Dose conversion factor between cyclosporine and tacrolimus in pediatric heart transplant recipients

Abstract

Calcineurin inhibitors (CNIs) are the cornerstone of immunosuppression after pediatric heart transplantation (HTx). However, many patients require conversion from one drug to another because of undesired adverse effects or breakthrough rejection. After conversion, it is important to achieve stable target blood levels of the newly introduced CNI as soon as possible to limit the risk of rejection, graft loss, and drug toxicity. Current guidelines direct clinicians converting patients between cyclosporine A (CyA) and tacrolimus (TAC) to dose pediatric patients according to weight (mg/kg), then adjust the dose relative to blood levels. However, dose requirements between patients vary widely because of individual differences in metabolism. Because both drugs are metabolized through the cytochrome P-450 pathway, dose requirements are strongly associated with each other as shown in adults after kidney transplant. Our primary aim was to examine the relationship between CyA and TAC dosing in pediatric HTx patients, seeking a conversion factor between CNIs that would account for individual differences in drug metabolism. This conversion factor could be used to dose the new drug relative to each patient’s unique, stable dosing of the previous drug and might provide more accurate dosing than the traditional mg/kg guidelines. A conversion factor for CNIs is defined as a patient’s stable 24-hour CyA dose/stable 24-hour TAC dose. For adult kidney transplant patients, conversion factors have been determined to be 25 and 30. These conversion factors may not apply to children because their drug metabolism is different from adults. CNI dosing at 1 year post-HTx was also compared with current mg/kg dosing recommendations. The mean CNI dose at 1 year post-HTx was recorded for all HTx patients aged r18 years receiving post-HTx care at Seattle Children’s Hospital. All patients who were switched from a stable CyA dose to TAC, or vice versa, were