Icosapent Ethyl - Warnings, Precautions, Side Effects, and Dosage

What Is Icosapent Ethyl?

Icosapent ethyl is a purified preparation of the eicosapentaenoic acid (EPA). This is an omega-3 fatty acid.

The drug is indicated in the following situations:

• As adjunctive therapy to statin therapy for the reduction of stroke risk, myocardial infarction (heart attack), coronary revascularization (stenting or bypass), and unstable angina (chest pain) that necessitates hospitalization in adults who also display increased triglyceride levels (more than or equal to 150 mg/dL), and any of the following:

• Cardiovascular disease.

• Diabetes mellitus, and at least two other risk factors for cardiovascular disease.

• Dietary supplement for people with severe hypertriglyceridemia (≥ 500 mg/dL) to lower their triglyceride levels.

Icosapent ethyl works by reducing the amount of triglycerides and fats produced by the liver.

The drug was approved by the United States Food and Drug Administration (FDA) in July 2012 for the management of severe hypertriglyceridemia.

How Does Icosapent Ethyl Work?

Icosapent ethyl is an ethyl ester of eicosapentaenoic acid (EPA). Its action is facilitated by the actions of the EPA. EPA reduces the synthesis or secretion of triglycerides made in the liver, specifically the very low-density lipoprotein triglycerides (VLDL-TG). It also increases the clearance and removal of triglycerides from very low-density lipoprotein particles circulating in the blood.

• Ethyl Ester:

An ethyl ester is produced by reacting ethanol and industrial alcohol with crude fish oil (in free fatty acid form) to produce a synthetic substrate that is heat-distilled under a vacuum. The resulting solution is a concentrated omega-3 ethyl ester solution.

• Eicosapentaenoic Acid (EPA):

An omega-3 fatty acid found in fatty fish like salmon and in fish-oil supplements, along with docosahexaenoic acid (DHA).

Dosage Restrictions

Route of Administration:

Oral.

Dosage Form:

Amber-colored, liquid-filled soft gelatin capsules.

Available Strengths:

• 0.5 gm (grams) capsules.

• 1 gm capsules.

Special Considerations:

• Pancreatitis Risk:

The risk of pancreatitis (inflammation of the pancreas) in patients with severe triglyceridemia who consume Icosapent ethyl is unknown and, therefore, a matter of concern.

• Bleeding:

Patients on Icosapent ethyl and concomitant anticoagulants and antiplatelets should be closely monitored for prolonged bleeding time.

Warnings and Contraindications

Contraindications:

Icosapent ethyl is contraindicated in patients who display hypersensitivity to the drug itself or to any of the components in the formulation.

Warnings and Precautions:

• Allergic Reactions:

Patients with a known allergy to fish or shellfish may develop allergies on consumption of Icosapent ethyl, as it contains ethyl esters of the eicosapentaenoic acid (EPA) derived from fish oil.

• Atrial Fibrillation or Flutter:

Icosapent ethyl is interlinked with an elevated risk of atrial fibrillation (abnormal heart rhythm) or flutter, particularly in patients with a previous history of either condition. There may be a need for hospitalization in these patients.

• Bleeding:

An increased risk of bleeding has been noted with the administration of Icosapent ethyl, especially in patients taking antithrombotic medicines like Aspirin, Warfarin, and Clopidogrel.

For Patients

What Are Triglycerides?

Triglycerides are a kind of fat found in the blood. The body converts calories you do not immediately need from the food you eat into triglycerides, making them the main constituents of fat in the body.

What Is Hypertriglyceridemia?

An excessively high level of triglycerides in the blood is referred to as hypertriglyceridemia.

What Does a High Triglyceride Level Indicate?

High triglyceride levels usually occur due to obesity, unhealthy dietary patterns, substance abuse, disorders like uncontrolled diabetes, kidney disease, hypothyroidism, and genetics. They usually point to an increased risk of heart conditions and stroke.

Why Is Icosapent Ethyl Prescribed for Increased Triglyceride Levels or Hypertriglyceridemia?

Icosapent ethyl lowers triglyceride levels in two ways:

• Lowers triglyceride production in the liver.

• It increases the removal of triglycerides from the blood.

Icosapent ethyl may be used as a dietary adjunct in patients with hypertriglyceridemia.

Facts You Should Know About Icosapent Ethyl

Icosapent ethyl is available in capsule form and should be taken twice daily, with a total daily dose of 4 g. Always take the drug with food.

How Should You Take Icosapent Ethyl?

• Take Icosapent ethyl twice daily as prescribed by the doctor.

• Never attempt to change the dose or stop taking the drug without your doctor’s consent. If you are having any difficulties or experiencing side effects, let the doctor know.

• Swallow the capsules whole. Do not chew, break open, crush, or dissolve them.

• If you miss a dose, take it when you do remember. However, never attempt to double-dose if you miss a day of taking the drug.

• If your doctor prescribes dietary changes before starting the drug, make sure to follow the instructions correctly.

Checklist for Patient Safety:

• Allergies:

Look for sensitivities to fish or shellfish.

• Medication:

Enumerate all vitamins and blood thinners.

• Family:

Talk about intentions for breastfeeding or pregnancy.

Is Icosapent Ethyl Safe?

Icosapent ethyl is relatively safe but may cause severe side effects in some people. Patients experiencing side effects must contact their doctor immediately, who will decide on alternative treatment options or other solutions.

Is Icosapent Ethyl Effective?

4 gms of Icosapent ethyl per day has been shown to effectively reduce median triglyceride, very low-density lipoprotein-cholesterol (VLDL-C), and apolipoprotein B (Apo B) levels compared with placebo.

What Are the Side Effects of Icosapent Ethyl?

The side effects you are most likely to include are the following:

• Muscle pain.

• Joint pain.

• Gout.

• Constipation.

• Swelling of the hands, legs, and feet.

• Excessive bleeding, especially if you are already taking blood thinners.

• Problems with the heart rhythm (atrial fibrillation or flutter).

• If you develop an allergy to fish (shellfish), there is a high possibility of an allergy to Icosapent ethyl.

Can You Stop Taking Icosapent Ethyl Without Your Doctor's Advice?

• Do not stop taking Icosapent ethyl without your doctor’s approval. The only time you may stop taking the drug with immediate effect is if you experience severe side effects such as allergies or excessive bleeding.

• Make sure to contact your physician or emergency services for any side effects or in case of an emergency.

Are There Any Dietary Restrictions to Consider When Taking Icosapent Ethyl?

Your doctor may ask you to modify your diet in the following ways before starting Icosapent ethyl:

• Less saturated fat content.

• Less cholesterol content.

• Fewer carbohydrates.

• Reduced intake of added sugars.

Also, always remember to take Icosapent ethyl with food.

Should You Undergo Any Tests or Laboratory Investigations Before Starting Icosapent Ethyl?

You may need blood tests to check triglyceride and other lipid levels before starting Icosapent ethyl treatment.

How Should You Store and Dispose of Icosapent Ethyl?

• Icosapent ethyl should be stored at room temperature between 68° and 77° Fahrenheit (20° to 25° C or degrees Celsius).

• Store the capsules in the same container that they are sold in, and keep the lid tightly closed.

What Can You Do in Case of Overdose?

High doses of Icosapent ethyl may cause serious side effects like irregular heartbeats and severe bleeding. If an overdose occurs, immediately consult the local poison helpline or visit the emergency room or a physician. Immediate medical attention is a must.

For Doctors:

Pharmacology

Description:

Icosapent ethyl is an ethyl ester of eicosapentaenoic acid (EPA), an omega-3 fatty acid. It has the empirical formula C22H34O2, and a molecular weight of 330.51.

Components:

• Active Components:

  • 0.5 gm Capsule: 0.5 gms Icosapent ethyl.

  • 1.0 gm Capsule: 1 gm Icosapent ethyl.

• Inactive Components:

  • Tocopherol.

  • Gelatin.

  • Glycerin.

  • Maltitol.

  • Sorbitol.

  • Purified water.

Clinical Pharmacology

Mechanism of Action:

Icosapent ethyl is an ethyl ester of eicosapentaenoic acid (EPA), an omega-3 fatty acid. EPA is known to perform the following actions:

• Reduces the synthesis or secretion of very low-density lipoprotein triglycerides (VLDL-TG) in the liver.

• Enhances the clearance of triglycerides from circulating VLDL particles.

How these actions are performed may include the following:

• Increased beta-oxidation.

• Inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT).

• Reduced lipogenesis in the liver.

• Increased activity of plasma lipoprotein lipase.

EPA may also inhibit platelet aggregation in ex vivo (outside the living body) conditions.

Pharmacodynamics:

Patients with severe hypertriglyceridemia who were on Icosapent ethyl 4 g per day in a dose-ranging study for 12 weeks displayed reduced median TG from baseline relative to placebo.

Pharmacokinetics:

• During absorption, Icosapent ethyl de-esterifies into the active metabolite EPA, functioning as a prodrug. Through the thoracic duct, it enters the systemic circulation and reaches its maximal plasma concentration in five hours.

• For best absorption, it must be taken with food. EPA has a broad distribution and more than 99% protein binding. It is mainly broken down in the liver via beta-oxidation, which uses the Krebs cycle to produce energy by metabolizing dietary fatty acids.

• With a half-life of 89 hours and a clearance rate of 684 mL/hr (milliliter per hour), elimination is sluggish. The absence of renal excretion is noteworthy.

Special Considerations:

• Gender:

No significant variations have been noted in the total plasma EPA concentrations between men and women.

• Hepatic Impairment:

No data exist on the pharmacological effects in patients with hepatic impairment.

• Renal Impairment:

No data exist on the pharmacological effects in patients with renal impairment.

• Pediatric Population:

No data exist on the pharmacokinetic effects of Icosapent ethyl in children.

Drug Interactions:

No significant drug interactions or changes in the steady-state area under the curve of dosing interval (AUCτ) or Cmax have occurred with the concurrent administration of Icosapent ethyl and the following drugs:

• Warfarin.

• Omeprazole.

• Rosiglitazone.

• Atorvastatin.

Cmax:

The maximum serum concentration achieved by a drug after administration, and before the second dose administration.

Clinical Trials

High-dose icosapent ethyl dramatically lowers cardiovascular risk in patients with increased triglycerides, according to the study. Compared with placebo, 4g of icosapent ethyl daily reduced the primary composite endpoint (CV mortality, MI, stroke, revascularization, or unstable angina) by 25% in this double-blind study with 8,179 participants.

There was also a 26% decrease in important secondary events, such as stroke and CV death. Although your description omitted particular adverse effects, the experiment notoriously reported that the treatment group experienced a greater frequency of atrial fibrillation and mild hemorrhage than the mineral oil placebo.

Patient Counseling Information:

Administration Instructions:

• The capsules must be swallowed whole, not broken, chewed, crushed, or dissolved.

• Advise patients to use Icosapent ethyl only for the condition prescribed, and never to share the drug with anyone else for any illness, unless prescribed by the doctor.

Complications or Side Effects:

• Hypersensitivity:

Inform patients with known hypersensitivity to the components of the drug, or with allergies to fish or shellfish, of the possibility of developing allergic reactions.

• Bleeding:

Severe bleeding may develop, especially in patients taking antithrombotic drugs. They must therefore be made aware of this side effect.

• Atrial Fibrillation or Flutter:

Patients may develop issues with their heart rhythm (atrial fibrillation or flutter) and must be warned of the same.

• Pregnancy:

The effects of the drug on pregnancy are unknown, so patients should be advised to report pregnancy or plans for pregnancy if they take Icosapent ethyl.

• Lactation:

Icosapent ethyl may be present in breast milk and harm babies, so you must inform your physician if you are breastfeeding.