to co mpare the efficacy and safety of cyclosporine with tacrolimus (FK506) have demonstrated comparable long-term patient survival and graft survival in li ver and renal transplant recipients. Importantly, treatment with tacrolimus was associated with reductions in the incidence and severity of acute reje ction episodes. However, tacrolimus-based therapy was also associated with increased toxicities in comparison to conventional cyclosporine-based thera py. It is becoming increasingly accepted that earlier trials may have emplo yed high or supratherapeutic doses of tacrolimus and may have been unbalanc ed with respect to study design. In addition, these pivotal comparative tri als were performed with the original formulation of cyclosporine, and not t he cyclosporine microemulsion preparation. This critical review of the lite rature focuses on the United States and European tacrolimus multicenter cli nical trials and examines the efficacy and safety of the two primary immuno suppressants, cyclosporine and tacrolimus, obtained in these and other stud ies. The preliminary findings of ongoing studies comparing the efficacy and safety of the improved formulation, cyclosporine microemulsion, with tacro limus are also discussed. The overall efficacy of the two agents appears to be similar. The safety profile shows differing toxicities of the two medic ations. The availability of these two immunosuppressants allows the clinici an improved options when choosing an immunosuppressive regimen in solid org an transplantation.