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2012年7月26日，FDA批准专利合成药乙基二十五碳五烯酸（EPA）（Vascepa，既往称为AMR101）用于治疗高甘油三酯血症，Vascepa成为市场上第二个ω-3多不饱和脂肪酸（PUFA）处方药。
该药制造商Amarin的报告指出，Vascepa是一种纯化的海洋油制剂，含有“不低于96%”的EPA，而另一种活性ω-3 PUFA（二十二碳六烯酸，DHA）的含量很低。后者是非处方鱼油胶囊以及FDA于几年前批准的非处方药Lovaza（葛兰素史克公司）的主要成分。
对类似EPA/DHA ω-3胶囊（包括Lovaza）长期不良反应观察证实，仅含EPA的Vascepa可能并不升高低密度脂蛋白-胆固醇(LDL-C)水平，推测机制可能是EPA的ω-3PUFA对LDL的氧化作用低于EPA/DHA制剂。
FDA批准该项目是基于一项为期12周的MARINE研究3期试验，结果表明Vascepa能够降低甘油三酯，还能改善总胆固醇、载脂蛋白B（apo-B）、脂蛋白相关磷脂酶A 2 (Lp-PLA2)、高敏C反应蛋白(hs-CRP)水平，同时并未显著增加LDL-C水平。
关于Vascepa(icosapent ethyl)胶囊
Vascepa (icosapent ethyl)胶囊，在科学文献中已知为AMR101，是一种获专利的，超纯的ω(omega)-3脂肪酸产品，在1g胶囊中由不低于96%二十碳五烯酸(eicosapentaenoic acid，EPA)组成。
批准日期：2012年7月26日：公司：Company: Amarin Corporation plc
VASCEPA(二十碳五烯酸 icosapent ethyl)胶囊，为口服使用
美国初次批准：2012
一般描述
VASCEPA，一种脂质-调节药，以一种1-g琥珀色，充液软明胶胶囊为口服给药供应。
每粒VASCEPA胶囊含1 g icosapent ethyl。Icosapent ethyl是ω-3脂肪酸二十碳五烯酸(EPA)的乙酯。Icosapent ethyl的经验式是C22H34O2和分子量是330.51。Icosapent ethyl的化学名ethyl all-cis-5,8,11,14,17-icosapentaenoate 有下列化学结构式：
VASCEPA 1gram胶囊还含下列无活性成分：维生素E，明胶，甘油，麦芽糖醇，山梨醇，和纯水。
作用机制
研究提示EPA减低肝非常低密度脂蛋白甘油三脂(VLDL-TG)合成和/或分泌和增强从循环VLDL颗粒清除TG。潜在的作用机制包括增加β-氧化；酰基辅酶A的抑制：1, 2-甘油二酯酰基转移酶(DGAT)；减低肝脏中脂质生成；和增加血浆脂蛋白脂肪酶活性。
适应证和用途
VASCEPA是一种二十碳五烯酸的乙酯(EPA)适用在有严重(≥ 500 mg/dL)高甘油三酯血症成年患者中作为膳食辅助减低甘油三酸酯(TG)水平。
使用的限制：
（1）尚未确定有严重高甘油三酯血症患者中VASCEPA对胰腺炎的风险的影响。
（2）尚未确定有严重高甘油三酯血症患者中VASCEPA对心血管死亡率和发病率的影响。
剂量和给药方法
VASCEPA的每天剂量是4g每天服粒2胶囊每天2次与食物。
应劝告患者整吞VASCEPA胶囊。不要破开，粉碎，溶解，或咀嚼VASCEPA。
剂型和规格
胶囊：1g
禁忌证
已知超敏性(如，过敏反应)对VASCEPA或任何其组分患者中禁忌VASCEPA。
警告和注意事项
在肝受损患者中，治疗期间定期监查ALT和AST水平。
在已知对鱼和/或贝类超敏性患者中慎用。
不良反应
最常报道不良反应(发生率>2%和大于安慰剂)是关节炎。
药物相互作用
ω-3酸可能延长出血时间。接受VASCEPA治疗和其他影响凝血药物(如，抗血小板药物)患者应被定期监查。
在特殊人群中使用
妊娠：只有如潜在获益大于对胎儿的潜在危险在妊娠时才应使用。
儿童使用：尚未确定在儿童患者中安全性和有效性。
如何供应/贮存和处置
VASCEPA(icosapent ethyl)胶囊以1-g琥珀色软-明胶胶囊印有VASCEPA供应。
120片瓶：NDC 52937-001-20.
贮存在20°至25°C(68°至77°F)；外出允许至15°至30° C(59°至86°F)[见USP控制室温]。远离儿童达到处保存。
患者咨询资料
对患者信息
已知对鱼和/或贝类过敏或变态反应患者应慎用VASCEPA[见警告和注意事项]。
应劝告患者使用脂质-调节药不应减低适当摄入营养物和身体活动的重要性[见剂量和给药方法]。
应劝告患者不要以任何方式改变VASCEPA胶囊和只能摄取完整胶囊[见剂量和给药方法]。
指导患者按处方服用VASCEPA。如丢失一剂，患者记起时应立即服用。但是丢失一天的VASCEPA，他们不应服用加倍剂量。
Amarin Announces Market Introduction of Vascepa(R) (icosapent ethyl) Capsules for the Treatment of Very High Triglycerides (VHTG)
-First and Only FDA Approved Pure-EPA Omega-3 Prescription Therapy Now Available--Vascepa Reduces VHTG Without Raising LDL Cholesterol-
BEDMINSTER, N.J., and DUBLIN, Ireland, Jan. 24, 2013 (GLOBE NEWSWIRE) -- Amarin Corporation plc (Nasdaq:AMRN), a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health, today announced that Vascepa® (icosapent ethyl) capsules, a therapy for patients in the United States to treat severe (≥500 mg/dL) hypertriglyceridemia more commonly known as very high triglycerides, or VHTG, is now available by way of physician prescription, and will be supported with a national commercial launch on January 28, 2013.
Vascepa is a new prescription pure-EPA omega-3 therapy approved by the U.S. Food and Drug Administration (FDA) as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. Triglycerides, like cholesterol, are a type of fat in the bloodstream. It is estimated that approximately four million adults in the United States have VHTG levels.
Vascepa is the first FDA-approved VHTG therapy to have demonstrated, in published controlled clinical trials, significant reduction in levels of triglycerides without elevation in levels of LDL-C and with a tolerability and safety profile similar to placebo. LDL-C is commonly referred to as "bad cholesterol" and is a primary cardiovascular risk factor. Vascepa also significantly improved many other important lipid parameters including apo B, non-HDL-C, TC and VLDL-C.
"Guidelines for the management of very high triglycerides state that reducing TG levels is the primary focus of therapy in patients with VHTG, due to the fact that severe hypertriglyceridemia contributes to the risk of acute pancreatitis," said Eliot A. Brinton, MD, Director, Atherometabolic Research, Utah Foundation for Biomedical Research, and Vice President, American Board of Clinical Lipidology. "Ideally, therapy that lowers very high triglycerides should not elevate LDL-C — a major risk factor for cardiovascular disease, but other VHTG therapies substantially raise LDL-C."
"Amarin has worked closely with leading clinical experts and regulatory authorities to bring this important new prescription pure-EPA omega-3 therapy to patients with very high triglycerides," stated Joseph Zakrzewski, Chairman and Chief Executive Officer of Amarin. "Other approved products for treating very high triglycerides have long been associated with raising LDL-C — commonly called bad cholesterol. Vascepa is the first prescription medicine for VHTG that does not raise LDL-C while significantly reducing very high triglycerides and providing a spectrum of additional lipid treatment benefits with a tolerability and safety profile similar to placebo. We expect this to be an important consideration in patient care as we educate physicians and other providers about the product."
About Vascepa® (icosapent ethyl) Capsules
Vascepa® (icosapent ethyl) capsules, known in scientific literature as AMR101, is a patented, pure-EPA omega-3 prescription product in a 1 gram capsule.
Vascepa(icosapent ethyl) is indicated for use in the United States as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.
The effect of Vascepa on the risk for pancreatitis or on cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.
Amarin is currently conducting a cardiovascular outcomes study called REDUCE-IT. This study is designed to evaluate the efficacy of Vascepa in reducing major cardiovascular events in an at-risk patient population on statin therapy.
The only reported adverse reaction with an incidence > 2% and greater than placebo in Vascepa treated patients was arthralgia (2.3% for Vascepa vs. 1.0% for placebo).
Pharmacological Class:
Lipid-regulating agent.
Active Ingredient(s):
Icosapent ethyl 1g; soft gelatin capsules.
Indication(s):
Adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. Limitations of use: The effect of Vascepa on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. The effect of Vascepa on cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.
Pharmacology:
Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Studies suggest that eicosapentaenoic acid reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased ß-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.
Clinical Trials:
The effects of Vascepa 4g per day were assessed in a randomized, placebo-controlled, double-blind, parallel-group study of adult patients (76 on Vascepa, 75 on placebo) with severe hypertriglyceridemia. Patients whose baseline TG levels were between 500 and 2,000mg/dL were enrolled in this study for 12 weeks. The median baseline TG and LDL-C levels in these patients were 684mg/dL and 86mg/dL, respectively. Median baseline HDL-C level was 27mg/dL. The randomized population in this study was mostly Caucasian (88%) and male (76%). The mean age was 53 years and the mean body mass index was 31kg/m2. Twenty five percent of patients were on concomitant statin therapy, 28% were diabetics, and 39% of the patients had TG levels >750mg/dL.
At endpoint, patients treated for 12 weeks with the 4g dose of Vascepa demonstrated a statistically significant placebo-adjusted median triglyceride reduction of 33% (p<0.001), and did not show an increase in LDL-C levels relative to placebo. Vascepa 4g per day also showed statistically significant placebo-adjusted median reductions from baseline in non-high-density lipoprotein cholesterol (non-HDL-C) of 18%, total cholesterol (TC) of 16%, very low density lipoprotein cholesterol (VLDL-C) of 29%, and apolipoprotein B (ApoB) of 9%. Among the patients with a baseline TG level>750mg/dL, Vascepa 4g/day reduced the placebo-corrected median TG levels by 45% (p<0.001).
Legal Classification:
Rx
Adults:
Swallow whole. Do not crush, dissolve, or chew. 2 capsules twice daily with food; maximum 4g per day.
Children:
Not established.
Warnings/Precautions:
Obtain baseline lipids before initiating therapy. Identify other causes of high triglycerides and manage appropriately (eg, diabetes, hypothyroidism, or alcohol intake). Hepatic impairment; monitor ALT and AST levels periodically during therapy. Fish and/or shellfish allergy. Pregnancy (Category C). Nursing mothers.
Interaction(s)
Monitor periodically with concomitant drugs that affect coagulation (eg, antiplatelet agents).
Adverse Reaction(s)
Arthralgia.
Notes:
To report suspected adverse reactions, contact Amarin Pharma at (855) 827-2372 or the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
How Supplied:
Caps—120
LAST UPDATED:
2/4/2013
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9c1a2828-1583-4414-ab22-a60480e8e508
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