The Association of Tacrolimus Formulation Switching with Trough Concentration Variability: A Retrospective Cohort Study of Tacrolimus Use Post-Kidney Transplantation Based on National Drug Code (NDC) Numbers.

INTRODUCTION: It was hypothesized that patients experiencing at least one tacrolimus formulation switch may require more frequent therapeutic drug monitoring, subsequent dose adjustments, and a potential for untoward clinical outcomes than patients who remain on a single formulation. METHODS: Eligible patients were adult kidney transplant recipients with stable renal function at month 3 post-transplant and no evidence of acute rejection, receiving an oral, tacrolimus-based regimen. Patients were categorized into two groups (fixed or variable formulation) using the US National Drug Code (NDC) on the basis of tacrolimus formulation usage over the 12-month period. RESULTS: A total of 305 patients were enrolled from four US transplant centers; 44 (14.4%) received multiple formulations and 261 (85.6%) received a single formulation. Mean number of tacrolimus dose adjustments and mean cumulative milligram dose change were not statistically different between the two groups. Mean trough-to-dose ratio, frequency of trough level measurements, and mean number of excursions above 120% or below 80% of the patient's mean trough concentration were significantly higher in the variable compared to the fixed formulation group. CONCLUSION: A variable tacrolimus formulation regimen was associated with a higher frequency of trough level measurements and a greater number of excursions in trough levels compared with continuing on a fixed formulation regimen of tacrolimus in this retrospective chart review study. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

Ten-year follow-up of a randomized trial of pravastatin in heart transplant patients.

BACKGROUND: Outcomes from this trial's first year data demonstrated significant benefit in heart transplant patients treated with pravastatin in cholesterol levels, survival, rejection with hemodynamic compromise, the development of cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity. Other heart transplant studies have shown similar benefit. We now report the 10-year follow-up of this study. METHODS: Ninety-seven heart transplant recipients were randomized to pravastatin (n = 47) or no pravastatin (n = 50) within 2 weeks after surgery both in combination with cyclosporine and corticosteroids. Ten-year outcomes include survival, cholesterol levels, and development of cardiac allograft vasculopathy documented by coronary angiography. RESULTS: Forty-two percent of the control patients crossed over to pravastatin treatment during the second year of the study, and 81% of the control patients were eventually placed on statin therapy by the 10-year follow-up. The control group had subsequent low and comparable cholesterol levels in Years 2 to 10 of the study compared with the patients originally randomized to pravastatin. Intent-to-treat analysis demonstrated that the pravastatin group compared with control had increased 10-year survival (68% vs 48%, p = 0.026). The 10-year freedom from angiographic cardiac allograft vasculopathy and/or death in the pravastatin group was significantly greater compared with the control group (43% vs 20%, p = 0.009). CONCLUSION: The 10-year follow-up of this study suggests that the use of pravastatin in heart transplant patients maintains survival benefit and appears to reduce the development of cardiac allograft vasculopathy.