Tacrolimus: a new immunosuppressive agent.

The mechanism of action, pharmacokinetics, drug interactions, clinical efficacy, and adverse effects of tacrolimus, a newly approved immunosuppressant drug for use in the prophylaxis of organ rejection after transplantation, are reviewed. Tacrolimus prevents rejection of the transplanted organ by inhibiting the expression of interleukin-2 in T cells and inhibiting T-cell growth and proliferation. Bioavailability after oral administration is 5-67%, and the half-life is 4-41 hours. Tacrolimus is extensively metabolized by cytochrome P-450 3A4 isoenzyme, resulting in several known drug interactions. Most experience with tacrolimus has been at one institution, where clinical trials have been conducted in liver, kidney, heart, lung, and intestinal transplantation. Clinical trials have shown that tacrolimus is an effective alternative to cyclosporine for both primary immunosuppression and rescue therapy in liver transplant patients. Fewer reports have been published regarding tacrolimus use in other types of transplantation, but the results show that tacrolimus may be a useful alternative to cyclosporine. The major adverse effects of tacrolimus therapy are nephrotoxicity and neurotoxicity. Tacrolimus is an effective alternative to cyclosporine as a primary immunosuppressant in the prevention of organ rejection and may reduce the incidence of rejection after organ transplantation.