Omacor

Generic Name: Omega-3-acid Ethyl Esters
Class: Antilipemic Agents, Miscellaneous
VA Class: CV350
Chemical Name: EPA ethyl ester: (all-Z)-5,8,11,14,17-Eicosapentaenoic acid ethyl ester. DHA ethyl ester: (all-Z)-4,7,10,13,16,19-Docosahexaenoic acid ethyl ester.
Molecular Formula: EPA ethyl ester: C22H34O2. DHA ethyl ester: C24H36O2
CAS Number: 86227-47-6

Introduction

Antilipemic agent; combination consisting predominantly of ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).1 2 8

Uses for Omacor

Dyslipidemias

Adjunct to dietary therapy to reduce very high (≥500 mg/dL) triglyceride concentrations in adults.1 2 8 Efficacy in reducing risk of pancreatitis or risk of cardiovascular morbidity or mortality in these patients not established.1 2 8

Has been used as monotherapy to reduce high (200–499 mg/dL) triglyceride concentrations in adults.2 13 However, because most of these patients are expected to receive statins as initial therapy,2 4 some experts state that efficacy should be further evaluated in patients receiving concomitant statin therapy.2 Preliminary data indicate additive effects on reduction of triglyceride and VLDL-cholesterol concentrations when used with statins.2 8 9 13 14 15

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Treatment may result in increases in LDL- and non-HDL-cholesterol concentrations in some individuals.1 2 8

Prevention of Cardiovascular Events

Marine- and plant-derived omega-3 fatty acids (i.e., EPA, DHA, α-linolenic acid) have been used for primary or secondary prevention of CHD.3 4 5 10 However, additional studies needed to confirm and further define the health benefits of omega-3 fatty acids for such use.3 4 5 (See Prevention of Cardiovascular Events under Dosage and Administration.)

Omacor Dosage and Administration

General

  • Patients should be placed on a standard cholesterol-lowering diet before initiation of omega-3-acid ethyl esters therapy and should remain on this diet during treatment with the drug.1 2

Administration

Oral Administration

Administered with meals in clinical studies.1 2 8

Dosage

Each 1-g capsule contains ≥900 mg of the ethyl esters of omega-3 fatty acids (approximately 465 mg from ethyl esters of EPA and 375 mg from ethyl esters of DHA).1 2

Adults

Dyslipidemias
Hypertriglyceridemia
Oral

Patients with very high (≥500 mg/dL) triglyceride concentrations: 4 g daily administered as a single dose or in 2 equally divided doses.1 2 8 Discontinue if adequate response not achieved after 2 months of therapy.1

Prevention of Cardiovascular Events
Oral

AHA suggests incorporating omega-3 fatty acids in diet,3 although benefit in reducing CHD risk or total mortality not established.5 For primary prevention, AHA suggests consumption of a variety of fish (preferably fatty fish such as herring, mackerel, salmon, sardines, or tuna) at least twice weekly and inclusion of oils and foods rich in α-linolenic acid (e.g., canola/flaxseed/soybean oils, flaxseeds, English walnuts) in diet.3 For secondary prevention, AHA suggests consumption of approximately 1 g of a combination of EPA and DHA daily, preferably through dietary means (i.e., consumption of fatty fish); if intake cannot be achieved with diet alone, may consider supplements, but only in consultation with a clinician.3

National Cholesterol Education Program (NCEP) expert panel has not recommended specific amount of omega-3 fatty acids for daily intake but does support AHA's recommendation to include fish in diet.4 Higher dietary intakes (1–2 g daily) identified by NCEP expert panel as an option for secondary prevention, but more definitive clinical trials required before such high dosages can be strongly recommended for either primary or secondary prevention.4

Special Populations

No special population recommendations at this time.13

Cautions for Omacor

Contraindications

  • Known hypersensitivity to omega-3-acid ethyl esters or any ingredient in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Fish Sensitivity

Use with caution in patients with known hypersensitivity to fish or shellfish.1 13

Major Toxicities

Hepatic Effects

Increases in ALT concentrations without a concurrent increase in AST concentrations reported in some patients.1 Monitor ALT concentrations periodically during therapy.1

General Precautions

Laboratory Monitoring

Prior to initiating therapy, evaluate lipoprotein profiles to confirm the presence of persistent hypertriglyceridemia.1 13 During therapy, obtain lipoprotein profiles periodically to monitor clinical response (i.e., reduction in triglyceride concentrations) or adverse effects (i.e., excessive increases in LDL-cholesterol concentrations).1 Discontinue therapy if adequate response not achieved after 2 months of therapy.1

Monitor ALT concentrations periodically during therapy.1 (See Hepatic Effects under Cautions.)

Adjunctive Measures

Prior to initiating therapy, vigorously attempt to control serum triglyceride concentrations with appropriate dietary regimens, exercise, weight reduction, and treatment of any underlying disorder that might be the cause of triglyceride abnormalities (e.g., diabetes mellitus, hypothyroidism).1

If possible, discontinue or change drugs known to exacerbate hypertriglyceridemia (e.g., β-adrenergic blocking agents, thiazides, estrogens) before initiating therapy.1

Prolongation of Bleeding Time

Prolongation of bleeding time observed with omega-3 fatty acids;1 10 however, such prolongation has not exceeded normal limits and was not associated with clinically significant bleeding episodes.1 Manufacturer states that blood testing is not required but recommends that patients be monitored for manifestations of bleeding prior to and during therapy.13 (See Anticoagulants under Interactions.)

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether omega-3-acid ethyl esters is distributed into milk.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Experience in patients >65 years of age is limited.1 In pooled analyses, no substantial differences in safety and efficacy observed between patients >60 years of age (approximately 25% of study population) and younger patients.1

Common Adverse Effects

Eructation,8 infection, flu syndrome, dyspepsia,8 taste perversion,8 back pain, pain, rash, angina pectoris.1

Interactions for Omacor

Drugs Metabolized by Hepatic Microsomal Enzymes

Free forms of EPA and DHA shown to cause modest inhibition of CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A in vitro.1 2 13 However, because free forms of EPA and DHA are undetectable in systemic circulation (<1 mcM), clinically important interactions with drugs metabolized by the CYP enzyme system not expected to occur in humans.1 2

Omega-3 fatty acid-containing preparations shown to increase hepatic concentrations of CYP and activity of certain CYP isoenzymes in rats.1 Potential for omega-3-acid ethyl esters to induce CYP activities in humans not studied.1

Specific Drugs

Drug

Interaction

Comments

Anticoagulants

Concomitant use not adequately studied1 13

Monitor PT/INR periodically during concomitant use1 13

Omacor Pharmacokinetics

Pharmacokinetic data in pediatric patients currently not available.1

Absorption

Bioavailability

EPA and DHA are absorbed systemically following oral administration as ethyl esters.1

Distribution

Extent

Oral administration of omega-3-acid ethyl esters results in substantial, dose-dependent increases in EPA content in serum phospholipids and less substantial, non-dose-dependent increases in DHA content.1 9

Special Populations

Uptake of EPA and DHA into serum phospholipids is independent of age.1 EPA uptake, however, appears to be higher in women than in men.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C); do not freeze.1

Actions

  • EPA and DHA, collectively known as marine-derived omega-3 fatty acids (n-3 fatty acids), are long-chain, polyunsaturated fatty acids (PUFAs) obtained primarily from marine sources such as fatty fish (e.g., herring, mackerel, salmon, sardines, tuna).3 10 12

  • Mechanism of action not completely understood; may inhibit diacylglycerol O-acyltransferase and increase peroxisomal β-oxidation in the liver.1 2

  • May reduce synthesis of triglycerides and VLDL-cholesterol8 in the liver; also may inhibit esterification of other fatty acids.1 2

Advice to Patients

  • Importance of adherence to NCEP's dietary recommendations.1 13

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Omega-3-acid Ethyl Esters

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

1 g

Omacor

Reliant

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lovaza 1GM Capsules (GLAXO SMITH KLINE): 120/$190.99 or 360/$541.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Reliant Pharmaceuticals, Inc. Omacor (omega-3-acid ethyl esters) capsules prescribing information. Liberty Corner, NJ; 2005 Sep.

2. Reliant Pharmaceuticals, Inc. Omacor (omega-3-acid ethyl esters) formulary dossier. Liberty Corner, NJ; 2005 Aug 28.

3. Kris-Etherton PM, Harris WS, Appel LJ et al. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. An American Heart Association Scientific Statement from the Nutrition Committee.Circulation. 2002; 106:2747-57.

4. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From AHA web site.

5. Hooper L, Thompson RL, Harrison RA et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease (Cochrane Review). In: The Cochrane Library. Issue 2, 2005. Chichester, UK: John Wiley & Sons, Ltd.

6. Harris WS, Ginsberg HN, Arunakul N et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997; 4:385-91. [PubMed 9865671]

7. Pownall HJ, Brauchi D, Kilinc C et al. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins. Atherosclerosis. 1999;143:285-97.

8. Anon. Omega-3 polyunsaturated fatty acids (Omacor) for hypertriglyceridemia. Med Lett Drugs Ther. 2005; 47:91-2.

9. Durrington PN, Bhatnagar D, Mackness MI et all. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001; 85:544-8. [PubMed 11303007]

10. Stone NJ. Fish Consumption, fish oil, lipids, and coronary heart disease. An American Heart Association Science Advisory from the Nutrition Committee.Circulation. 1996; 94:2337-40. [PubMed 8901708]

11. Studer M, Briel M, Leimenstoll B et al. Effect of different antilipidemic agents and diets on mortality. Arch Intern Med. 2005; 165:725-30. [PubMed 15824290]

12. Harris WS. Fish oil supplementation: evidence for health benefits. Cleve Clin J Med. 2004;71:208-10, 212, 215-8.

13. Reliant Pharmaceuticals, Liberty Corners, NJ: Personal communication.

14. Chan DC, Watts GF, Barrett PHR et al. Regulatory effects of HMG CoA reductase inhibitor and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes. 2002; 51:2377-86. [PubMed 12145148]

15. Nordoy A, Bonaa KH, Nilsen H et al. Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidemia. J Intern Med. 1998; 243:163-70. [PubMed 9566646]

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