Sibley Rachel A, Katz Alyson, Papadopoulos John
New York University School of Medicine, New York City, USA.
Hosp Pharm. 2021 Oct;56(5):537-542. doi: 10.1177/0018578720928262. Epub 2020 Jun 17.
Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature.
We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status.
The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein.
Future pharmacokinetic studies are warranted to better understand the interaction.
药物相互作用是发病和死亡的常见原因，由于有害副作用可能需要迅速停用治疗方案。急性冠状动脉综合征患者可能会被开具多种通过细胞色素P450系统代谢的药物，从而增加了药物相互作用的可能性。众所周知，阿托伐他汀和辛伐他汀都与口服P2Y12药物替格瑞洛相互作用。本文的目的是描述替格瑞洛与瑞舒伐他汀相互作用导致横纹肌溶解，这在文献中定义不太明确。
我们报告了一例74岁男性病例，该患者在因药物洗脱支架而服用替格瑞洛时，已经在服用瑞舒伐他汀，出现双侧下肢无力和行走困难一个月。他的临床表现和实验室检查结果与横纹肌溶解的诊断一致。他的药物调整为氯吡格雷和阿利西尤单抗方案。一个月后，他恢复到基线状态。
瑞舒伐他汀和替格瑞洛之间的相互作用机制似乎是多因素的。它可能是由同工酶之间少量交叉的CYP450介导的代谢引起的。替格瑞洛也可能导致急性肾损伤，增加瑞舒伐他汀的浓度。其他相互作用机制包括有机阴离子转运多肽的基因差异和通过P-糖蛋白的转运。
有必要进行进一步的药代动力学研究，以更好地了解这种相互作用。
