Optimal Dosing of Cyclosporine and Tacrolimus to Improve Medication Adherence after Heart Transplantation

PURPOSE The number of daily tablets is shown to be crucial for medical adherence of patients after heart transplantation (HTx) to improve long-term outcome. In this study we identified two methods to reduce the daily count of tablets: substitution of innovator-Tacrolimus (TAC) with generic-TAC, which offer various dosages, and simplification and systematic adjustment of Cyclosporine A (CsA) intake. METHODS A retrospective study of the immunosuppressive therapy was conducted on 63 patients who received a HTx in our center from 2009 to 2014. The daily dosage was recorded and the daily tablet amount was counted. In a theoretic model, innovator-TAC was replaced by generic drug, which is available with five different dosages, with the same daily TAC-dosage. For ideal CsA-dosing, we established 3 models, namely model A, with systematic and targeted adjustment of partial CsA-dosages but keeping the same cumulative daily dose, and model B and C, with lowest daily pill count by allowing the change of cumulative daily dose within 5% and 10%, respectively. Then we compared the daily tablet amount and costs over the study period. RESULTS Our patient population was comparable to current international and national databases. The average innovator-TAC dosage was 4.8±3.3mg/d, and the daily innovator-TAC pill count was 4.1±1.7. The replacement of innovator-TAC by generic-TACcould lead to a 20.8% volume reduction of TAC tablets. The number of TAC tablets could be significantly decreased to an average of 3.3±1.1mg/day. Furthermore, an annually cost reduction of 19.2% (528 193.01€) could be achieved. The average CsA dosage was 148.9±42.6mg/day; the daily pill count was 4.3±1.1. Using model A, a 24.4% reduction of daily tablets intake could be achieved. Allowing an average change of the cumulative daily dose of 1.3±1.1% (model B) or 1.4±1.2% (model C) could result in a 34.3% and 39.2% reduction of daily tablet-count of CsA, respectively. CONCLUSION In this study we were able to show that the replacement of innovator-TAC by generic-TAC with multiple available dosages, and the simplification and systematic adjustment of CsA dosing could significantly reduce the daily tablet count, and even the total amount of cost. The reduction of the daily tablets could, therefore, increase medication adherence and help to improve outcome after HTx.