title: Supra-therapeutic tacrolimus concentrations associated with concomitant nicardipine in pediatric liver transplant recipients.
abstract: Tacrolimus is prescribed to prevent allograft rejection in pediatric liver transplant recipients; however, its metabolism through the cytochrome P-450 enzyme system presents a multitude of challenges in regard to drug interactions. Here, we describe four children (ages 1.4-8.7 yr) who acutely developed supra-therapeutic serum tacrolimus trough concentrations, despite standard dosing, while on concomitant nicardipine therapy following liver transplantation. Even though tacrolimus regimens were altered (dosage reductions and held doses), serum tacrolimus concentrations remained elevated. Resolution of high tacrolimus concentrations was achieved only after the discontinuation of nicardipine. Following the termination of nicardipine, all children eventually required dosage increases in their tacrolimus regimens to re-achieve target serum concentrations. We conclude that concomitant use of tacrolimus and nicardipine can result in high tacrolimus concentrations due to the inhibition of cytochrome p450 enzymes responsible for the metabolism of tacrolimus. We encourage clinicians to consider alternative antihypertensive options in children on tacrolimus therapy. If nicardipine therapy is necessary, we recommend a 50% reduction in tacrolimus dose and daily serum concentration monitoring.
authors: Department of Pharmacy, Children's Hospital Colorado, Aurora, CO, USA.
authors: Amanda L
authors: AL
authors: Hurst
authors: Natalie
authors: N
authors: Clark
authors: Todd C
authors: TC
authors: Carpenter
authors: Shikha S
authors: SS
authors: Sundaram
authors: Pamela D
authors: PD
authors: Reiter
mesh_terms: D016738:Alagille Syndrome / Q000601:surgery; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001656:Biliary Atresia / Q000601:surgery; D006528:Carcinoma, Hepatocellular / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000601:surgery; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D007223:Infant; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000627:therapeutic use*; D012086:Reoperation; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D009529:Nicardipine; D016559:Tacrolimus
keywords: cytochrome P-450 enzyme system; liver transplantation; nicardipine; pediatrics; tacrolimus