Are there prescription eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) available for medical conditions?

Prescription EPA and DHA Products

Yes, prescription formulations of EPA and/or DHA are FDA-approved and available in the United States for treating severe hypertriglyceridemia (≥500 mg/dL), with icosapent ethyl being the only omega-3 preparation also approved for cardiovascular risk reduction. 1

Available Prescription Formulations

Three distinct prescription omega-3 fatty acid products are FDA-approved in the United States:

• Omega-3 acid ethyl esters (OM3EE) - Contains a mixture of EPA and DHA ethyl esters (marketed as Lovaza®, Omtryg™, and generics) 2, 3

• Icosapent ethyl (IPE) - Contains only EPA ethyl esters (marketed as Vascepa®), which is unique as the sole prescription omega-3 approved for both severe hypertriglyceridemia and cardiovascular risk reduction 1, 2

• Omega-3 carboxylic acids (OM3CA) - Contains EPA, DHA, and docosapentaenoic acid in free fatty acid form (marketed as Epanova®) 2

FDA-Approved Indications

For severe hypertriglyceridemia (≥500 mg/dL):

• All three prescription formulations are approved as adjunct to diet for reducing triglyceride levels in adults with severe hypertriglyceridemia 1, 2
• The standard dose is 4 grams per day, which reduces triglycerides by 25-30% or more 4, 2, 3

For cardiovascular risk reduction:

• Only icosapent ethyl is FDA-approved as adjunct to maximally tolerated statin therapy to reduce risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adults with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease or diabetes with multiple risk factors 1

Critical Distinction from Over-the-Counter Products

Prescription omega-3 products are NOT interchangeable with over-the-counter fish oil supplements:

• Over-the-counter supplements have variable content and quality, may contain impurities or contaminants, and are not subject to FDA pharmaceutical standards for safety, efficacy, and purity 4, 5, 6

• Non-prescription products are not FDA-approved for treating elevated triglycerides and are not recommended for cardiovascular risk reduction 4

• The American Heart Association advises that therapy with EPA and DHA to lower very high triglyceride levels should be used only under a physician's care with prescription products 3

Dosing and Administration

• The daily dose is 4 grams per day taken as either four 0.5 gram capsules twice daily with food OR two 1 gram capsules twice daily with food 1

• Capsules must be swallowed whole and should not be broken, crushed, dissolved, or chewed 1

• Patients should engage in appropriate nutritional intake and physical activity before and during treatment 1

Important Safety Considerations

Atrial fibrillation risk:

• The American College of Cardiology notes that increased risk of atrial fibrillation is associated with higher doses (1.8-4 g daily) of prescription omega-3 preparations 4
• In clinical trials, icosapent ethyl was associated with a 50% increased risk of atrial fibrillation or atrial flutter requiring hospitalization (3% vs 2% with placebo), with greater incidence in patients with previous history of atrial arrhythmias 1

Bleeding risk:

• Icosapent ethyl is associated with increased bleeding risk (12% vs 10% with placebo), with serious bleeding events occurring in 3% vs 2% of patients 1
• Risk is greater in patients receiving concomitant antithrombotic medications such as aspirin, clopidogrel, or warfarin 1

Fish allergy:

• Patients with known hypersensitivity to fish and/or shellfish should be informed about potential allergic reactions and advised to discontinue and seek medical attention if reactions occur 1

Effects on Lipid Profile

• EPA+DHA formulations reduce triglycerides by ≥30% at 4 g/day but may increase LDL-C by 5-10% in patients with very high triglycerides 2, 7

• EPA-only (icosapent ethyl) did not raise LDL-C in patients with very high triglycerides 7

• When used for moderate hypertriglyceridemia (150-499 mg/dL), neither EPA+DHA nor EPA-only increase LDL-C when used as monotherapy or combined with statins 7

• Both formulations modestly decrease non-HDL cholesterol and apolipoprotein B, indicating reductions in total atherogenic lipoproteins 7

Guideline-Based Treatment Algorithm

For triglycerides 150-499 mg/dL:

• Implement lifestyle modifications and consider statin therapy based on cardiovascular risk 4
• Consider icosapent ethyl if triglycerides remain elevated despite statin therapy, particularly in patients with established cardiovascular disease or diabetes with additional risk factors 4

For triglycerides ≥500 mg/dL:

• Implement aggressive lifestyle modifications with very-low-fat diet (10-15% of calories from fat) 4
• Add prescription omega-3 fatty acids at 4 g/day 4, 7

For triglycerides ≥1,000 mg/dL:

• Implement extreme dietary fat restriction (<5% of calories) until levels decrease to <1,000 mg/dL 4
• Add prescription omega-3 fatty acids and consider fibrate therapy 4
• Address secondary causes aggressively 4

Monitoring Requirements

• Assess lipid levels before initiating therapy and identify other causes of hypertriglyceridemia 1
• Monitor for gastrointestinal disturbances, skin changes, and bleeding when EPA and/or DHA are used for severe hypertriglyceridemia 8
• Periodic monitoring of LDL-C is required as levels may increase by 5-10% with EPA+DHA formulations 2