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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Associated Conditions

• Hypertriglyceridemias

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	antagonist	Humans
A3-hydroxyacyl-CoA dehydrogenase type-2	potentiator	Humans
AEnoyl-CoA hydratase, mitochondrial	potentiator	Humans
AHydroxyacyl-coenzyme A dehydrogenase, mitochondrial	potentiator	Humans
AElongation of very long chain fatty acids protein 4	potentiator	Humans
ALipoprotein lipase	stimulator	Humans

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abciximab	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.

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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

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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

Categories

Drug Categories

• Fatty Acids, Omega-3

Classification

Not classified

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

F85N2YHE4E

CAS number

Not Available

References

General References

1. 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]
2. 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]
3. Brahm A, Hegele RA: Hypertriglyceridemia. Nutrients. 2013 Mar 22;5(3):981-1001. doi: 10.3390/nu5030981. [Article]
4. FDA approval [Link]
5. Epanova [Link]
6. FDA reports [Link]
7. FDA reports [Link]

External Links

PubChem Substance

347910465

RxNav

1652071

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
US5792795	No	1998-08-11	2016-05-13
US8383678	No	2013-02-26	2025-02-07
US9132112	No	2015-09-15	2025-02-07
US9012501	No	2015-04-21	2025-02-07
US9050308	No	2015-06-09	2033-01-04
US9050309	No	2015-06-09	2033-01-04
US7960370	No	2011-06-14	2025-02-07
US10117844	No	2018-11-06	2033-01-04

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

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Details1. Diacylglycerol O-acyltransferase 2

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

1. 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]

Details2. 3-hydroxyacyl-CoA dehydrogenase type-2

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

1. 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]

Details3. Enoyl-CoA hydratase, mitochondrial

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

1. 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]

Details4. Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial

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

1. 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]

Details5. Elongation of very long chain fatty acids protein 4

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

1. 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]

Details6. Lipoprotein lipase

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

1. 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]

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Drug created at November 30, 2015 19:10 / Updated at May 21, 2021 10:21