影响他汀类药物伍用其他药物发生不良反应的可能因素及原因分析

Analysis of the possible factors and causes of adverse reaction of statins combined with other drugs

目的分析他汀类药物伍用其他药物发生不良反应(ADR)的可能因素。方法回顾性分析该院因他汀类药物联用其他药物而出现ADR的78例患者的临床资料,统计患者的性别、年龄、他汀类药物品种、联合用药种类及名称、DAR临床表现等。结果 (1)在ADR类型中,肌肉毒性占39.7%,肝毒性占26.9%,消化系统症状占10.2%,皮肤不适占9.0%,神经系统症状占9.0%,泌尿系统症状占5.1%。(2)引起ADR的他汀类药品种,辛伐他汀41例,占52.6%,阿托伐他汀23例占29.5%,洛伐他汀占11.5%,普伐他汀占5.1%,氟伐他汀占1.3%。(3)联合用药种类中,降压药或抗心肌药占25.6%,贝特类调脂药占19.2%,抗血小板药或抗凝药占15.4%,抗菌药占15.4%,抗病毒药占11.5%,抗糖尿病药占7.7%,中成药或注射剂占5.1%。(4)男性占55.1%,女性占44.9%。(5)<30岁占3.8%,30~39岁占6.4%,40~49岁占9.0%,50~59岁占12.8%,60~69岁占21.8%,70~79岁占30.8%,>80岁占15.4%。结论他汀类药物伍用其他药物导致ADR主要以肌肉毒性和肝毒性为主,年龄和联用药物间相互作用可能是其中的影响因素,其他药物通过竞争性抑制共通代谢途径导致他汀类药物暴露增加继发肌肉与肝脏毒性。

Objective To analyze the possible factors and causes of adverse reaction（ADR）of statins combined with other drugs. Methods The clinical data of 78 patients with ADR treated with statins and other drugs were retrospectively analyzed. The gender, age, type of statins, type and name of combined drugs and clinical manifestations of DAR were statistically collected. Results ①The ADR types included muscle toxicity（39.7%）, liver toxicity（26.9%）, digestive symptoms（10.2%）, skin discomfort（9.0%）, neurological symptoms（9.0%）and urinary symptoms（5.1%）. ②Statins that caused ADR included simvastatin in 41 cases（52.6%）, atorvastatin in 23 cases（29.5%）, lovastatin 11.5%, pravastatin 5.1%, and fluvastatin 1.3%. ③Of the combined drugs, antihypertensive drugs or anti cardiac drugs accounted for 25.6%, fibrate 19.2%, antiplatelet or anticoagulant drugs 15.4%, antibacterial drugs 15.4% of, antiviral drugs 11.5%, anti diabetic drugs 7.7%, and Chinese medicine or injections 5.1%. ④Males accounted for 55.1%, and females 44.9%. ⑤Those 〈30 years old accounted for 3.8%, 30-39 years old 6.4%, 40-49 years old 9.0%, 50-59 years old 12.8%, 60-69 years old 21.8%, 70-79 years old 30.8%, and 〉80 years old 15.4%. Conclusions Statins combined with other drugs mainly lead to muscle toxic and hepatotoxic ADR. Age and the interaction between drugs may be the influencing factors. The combined drugs lead to statin exposure by competitive inhibition of the common metabolic pathway, thus increasing the secondary muscle and liver toxicity.