Ethyl eicosapentaenoic acid

{{Short description|Medication}} {{Globalize|article|United States|date=June 2021}} {{Use dmy dates|date=April 2025}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | drug_name = Icosapent ethyl | Verifiedfields = changed | Watchedfields = changed | image = Ethyl eicosapentaenoate.png | image_class = skin-invert | width = 200 | alt = | caption = | USAN = Icosapent ethyl

| pronounce = | tradename = Vascepa, Vazkepa | Drugs.com = {{drugs.com|monograph|icosapent-ethyl}} | MedlinePlus = a613024 | DailyMedID = Icosapent ethyl | pregnancy_AU = B1 | pregnancy_AU_comment = <ref name="Vazkepa APMDS" /> | pregnancy_category= | routes_of_administration = By mouth | class = Antilipemic Agents | ATC_prefix = None | ATC_suffix = | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = <ref name="Vazkepa APMDS">{{cite web | title=Vazkepa | website=Therapeutic Goods Administration (TGA) | date=22 November 2022 | url=https://www.tga.gov.au/resources/auspmd/vazkepa | access-date=29 April 2023 | archive-date=5 February 2023 | archive-url=https://web.archive.org/web/20230205203511/https://www.tga.gov.au/resources/auspmd/vazkepa | url-status=live }}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Summary Basis of Decision (SBD) for Vascepa | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00472&lang=en | access-date=29 May 2022 | archive-date=31 May 2022 | archive-url=https://web.archive.org/web/20220531043123/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00472&lang=en | url-status=live }}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Vascepa FDA label" /> | legal_EU = Rx-only | legal_EU_comment = <ref name="Vazkepa EPAR">{{cite web | title=Vazkepa EPAR | website=European Medicines Agency (EMA) | date=25 January 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/vazkepa | access-date=7 July 2021 | archive-date=9 July 2021 | archive-url=https://web.archive.org/web/20210709190225/https://www.ema.europa.eu/en/medicines/human/EPAR/vazkepa | url-status=live }}</ref><ref>{{cite web | title=Vazkepa Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1524.htm | access-date=3 March 2023 | archive-date=5 March 2023 | archive-url=https://web.archive.org/web/20230305044707/https://ec.europa.eu/health/documents/community-register/html/h1524.htm | url-status=live }}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 86227-47-6 | CAS_supplemental = | PubChem = 9831415 | IUPHAR_ligand = 7441 | DrugBank_Ref = | DrugBank = DB08887 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 8007147 | UNII_Ref = | UNII = 6GC8A4PAYH | KEGG_Ref = | KEGG = D01892 | KEGG2_Ref = | KEGG2 = C16184 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 84883 | ChEMBL_Ref = | ChEMBL = 2095209 | NIAID_ChemDB = | PDB_ligand = | synonyms = Eicosapentaenoic acid ethyl ester; EPA ethyl ester; Ethyl eicosapentaenoic acid; E-EPA; Eicosapent

| IUPAC_name = Ethyl (5''Z'',8''Z'',11''Z'',14''Z'',17''Z'')-icosa-5,8,11,14,17-pentaenoate | C=22 | H=34 | O=2 | SMILES = CCC=CCC=CCC=CCC=CCC=CCCCC(=O)OCC | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C22H34O2/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24-4-2/h5-6,8-9,11-12,14-15,17-18H,3-4,7,10,13,16,19-21H2,1-2H3/b6-5-,9-8-,12-11-,15-14-,18-17- | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = SSQPWTVBQMWLSZ-AAQCHOMXSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Icosapent ethyl''' (USAN, EMA), 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<ref name="Vazkepa EPAR" /> and hypertriglyceridemia.<ref name="Vascepa FDA label" /> 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 (maximally-tolerated dose).<ref name="FDA PR">{{cite press release | title=FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups | website=U.S. Food and Drug Administration (FDA) | date=13 December 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups | archive-url=https://web.archive.org/web/20191222104006/https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups | archive-date=22 December 2019 | url-status=dead | access-date=21 December 2019}} {{PD-notice}}</ref>

The most common side effects are musculoskeletal pain, peripheral edema (swelling of legs and hands), atrial fibrillation, and arthralgia (joint pain).<ref name="FDA PR" /> Other common side effects include bleeding, constipation, gout, and rash.<ref name="Vazkepa EPAR" />

It is made from the omega−3 fatty acid eicosapentaenoic acid (EPA).<ref name="FDA PR" /> The US Food and Drug Administration (FDA) granted the approval of icosapent ethyl in 2012, to Amarin Corporation, and it became the second fish oil-based medication after omega-3-acid ethyl esters (brand named Lovaza, itself approved in 2004).<ref name=2015CompareRev /> In December 2019, the FDA also approved Vascepa as the first drug specifically "to reduce cardiovascular risk among people with elevated triglyceride levels".<ref name="FDA PR"/> It is available as a generic medication.<ref>{{cite web | title=Icosapent ethyl: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209457 | access-date=15 August 2020 | archive-date=19 October 2020 | archive-url=https://web.archive.org/web/20201019092816/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209457 | url-status=dead }}</ref> Vazkepa was approved in Europe in 2021.<ref name=ema>{{cite web |title=Vazkepa {{!}} European Medicines Agency (EMA) |url=https://www.ema.europa.eu/en/medicines/human/EPAR/vazkepa |website=www.ema.europa.eu |language=en |date=14 April 2021}}</ref> In 2023, it was the 244th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Icosapent Ethyl Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/IcosapentEthyl | access-date = 20 August 2025 }}</ref>

==Medical uses== In the European Union, icosapent ethyl is indicated to reduce cardiovascular risk as an adjunct to statin therapy.<ref name="Vazkepa EPAR" />

In the United States, icosapent ethyl is indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adults with elevated triglyceride levels (≥ 150 mg/dL) and established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.<ref name="Vascepa FDA label">{{cite web | title=Vascepa- icosapent ethyl capsule | website=DailyMed | date=23 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9c1a2828-1583-4414-ab22-a60480e8e508 | access-date=15 January 2020 | archive-date=5 February 2021 | archive-url=https://web.archive.org/web/20210205220629/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9c1a2828-1583-4414-ab22-a60480e8e508 | url-status=live }}</ref> It is also indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia.<ref name="Vascepa FDA label" />

Intake of large doses (2.0 to 4.0 g/day) of long-chain omega−3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater that 500 mg/dL).{{medical citation needed|date=July 2021}} It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides; however, DHA alone appears to raise low-density lipoprotein (the variant which drives atherosclerosis; sometimes {{According to whom|very inaccurately|date=February 2023}} called "bad cholesterol") and LDL-C values (most typically only a calculated estimate and not measured by labs from person's blood sample for technical and cost reasons; however, this is accurately calculated with a less common NMR lipid panel lab), whilst eicosapentaenoic acid (EPA) alone does not and instead lowers the parameters aforementioned.<ref name=NLApt2-2015>{{cite journal | vauthors = Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, Underberg JA | display-authors = 6 | title = National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2 | journal = Journal of Clinical Lipidology | volume = 9 | issue = 6 Suppl | pages = S1–122.e1 | date = 2015 | pmid = 26699442 | doi = 10.1016/j.jacl.2015.09.002 | doi-access=free | title-link=doi }}</ref>

=== 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:<ref name=2014rev/><ref name=2015CompareRev /><ref>{{cite journal |vauthors=Brinton EA, Mason RP |title=Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA) |journal=Lipids Health Dis |volume=16 |issue=1 |article-number=23 |date=January 2017 |pmid=28137294 |pmc=5282870 |doi=10.1186/s12944-017-0415-8 | doi-access=free | title-link=doi }}</ref>

* Omega-3-acid ethyl esters (brand names Omacor [renamed Lovaza in the U.S. to avoid confusion with Amicar and Omtryg]),<ref>{{Cite web |url=http://pharmacyservices.utah.edu/alerts/251.html |title=University of Utah Pharmacy Services (15 August 2007) "Omega-3-acid Ethyl Esters Brand Name Changed from Omacor to Lovaza" |access-date=1 April 2016 |archive-url=https://web.archive.org/web/20160303225225/http://pharmacyservices.utah.edu/alerts/251.html |archive-date=3 March 2016 |url-status=dead }}</ref><ref>{{cite web | title=Omtryg- omega-3-acid ethyl esters capsule | website=DailyMed | date=31 March 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5fe15bdb-f59f-4b87-8e5d-8a3d5683eb3d | access-date=15 January 2020 | archive-date=11 January 2017 | archive-url=https://web.archive.org/web/20170111174849/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5fe15bdb-f59f-4b87-8e5d-8a3d5683eb3d | url-status=live }}</ref> and as of March 2016, four generic versions<ref name=USgenerics>[https://web.archive.org/web/20150905135219/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=OMEGA%2D3%2DACID%20ETHYL%20ESTERS FDA Omega-3 acid ethyl esters products] Page accessed 31 March 2016</ref><ref>{{cite web | title=Omega-3-acid ethyl esters | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=OMEGA-3-ACID+ETHYL+ESTERS | access-date=2 February 2020 | archive-date=2 February 2020 | archive-url=https://web.archive.org/web/20200202230037/https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=OMEGA-3-ACID+ETHYL+ESTERS | url-status=live }}</ref> * Omega-3-carboxylic acids (Epanova);<ref>{{cite web|title=Epanova (omega-3-carboxylic acids)|url=http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1324/epanova-omega-3-carboxylic-acids|website=CenterWatch|access-date=15 December 2014|archive-date=25 December 2014|archive-url=https://web.archive.org/web/20141225155451/http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1324/epanova-omega-3-carboxylic-acids|url-status=dead}}</ref><ref>{{cite web | title=Drug Approval Package: Epanova (Omega-3-carboxylic acids) | website=U.S. Food and Drug Administration (FDA) | date=28 March 2016 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205060Orig1EpanovaTOC.cfm | access-date=15 January 2020 | archive-date=15 January 2020 | archive-url=https://web.archive.org/web/20200115113008/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205060Orig1EpanovaTOC.cfm | url-status=dead }}</ref> the Epanova brand name was discontinued in the United States.<ref>{{cite web | title=Epanova (omega-3-carboxylic acids) FDA Approval History | website=Drugs.com | date=5 May 2014 | url=https://www.drugs.com/history/epanova.html | access-date=15 January 2020 | archive-date=16 January 2020 | archive-url=https://web.archive.org/web/20200116063138/https://www.drugs.com/history/epanova.html | url-status=live }}</ref>

=== 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,<ref>{{cite journal | vauthors = Hu Y, Hu FB, Manson JE | title = Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants | journal = Journal of the American Heart Association | volume = 8 | issue = 19 | article-number = e013543 | date = October 2019 | pmid = 31567003 | pmc = 6806028 | doi = 10.1161/JAHA.119.013543 }}</ref> and premature death.<ref>{{cite journal | vauthors = Harris WS, Tintle NL, Imamura F, Qian F, Korat AV, Marklund M, Djoussé L, Bassett JK, Carmichael PH, Chen YY, Hirakawa Y, Küpers LK, Laguzzi F, Lankinen M, Murphy RA, Samieri C, Senn MK, Shi P, Virtanen JK, Brouwer IA, Chien KL, Eiriksdottir G, Forouhi NG, Geleijnse JM, Giles GG, Gudnason V, Helmer C, Hodge A, Jackson R, Khaw KT, Laakso M, Lai H, Laurin D, Leander K, Lindsay J, Micha R, Mursu J, Ninomiya T, Post W, Psaty BM, Risérus U, Robinson JG, Shadyab AH, Snetselaar L, Sala-Vila A, Sun Y, Steffen LM, Tsai MY, Wareham NJ, Wood AC, Wu JH, Hu F, Sun Q, Siscovick DS, Lemaitre RN, Mozaffarian D | display-authors = 6 | title = Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies | journal = Nature Communications | volume = 12 | issue = 1 | article-number = 2329 | date = April 2021 | pmid = 33888689 | pmc = 8062567 | doi = 10.1038/s41467-021-22370-2 }}</ref> These effects may not carry over in other populations such as people who have diabetes.<ref>{{cite journal | title = 5. Facilitating Behavior Change and Well-being to Improve Health Outcomes: ''Standards of Medical Care in Diabetes-2020'' | journal = Diabetes Care | volume = 43 | issue = Suppl 1 | pages = S48–S65 | date = January 2020 | pmid = 31862748 | doi = 10.2337/dc20-S005 | publisher = American Diabetes Association | doi-access = free | author-link = American Diabetes Association | author1 = American Diabetes Association }}</ref><ref>{{cite journal | vauthors = Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, Grunberger G, Guerin CK, Bell DS, Mechanick JI, Pessah-Pollack R, Wyne K, Smith D, Brinton EA, Fazio S, Davidson M | display-authors = 6 | title = American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease | journal = Endocrine Practice | volume = 23 | issue = Suppl 2 | pages = 1–87 | date = April 2017 | pmid = 28437620 | doi = 10.4158/EP171764.APPGL | publisher = AACECOR | doi-access = free }}</ref><ref>{{cite journal | vauthors = Skulas-Ray AC, Wilson PW, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, Jacobson TA, Engler MB, Miller M, Robinson JG, Blum CB, Rodriguez-Leyva D, de Ferranti SD, Welty FK | display-authors = 6 | title = Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association | journal = Circulation | volume = 140 | issue = 12 | pages = e673–e691 | date = September 2019 | pmid = 31422671 | doi = 10.1161/CIR.0000000000000709 | publisher = Lippincott Williams & Wilkins | doi-access = free }}</ref> Compared to dietary supplements, the ingredients in prescription drugs are more carefully controlled and are typically fixed and tested in clinical trials.<ref name=emedDrugs>{{cite web | vauthors = Sweeney ME | url = http://emedicine.medscape.com/article/126568-treatment#d8 | title = Hypertriglyceridemia Pharmacologic Therapy | work = Medscape Drugs & Diseases | veditors = Khardori R | date = 14 April 2015 | access-date = 1 April 2016 | archive-date = 8 April 2018 | archive-url = https://web.archive.org/web/20180408235404/https://emedicine.medscape.com/article/126568-treatment#d8 | url-status = live }}</ref> The prescription forms are also typically more concentrated, requiring fewer capsules to be taken and increasing the likelihood of compliance.<ref name="2015CompareRev">{{cite journal |vauthors=Ito MK |date=December 2015 |title=A Comparative Overview of Prescription Omega-3 Fatty Acid Products |url=http://www.ptcommunity.com/journal/article/full/2015/12/826/comparative-overview-prescription-omega-3-fatty-acid-products |url-status=dead |journal=P & T |volume=40 |issue=12 |pages=826–857 |pmc=4671468 |pmid=26681905 |archive-url=https://web.archive.org/web/20200116063152/http://www.ptcommunity.com/journal/article/full/2015/12/826/comparative-overview-prescription-omega-3-fatty-acid-products |archive-date=16 January 2020 |access-date=16 January 2020}}</ref>

== Side effects == Special caution should be taken with people who have fish and shellfish allergies.<ref name="Vascepa FDA label"/> In addition, as with other omega−3 fatty acids, taking ethyl eicosapentaenoic acid (E-EPA) puts people who are on anticoagulants at risk for prolonged bleeding time.<ref name="Vascepa FDA label"/><ref name=NLApt2-2015/> The most commonly reported side effect in clinical trials has been joint pain; some people also reported pain in their mouth or throat.<ref name="Vascepa FDA label"/> E-EPA has not been tested in pregnant women;<ref name="Drugs.com pregnancy">{{cite web | title=Icosapent (Vascepa) Use During Pregnancy | website=Drugs.com | date=18 February 2019 | url=https://www.drugs.com/pregnancy/icosapent.html | access-date=15 January 2020 | archive-date=22 December 2019 | archive-url=https://web.archive.org/web/20191222112002/https://www.drugs.com/pregnancy/icosapent.html | url-status=live }}</ref> it is excreted in breast milk and the effects on infants are not known.<ref name="Vascepa FDA label"/>

==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.<ref name="Vascepa FDA label"/>

==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.<ref name="Vascepa FDA label"/><ref name=2014rev>{{cite journal | vauthors = Weintraub HS | title = Overview of prescription omega-3 fatty acid products for hypertriglyceridemia | journal = Postgraduate Medicine | volume = 126 | issue = 7 | pages = 7–18 | date = November 2014 | pmid = 25387209 | doi = 10.3810/pgm.2014.11.2828 | s2cid = 12524547 }}</ref>

==Chemistry== Ethyl eicosapentaenoic acid (E-EPA) is an ethyl ester of eicosapentaenoic acid, which is an omega−3 fatty acid.<ref name="Vascepa FDA label"/>

==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;<ref>{{cite web | title=Drug Approval Package: Vascepa (icosapent ethyl) NDA #202057 | website=U.S. Food and Drug Administration (FDA) | date=6 March 2013 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057_vascepa_toc.cfm | access-date=15 January 2020 | archive-date=15 January 2020 | archive-url=https://web.archive.org/web/20200115111124/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057_vascepa_toc.cfm | url-status=dead }}</ref> Amarin Corporation had developed the drug.<ref>CenterWatch [http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1215/vascepa-icosapent-ethyl Vascepa (icosapent ethyl)] {{Webarchive|url=https://web.archive.org/web/20190805014955/https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1215/vascepa-icosapent-ethyl |date=5 August 2019 }} Page accessed 31 March 2016</ref> 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.<ref>{{cite news|url=http://healthlawreporter.bbablogs.org/2016/03/28/health-law-case-brief-amarin-pharma-inc-v-fda/|accessdate=1 November 2021|date=28 March 2016|vauthors=Mariani E|title=Health Law Case Brief: Amarin Pharma, Inc. v. FDA|publisher=Boston Bar Association|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031234335/http://healthlawreporter.bbablogs.org/2016/03/28/health-law-case-brief-amarin-pharma-inc-v-fda/|url-status=usurped}}</ref>

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.<ref>{{cite web | title=Drug Approval Package: Omacor (Omega-3-Acid Ethyl Esters) NDA #021654 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-654_Omacor.cfm | access-date=15 January 2020 | archive-date=2 February 2020 | archive-url=https://web.archive.org/web/20200202225833/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-654_Omacor.cfm | url-status=dead }}</ref><ref name=2015CompareRev /><ref name=PBM2005>VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. October 2005 [http://www.pbm.va.gov/clinicalguidance/drugmonographs/Omega3acidethylestersLovazaformerlyOmacor.pdf National PBM Drug Monograph Omega-3-acid ethyl esters (Lovaza, formerly Omacor)] {{Webarchive|url=https://web.archive.org/web/20161222180834/http://www.pbm.va.gov/clinicalguidance/drugmonographs/Omega3acidethylestersLovazaformerlyOmacor.pdf |date=22 December 2016 }}</ref>) 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.<ref>{{cite web | vauthors = Herper M | work = Forbes | date = 17 October 2013 | url = https://www.forbes.com/sites/matthewherper/2013/10/17/why-the-fda-is-right-to-block-amarins-push-to-market-fish-oil-to-millions | title = Why The FDA Is Right To Block Amarin's Push To Market Fish Oil To Millions | access-date = 27 August 2017 | archive-date = 2 December 2020 | archive-url = https://web.archive.org/web/20201202173106/https://www.forbes.com/sites/matthewherper/2013/10/17/why-the-fda-is-right-to-block-amarins-push-to-market-fish-oil-to-millions/ | url-status = live }}</ref> In response, in May 2015, Amarin sued the FDA for infringing its First Amendment rights,<ref>{{cite news | vauthors=Thomas K | newspaper=The New York Times | date=7 May 2015 | url=https://www.nytimes.com/2015/05/08/business/drugmaker-sues-fda-over-right-to-discuss-off-label-uses.html | title=Drugmaker Sues F.D.A. Over Right to Discuss Off-Label Uses | access-date=17 May 2017 | archive-date=22 December 2020 | archive-url=https://web.archive.org/web/20201222184627/https://www.nytimes.com/2015/05/08/business/drugmaker-sues-fda-over-right-to-discuss-off-label-uses.html | url-status=live }}</ref> 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."<ref>{{cite news | title=Court Forbids F.D.A. From Blocking Truthful Promotion of Drug | website=The New York Times | date=7 August 2015 | vauthors=Pollack A | url=https://www.nytimes.com/2015/08/08/business/court-forbids-fda-from-blocking-truthful-promotion-of-drug.html | access-date=21 December 2019 | archive-date=22 December 2020 | archive-url=https://web.archive.org/web/20201222184657/https://www.nytimes.com/2015/08/08/business/court-forbids-fda-from-blocking-truthful-promotion-of-drug.html | url-status=live }}</ref> 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.<ref>{{cite news | title=F.D.A. Deal Allows Amarin to Promote Drug for Off-Label Use | website=The New York Times | date=9 March 2016 | vauthors=Thomas K | url=https://www.nytimes.com/2016/03/09/business/fda-deal-allows-amarin-to-promote-drug-for-off-label-use.html | access-date=21 December 2019 | archive-date=8 November 2020 | archive-url=https://web.archive.org/web/20201108143616/http://www.nytimes.com/2016/03/09/business/fda-deal-allows-amarin-to-promote-drug-for-off-label-use.html | url-status=live }}</ref>

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.<ref name="FDA PR" /> People must also have either established cardiovascular disease alone or diabetes along with two or more additional risk factors for cardiovascular disease.<ref name="FDA PR" />

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.<ref name="FDA PR" />

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.<ref name="FDA PR" /> Participants who received icosapent ethyl were significantly less likely to experience a cardiovascular event, such as a stroke or heart attack.<ref name="FDA PR" />

In clinical trials, icosapent ethyl was associated with an increased risk of atrial fibrillation or atrial flutter (irregular heart rhythms) requiring hospitalization.<ref name="FDA PR" /> The incidence of atrial fibrillation was greater among participants with a history of atrial fibrillation or atrial flutter.<ref name="FDA PR" /> Icosapent ethyl was also associated with an increased risk of bleeding events.<ref name="FDA PR" /> 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.<ref name="FDA PR" />

== 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.<ref name="Vazkepa: Pending EC decision" /> The applicant for this medicinal product is Amarin Pharmaceuticals Ireland Limited.<ref name="Vazkepa: Pending EC decision">{{cite web | title=Vazkepa: Pending EC decision | website=European Medicines Agency (EMA) | date=29 January 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/vazkepa | access-date=1 February 2021 | archive-date=1 February 2021 | archive-url=https://web.archive.org/web/20210201105334/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/vazkepa | url-status=live }}</ref> It was approved for medical use in the European Union in March 2021.<ref name="Vazkepa EPAR" />

== References == {{Reflist}}

{{DEFAULTSORT:Ethyl Eicosapentaenoic Acid}} Category:Biochemistry Category:Ethyl esters Category:Fatty acid esters Category:Polyolefins Category:Treatment of bipolar disorder Category:Fish products Category:Lipid-lowering agents