Department of Cardiovascular Diseases, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
Safety and Vigilance, WHO, Geneva, Switzerland.
Basic Clin Pharmacol Toxicol. 2018 Oct;123(4):509-518. doi: 10.1111/bcpt.13035. Epub 2018 Jun 29.
Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug-drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition. We reviewed all available cases plus the case of an 87-year-old female Croatian/Caucasian patient who developed rhabdomyolysis following concomitant treatment with rosuvastatin and ticagrelor. The results of the pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles CYP2C9*1/3, CYP3A41/22, CYP3A53/3, CYP2D61/4, UGT1A128/*28, UGT2B7 -161C/T, ABCB1 3435C/T and ABCB1 1237C/T which could have added to the interactions not only between ticagrelor and rosuvastatin but also other concomitantly prescribed medicines, such as amiodarone and proton pump inhibitors. In this case report, the possible multifactorial causes for rhabdomyolysis following concomitant use of rosuvastatin and ticagrelor such as old age, polypharmacy, renal impairment, along with pharmacogenetics will be discussed.
截至 2018 年初，在全球世界卫生组织（WHO）药物不良反应（ADR）数据库（VigiBase）以及现有文献中，共记录了 8 例描述瑞舒伐他汀与替格瑞洛之间罕见但具有重要临床意义的药物相互作用导致横纹肌溶解的病例。有几个可能的因素可能导致横纹肌溶解症的发生：年龄较大、最初瑞舒伐他汀剂量过大、代谢酶（CYPs 和 UGTs）和药物转运体水平（ABCB1、ABCG2、OATP1B1）的药物-药物相互作用（DDI）以及药物遗传学易感性。我们回顾了所有可用的病例，加上一名 87 岁的克罗地亚/高加索女性患者的病例，该患者在同时接受瑞舒伐他汀和替格瑞洛治疗后出现横纹肌溶解症。药物遗传学分析的结果表明，该患者是 CYP2C9*1/3、CYP3A41/22、CYP3A53/3、CYP2D61/4、UGT1A128/*28、UGT2B7-161C/T、ABCB1 3435C/T 和 ABCB1 1237C/T 失活等位基因的携带者，这些基因可能不仅增加了替格瑞洛和瑞舒伐他汀之间的相互作用，还增加了其他同时开的药物，如胺碘酮和质子泵抑制剂之间的相互作用。在本病例报告中，将讨论瑞舒伐他汀和替格瑞洛同时使用后横纹肌溶解症的可能多因素原因，如年龄较大、多种药物治疗、肾功能损害以及药物遗传学。
