From the Guidelines
Taking a high dose of omega-3 fatty acids (4g per day) requires caution in patients with bleeding risks or those on anticoagulant therapy like warfarin due to potential increased bleeding risk and other side effects. The most frequent adverse effects of prescription omega-3 fatty acid preparations include eructation, dyspepsia, taste perversion for ethyl ester preparations and musculoskeletal pain, peripheral edema, constipation, gout, and AF for IPE 1.
Risks and Considerations
- Patients on anticoagulants, such as warfarin, should consult their healthcare provider before starting high-dose omega-3 supplements due to potential increased bleeding risk.
- Omega-3 fatty acids have antiplatelet effects that can inhibit platelet aggregation and prolong bleeding time, especially at doses above 3g daily.
- For patients on warfarin, omega-3 supplements may enhance warfarin's anticoagulant effect, potentially increasing INR values and bleeding risk.
- If a patient on anticoagulants does take omega-3 supplements, more frequent INR monitoring is recommended, particularly when starting, stopping, or changing the dose.
Potential Side Effects
- Gastrointestinal discomfort
- Fishy aftertaste
- Potential drug interactions with other medications that affect bleeding risk, such as aspirin or NSAIDs
Cardiovascular Considerations
- Multiple randomized controlled trials of prescription ethyl ester and carboxylic acid preparations of DHA and EPA mixtures and pure EPA as IPE at higher doses (1.8 to 4 g daily) have demonstrated an increase in the risk of AF with therapy 1.
- Patients with specific cardiovascular conditions may benefit from prescription-grade omega-3s despite being on anticoagulants, but this requires individualized risk-benefit assessment.
Management
- The management of patients treated with warfarin who require interruption of anticoagulation for surgery or other invasive procedures can be problematic, and several approaches can be taken, according to the risk of thromboembolism 1.
From the FDA Drug Label
5.3 Bleeding Icosapent ethyl is associated with an increased risk of bleeding. In a double-blind, placebo- controlled trial of 8,179 patients, 482 (12%) patients receiving icosapent ethyl experienced a bleeding event compared to 404 (10%) patients receiving placebo. Serious bleeding events occurred in 111 (3%) of patients on icosapent ethyl vs. 85 (2%) of patients receiving placebo The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel, or warfarin. 7.1 Increased Bleeding Risk with Anticoagulants and Antiplatelet Agents Some published studies with omega-3 fatty acids have demonstrated prolongation of bleeding time. The prolongation of bleeding time reported in those studies has not exceeded normal limits and did not produce clinically significant bleeding episodes Monitor patients receiving icosapent ethyl and concomitant anticoagulants and/or antiplatelet agents for bleeding.
The side effects of a prescription strength dose of omega-3 fatty acids 4g a day include:
- Bleeding: Icosapent ethyl is associated with an increased risk of bleeding, with 12% of patients experiencing a bleeding event compared to 10% of patients receiving placebo.
- Serious bleeding events: Occurred in 3% of patients on icosapent ethyl vs. 2% of patients receiving placebo.
- Other adverse reactions (incidence ≥3% on icosapent ethyl and ≥1% more frequent than placebo) included:
- Musculoskeletal pain
- Peripheral edema
- Constipation
- Gout
- Atrial fibrillation Patients on anticoagulant therapy, such as warfarin, may be at increased risk of bleeding when taking icosapent ethyl. It is recommended to monitor patients receiving icosapent ethyl and concomitant anticoagulants and/or antiplatelet agents for bleeding 2.
From the Research
Side Effects of High-Dose Omega-3 Fatty Acids
The use of high-dose omega-3 fatty acids, specifically 4g per day, has been studied in various contexts, including its effects on patients with potential bleeding risks or those on anticoagulant therapy, such as warfarin.
- The active ingredients of omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are responsible for triglyceride lowering 3.
- In patients with triglyceride levels above 500 mg/dl, approximately 4 g/day of EPA and DHA reduces triglyceride levels 45% and very low-density lipoprotein cholesterol levels by more than 50% 3.
- However, the use of omega-3 fatty acids, particularly in high doses, may increase the risk of bleeding in patients taking anticoagulant medications, such as warfarin 4, 5.
- Clinical trial evidence has not supported increased bleeding with omega-3 fatty acid intake, even when combined with other agents that might also increase bleeding (such as aspirin and warfarin) 6.
- A systematic review and meta-analysis of randomized controlled trials found that prescription omega-3 fatty acids were associated with more treatment-related dysgeusia (fishy taste) and skin abnormalities (eruption, itching, exanthema, or eczema) compared with the control group 7.
Risks and Considerations
When considering the use of high-dose omega-3 fatty acids, particularly in patients with potential bleeding risks or those on anticoagulant therapy, several factors should be taken into account:
- The potential antithrombotic effect of fish oils may theoretically increase the risk for bleeding 6.
- The susceptibility of omega-3 fatty acid preparations to undergo oxidation, which contributes to patient intolerance and potential toxicity 6.
- The risks of exposure to environmental toxins and hypervitaminosis with fish consumption are substantially reduced through purification processes used to develop selected concentrated fish oil supplements and prescription preparations 6.
- Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions 4.