Icosapent Ethyl

Icosapent Ethyl is approved for the following uses:

• Severe Hypertriglyceridemia: As an adjunct to diet to reduce triglyceride levels in adult patients with fasting triglycerides ≥500 mg/dL.
• Cardiovascular Risk Reduction: In combination with maximally tolerated statin therapy to reduce the risk of cardiovascular events (including myocardial infarction, stroke, coronary revascularization, and cardiovascular death) in adults with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease or diabetes mellitus with additional risk factors.

Off-label Uses:

• Investigational uses include other lipid disorders and inflammatory conditions; these are not approved indications.

Adults:

• Recommended dose: 2 grams orally twice daily with meals (total daily dose 4 grams).

Pediatrics:

• Safety and efficacy have not been established in pediatric populations.

Elderly:

• No dose adjustment is required based on age alone.

Renal Impairment:

• No dosage adjustment is necessary for patients with mild to moderate renal impairment. Limited data in severe impairment; caution advised.

Hepatic Impairment:

• Not recommended in patients with severe hepatic impairment. Use cautiously in mild to moderate hepatic dysfunction.

Administration Instructions:

• Swallow capsules whole with food to enhance absorption.
• Capsules should not be crushed, chewed, or broken.

Duration:

• Continue treatment as long as clinically indicated and tolerated.

Icosapent Ethyl is a purified ethyl ester of eicosapentaenoic acid (EPA), an omega-3 fatty acid. It lowers serum triglyceride levels by reducing hepatic triglyceride synthesis and increasing triglyceride clearance from plasma through decreased very-low-density lipoprotein (VLDL) production. EPA also exhibits anti-inflammatory, plaque-stabilizing, and anti-thrombotic effects, which contribute to the reduction of cardiovascular risk beyond triglyceride lowering.

• Absorption: Rapid oral absorption with peak plasma EPA concentrations at approximately 5 hours post-dose when taken with food.
• Bioavailability: Food significantly enhances absorption; thus, administration with meals is recommended.
• Distribution: Incorporated into plasma lipids and cellular membranes, particularly in cardiovascular tissues.
• Metabolism: Primarily metabolized via beta-oxidation in the liver; minimal cytochrome P450 involvement.
• Half-life: Approximately 89 hours for total EPA after multiple dosing.
• Excretion: Eliminated mainly through urinary excretion of metabolites.

• Pregnancy: No assigned FDA pregnancy category. Limited human data; animal studies have not demonstrated fetal harm at therapeutic doses. Use only if benefits outweigh risks.
• Lactation: It is unknown whether icosapent ethyl or its metabolites are excreted in human milk. Caution is advised when administering to breastfeeding mothers.

• Primary Class: Lipid-regulating agent
• Subclass: Omega-3 fatty acid ethyl ester

• Known hypersensitivity to icosapent ethyl, eicosapentaenoic acid (EPA), or any formulation components.
• Precaution advised in patients with fish or shellfish allergies due to source of EPA.

• Bleeding Risk: May increase bleeding tendency, particularly in patients receiving anticoagulants or antiplatelet therapy; monitor accordingly.
• Atrial Fibrillation/Flutter: Increased incidence reported; monitor patients with history of arrhythmias.
• Hypersensitivity Reactions: Allergic reactions may occur; discontinue if severe.
• Hepatic Effects: Monitor liver function tests during prolonged therapy, especially in patients with hepatic impairment.
• Lipid Changes: May cause increases in LDL cholesterol; monitor lipid profile regularly.

Common Adverse Effects:

• Arthralgia (joint pain)
• Peripheral edema
• Constipation
• Diarrhea
• Extremity pain
• Back pain

Serious but Rare Adverse Effects:

• Atrial fibrillation or flutter
• Hypersensitivity reactions
• Bleeding complications

Adverse effects are generally mild to moderate and tend to appear early in treatment.

• Anticoagulants and Antiplatelets: May increase bleeding risk; close monitoring recommended.
• Statins: No significant interaction; commonly co-administered.
• CYP450 Substrates: Minimal interaction potential due to negligible CYP metabolism.
• Other Lipid-Lowering Agents: Generally safe; monitor for efficacy and tolerance.
• Alcohol: No specific interactions, though alcohol may exacerbate hypertriglyceridemia.

• Cardiovascular outcome studies have confirmed the benefit of icosapent ethyl added to statin therapy in reducing major adverse cardiovascular events in high-risk patients with elevated triglycerides.
• Regulatory agencies have expanded indications to include cardiovascular risk reduction in appropriate populations.
• Clinical guidelines now recommend considering icosapent ethyl for patients with elevated triglycerides and established cardiovascular disease despite statin use.
• Updated safety warnings highlight bleeding and atrial fibrillation risks necessitating clinical vigilance.

• Store at 20°C to 25°C (68°F to 77°F); excursions allowed between 15°C and 30°C (59°F to 86°F).
• Protect from moisture and light.
• Keep capsules in original container tightly closed.
• Do not freeze.
• Keep out of reach of children.