신이식 환자에서 Cyclosporine의 Rosuvastatin 혹은Pravastatin과의 상호작용 발현 결과 비교

Abstract

Co-administration of cyclosporine(CsA) with HMG-CoA reductase inhibitors(statins)may result in an increase in the plasma concentration of statins and induce toxicity of myopathy and hepatotoxicity. Furthermore, it is referred in the label of rosuvastatin that the maximum concentrations(Cmax) and the area under the concentration-time curve(AUC) of rosuvastatin are an approximate of 2-folds for Asians as compared with Caucasians. Therefore, the Clinical Decision Support System notifies the contraindication of rosuvastatin and CsA by alerts such as pop-ups and recommends that the dosage of rosuvastatin should be limited to 5 mg daily for patients receiving CsA in Seoul St. Mary’s Hospital. This study is therefore designed to compare the drug-interactions of CsA with rosuvastatin and with pravastatin which is not significantly metabolized by the CYP system. Renal transplant recipients who received CsA between March and July 2010 in the Catholic University of Seoul St.Mary’s Hospital are categorized into 2 groups: Rosu group(n=106) which prescribed rosuvastatin despite of CDSS alerts and Prava group(n=65) which prescribed pravastatin. We reviewed the symptoms of myopathy, the serum level of aspartate aminotransferase (AST), alanine aminotransferase(ALT), and creatine phosphokinase(CPK), and the dose modification through the electronic medical record charts. As a result, the symptoms of myopathy occurred in about 6.6% of the patients from the Rosu group, 1.5% of the patients in Prava group(p=0.128). Elevation of AST/ALT occurred in 9.4%, 3.1% of the patients in each group(p=0.114), however we couldn’t compare CPK level because of a few data. In the Rosu group,22 patients decreased their daily rosuvastatin dosage from 10 mg to 5 mg after the CDSS alert,and 7 patients either decreased or stopped rosuvastatin because of adverse events or abnormal results from the laboratory test, but 7 patients increased the daily dosage from 5 mg to 10 mg to improve effects. Prava group didn’t modify the dosage except in the case of stopping due to abnormal laboratory results. As a result of the sub-group analysis, symptoms of myopathy occurred in 9.6% of the Rosu with 10 mg and above group and in 1.6% of Prava with 40 mg group(p=0.036), but, the Rosu 5 mg group didn’t occur. Elevation of AST/ALT occurred in 9.1%, 9.6% of Rosu 5 mg, 10 mg group,which happened to 3.3% of Prava 40 mg group. In conclusion, the muscular adverse drug events increased for renal transplant recipients receiving CsA as prescribed with rosuvastatin 10 mg and above, and some cases increased rosuvastatin doses from 5 mg to 10 mg in order to enhance therapeutic effects. Therefore, we could deduce the differences between the medical reference and clinical case. Consequently, we can judge the pravastatin as having reduced side effects than rosuvastatin when recommending to patients receiving CsA.