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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
Brands: Lovaza

Medically reviewed by Drugs.com on Oct 4, 2021. Written by ASHP.

Introduction

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

Uses for Omega-3-acid Ethyl Esters

Severe Hypertriglyceridemia

Adjunct to dietary therapy to reduce triglyceride concentrations in adults with severe hypertriglyceridemia (triglyceride concentration ≥500 mg/dL). Efficacy in reducing risk of pancreatitis or risk of cardiovascular morbidity or mortality not established.

Has been used as monotherapy to reduce high (200–499 mg/dL) triglyceride concentrations in adults. However, because most of these patients are expected to receive statins as initial therapy, efficacy should be further evaluated in patients receiving concomitant statin therapy. Additive effects on reduction of triglyceride and VLDL-cholesterol concentrations observed when used with statins.

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

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 atherosclerotic cardiovascular disease (ASCVD).

AHA/ACC cholesterol management guidelines state that lifestyle modification is the foundation of ASCVD risk reduction. If pharmacologic therapy is needed, statins are first-line drugs of choice.

Hypertriglyceridemia is an independent risk factor for ASCVD; some patients with elevated triglyceride concentrations despite adequate treatment with a statin may benefit from a triglyceride-lowering agent.

In a cardiovascular outcomes study, use of an omega-3 fatty acid preparation containing EPA only reduced ASCVD risk in statin-treated patients with hypertriglyceridemia (fasting levels of 135–499 mg/dL) who had established ASCVD or were at high risk of ASCVD. However, results of this study should not be generalized to other omega-3 fatty acid preparations containing EPA and DHA.

Omega-3-acid Ethyl Esters Dosage and Administration

General

    Pretreatment Screening
  • Assess lipoprotein profile before initiating therapy. Identify and manage other causes of hypertriglyceridemia (e.g., diabetes mellitus, hypothyroidism, current drug therapy) as appropriate.

    Other General Considerations
  • Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modification therapies that reduce the risk of atherosclerotic cardiovascular disease (ASCVD).

  • Periodically reinforce adherence to lifestyle modifications. Manufacturer states that patients should be placed on a standard lipid-lowering diet and exercise regimen prior to initiating the drug and should continue this diet and exercise regimen during treatment.

Administration

Oral Administration

Lovaza was administered with meals in clinical studies.

Swallow capsules whole; do not break, crush, dissolve, or chew.

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).

Adults

Severe Hypertriglyceridemia
Oral

4 g daily (administered as a single dose or in 2 equally divided doses).

Cautions for Omega-3-acid Ethyl Esters

Contraindications

  • Known hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters or any ingredient in the formulation.

Warnings/Precautions

Laboratory Monitoring

Prior to initiating therapy, evaluate lipoprotein profiles to confirm the presence of persistent hypertriglyceridemia. During therapy, obtain lipoprotein profiles periodically to monitor clinical response (i.e., reduction in triglyceride concentrations) or adverse effects (i.e., increases in LDL-cholesterol concentrations).

In patients with hepatic impairment, monitor ALT and AST concentrations periodically during therapy.

Allergic Reactions in Patient with Fish Allergy

Obtained from the oil of several fish sources. Not known whether patients with hypersensitivity to fish and/or shellfish are at increased risk of allergic reactions; therefore, use with caution in such patients.

Anaphylactic reactions reported during postmarketing experience.

Atrial Fibrillation or Flutter

Recurrent atrial fibrillation or flutter reported in patients with symptomatic paroxysmal or persistent atrial fibrillation receiving omega-3-acid ethyl esters. Clinical importance unknown; however, possible association between use of the drug and more frequent recurrences of symptomatic atrial fibrillation or flutter in such patients, especially within 2–3 months of initiation of therapy.

Not indicated for treatment of atrial fibrillation or flutter.

Specific Populations

Pregnancy

Available data insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

No teratogenic or adverse developmental effects observed in animal reproduction studies.

Lactation

Distributed into milk; possible effects on nursing infants unknown. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Experience in patients >65 years of age is limited. No substantial differences in safety and efficacy observed between patients >60 years of age and younger patients.

Hepatic Impairment

Monitor ALT and AST concentrations periodically.

Common Adverse Effects

Eructation, dyspepsia, taste perversion.

Interactions for Omega-3-acid Ethyl Esters

Drugs Metabolized by Hepatic Microsomal Enzymes

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

Specific Drugs

Drug

Interaction

Comments

Anticoagulants

Concomitant use not adequately studied

Monitor PT/INR periodically during concomitant use

Antiplatelet agents

Monitor coagulation status periodically during concomitant use

HMG-CoA reductase inhibitors (statins) (i.e., atorvastatin, rosuvastatin, simvastatin)

No effect on peak concentration or AUC of statins and their metabolites

Omega-3-acid Ethyl Esters Pharmacokinetics

Absorption

Bioavailability

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

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.

Special Populations

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

Pharmacokinetics not studied in pediatric patients or patients with renal or hepatic impairment.

Stability

Storage

Oral

Capsules

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

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).

  • Mechanism of action not completely understood; may inhibit diacylglycerol O-acyltransferase, increase mitochondrial and peroxisomal β-oxidation in the liver, decrease lipogenesis in the liver, and increase plasma lipoprotein lipase activity.

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

Advice to Patients

  • Importance of adhering to standard cholesterol-lowering diet.

  • Risk of hypersensitivity. Advise patients to use the drug with caution if they have known hypersensitivity to fish and/or shellfish.

  • Importance of swallowing omega-3-acid ethyl esters capsules whole; do not break, crush, dissolve, or chew capsules.

  • Importance of taking omega-3-acid ethyl esters as prescribed. If a dose is missed, take the dose as soon as it is remembered. If one day of omega-3-acid ethyl esters therapy is missed, do not double the dose.

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Omega-3-acid Ethyl Esters

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

1 g*

Lovaza

GlaxoSmithKline

Omega-3-acid Ethyl Esters Capsules

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 4, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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