Identification

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Name
Omega-3-carboxylic acids
Accession Number
DB09568
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EpanovaCapsule, gelatin coated1 g/1OralAstra Zeneca Lp2015-06-012015-06-01Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
F85N2YHE4E
CAS number
Not Available

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

Associated Conditions
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

TargetActionsOrganism
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

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

Affected organisms
  • Humans and other mammals
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.
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Omega-3-carboxylic acids.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Omega-3-carboxylic acids.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Omega-3-carboxylic acids.
AbciximabThe therapeutic efficacy of Abciximab can be increased when used in combination with Omega-3-carboxylic acids.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Omega-3-carboxylic acids.
Acetylsalicylic acidThe therapeutic efficacy of Acetylsalicylic acid can be increased when used in combination with Omega-3-carboxylic acids.
AlteplaseThe therapeutic efficacy of Alteplase can be increased when used in combination with Omega-3-carboxylic acids.
AmediplaseThe therapeutic efficacy of Amediplase can be increased when used in combination with Omega-3-carboxylic acids.
AnagrelideThe therapeutic efficacy of Anagrelide can be increased when used in combination with Omega-3-carboxylic acids.
AncrodThe therapeutic efficacy of Ancrod can be increased when used in combination with Omega-3-carboxylic acids.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
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. [PubMed:28003756]
  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. [PubMed:25387209]
  3. Brahm A, Hegele RA: Hypertriglyceridemia. Nutrients. 2013 Mar 22;5(3):981-1001. doi: 10.3390/nu5030981. [PubMed:23525082]
  4. FDA approval [Link]
  5. Epanova [Link]
  6. FDA reports [Link]
  7. FDA reports [Link]
External Links
PubChem Substance
347910465
FDA label
Download (185 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAUC / Cmax / Pharmacokinetics / Relative Bioavailability1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHypertriglyceridemias3
1CompletedTreatmentSevere Hypertriglyceridemia1
2CompletedTreatmentExocrine Pancreatic Insufficiency / Type 2 Diabetes Mellitus1
2CompletedTreatmentSevere Hypertriglyceridemia1
2, 3CompletedTreatmentSevere Hypertriglyceridemia1
3Active Not RecruitingTreatmentEligible Men or Women Considered High Risk for Atherosclerotic Cardiovascular Disease (CVD)1
3CompletedTreatmentCardiovascular Heart Disease / Hypertriglyceridemias1
3CompletedTreatmentCrohn's Disease (CD)2
3CompletedTreatmentHypertriglyceridemias2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Capsule, gelatin coatedOral1 g/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5948818No1999-09-072016-05-13Us
US5792795No1998-08-112016-05-13Us
US8383678No2013-02-262025-02-07Us
US9132112No2015-09-152025-02-07Us
US9012501No2015-04-212025-02-07Us
US9050308No2015-06-092033-01-04Us
US9050309No2015-06-092033-01-04Us
US7960370No2011-06-142025-02-07Us
US10117844No2018-11-062033-01-04Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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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

Taxonomy

Classification
Not classified

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
  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. [PubMed:25387209]
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. [PubMed:25387209]
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. [PubMed:25387209]
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. [PubMed:25387209]
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. [PubMed:25387209]
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. [PubMed:25387209]

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:
References
  1. FDA reports [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da
References
  1. 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
  1. 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
  1. FDA reports [Link]

Drug created on November 30, 2015 12:10 / Updated on December 02, 2019 08:46