Simvastatin과 cyclosporine의 약물 상호 작용
Analysis of Drug Interaction between Simvastatin and Cyclosporine
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Background: Concomitant use of cyclosporine (CYP3A4 inhibitors) has been shown to inhibit the metabolism of simvastatin and increase the risk of liver toxicity and myopathy. To prevent potential harms, it has been recommended that the maximum daily dose of simvastatin should not exceed 10 mg when it is coadministered with cyclosporine. The purpose of this study was to investigate frequency and risk factors of liver toxicity and myopathy due to drug interactions between simvastatin and cyclosporine. Method: A retrospective review was performed on Asan Medical Center outpatients’EMR during February 2009. Patients were divided into 4 groups: simvastatin only group with dose ≤ 10 mg (S1), simvastatin with dose ≤ 10 mg and cyclosporine combination group (C1), simvastatin only group with dose > 10 mg (S2), and simvastatin with dose > 10 mg and cyclosporine combination group (C2). Several parameters were analyzed, including AST (Aspartate Transaminase), ALT (Alanine Transaminase), and CK (Creatine Kinase) for each group. Results: A total of 1,939 patients were enrolled in this study; the number of patients in C1 and C2 was 17(28.3%) and 43(71.7%) while that in S1 and S2 was 19(27.9%) and 49(72.1%), respectively. AST, ALT levels were higher in C1 group compared to S1 even though it was not statistically significant. On the other hands AST, ALT levels in C2 group were significantly higher than S2 (P < 0.05). The risk factors for the elevation of AST, ALT were the age ≥ 60 (OR 5.33; 95% Confidence Interval[CI] 1.20-23.66) and the concomitant use of interacting drugs (OR 4.4; 95% CI 1.77-39.93). Conclusion: It is recommended that simvastatin dose should remain 10 mg or below 10 mg when it is coadministered with cyclosporine. Those who have risk factors for AST or ALT elevation should be carefully monitored for liver toxicity.
Abstract
Background: Concomitant use of cyclosporine (CYP3A4 inhibitors) has been shown to inhibit the metabolism of simvastatin and increase the risk of liver toxicity and myopathy. To prevent potential harms, it has been recommended that the maximum daily dose of simvastatin should not exceed 10 mg when it is coadministered with cyclosporine. The purpose of this study was to investigate frequency and risk factors of liver toxicity and myopathy due to drug interactions between simvastatin and cyclosporine. Method: A retrospective review was performed on Asan Medical Center outpatients’EMR during February 2009. Patients were divided into 4 groups: simvastatin only group with dose ≤ 10 mg (S1), simvastatin with dose ≤ 10 mg and cyclosporine combination group (C1), simvastatin only group with dose > 10 mg (S2), and simvastatin with dose > 10 mg and cyclosporine combination group (C2). Several parameters were analyzed, including AST (Aspartate Transaminase), ALT (Alanine Transaminase), and CK (Creatine Kinase) for each group. Results: A total of 1,939 patients were enrolled in this study; the number of patients in C1 and C2 was 17(28.3%) and 43(71.7%) while that in S1 and S2 was 19(27.9%) and 49(72.1%), respectively. AST, ALT levels were higher in C1 group compared to S1 even though it was not statistically significant. On the other hands AST, ALT levels in C2 group were significantly higher than S2 (P < 0.05). The risk factors for the elevation of AST, ALT were the age ≥ 60 (OR 5.33; 95% Confidence Interval[CI] 1.20-23.66) and the concomitant use of interacting drugs (OR 4.4; 95% CI 1.77-39.93). Conclusion: It is recommended that simvastatin dose should remain 10 mg or below 10 mg when it is coadministered with cyclosporine. Those who have risk factors for AST or ALT elevation should be carefully monitored for liver toxicity.
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