Icosapent Ethyl (Monograph)

Brand name: Vascepa
Drug class:

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

Introduction

Antilipemic agent; an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA).^{1 3 4 5 10 11}

Uses for Icosapent Ethyl

Severe Hypertriglyceridemia

Adjunct to dietary therapy to reduce triglyceride concentrations in adults with severe hypertriglyceridemia (triglyceride concentration ≥500 mg/dL).^{1 3 12} Effect on risk of pancreatitis not established.¹

Reductions in triglyceride concentrations not associated with increases in LDL-cholesterol concentrations.^{1 3}

Reduction in Risk of Cardiovascular Events

Adjunct to maximally tolerated hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (i.e., statin) therapy to reduce risk of MI, stroke, coronary revascularization, and unstable angina requiring hospitalization in patients with elevated triglyceride concentrations (≥150 mg/dL) who have either established cardiovascular disease or diabetes mellitus and ≥2 additional risk factors for cardiovascular disease.^{1 13 16 19}

AHA/ACC cholesterol management guidelines state that lifestyle modification is the foundation of atherosclerotic cardiovascular disease (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}

Some clinical practice guidelines state icosapent ethyl is recommended or may be considered in certain patients with ASCVD or risk of ASCVD who have elevated triglyceride concentrations on optimal statin therapy; recommendations based primarily on a cardiovascular outcomes study (REDUCE-IT).^{15 18 21}

Icosapent Ethyl 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 before receiving icosapent ethyl and should continue this diet and exercise regimen during treatment with the drug.¹

Administration

Oral Administration

Administer orally twice daily with food.¹

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

Dosage

Each 1-g capsule contains 1 g of a highly purified (≥96%), esterified form of the omega-3 fatty acid EPA;^{1 3 4 5 10 11} does not contain docosahexaenoic acid (DHA).^{3 11}

Adults

Severe Hypertriglyceridemia

Oral

Vascepa or generics: 4 g daily (administered as four 0.5-g capsules or two 1-g capsules twice daily with food).¹

Reduction in Risk of Cardiovascular Events

Oral

Vascepa: 4 g daily (administered as four 0.5-g capsules or two 1-g capsules twice daily with food) as an adjunct to statin therapy.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Icosapent Ethyl

Contraindications

• Known hypersensitivity (e.g., anaphylactic reaction) to icosapent ethyl or any ingredient in the formulation.¹

Warnings/Precautions

Atrial Fibrillation or Flutter

Risk of atrial fibrillation or flutter requiring hospitalization.¹ Incidence was greater in patients with history of atrial fibrillation or atrial flutter.¹

Allergic Reactions in Patients with Fish Allergy

Contains ethyl esters of the omega-3 fatty acid eicosapentaenoic acid (EPA), which is obtained from fish oil.¹ Not known whether patients with fish and/or shellfish allergies are at increased risk of allergic reactions to the drug.¹

Use with caution in patients with known hypersensitivity to fish and/or shellfish.¹ Inform patients about the potential for allergic reactions, and if any reactions occur, to discontinue the drug.¹

Bleeding

Risk of bleeding, including serious bleeding events.¹ Incidence was greater in patients receiving concomitant antithrombotic agents (e.g., aspirin, clopidogrel, warfarin).¹ Monitor patients receiving such concomitant therapy for bleeding.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 Minor developmental findings observed in some animal reproductive studies.¹

Lactation

Omega-3 fatty acids, including eicosapentaenoic acid (EPA), distribute into human milk.¹ Effects of omega-3 fatty acid ethyl esters on the breast-fed infant or on milk production not known.¹

Consider known benefits of breast-feeding along with mother’s clinical need for icosapent ethyl and any potential adverse effects on the breast-fed child from icosapent ethyl or from underlying maternal condition.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

No overall differences in safety or efficacy observed between geriatric and younger adults.¹

Hepatic Impairment

Not studied in patients with hepatic impairment.¹

Monitor ALT and AST concentrations periodically during therapy in patients with hepatic impairment.¹

Renal Impairment

Not studied in patients with renal impairment.¹

Common Adverse Effects

Adverse effects reported more frequently than placebo in hypertriglyceridemia trials: Arthralgia, oropharyngeal pain.¹

Adverse effects reported in ≥3% of patients receiving icosapent ethyl and occurring more frequently than with placebo in the cardiovascular outcomes trial (REDUCE-IT): Musculoskeletal pain, peripheral edema, constipation, gout, atrial fibrillation.¹

Drug Interactions

CYP isoenzymes play a minor role in metabolism of EPA.¹

Specific Drugs

Icosapent Ethyl Pharmacokinetics

Absorption

Bioavailability

Following oral administration, icosapent ethyl is de-esterified during absorption; the active metabolite, EPA, is absorbed in the small intestine and enters systemic circulation mainly by the thoracic duct lymphatic system.¹

EPA: Peak plasma concentrations achieved approximately 5 hours following oral administration of icosapent ethyl.¹ Steady-state plasma concentrations reached in 7–10 days.⁵

Food

Administered with or following a meal in clinical studies; no food effect studies performed.¹

Special Populations

Gender: Plasma total EPA concentrations not substantially different between men and women.¹

Pediatric patients: Pharmacokinetics not studied.¹

Distribution

Extent

EPA: Majority circulating in plasma is incorporated in phospholipids, triglycerides, and cholesteryl esters; <1% present as unesterified fatty acid.¹

Distributed into milk in rats.^{1 6} (See Lactation under Cautions.)

Plasma Protein Binding

Unesterified EPA: >99%.¹

Elimination

Metabolism

EPA: Mainly metabolized in liver by β-oxidation similar to dietary fatty acids; β-oxidation splits long carbon chain into acetyl-coenzyme A, which is converted into energy via the Krebs cycle.¹

EPA: CYP isoenzymes play a minor role in metabolism of EPA.¹

Elimination Route

Icosapent ethyl: Not renally excreted.¹

Half-life

EPA: Approximately 89 hours.¹

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C).¹

Actions

• Purified preparation of eicosapentaenoic acid (EPA), an omega-3 fatty acid.^{1 3 4 5 10 11}

• EPA is a long-chain, polyunsaturated fatty acid (PUFA) obtained mainly from marine sources such as fatty fish (e.g., herring, mackerel, salmon, sardines, tuna).^{1 7 8 9 10}

• Mechanism by which EPA and other omega-3 fatty acids reduce triglyceride concentrations not completely understood;⁵ EPA may reduce hepatic synthesis and/or secretion of VLDL-triglycerides and enhance triglyceride clearance from circulating VLDL particles.^{1 5}

• May decrease synthesis of VLDL-triglycerides or triglycerides by reducing amount of substrate (fatty acids) available for triglyceride formation (i.e., by increasing β-oxidation, decreasing delivery of free fatty acid to liver, decreasing hepatic lipogenesis, increasing phospholipid synthesis, and/or inhibiting hormone-sensitive lipase in adipose tissue).^{1 5}

• Also may reduce synthesis of triglycerides by limiting activity of key triglyceride-synthesizing enzymes (e.g., diacylglycerol O-acyltransferase, phosphatidate phosphatase).^{1 5}

• May enhance activity of lipoprotein lipase in peripheral adipose tissue, resulting in increased peripheral conversion of VLDL particles to LDL particles.⁵

• Mechanism of action in reducing risk of atherosclerotic cardiovascular disease (ASCVD) not clear, but likely multifactorial (e.g., membrane stabilizing, anti-inflammatory, antithrombotic, and antiarrhythmic effects; reduction in coronary plaque progression).^{1 13 17 20}

Advice to Patients

• Advise patient to read the FDA-approved patient labeling before starting icosapent ethyl (Patient Information).¹

• Inform patients that icosapent ethyl may increase their risk for atrial fibrillation or atrial flutter.¹

• Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions to icosapent ethyl and advise them to discontinue the drug and seek medical attention if any reactions occur.¹

• Inform patients that icosapent ethyl may increase their risk for bleeding, especially if they are receiving other antithrombotic agents.¹

• Advise patients to swallow capsules whole and not break, crush, dissolve, or chew capsules.¹

• Importance of taking icosapent ethyl as prescribed.¹ If a dose is missed, take the dose as soon as it is remembered.¹ If one day of 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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

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