Omega-3-carboxylic acids
Identification
- Summary
Omega-3-carboxylic acids is a medication used with other medications to lower triglyceride levels in adult patients with severe hypertriglyceridemia.
- Generic Name
- Omega-3-carboxylic acids
- DrugBank Accession Number
- DB09568
- Background
The omega-3 carboxylic acid (OM3-CA) is a new formulation of omega-3 fatty acids that present an enhanced bioavailability in the treatment of dyslipidemia. The increased bioavailability is explained because OM3-CA is found in a form of polyunsaturated free fatty acids as opposed to other products whose form is as ethyl esters. It is a complex mixture of the free fatty acids form containing eicosapentaenoic acid and docosahexaenoic acid as the most abundant species found in a proportion of 55% and 20% respectively. The rest of the concentration is represented by docosapentaenoic acid and traces of some other components such as alpha-tocopherol, gelatin, glycerol, sorbitol and purified water.1 It was developed by AstraZeneca Pharmaceuticals and firstly approved by the FDA on May 05, 2014.4
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Synonyms
- Omega-3-carboxylic acids
Pharmacology
- Indication
OM3-CA is indicated as an adjunct to diet to reduce triglycerides levels in adults patients with severe hypertriglyceridemia (>500 mg/dL). The patients involved in this treatment should be laced with an appropriate lipid-lowering diet.5
Hypertriglyceridemia is defined as an elevated plasma triglyceride concentration. It is usually correlated to other secondary conditions such as poor diet, alcohol use, obesity, metabolic syndrome and type 2 diabetes.3
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- Contraindications & Blackbox Warnings
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- Pharmacodynamics
OM3-CA is very effective in reducing triglyceride levels. After 14 days of treatment, it is possible to observe even a 21% reduction.1 The reduction of the triglycerides could reach even to 25% in cases with the maximal used concentration of 4 g.6
- Mechanism of action
The reduction of the synthesis of triglycerides in the liver may be caused because the main components of OM3-CA, eicosapentaenoic acid, and docosahexaenoic acid, are poor substrates for the enzymes responsible for the synthesis of triglycerides. These two major components inhibit the esterification of other fatty acids. OM3-CA is also thought to enhance the clearance of triglycerides from the circulating very low-density lipoprotein particles by different potential effects such as inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increase in mitochondrial and peroxisomal beta-oxidation in the liver, decrease lipogenesis in the liver and increase lipoprotein lipase activity.2
Target Actions Organism ADiacylglycerol O-acyltransferase 2 antagonistHumans A3-hydroxyacyl-CoA dehydrogenase type-2 potentiatorHumans AEnoyl-CoA hydratase, mitochondrial potentiatorHumans AHydroxyacyl-coenzyme A dehydrogenase, mitochondrial potentiatorHumans AElongation of very long chain fatty acids protein 4 potentiatorHumans ALipoprotein lipase stimulatorHumans - Absorption
When compared to omega-3 -acid ethyl esters, OM3-CA present a 4-fold higher bioavailability.1 OM3-CA is absorbed directly in the small intestine and the maximal plasma concentration is reached between 4.5-5 hours after initial administration.1 The absorbed dosage is transferred to the general circulation via the lymphatic system and distributed within tissues throughout the body. The absorption speed and extent is highly promoted by the bile. In preclinical studies performed in dogs, the Cmax, tmax and AUC were reported to be 15.1 mcg/ml, 24 hours and 1210.3 mcg.h/ml, respectively.7
- Volume of distribution
This pharmacokinetic property is not available.
- Protein binding
Once OM3-CA is absorbed, it is rapidly incorporated in phospholipids, triglycerides, and cholesteryl esters with only about 1% of the administered dose found as free-unesterified fatty acid.6 The majority of the eicosapentaenoic acid is bound to plasma proteins and it can represent even 98.5% of the administered dose.7
- Metabolism
OM3-CA is metabolized in the liver following the normal fatty acid oxidation.1 Once absorbed, they are incorporated into triglycerides, cholesterol esters and phospholipids in tissues. The metabolism is marked by beta-oxidation followed by tricarboxylic acid cycle. It is reported that OM3-CA is an inhibitor of several enzymes such as CYP2C9, CYP2C19 and to a lesser extent to CYP1A2, CYP2E1, CYP3A4. It is thought that the metabolism of OM3-CA is mainly done by CYP3A and CYP4F3B.7
- Route of elimination
OM3-CA does not go under renal excretion.6 After the metabolism, all the dose is excreted as CO2 and water in the form of expelled air and the rest is excreted in feces.7
- Half-life
The half-life of OM3-CA depends on the type of component in which for eicosapentaenoic acid it is estimated to be of approximately 4.7-10.8 hours while for docosahexaenoic acid is reported to be of about 7 hours.1 The half-life of baseline-adjusted at steady-state is of 36 and 46 hours respectively for eicosapentaenoic acid and docosahexaenoic acid.6
- Clearance
The registered clearance rate at steady-state is of 548 ml/h for eicosapentaenoic acid and 518 ml/h for docohexaenoic acid.6
- Adverse Effects
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- Toxicity
Preclinical studies with OM3-CA have shown an absence of a potential carcinogenic effect in males but it is reported to increase the incidence of benign ovarian sex cord-stromal tumors. OM3-CA is not mutagenic, clastogenic and it did not have any effect on fertility.6
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The therapeutic efficacy of Abciximab can be increased when used in combination with Omega-3-carboxylic acids. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Omega-3-carboxylic acids. Alteplase The therapeutic efficacy of Alteplase can be increased when used in combination with Omega-3-carboxylic acids. Ancrod The therapeutic efficacy of Ancrod can be increased when used in combination with Omega-3-carboxylic acids. Anistreplase The therapeutic efficacy of Anistreplase can be increased when used in combination with Omega-3-carboxylic acids. Antithrombin Alfa The therapeutic efficacy of Antithrombin Alfa can be increased when used in combination with Omega-3-carboxylic acids. Antithrombin III human The therapeutic efficacy of Antithrombin III human can be increased when used in combination with Omega-3-carboxylic acids. Apixaban The therapeutic efficacy of Apixaban can be increased when used in combination with Omega-3-carboxylic acids. Ardeparin The therapeutic efficacy of Ardeparin can be increased when used in combination with Omega-3-carboxylic acids. Argatroban The therapeutic efficacy of Argatroban can be increased when used in combination with Omega-3-carboxylic acids. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Take with or without food. Taking omega-3-carboxylic acids with a high-fat meal may increase the absorption of eicosapentaenoic acid (EPA).
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Epanova Capsule, gelatin coated 1 g/1 Oral Astra Zeneca Lp 2015-06-01 2015-06-01 US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- F85N2YHE4E
- CAS number
- Not Available
References
- General References
- Benes LB, Bassi NS, Davidson MH: Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia. Vasc Health Risk Manag. 2016 Dec 12;12:481-490. doi: 10.2147/VHRM.S58149. eCollection 2016. [Article]
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
- Brahm A, Hegele RA: Hypertriglyceridemia. Nutrients. 2013 Mar 22;5(3):981-1001. doi: 10.3390/nu5030981. [Article]
- FDA approval [Link]
- Epanova [Link]
- FDA reports [Link]
- FDA reports [Link]
- External Links
- FDA label
- Download (185 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Cardiovascular Disease (CVD) / Hypertriglyceridemias 1 3 Completed Treatment Crohn's Disease (CD) 2 3 Completed Treatment Eligible Men or Women Considered High Risk for Atherosclerotic Cardiovascular Disease (CVD) 1 3 Completed Treatment Hypertriglyceridemias 2 2 Completed Treatment Exocrine Pancreatic Insufficiency / Type 2 Diabetes Mellitus 1 2 Completed Treatment Severe Hypertriglyceridemia (sHTG) 1 2, 3 Completed Treatment Severe Hypertriglyceridemia (sHTG) 1 1 Completed Basic Science AUC / Cmax / Pharmacokinetics / Relative Bioavailability 1 1 Completed Basic Science Healthy Subjects (HS) 1 1 Completed Treatment Hypertriglyceridemias 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral Capsule, gelatin coated Oral 1 g/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5948818 No 1999-09-07 2016-05-13 US US5792795 No 1998-08-11 2016-05-13 US US8383678 No 2013-02-26 2025-02-07 US US9132112 No 2015-09-15 2025-02-07 US US9012501 No 2015-04-21 2025-02-07 US US9050308 No 2015-06-09 2033-01-04 US US9050309 No 2015-06-09 2033-01-04 US US7960370 No 2011-06-14 2025-02-07 US US10117844 No 2018-11-06 2033-01-04 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage of intracellular triglycerides. Probably plays a central role in cytosolic lipid accumulation. In liver, is primarily responsible for incorporating endogenously synthesized fatty acids into triglycerides (By similarity). Functions also as an acyl-CoA retinol acyltransferase (ARAT).
- Specific Function
- 2-acylglycerol o-acyltransferase activity
- Gene Name
- DGAT2
- Uniprot ID
- Q96PD7
- Uniprot Name
- Diacylglycerol O-acyltransferase 2
- Molecular Weight
- 43830.475 Da
References
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Testosterone dehydrogenase [nad(p)] activity
- Specific Function
- Functions in mitochondrial tRNA maturation. Part of mitochondrial ribonuclease P, an enzyme composed of MRPP1/TRMT10C, MRPP2/HSD17B10 and MRPP3/KIAA0391, which cleaves tRNA molecules in their 5'-en...
- Gene Name
- HSD17B10
- Uniprot ID
- Q99714
- Uniprot Name
- 3-hydroxyacyl-CoA dehydrogenase type-2
- Molecular Weight
- 26922.87 Da
References
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Enoyl-coa hydratase activity
- Specific Function
- Straight-chain enoyl-CoA thioesters from C4 up to at least C16 are processed, although with decreasing catalytic rate.
- Gene Name
- ECHS1
- Uniprot ID
- P30084
- Uniprot Name
- Enoyl-CoA hydratase, mitochondrial
- Molecular Weight
- 31387.085 Da
References
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Nad+ binding
- Specific Function
- Plays an essential role in the mitochondrial beta-oxidation of short chain fatty acids. Exerts it highest activity toward 3-hydroxybutyryl-CoA.
- Gene Name
- HADH
- Uniprot ID
- Q16836
- Uniprot Name
- Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
- Molecular Weight
- 34293.275 Da
References
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Transferase activity
- Specific Function
- Catalyzes the first and rate-limiting reaction of the four that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 ...
- Gene Name
- ELOVL4
- Uniprot ID
- Q9GZR5
- Uniprot Name
- Elongation of very long chain fatty acids protein 4
- Molecular Weight
- 36828.905 Da
References
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Stimulator
- General Function
- Triglyceride lipase activity
- Specific Function
- The primary function of this lipase is the hydrolysis of triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL). Binding to heparin sulfate proteogylcans at the cell sur...
- Gene Name
- LPL
- Uniprot ID
- P06858
- Uniprot Name
- Lipoprotein lipase
- Molecular Weight
- 53162.07 Da
References
- Weintraub HS: Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014 Nov;126(7):7-18. doi: 10.3810/pgm.2014.11.2828. [Article]
Enzymes
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Components:
Name | UniProt ID |
---|---|
Cytochrome P450 3A4 | P08684 |
Cytochrome P450 3A43 | Q9HB55 |
Cytochrome P450 3A5 | P20815 |
Cytochrome P450 3A7 | P24462 |
References
- FDA reports [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Phosphatidylcholine transporter activity
- Specific Function
- Catalyzes the transfer of phosphatidylcholine between membranes. Binds a single lipid molecule.
- Gene Name
- PCTP
- Uniprot ID
- Q9UKL6
- Uniprot Name
- Phosphatidylcholine transfer protein
- Molecular Weight
- 24843.145 Da
References
- FDA reports [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Serine-type endopeptidase inhibitor activity
- Specific Function
- Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin b...
- Gene Name
- PEBP1
- Uniprot ID
- P30086
- Uniprot Name
- Phosphatidylethanolamine-binding protein 1
- Molecular Weight
- 21056.65 Da
References
- FDA reports [Link]
Drug created at November 30, 2015 19:10 / Updated at May 21, 2021 10:21