Omega-3 carboxylic acids

Omega-3 carboxylic acids[1] (Epanova) is an FDA approved prescription medication used alongside a low fat and low cholesterol diet that lowers high triglyceride (fat) levels in adults with very high levels.[2] This was the third class of fish oil-based drug to be approved for use as a drug. The first approval was granted in the US came in 2014. These fish oil drugs are similar to fish oil dietary supplements but the ingredients are better controlled and have been tested in clinical trials.

Medical Uses

Omega-3 carboxylic acids are used in addition to changes in diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia.[3]

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). It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides, but DHA appears to raise LDL-C ("bad cholesterol") more than EPA, while DHA raises HDL-C ("good cholesterol") while EPA does not. [4]

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.[5]

Dietary supplements

There are many fish oil dietary supplements on the market.[10] There appears to be little difference between in effect between dietary supplement and prescription forms of omega-3 fatty acids but EPA and DHA ethyl esters (prescription forms) work less well when taken on an empty stomach or with a low-fat meal.[4] The ingredients of dietary supplements are not as carefully controlled as prescription products and have not been fixed and tested in clinical trials, as prescription drugs have,[11] and the prescription forms are more concentrated, requiring fewer capsules to be taken and increasing the likelihood of compliance.[10]

Side Effects

Special caution should be taken with people who have with fish and shellfish allergies.[3] In addition, as with other omega-3 fatty acids, taking omega-3 carboxylic acids puts people who are on anticoagulants at risk for prolonged bleeding time.[3][4]

Side effects include diarrhea, nausea, abdominal pain, and burping.[3]

Omega-3 carboxylic acids have not been tested in pregnant women and are rated pregnancy category C; it is excreted in breast milk and the effects on infants are not known.[3]

Pharmacology

Omega-3 carboxylic acids are directly absorbed in the small intestine; maximum plasma concentrations are achieved between 5-8 hours after dosing for total EPA and between 5-9 hours after dosing for total DHA. Both DHA and EPA are mainly metabolized in the liver like other fatty acids derived from food. The half-life of EPA from Omega-3 carboxylic acids is about 37 hours, and for DHA about 46 hours.[3]

Mechanism of action

Omega-3 carboxylic acids, 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.[5]

Physical and chemical properties

Omega-3 carboxylic acids are derived from fish oil and are a purified mixture of the polyunsaturated free fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).[10] The drug contains a concentration of DHA at 15-25 % and a concentration of EPA at 50-60%.[3]

History

Omega-3 carboxylic acids was approved by the US FDA in May 2014[12] and was the third prescription form of an omega-3 product approved in the United States but the first in free fatty acid form.[2][13] Development was completed and regulatory was obtained by AstraZeneca,[14] but omega-3 carboxylic acids were first created at Chrysalis Pharma in Switzerland; Princeton-based Omthera had obtained rights from Chysalis, and Astrazeneca acquired Omthera in 2013 for $323 million in cash along with up to $120 million in milestones.[15] At the time Epanova was approved, AstraZeneca's plan was to develop a combination product with rosuvastatin, the patent on which was set to expire in 2016.[15]

References

  1. ↑ "Omega-3 carboxylic acids" is the USAN, see here under 2014 and the proposed INN - see 3.8 here
  2. 1 2 Hypertriglyceridemia at eMedicine
  3. 1 2 3 4 5 6 7 Epanova label Revised: May, 2014. Updates can be found at FDA label page here
  4. 1 2 3 Jacobson TA, et al, NLA Expert Panel. National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2. J Clin Lipidol. 2015 Nov-Dec;9(6 Suppl):S1-S122.e1. PMID 26699442 Free full text
  5. 1 2 Weintraub, HS (2014). "Overview of prescription omega-3 fatty acid products for hypertriglyceridemia". Postgrad Med. 126: 7–18. doi:10.3810/pgm.2014.11.2828. PMID 25387209. Retrieved 20 April 2015.
  6. ↑ University of Utah Pharmacy Services (August 15, 2007) "Omega-3-acid Ethyl Esters Brand Name Changed from Omacor to Lovaza"
  7. ↑ Omtryg Label Revised April 2014
  8. ↑ FDA Omega-3 acid ethyl esters products Page accessed March 31, 2016
  9. ↑ CenterWatch Vascepa (icosapent ethyl) Page accessed March 31, 2016
  10. 1 2 3 Ito MK. A Comparative Overview of Prescription Omega-3 Fatty Acid Products. P T. 2015 Dec;40(12):826-57. PMID 26681905 Free PMC Article PMC 4671468
  11. ↑ Sweeney MET. Hypertriglyceridemia Pharmacologic Therapy for Medscape Drugs & Diseases, Ed. Khardori R. Updated: Apr 14, 2015, page accessed April 1, 2016
  12. ↑ "Epanova (omega-3-carboxylic acids)". CenterWatch. Retrieved 15 December 2014.
  13. ↑ Blair HA, Dhillon S. Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia. Am J Cardiovasc Drugs. 2014 Oct;14(5):393-400. PMID 25234378
  14. ↑ "Epanova (omega-3-carboxylic acids)". CenterWatch. Retrieved 15 December 2014.
  15. 1 2 John Carroll for FierceBiotech.May 6, 2014. AstraZeneca wins FDA OK for another fish-oil heart pill, enters crowded market
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