HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity.

译文

:HMG-CoA还原酶抑制剂(他汀类药物)是血脂异常药理管理的主要手段。由于它们被广泛地规定,因此它们的安全性仍然是一个值得关注的问题。罗苏伐他汀已被证明可有效改善血脂水平。 JUPITER研究最近发表的数据证实了他汀类药物在具有多种危险因素和炎症迹象的老年患者的一级预防中的功效。罗苏伐他汀表现出高的亲水性和肝选择性,以及低的全身生物利用度,同时通过细胞色素P450系统进行的代谢最少。因此,罗苏伐他汀具有有趣的药代动力学特征,不同于其他他汀类药物。但是,与其他药物相比,此他汀类药物能否转化为更好的安全性和更少的药物相互作用,还有待确定。本文中,我们回顾了有关这种他汀类药物的安全性及其与临床环境中通常规定的药物相互作用的证据。与其他他汀类药物一样,瑞舒伐他汀治疗与严重肌病,横纹肌溶解和肾衰竭相对较低的发生率有关。罗苏伐他汀的无症状肝酶升高与其他他汀类药物的发生率相似。瑞舒伐他汀治疗还与胃肠道和中枢神经系统相关的不良反应有关,这在许多其他药物中也很常见。罗苏伐他汀诱导的蛋白尿可能与他汀类药物引起的肾小管对低分子量蛋白重吸收的抑制有关。较高剂量的瑞舒伐他汀与肾功能衰竭有关。同样,将瑞舒伐他汀与增加瑞舒伐他汀血药浓度的药物合用可能对肾脏有害。此外,已知横纹肌溶解被认为是他汀类药物的一种作用,涉及肾脏损害。 JUPITER研究的结果引起了人们的关注,这表明瑞舒伐他汀可能会稍微增加医师报告的糖尿病的发病率,以及具有多种危险因素和低度炎症的老年患者的糖化血红蛋白水平。临床试验表明,与安慰剂相比,瑞舒伐他汀治疗不会导致瘤形成的发生率增加。拮抗有机阴离子转运蛋白1B1介导的瑞舒伐他汀肝摄取的药物更可能与他汀类药物相互作用。当瑞舒伐他汀与维生素K拮抗剂,环孢菌素(环孢素),吉非贝齐和抗逆转录病毒药物合用时,临床医生应谨慎,因为与这些药物的潜在药代动力学相互作用可能会增加中毒的风险。另一方面,瑞舒伐他汀与非诺贝特,依折麦布,omega-3-脂肪酸,抗真菌唑类药物,利福平(利福平)或氯吡格雷联合治疗似乎是安全的,因为没有证据支持瑞舒伐他汀与瑞舒伐他汀的任何药代动力学或药效学相互作用这些药物中的任何一种。因此,瑞舒伐他汀似乎相对安全并且耐受性良好,与他汀类药物的共同作用具有共同的不良作用。当将瑞舒伐他汀与可能会增加瑞舒伐他汀相关毒性风险的药物一起开处方时,所有医学实践的医生应保持警惕。

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