Lovastatin

一、处方溯源 【药品名称】血脂康胶囊 【处方组成】红曲 【剂型】胶囊剂 【药品类型】处方药 【功能主治】除湿祛痰，活血化淤，健脾消食。用于脾虚痰淤阻滞症的气短、乏力、头晕、头痛、胸闷、腹胀、食少纳呆等；高脂血症；也可用于由高脂血症及动脉粥样硬化引起的心脑血管疾病的辅助治疗。 二、现代研究 【中医理论】血脂异常通常指血清中胆固醇(TC)和(或)甘油三酯(TG)水平升高，俗称高脂血症。以低密度脂蛋白胆固醇(LDL-C)或TC升高为特点的血脂异常是动脉粥样硬化性心血管疾病(ASCVD)重要的危险因素；降低LDL-C水平，可显著减少ASCVD的发病及死亡危险[1]。 中医理论认为脾主运化，《素问.至真要大论》：“诸湿肿满，皆属于脾。”脾虚则运化水湿无力，导致痰湿淤阻而病自生。高血脂症为痰瘀互阻于脉而造成，古书中有“膏人”“脂人”“脂肥”的记载，治疗要从化痰除湿祛瘀入手。 血脂康胶囊”由特制红曲加入稻米生物发酵精制而成，主要成份为13种天然复合他汀，系无晶型结构的洛伐他汀及其同类物。“血脂康胶囊”可用于轻、中度的高脂血症患者[2]，中国冠心病二级预防研究(CCSPS)及其他临床研究证实，血脂康胶囊能够降低胆固醇，并显著降低冠心病患者总死亡率、冠心病死亡率以及心血管事件发生率，不良反应少[3]。 【上市情况】 【对照药品选择】“血脂康胶囊”已被现行《中国药典》（2020版）收载，质量标准明确，符合《同名同方研究技术指导原则》（试行）中“具有充分有效性、安全性”品种的规定，且该品种为北大维信生物科技公司生产的独家品种，可以作为同名同方药的对照药品。 【处方药味】 【临床试验】 “血脂康胶囊”临床适应症主要为高脂血症及动脉动脉粥样硬化引起的心脑血管疾病。 1、高脂血症 张海川[4]等选取80例受试者（对照组40例，氟伐他汀）采用随机双盲对照试验，两组均应在饮食和治疗性生活方式干预的基础上进行服药，且入组时两组在性别、年龄、身高、体重、生命体征、合并疾病和药物、患者用药依从性及以及临床诊断类型等比较,无显著差异(P>0.05)。治疗后，观察组和受试组的C反应蛋白（CRP）浓度具有明显改善，且两组血脂指标干预后的差异无统计学意义（P＜0.05）。研究结果表明，血脂康胶囊能够减少肝内胆固醇形成，调节LDL-C异常，对高血脂症的治疗有良好临床效果。 2、动脉粥样硬化性心脏病 叶芬，俞子恒[5]等选取106例受试者（对照组53例）采用随机对照试验，对照组患者入院后给予西医常规治疗，观察组在对照组基础上给予患者血脂康胶囊。对比两组治疗前后的血管内皮功能[血浆内皮素-1(ET-1)、血浆一氧化氮(NO)]、心脏功能指标[左室射血分数(LVEF)、舒张末期左室内径(LVEDD)、收缩末期左室内径(LVSDD)、二尖瓣心室充盈早期血流速度峰值/晚期心室充盈心房收缩血流速度峰值比值(E/A)]。两组在治疗过程中出现各类不良反应的比例数据差异均没有统计学意义(P>0.05)。观察组的治疗效果优于对照组(P<0.05)。结果表明，血脂康胶囊联合西医常规方法治疗冠心病患者，有助于改善血管内皮功能以及心脏功能，安全性良好，提升治疗效果。  【安全性】血脂康胶囊上市十余年的临床应用以及中国冠心病二级预防研究院（CCSPS）中国人群研究等临床试验证据表明，血脂康胶囊不良反应少而轻。主要为胃肠不适，偶见过敏反应。很少出现实验室检查指标如肝酶(ALT)、尿素氮(BUN)、肌酐(Cr)和肌酸激酶(CK)等异常，临床尚未发生血脂康胶囊所致的横纹肌溶解及其他严重不良反应。研究显示血脂康胶囊用于冠心病、糖尿病、高血压及老年患者，安全性良好[6]。 1.不良反应：在CCSPS中的4870例患者中，不良反应主要为胃肠反应和过敏反应；总的不良反应发生率低，血脂康胶囊组43例次(0．018％)，安慰剂组发生39例次(0．016％)，两组间差异无统计学意义(P=0．6842)。实验室指标如ALT、BUN、Cr和CK在两组问也无统计学差异，血脂康胶囊治疗组患者未出现CK升高5倍以上、肌病或横纹肌溶解症[6]。 2.使用禁忌：根据临床使用经验活动性肝炎或无法解释的血清氨基转移酶升高者、对本品过敏者禁用。 【药理毒理】血脂康胶囊作用机制为：(1)全面抑制血管平滑肌增殖以及迁移，继而有效抑制了病变血管内膜增生，积极预防动脉粥样硬化进展。同时也能够降低完成血管形成术后再狭窄发生概率。(2)该药中的有效成分能够全面抑制巨噬细胞所分泌的基质金属蛋白酶-2(MMP-2) 活性程度，其能够全面防止动脉粥样硬化斑块破裂所引发的急性心血管事件发生[7]。(3)针对于低密度脂蛋白氧化抑制效用，能够取得满意效果。其随着浓度增加和时间的延长，而呈现出增强趋势。(4)血脂康胶襄可全面减少黏附因子表达度，同时也进一步降低了单核细胞黏附度。(5)该类药物能够有效改善人体血管内皮功能。(6)血脂康胶襄可以有效减少冠心病患者机体血液中C反应蛋白水平程度，减少炎症反应度，有效稳定动脉粥样硬化斑块。(7)经过降低斑块内脂质成分，进而促进斑块稳定性。(8)血脂康胶襄中的有效成分可以全面促进线粒体氧化磷酸化，降低细胞内自由基生成度。另外也能够加速肝细胞线粒体膜去极化度，有效保护了人体线粒体中的功能[4]。 【参考文献】 [1]诸骏仁，高润霖，等.中国成人血脂异常防治指南(2016年修订版)[J].中国循环杂志，2016，31(10):937-953. [2]刘小平，夏军，等. 2011～2012年某院降脂药物用药分析[J]. 黑龙江医药，2013，26( 03) : 468-470. [3]邱春凤，郑建洪，等.我院 2014～2016年降脂药物应用分析[J]. 海峡药学，2017，29(9). [4]张海川.血脂康胶囊治疗高脂血症有效性和安全性分析[J]. 山西医药杂志，2020,49(11). [5]叶芬，俞子恒，杨江华，高卫利，等.血脂康胶囊辅助治疗冠状动脉粥样硬化性心脏病的疗效及对血管内皮功能、心脏功能的影响[J]. 中华中医药学刊，2022,40(04). [6]中国医师协会心血管内科医师分会.中国老年学学会心脑血管病专业委员会.中国医师协会循证医学专业委员会，等.血脂康胶囊临床应用中国专家共识[J]. 中国医刊，2009，44(11). [7]王景文，孙兰军，董村，等，血脂胶治疗高脂血症的临床疗效观察[J]，现代药物与临床，2014,29(7):804-807. END ★ 点击下方卡片，发现更多精彩

REDWOOD CITY, Calif.--( BUSINESS WIRE )--Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, today announced that the primary endpoint was met in the treatment phase of CATALYST, a randomized, double-blind, placebo-controlled study of Korlym ® in patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control type 2 diabetes. CATALYST is a prospective, Phase 4 study with two parts. The first part assessed the prevalence of hypercortisolism by screening 1057 patients with difficult-to-control type 2 diabetes, defined as hemoglobin A1c greater than 7.5 percent despite receiving optimal therapies, including GLP-1 agonists. Of these patients, 23.8 percent were identified as having hypercortisolism and were eligible to enter CATALYST’s treatment phase, in which 136 patients were randomized, 2:1, to receive either Korlym or placebo for 24 weeks. The primary endpoint was the reduction in hemoglobin A1c between these groups. CATALYST met its primary endpoint. Patients who received Korlym exhibited a clinically meaningful and statistically significant improvement in hemoglobin A1c, with a decrease from baseline of 1.47 percent as compared to a decrease of 0.15 percent in patients who received placebo (placebo-adjusted reduction of 1.32 percent; p-value: < 0.0001). The safety profile of Korlym in this study was consistent with the medication’s label and no new side effects or adverse events were identified. Complete results from CATALYST will be presented at a medical conference next year. “CATALYST’s first part showed that hypercortisolism is much more common than previously assumed. The results announced today show that Korlym is a safe and effective treatment option,” said Ralph DeFronzo, MD, chief of the Diabetes Division and professor of medicine at UT Health San Antonio and CATALYST study investigator. “Reductions in hemoglobin A1c of this magnitude are of great clinical benefit. They are particularly compelling, given that the patients in CATALYST had been receiving our best therapies – but continued to experience serious disease. These findings should prompt expanded screening for hypercortisolism, more effective treatment and better health outcomes for patients who are struggling today.” “The results of the CATALYST study will enable physicians to more accurately diagnose and treat patients with hypercortisolism - a serious and deadly disease,” said Bill Guyer, PharmD, Corcept’s Chief Development Officer. “One in four patients with difficult-to-control type 2 diabetes have hypercortisolism and Korlym, a cortisol modulator, was highly effective in controlling hyperglycemia in this patient population.” About Hypercortisolism (Cushing’s Syndrome) Hypercortisolism is caused by excessive activity of the hormone cortisol. Symptoms vary, but most patients experience one or more of the following manifestations: hypertension, central obesity, elevated blood sugar and difficult-to-control type 2 diabetes, severe fatigue and weak muscles. Irritability, anxiety, depression and cognitive disturbances are common. Hypercortisolism can affect every organ system and can be lethal if not treated effectively. Important information about Korlym follows, and full Prescribing Information, including BOXED WARNING , and a Medication Guide are available at www.korlym.com . IMPORTANT SAFETY INFORMATION INDICATIONS AND USAGE Korlym (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. IMPORTANT LIMITATIONS OF USE Do not use for the treatment of type 2 diabetes mellitus unrelated to endogenous Cushing’s syndrome. BOXED WARNING: TERMINATION OF PREGNANCY Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym and prevented during treatment and for one month after stopping treatment by the use of a nonhormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential. DOSAGE AND ADMINISTRATION Obtain a negative pregnancy test prior to initiating treatment with Korlym in females of reproductive potential, or if treatment is interrupted for more than 14 days. Administer once daily orally with a meal. The recommended starting dose is 300 mg once daily. Renal impairment: Do not exceed 600 mg once daily. Mild-to-moderate hepatic impairment: Do not exceed 600 mg once daily. Do not use in severe hepatic impairment. Based on clinical response and tolerability, the dose may be increased in 300-mg increments to a maximum of 1200 mg once daily. Do not exceed 20 mg/kg per day. Concomitant use of Korlym with a strong CYP3A inhibitor resulted in a 38% increase in mean plasma concentration of mifepristone. For patients already being treated with a strong CYP3A inhibitor, start with a Korlym dose of 300 mg per day and titrate to a maximum of 900 mg per day if clinically indicated. When a strong CYP3A inhibitor is administered to patients already receiving Korlym, adjust the dose as follows: for patients receiving a daily dose of 600 mg, reduce dose to 300 mg. For patients receiving a daily dose of 900 mg, reduce dose to 600 mg. For patients receiving a daily dose of 1200 mg, reduce dose to 900 mg. Titrate if clinically indicated and do not exceed a Korlym dose of 900 mg in combination with a strong CYP3A inhibitor. CONTRAINDICATIONS Pregnancy; patients taking simvastatin or lovastatin and CYP3A substrates with narrow therapeutic ranges; patients receiving systemic corticosteroids for lifesaving purposes; women with a history of unexplained vaginal bleeding or endometrial hyperplasia with atypia or endometrial carcinoma; patients with known hypersensitivity to mifepristone or to any of the product components. WARNINGS AND PRECAUTIONS Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency. Hypokalemia: Hypokalemia should be corrected prior to treatment and monitored for during treatment. Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if the patient also has a hemorrhagic disorder or is on anticoagulant therapy. QT interval prolongation: Avoid use with QT interval-prolonging drugs, or in patients with potassium channel variants resulting in a long QT interval. Use of strong CYP3A inhibitors: Concomitant use increases mifepristone plasma levels. Adjust Korlym dose as described in Dosage and Administration . Use only when necessary and do not exceed a Korlym dose of 900 mg. ADVERSE REACTIONS Most common adverse reactions in Cushing’s syndrome (≥20%): nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, endometrial hypertrophy. DRUG INTERACTIONS Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with Korlym. CYP3A inhibitors: Caution should be used when Korlym is used with strong CYP3A inhibitors. Adjust Korlym dose as described in Dosage and Administration . Use only when necessary, and do not exceed a Korlym dose of 900 mg. CYP3A inducers: Do not use Korlym with CYP3A inducers. Drugs metabolized by CYP2C8/2C9: Use the lowest dose of CYP2C8/2C9 substrates when used with Korlym. Drugs metabolized by CYP2B6: Use of Korlym should be done with caution with bupropion and efavirenz. Hormonal contraceptives: Do not use with Korlym. USE IN SPECIFIC POPULATIONS Lactation: Mifepristone is present in human milk, however, there are no data on the amount of mifepristone in human milk, the effects on the breastfed infant, or the effects on milk production during long term use of mifepristone. About Corcept Therapeutics For over 25 years, Corcept’s focus on cortisol modulation and its potential to treat patients with a wide variety of serious disorders has led to the discovery of more than 1,000 proprietary selective cortisol modulators. Corcept is conducting advanced clinical trials in patients with hypercortisolism, solid tumors, ALS and liver disease. In February 2012, the company introduced Korlym, the first medication approved by the U.S. Food and Drug Administration for the treatment of patients with endogenous hypercortisolism. Corcept is headquartered in Redwood City, California. For more information, visit Corcept.com. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements based on our current plans and expectations and are subject to risks and uncertainties that might cause our actual results to differ materially from those such statements express or imply. These risks and uncertainties are set forth in our SEC filings, which are available at our website and the SEC’s website. In this press release, forward-looking statements include those concerning the full results of CATALYST and the date and manner of their publication; changes in medical practice, including in the frequency and clinical outcome of screening patients for hypercortisolism; the adoption of Korlym as a treatment for patients with hypercortisolism and difficult-to-control diabetes; and Korlym’s commercial prospects. We disclaim any intention or duty to update forward-looking statements made in this press release.