A risk-benefit assessment of tacrolimus in transplantation.

Tacrolimus is a new macrolide immunosuppressant that was isolated from Streptomyces tsukubaensis in 1984. In vitro, on a molecular basis, tacrolimus is 50 to 100 times more potent that cyclosporin. Since 1989, numerous clinical trials have been completed comparing the usefulness of tacrolimus with that of cyclosporin for baseline immunosuppression in solid organ transplantation. Almost all of these studies demonstrated the superior immunosuppressive potency of tacrolimus. However, in most of these trials, tacrolimus-based immunosuppression was associated with a higher overall frequency of drug-related adverse effects compared with cyclosporin. Based on the efficacy and tolerability profile of tacrolimus that has been demonstrated in the various clinical trials so far, tacrolimus is a relevant alternative to cyclosporin for baseline immunosuppression in liver transplantation. In addition to primary immunosuppression, conversion from cyclosporin to tacrolimus should be performed during episodes of severe graft rejection (e.g. resistant to steroid bolus therapy). The future role of tacrolimus for baseline immunosuppression in kidney and thoracic organ transplantation has yet to be defined by ongoing studies.