AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850 USA; University of Pennsylvania School of Medicine, Philadelphia, PA USA.
J Clin Lipidol. 2008 Dec;2(6):453-63. doi: 10.1016/j.jacl.2008.10.007. Epub 2008 Oct 28.
Patients may experience increased risk of adverse drug interactions when statins are administered concomitantly with cytochrome P450 3A4 (CYP3A4) inhibitors.
To determine patient numbers in routine clinical practice with concomitant exposure to CYP3A4-metabolized statins and CYP3A4 inhibitors and highlight potential risk for adverse drug interaction.
Exposure to prescription medications over 1 year (2005-2006) was evaluated from patient records: US PharMetrics Integrated Patient-Centric administrative claims database and the US General Electric Medical System (GEMS) database. Rates of concomitant prescribing of statins with CYP3A4 inhibitors (listed in United States of America product labels and all identified potential inhibitors) were examined in the cohort overall, in those aged ≥65 years, and in those receiving higher doses of statins.
Overall, 951,166 patient records were included (PharMetrics n = 650,825; GEMS, n = 300,341). Of these, 792,081 (83%) patients used a CYP3A4-metabolized statin as opposed to a non-CYP3A4-metabolized statin (17%). Findings from both databases were consistent. Overall, 25-30% of patients given a CYP3A4-metabolized statin were concomitantly exposed to a CYP3A4 inhibitor, including approximately 9% concomitantly exposed to a labeled inhibitor, findings consistent with those in patients aged ≥65 years, and patients on higher doses of statins.
Clinicians frequently co-prescribe CYP3A4-metabolized statins with CYP3A4 inhibitors. Physician education regarding the impact of these inhibitors on the metabolism of lovastatin, simvastatin, and atrovastatin is needed. Further studies are also needed to determine whether concomitant administration of a non-CYP3A4-metabolized statin (such as fluvastatin, pravastatin, or rosuvastatin) with a CYP3A4 inhibitor, may reduce adverse event rates in routine clinical practice.
当他汀类药物与细胞色素 P450 3A4（CYP3A4）抑制剂同时给药时，患者可能会经历增加的不良药物相互作用风险。
确定常规临床实践中同时暴露于 CYP3A4 代谢的他汀类药物和 CYP3A4 抑制剂的患者数量，并强调潜在的不良药物相互作用风险。
从患者记录中评估了一年（2005-2006 年）的处方药物暴露情况：美国 PharMetrics 综合患者为中心的行政索赔数据库和美国通用电气医疗系统（GEMS）数据库。在整个队列中、在年龄≥65 岁的患者中和在接受更高剂量他汀类药物的患者中，检查了与 CYP3A4 抑制剂同时开具他汀类药物的处方率（列在美国产品标签中和所有确定的潜在抑制剂中）。
总共纳入了 951,166 份患者记录（PharMetrics n = 650,825；GEMS，n = 300,341）。其中，792,081（83%）名患者使用了 CYP3A4 代谢的他汀类药物，而不是非 CYP3A4 代谢的他汀类药物（17%）。来自两个数据库的结果都是一致的。总体而言，给予 CYP3A4 代谢的他汀类药物的患者中有 25-30%同时暴露于 CYP3A4 抑制剂，包括约 9%同时暴露于标签抑制剂，这些结果与年龄≥65 岁的患者和服用较高剂量他汀类药物的患者一致。
临床医生经常同时开 CYP3A4 代谢的他汀类药物和 CYP3A4 抑制剂。需要对这些抑制剂对洛伐他汀、辛伐他汀和阿托伐他汀代谢的影响进行医生教育。还需要进一步研究以确定在常规临床实践中，同时给予非 CYP3A4 代谢的他汀类药物（如氟伐他汀、普伐他汀或罗苏伐他汀）与 CYP3A4 抑制剂是否可以降低不良事件发生率。
