Tacrolimus in cardiac transplantation: Efficacy and safety of a novel dosing protocol

Although used for more than 20 years, optimal dosing strategies of most immunosuppressants have never been determined. Tacrolimus, one of the newer agents used in solid-organ transplantation, is gaining increasing popularity because of its ability to reverse refractory rejection in cyclosporine-treated patients and its favorable side-effect profile. As with many other immunosuppressive agents, absorption and metabolism vary between individuals, which complicates dosing. We hypothesized that a 1-mg dose of tacrolimus may be used to gauge each patient's metabolism. A novel dosing scheme was evaluated to establish the safety and efficacy of this approach. Outcomes were incidence of renal insufficiency and treatment efficacy as assessed by the rejection grade on the first endomyocardial biopsy. The risk of renal insufficiency was low, with only a 3% rise in creatinine at 7 days posttransplant. The risk of renal insufficiency was highest during the first 3 days of tacrolimus therapy, and the change in tacrolimus level during this time was identified as the single best predictor of renal insufficiency. From days 4 to 7, the rise in tacrolimus level had much less influence on renal function. Ninety-two percent of patients had a low- or intermediate-grade first cardiac biopsy. It was shown that this conservative initial dosing approach, which guarantees renal safety, is not associated with an increased risk of allograft rejection. We conclude that administration of tacrolimus via a tailored protocol soon after transplantation ensures a safe and effective means of immunosuppression.