Omega-3-acid Ethyl Esters (Monograph)

Brand name: Lovaza
Drug class: Omega-3-mediated Antilipemics

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

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

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).^{1 2 8 21} Efficacy in reducing risk of pancreatitis or risk of cardiovascular morbidity or mortality not established.^{1 2 8}

Has been used as monotherapy to reduce high (200–499 mg/dL) triglyceride concentrations^{† [off-label]} in adults.^{2 13} However, because most of these patients are expected to receive statins as initial therapy,^{2 4} efficacy should be further evaluated in patients receiving concomitant statin therapy.² Additive effects on reduction of triglyceride and VLDL-cholesterol concentrations observed when used with statins.^{2 8 9 13 14 15}

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^{† [off-label]} or secondary prevention^{† [off-label]} of atherosclerotic cardiovascular disease (ASCVD).^{3 4 5 10}

AHA/ACC cholesterol management guidelines state that lifestyle modification is the foundation of ASCVD risk reduction.⁴⁰⁰ If pharmacologic therapy is needed, statins are first-line drugs of choice.⁴⁰⁰

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.^{13 15 18}

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.^{19 20} However, results of this study should not be generalized to other omega-3 fatty acid preparations containing EPA and DHA.¹⁹

Omega-3-acid Ethyl Esters Dosage and Administration

General

Pretreatment Screening

• Assess lipoprotein profile before initiating therapy.¹ Identify and manage other causes of hypertriglyceridemia (e.g., diabetes mellitus, hypothyroidism, current drug therapy) as appropriate.¹

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).⁴⁰⁰

• Periodically reinforce adherence to lifestyle modifications.⁴⁰⁰ 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.¹

Administration

Oral Administration

Lovaza was administered with meals in clinical studies.^{1 2 8}

Swallow capsules whole; do not break, crush, dissolve, or chew.¹

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 21}

Adults

Severe Hypertriglyceridemia

Oral

4 g daily (administered as a single dose or in 2 equally divided doses).^{1 2 8 21}

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.^{1 16}

Warnings/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., increases in LDL-cholesterol concentrations).¹

In patients with hepatic impairment, monitor ALT and AST concentrations periodically during therapy.¹

Allergic Reactions in Patient with Fish Allergy

Obtained from the oil of several fish sources.¹ 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.^{1 13}

Anaphylactic reactions reported during postmarketing experience.¹

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.^{1 16 17} 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.^{1 16}

Not indicated for treatment of atrial fibrillation or flutter.¹

Specific Populations

Pregnancy

Available data insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.¹

No teratogenic or adverse developmental effects observed in animal reproduction studies.¹

Lactation

Distributed into milk; possible effects on nursing infants unknown.¹ Caution if used in nursing women.^{1 16}

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

Experience in patients >65 years of age is limited.¹ No substantial differences in safety and efficacy observed between patients >60 years of age and younger patients.¹

Hepatic Impairment

Monitor ALT and AST concentrations periodically.¹

Common Adverse Effects

Eructation,^{1 8} dyspepsia,^{1 8 16} taste perversion.^{1 8}

Drug Interactions

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.^{2 13} 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.^{1 2}

Specific Drugs

Omega-3-acid Ethyl Esters Pharmacokinetics

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

Pharmacokinetics not studied in pediatric patients or patients with renal or hepatic impairment.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, increase mitochondrial and peroxisomal β-oxidation in the liver, decrease lipogenesis in the liver, and increase plasma lipoprotein lipase activity.^{1 2 16}

• 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 adhering to standard cholesterol-lowering diet.^{1 13}

• Risk of hypersensitivity.¹ Advise patients to use the drug with caution if they have known hypersensitivity to fish and/or shellfish.¹

• Importance of swallowing omega-3-acid ethyl esters capsules whole; do not break, crush, dissolve, or chew capsules.¹

• Importance of taking omega-3-acid ethyl esters as prescribed.¹ If a dose is missed, take the dose as soon as it is remembered.¹ If one day of omega-3-acid ethyl esters therapy is missed, do not double the dose.¹

• 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.

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

Frequently asked questions

• Lovaza vs. Vascepa - What's the difference between them?

Medical Disclaimer