Omega-3 Marine Triglycerides

Usage

Omega-3 marine triglycerides are primarily prescribed as an adjunct to diet and exercise for adults with very high hypertriglyceridemia (≥500 mg/dL). They are also used to reduce the risk of cardiovascular events in patients with established cardiovascular disease and persistently elevated triglyceride levels (≥150 mg/dL) despite statin therapy. Their pharmacological classification is as a lipid-lowering agent. The mechanism of action involves reducing the production of triglycerides in the liver and increasing their breakdown in the bloodstream.

Alternate Names

• Fish Oil
• Omega-3 Fish Oil
• N-3 Fatty Acids
• Polyunsaturated Fatty Acids (PUFAs)

Brand names:

• Lovaza
• Vascepa (icosapent ethyl - purified EPA)
• Epanova

How It Works

Pharmacodynamics: Omega-3 marine triglycerides primarily reduce triglyceride levels through multiple mechanisms: - Decreased hepatic very-low-density lipoprotein (VLDL) synthesis and secretion. - Increased lipoprotein lipase activity, which enhances triglyceride breakdown. - Reduced hepatic lipogenesis.

Pharmacokinetics: - Absorption: readily absorbed in the gastrointestinal tract, especially when taken with meals. - Metabolism: undergoes hepatic metabolism, similar to other fatty acids. - Elimination: eliminated through several routes, including biliary excretion, beta-oxidation and incorporation into cell membranes. No specific CYP enzyme interactions are known.

Mode of Action: Omega-3 fatty acids, specifically EPA and DHA, influence gene expression related to lipid metabolism, inflammation, and cell function. This occurs partly through binding to peroxisome proliferator-activated receptors (PPARs).

Dosage

Standard Dosage

Adults:

For hypertriglyceridemia (≥500 mg/dL): 4 g/day, usually taken as two 2-gram capsules twice daily with meals, or as four 1 gram capsules once or twice daily.

For cardiovascular risk reduction in patients with persistent hypertriglyceridemia despite statin therapy: 4 g/day icosapent ethyl (purified EPA), usually as two 2-gram capsules twice daily. Note, this purified EPA formulation is preferred by the AHA to avoid the potential of increased LDL-C levels.

Children:

Not FDA-approved for patients younger than 18. Limited data suggest potential benefits in specific conditions like pediatric non-alcoholic fatty liver disease (NAFLD), however, dosage recommendations are not yet established. Dosing has ranged from 450 to 1300 mg daily depending on age and weight in clinical trials.

Special Cases:

• Elderly Patients: No specific dosage adjustments are indicated.
• Patients with Renal Impairment: Dosage adjustments have not been defined.
• Patients with Hepatic Dysfunction: Dosage adjustments have not been defined. Close monitoring of liver function tests is advised.
• Patients with Comorbid Conditions: Careful consideration is necessary for patients with diabetes, as omega-3 fatty acids may increase LDL cholesterol, and cardiovascular disease.

Clinical Use Cases

Dosages for conditions other than hypertriglyceridemia are not well established and often based on research trials or expert opinions. These uses are considered off-label:

• Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations: Parenteral fish oil lipid emulsions are being investigated, but standard dosing guidelines haven’t been established. Doses used have varied greatly, ranging from 0.05 gm/kg/day to 6.5 g/day or even higher.

Dosage Adjustments

Data on dosage adjustments based on renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms are limited. Clinical judgment is essential.

Side Effects

Common Side Effects:

• Gastrointestinal disturbances (nausea, eructation, vomiting, abdominal distension, diarrhea, constipation)
• Acne or eczema
• Mild, transient elevation in liver enzymes

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, swelling, difficulty breathing)
• Excessive bleeding (especially in patients taking anticoagulants)

Long-Term Effects:

Limited information is available on potential long-term effects.

Adverse Drug Reactions (ADR):

Clinically significant ADRs are rare but require immediate intervention. These include severe allergic reactions and uncontrolled bleeding.

Contraindications

• Hypersensitivity to fish or fish oil.
• Active bleeding or bleeding disorders.

Drug Interactions

• Anticoagulants (e.g., warfarin): May increase bleeding risk. Close monitoring of INR is necessary.
• Antiplatelet agents (e.g., aspirin, clopidogrel): May also increase bleeding risk.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (animal studies show adverse effects, but no adequate and well-controlled studies in pregnant women; benefits may outweigh potential risks).
• Fetal risks: Limited data suggest no significant fetal harm, but avoiding high doses is recommended.
• Breastfeeding: Omega-3 fatty acids are present in breast milk, and limited data suggest that usual doses of omega-3 supplementation are safe for breastfeeding mothers and infants. The American Academy of Pediatrics recommends an intake for breastfeeding mothers of at least 2 servings of low-mercury fish weekly, equivalent to approximately 200-300 mg/day of DHA.

Drug Profile Summary

• Mechanism of Action: Reduces hepatic VLDL production and increases triglyceride breakdown via lipoprotein lipase activation.
• Side Effects: GI issues, skin reactions, mild liver enzyme elevations. Rarely, bleeding or allergic reactions.
• Contraindications: Hypersensitivity to fish oil, active bleeding.
• Drug Interactions: Anticoagulants, antiplatelet agents.
• Pregnancy & Breastfeeding: Use with caution during pregnancy. Generally considered safe during breastfeeding.
• Dosage: Hypertriglyceridemia: 4 g/day. Cardiovascular risk reduction in patients with persistent hypertriglyceridemia despite statin therapy: 4g/day icosapent ethyl (purified EPA).
• Monitoring Parameters: Triglyceride levels, LDL cholesterol, liver function tests, signs of bleeding (if taking anticoagulants).

Popular Combinations

• Statins: Often prescribed concurrently with omega-3 fatty acids, especially for patients with mixed dyslipidemia. However, the purified EPA formulation is favored by the AHA for patients on statins.

Precautions

• General Precautions: Evaluate for underlying causes of hypertriglyceridemia. Assess for bleeding risk. Monitor liver function tests.
• Specific Populations:
  • Pregnant Women: Use with caution. Discuss potential risks and benefits with the patient.
  • Breastfeeding Mothers: Limited data suggest safety, but high doses should be avoided.
  • Children & Elderly: No specific precautions.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Omega-3 Marine Triglycerides?

A: For adults with severe hypertriglyceridemia (≥500 mg/dL): 4 g/day, typically with meals. For cardiovascular risk reduction in patients with persistent hypertriglyceridemia despite statin therapy: 4g/day icosapent ethyl (purified EPA). Not recommended for children under 18.

Q2: How do omega-3s lower triglycerides?

A: They decrease VLDL production in the liver, increase triglyceride breakdown by activating lipoprotein lipase, and decrease liver lipogenesis.

Q3: What are the common side effects?

A: Gastrointestinal complaints (nausea, belching, loose stools), fishy aftertaste, and mild skin rashes.

Q4: Are there any serious side effects?

A: Rarely, allergic reactions and increased bleeding risk (especially with concomitant anticoagulants).

Q5: Can omega-3s be taken with statins?

A: Yes, but there are concerns that DHA may slightly increase LDL-C levels, so AHA suggests using purified EPA.

Q6: What is the difference between prescription and over-the-counter omega-3s?

A: Prescription formulations are more concentrated and purified, allowing for higher doses of EPA and DHA.

Q7: Can pregnant or breastfeeding women take omega-3s?

A: Generally, they should be used cautiously during pregnancy and breastfeeding. The benefits and potential risks should be discussed with the prescribing physician.

Q8: Are there any drug interactions I should be aware of?

A: Omega-3s may interact with anticoagulants (e.g., warfarin) and antiplatelet drugs, potentially increasing bleeding risk.

Q9: How long does it take for omega-3s to lower triglycerides?

A: Triglyceride levels may start to decrease within a few weeks, but optimal effects may take several months.

Q10: What should I monitor in patients taking omega-3s?

A: Triglyceride levels, LDL cholesterol, liver function tests, and for signs of bleeding, especially if the patient is also on anticoagulants.