Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression.

Abstract

BACKGROUNDGuatemala is a developing country in Central America with limited health resources. In order to expand successful renal transplant care to children and adolescents at the lowest possible cost, our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via inhibition of CYP3A4.AIMTo study the safety, efficacy and the associated cost reduction of ketoconazole in combination with tacrolimus in this pediatric population.METHODSA retrospective chart review was carried out among the cohort of pediatric renal transplant recipients treated at the Foundation for pediatric renal patients (Fundación para el Niño Enfermo Renal - FUNDANIER), a pediatric tertiary care renal transplant center in Guatemala City, Guatemala. Patient charts were reviewed to ascertain the number of transplant recipients who were transitioned from tacrolimus based immunosuppression to combination therapy with ketoconazole and tacrolimus. Twenty-five post-transplant patients that used ketoconazole combined with tacrolimus were identified. Anthropometric, clinical and laboratory data was collected from patient charts before and after the transition. RESULTSOf the 25 patient charts reviewed 12 (48%) patients were male and the average patient age was 13 years. Twenty-four (96%) transplants were from living donors. There was a non-significant difference between the mean tacrolimus doses six months and two months prior to ketoconazole: -0.10 ± 0.04 (95%CI: 0.007, -0.029), P = 0.23. However, the difference between the mean tacrolimus doses six months prior to ketoconazole initiation and six months after ketoconazole addition was significant: 0.06 ± 0.05 (95%CI: -0.034, -0.086) P < 0.001. All tacrolimus doses were reduced by 45% after the addition of ketoconazole. Therapeutic levels of tacrolimus ranged between 6.8-8.8 ng/mL during the study period and patients demonstrated an increase in estimated glomerular filtration rate. The combination of tacrolimus and ketoconazole resulted in a 21% reduction in cost.CONCLUSIONPatients experienced an effective dose-reduction of tacrolimus with the administration of ketoconazole. There was no relevant variations in tacrolimus serum levels, number of rejections, or significant liver toxicity. The strategy allowed a cost reduction in pediatric immunosuppressive therapy.