Holoshitz Noa, Alsheikh-Ali Alawi A, Karas Richard H
Molecular Cardiology Research Institute and Division of Cardiology, Department of Medicine, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA.
Am J Cardiol. 2008 Jan 1;101(1):95-7. doi: 10.1016/j.amjcard.2007.07.057. Epub 2007 Nov 26.
Previous analyses of fibrate safety may have been driven by a higher propensity for gemfibrozil to interact with cerivastatin, which is currently off the market because of safety concerns. We reviewed gemfibrozil- and fenofibrate-associated adverse event reports (AERs) submitted to the US Food and Drug Administration over a 5-year period. To control for cerivastatin's impact on fibrate-associated AERs, reports with concomitant cerivastatin use were excluded. Rates per million prescriptions were calculated for all AERs, serious AERs, rhabdomyolysis AERs, muscle-related AERs without rhabdomyolysis, and liver AERs. The rates of all AERs (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.69 to 0.83), serious AERs (OR 0.72, 95% CI 0.65 to 0.81), and liver AERs (OR 0.37, 95% CI 0.28 to 0.50) were significantly lower for gemfibrozil compared with fenofibrate (p <0.001 for each). In contrast, rates of rhabdomyolysis AERs (OR 2.67, 95% CI 2.11 to 3.39, p <0.001) and muscle-related AERs without rhabdomyolysis (OR 1.36, 95% CI 1.12 to 1.71, p = 0.002) were significantly higher for gemfibrozil compared with fenofibrate. In conclusion, the safety profiles of fibrates differ, with a higher rate of liver-related AERs associated with fenofibrate and a higher rate of muscle-related AERs associated with gemfibrozil. Rates of all AERs and serious AERs were higher with fenofibrate, but well within the range observed with commonly used lipid-altering medications.
以往对贝特类药物安全性的分析可能是由于吉非贝齐与西立伐他汀相互作用的倾向较高，西立伐他汀目前因安全问题已退出市场。我们回顾了5年期间提交给美国食品药品监督管理局的与吉非贝齐和非诺贝特相关的不良事件报告（AER）。为了控制西立伐他汀对贝特类药物相关AER的影响，排除了同时使用西立伐他汀的报告。计算了所有AER、严重AER、横纹肌溶解AER、无横纹肌溶解的肌肉相关AER和肝脏AER每百万处方的发生率。与非诺贝特相比，吉非贝齐的所有AER（比值比[OR]0.76，95%置信区间[CI]0.69至0.83）、严重AER（OR 0.72，95%CI 0.65至0.81）和肝脏AER（OR 0.37，95%CI 0.28至0.50）发生率显著较低（每项p<0.001）。相比之下，与非诺贝特相比，吉非贝齐的横纹肌溶解AER（OR 2.67，95%CI 2.11至3.39，p<0.001）和无横纹肌溶解的肌肉相关AER（OR 1.36，95%CI 1.12至1.71，p = 0.002）发生率显著较高。总之，贝特类药物的安全性概况不同，非诺贝特相关的肝脏相关AER发生率较高，吉非贝齐相关的肌肉相关AER发生率较高。非诺贝特的所有AER和严重AER发生率较高，但仍在常用降脂药物观察到的范围内。
