MarketEthyl eicosapentaenoic acid
Company Profile

Ethyl eicosapentaenoic acid

Icosapent ethyl, also known by its chemical name ethyl eicosapentaenoate and incorrect chemical name ethyl eicosapentaenoic acid (E-EPA), sold under the brand name Vascepa among others, is a medication used to treat dyslipidemia and hypertriglyceridemia. It is used in combination with changes in diet in adults with hypertriglyceridemia ≥ 150 mg/dL. Further, it is often required to be used with a statin.

Medical uses
In the European Union, icosapent ethyl is indicated to reduce cardiovascular risk as an adjunct to statin therapy. It is also indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia. Other fish-oil based drugs There are other omega−3 fish-oil based drugs on the market that have similar uses and mechanisms of action: • Omega-3-acid ethyl esters (brand names Omacor [renamed Lovaza in the U.S. to avoid confusion with Amicar and Omtryg]), and as of March 2016, four generic versions • Omega-3-carboxylic acids (Epanova); the Epanova brand name was discontinued in the United States. Effectiveness Ethyl eicosapentaenoic acid is a prescription medication in the US, but it closely resembles other marine based omega−3 dietary supplements. Evidence suggests that these supplements are able to reduce cardiovascular disease, and premature death. These effects may not carry over in other populations such as people who have diabetes. Compared to dietary supplements, the ingredients in prescription drugs are more carefully controlled and are typically fixed and tested in clinical trials. The prescription forms are also typically more concentrated, requiring fewer capsules to be taken and increasing the likelihood of compliance. == Side effects ==
Side effects
Special caution should be taken with people who have fish and shellfish allergies. it is excreted in breast milk and the effects on infants are not known. ==Pharmacology==
Pharmacology
After ingestion, ethyl eicosapentaenoic acid (E-EPA) is metabolized to eicosapentaenoic acid (EPA). EPA is absorbed in the small intestine and enters circulation. Peak plasma concentration occurs about five hours after ingestion, and the half-life is about 89 hours. EPA is lipolyzed mostly in the liver. ==Mechanism of action==
Mechanism of action
Eicosapentaenoic acid (EPA), the active metabolite of ethyl eicosapentaenoic acid (E-EPA), like other omega−3 fatty acid based drugs, appears to reduce production of triglycerides in the liver and to enhance clearance of triglycerides from circulating very low-density lipoprotein (VLDL) particles. The way it does that is not clear, but potential mechanisms include increased breakdown of fatty acids; inhibition of diglyceride acyltransferase, which is involved in biosynthesis of triglycerides in the liver; and increased activity of lipoprotein lipase in blood. ==Chemistry==
Chemistry
Ethyl eicosapentaenoic acid (E-EPA) is an ethyl ester of eicosapentaenoic acid, which is an omega−3 fatty acid. ==History==
History
In July 2012, the US Food and Drug Administration (FDA) approved ethyl eicosapentaenoic acid (E-EPA) for severe hypertriglyceridemia as an adjunct to dietary measures; Amarin Corporation had developed the drug. Amarin Corporation challenged the FDA's authority to limit its ability to market the drug for off-label use and won its case on appeal in 2015, changing the way the FDA regulates the marketing of medication. Ethyl eicosapentaenoic acid (E-EPA) was the second fish-oil drug to be approved, after omega-3-acid ethyl esters (GlaxoSmithKline's Lovaza, which was approved in 2004.) Initial sales were not as robust as Amarin had hoped. The labels for the two drugs were similar, but doctors prescribed Lovaza for people who had triglycerides lower than 500 mg/dL based on some clinical evidence. Amarin wanted to actively market E-EPA for that population as well which would have greatly expanded its revenue and applied to the FDA for permission to do so in 2013, which the FDA denied. In response, in May 2015, Amarin sued the FDA for infringing its First Amendment rights, and in August 2015, a judge ruled that the FDA could not "prohibit the truthful promotion of a drug for unapproved uses because doing so would violate the protection of free speech." The ruling left open the question of what the FDA would allow Amarin to say about E-EPA, and in March 2016 the FDA and Amarin agreed that Amarin would submit specific marketing material to the FDA for the FDA to review (as is usual for prescription medications). If the parties disagreed on whether the material was truthful, they would seek a judge to mediate. In December 2019, the FDA approved the use of icosapent ethyl as an adjunctive (secondary) therapy to reduce the risk of cardiovascular events among adults with elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. People must also have either established cardiovascular disease alone or diabetes along with two or more additional risk factors for cardiovascular disease. Icosapent ethyl is the first FDA approved drug to reduce cardiovascular risk among people with elevated triglyceride levels as an add-on to maximally tolerated statin therapy. The efficacy and safety of icosapent ethyl were established in a study with 8,179 participants who were either 45 years and older with a documented history of coronary artery, cerebrovascular, carotid artery and peripheral artery disease or 50 years and older with diabetes and additional risk factors for cardiovascular disease. Participants who received icosapent ethyl were significantly less likely to experience a cardiovascular event, such as a stroke or heart attack. In clinical trials, icosapent ethyl was associated with an increased risk of atrial fibrillation or atrial flutter (irregular heart rhythms) requiring hospitalization. The incidence of atrial fibrillation was greater among participants with a history of atrial fibrillation or atrial flutter. Icosapent ethyl was also associated with an increased risk of bleeding events. The incidence of bleeding was higher among participants who were also taking other medications that increase the risk of bleeding, such as aspirin, clopidogrel or warfarin at the same time. == Society and culture ==
Society and culture
Legal status In January 2021, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vazkepa, intended to reduce the risk of cardiovascular events in people at high cardiovascular risk. It was approved for medical use in the European Union in March 2021. == References ==
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