Introduction
Vascepa (icosapent ethyl) is a prescription medication containing a highly purified omega-3 fatty acid derived from fish oil. It is the first FDA-approved prescription-grade omega-3 product indicated specifically for cardiovascular risk reduction in conjunction with statin therapy. Unlike other omega-3 preparations, Vascepa contains ≥96% pure eicosapentaenoic acid (EPA) with minimal docosahexaenoic acid (DHA) content.
Mechanism of Action
Vascepa's primary active component, icosapent ethyl, is hydrolyzed to EPA, which incorporates into phospholipid membranes and exerts multiple cardioprotective effects. Its mechanisms include:
- Reduction of hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and secretion
- Inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, decreasing triglyceride synthesis
- Increased β-oxidation of fatty acids in the liver
- Anti-inflammatory effects through reduced production of pro-inflammatory eicosanoids
- Enhanced plaque stability through reduced macrophage uptake and foam cell formation
Indications
FDA-approved indications:
- Severe hypertriglyceridemia (≥500 mg/dL) as an adjunct to diet
- Cardiovascular risk reduction in adults with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease or diabetes mellitus plus ≥2 additional risk factors
Dosage and Administration
Standard dosing: 2 g twice daily or 4 g once daily with food Formulation: 1 g capsules Administration: Should be taken with meals to enhance absorption Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution in severe impairment
- Pediatric: Safety and effectiveness not established
- Geriatric: No dosage adjustment required
Pharmacokinetics
Absorption: Bioavailability increased approximately 3-fold when administered with a high-fat meal Distribution: EPA incorporates into phospholipid membranes; highly protein-bound Metabolism: Undergoes extensive β-oxidation in the liver similar to dietary fatty acids Elimination: Primarily excreted as carbon dioxide via respiration; half-life approximately 89 hours Steady-state: Achieved within 1-2 weeks of regular dosingContraindications
- Known hypersensitivity to icosapent ethyl or any component of the formulation
- Patients with demonstrated hypersensitivity to fish and/or shellfish
Warnings and Precautions
Atrial Fibrillation/Flutter: Increased risk observed in patients with cardiovascular disease or diabetes with risk factors Bleeding Risk: Potential increased risk of bleeding, particularly in patients receiving concomitant anticoagulants Liver Function: Monitor ALT and AST levels periodically during therapy Allergic Reactions: Possible in patients with fish or shellfish allergies Pancreatitis: Has not been shown to reduce the risk of pancreatitis in patients with severe hypertriglyceridemiaDrug Interactions
Anticoagulants/Antiplatelets: May potentiate effects of warfarin, apixaban, rivaroxaban, aspirin, and clopidogrel (monitor bleeding parameters) Other Omega-3 Products: Avoid concomitant use due to potential additive effects Cytochrome P450 Substrates: Unlikely to cause clinically significant interactionsAdverse Effects
Common (≥2% and >placebo):- Arthralgia (2.3%)
- Peripheral edema (2.1%)
- Constipation (2.0%)
- Atrial fibrillation (1.9%)
- Atrial fibrillation/flutter requiring hospitalization
- Significant bleeding events
- Hepatic enzyme elevations
Monitoring Parameters
- Fasting lipid panel (triglycerides, LDL-C, non-HDL-C) at baseline and 4-8 weeks after initiation
- Liver function tests (ALT, AST) at baseline and periodically during treatment
- Hemoglobin A1c in diabetic patients
- Signs/symptoms of atrial fibrillation (palpitations, dizziness, dyspnea)
- Bleeding parameters in patients on concomitant anticoagulation
- Allergic reactions in susceptible patients
Patient Education
- Take with meals to improve absorption and reduce gastrointestinal side effects
- Do not substitute with other omega-3 fatty acid products
- Report any signs of unusual bleeding or bruising
- Monitor for symptoms of atrial fibrillation (heart palpitations, dizziness)
- Continue adherence to prescribed diet and exercise regimen
- Inform all healthcare providers about Vascepa use, especially before surgical procedures
- Store at room temperature; protect from light and moisture
References
1. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. 2. Vascepa [package insert]. Bridgewater, NJ: Amarin Pharma Inc.; 2021. 3. Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011;108(5):682-690. 4. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups. US Food and Drug Administration. December 13, 2019. 5. Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330-343.