Prescription Omega-3 Fatty Acid Products
The prescription omega-3 fatty acid products approved by the FDA for treating hypertriglyceridemia include: icosapent ethyl (IPE), omega-3-acid ethyl esters (brand name Lovaza and generics), and omega-3 carboxylic acids. 1, 2, 3
FDA-Approved Prescription Formulations
The three distinct prescription omega-3 fatty acid formulations available in the United States are:
Icosapent ethyl (IPE): A highly purified ethyl ester of EPA (≥96% eicosapentaenoic acid) that is the only omega-3 product FDA-approved for cardiovascular risk reduction 1, 3
Omega-3-acid ethyl esters: A mixture of EPA and DHA ethyl esters (marketed as Lovaza, Omtryg, and generic equivalents), containing approximately 840 mg of EPA and DHA per 1-gram capsule 2, 3, 4
Omega-3 carboxylic acids: A mixture of omega-3 fatty acids in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (marketed as Epanova) 3
Critical Distinction: Prescription vs. Over-the-Counter Products
Prescription omega-3 products are fundamentally different from over-the-counter fish oil supplements and are not interchangeable. 1
Key differences include:
FDA approval status: Only prescription products are FDA-approved to treat elevated triglycerides; supplements are classified as dietary supplements without FDA approval for this indication 1, 2
Quality and purity: Prescription products undergo rigorous manufacturing processes ensuring consistent content and purity, while supplements may contain impurities, saturated fats, oxidized lipids, contaminants, or additional calories 1
Clinical evidence: Nonprescription fish oil products have not demonstrated cardiovascular outcomes benefits and are not recommended for ASCVD risk reduction 1
Specific Indications by Product Type
Icosapent ethyl (IPE) has the broadest FDA-approved indications 1:
As adjunct to maximally tolerated statin therapy to reduce risk of MI, stroke, coronary revascularization, and unstable angina requiring hospitalization in adults with elevated triglycerides (≥150 mg/dL) AND either established cardiovascular disease OR diabetes mellitus with ≥2 additional cardiovascular risk factors 1
As adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (≥500 mg/dL) 1
Omega-3-acid ethyl esters (Lovaza) and omega-3 carboxylic acids are indicated only 1, 2:
- As adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (≥500 mg/dL) 1, 2
Important Clinical Caveats
Atrial fibrillation risk: Multiple randomized controlled trials have demonstrated increased risk of atrial fibrillation with prescription omega-3 fatty acids at higher doses (1.8-4 g daily), including IPE (3.1% vs 2.1% hospitalization rate, P=0.004 in REDUCE-IT), requiring careful evaluation of net benefit in patients at high risk for AF 1
LDL-C monitoring: Omega-3-acid ethyl ester products may increase LDL-C levels by 5-10%, necessitating periodic monitoring during therapy 5, 2
Dosing: The standard dose for triglyceride lowering is 4 grams per day, which can be taken as a single 4-gram dose or divided into two 2-gram doses 2, 6