Neoral® rescue therapy in transplant patients with intolerance to tacrolimus

Background. The calcineurin inhibitors, cyclosporine and tacrolimus, are the mainstay of current immunosuppressive regimens for the prevention of acute rejection in organ transplantation. The choice of the individual agent used often depends on the preference of the Transplant Center and patient type. Adverse effects associated with tacrolimus may impact its clinical utility in many patients. This study characterizes the clinical outcomes of transplant recipients who experienced adverse effects from tacrolimus and were converted to cyclosporine-microemulsion-based (Neoral(R) [cyclosporine, USP] MODIFIED) therapy. Methods. Hepatic or renal allograft recipients unable to maintain adequate immunosuppression with a tacrolimus-based regimen for reasons of toxicity or efficacy were recruited for this study and converted to cyclosporine-microemulsion-based therapy. Data were collected on drug dosing, trough concentrations, and treatment duration, as well as detailed information on tacrolimus-associated toxicities that prompted rescue with cyclosporine-microemulsion. Furthermore, clinical and laboratory data related to the clinical course of the patients after conversion to cyclosporine-microemulsion were recorded for up to 1 yr following conversion. Results. One hundred and fifty-seven transplant recipients were enrolled in this study. Predominant reasons for discontinuation of tacrolimus were neurotoxicity (55%), diabetes (24%), nephrotoxicity (15%), and gastrointestinal intolerance (24%). Patients frequently had multiple symptoms prompting rescue therapy with cyclosporine-microemulsion. Over 70% of subjects had improvement or resolution of their tacrolimus-associated adverse symptoms within 3 months post-conversion. Acute rejection episodes occurred in 27% of patients converted to cyclosporine-microemulsion. Conclusions. Cyclosporine-microemulsion rescue therapy in patients experiencing adverse clinical effects associated with tacrolimus is an effective treatment option which leads to resolution of these adverse effects in the majority of patients, and allows for satisfactory clinical outcomes.