Omega-3-Acid Ethyl Esters 90: Uses, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Overview

Omega-3-acid ethyl esters 90, a medication authorized by the United States Food and Drug Administration (USFDA) in October 2004, is crucial in managing elevated triglyceride levels and mitigating cardiovascular risks. This therapeutic option, rich in Omega-3 fatty acids, particularly EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), offers a valuable complement to dietary measures. Omega-3-acid ethyl esters 90 address a significant health concern by prioritizing patient well-being and cardiovascular health. This article aims to highlight this medication's positive impact and importance in promoting heart health and overall well-being.

Drug Group

Omega-3-acid ethyl esters 90 belong to the drug class of lipid-regulating agents. These agents primarily focus on modifying lipid levels in the blood, often by targeting cholesterol and triglycerides.

Indications

Omega-3-acid ethyl esters are prescribed as a supplement to dietary measures to lower triglyceride (TG) levels in adult patients experiencing severe hypertriglyceridemia (HTG) that is more than or equal to 500 mg/dL (milligrams per deciliter).

Dosage Forms and Available Strengths

Omega-3-acid ethyl esters are available as transparent, soft gelatin capsules with a one-gram capacity. These capsules are filled with a light-yellow oil.

For Patients

What Does It Mean by High Triglycerides?

High triglycerides refer to elevated levels of triglycerides in the bloodstream. Triglycerides constitute a form of fat (lipid) in the bloodstream and are a common component of the human diet. They also include a significant form of energy storage in the body. However, when triglyceride levels become too high, it can be associated with various health concerns, particularly cardiovascular health.

Typically, triglyceride levels within the normal range are below 150 milligrams per deciliter (mg/dL).

Here is a general classification:

• Normal: Less than 150 mg/dL.

• Borderline High: 150 to 199 mg/dL.

• High: 200 to 499 mg/dL.

• Very High: 500 mg/dL or higher.

Increased triglyceride levels are viewed as a contributing factor to cardiovascular diseases, including heart disease and stroke (a sudden interruption of blood supply to the brain). High triglycerides may be influenced by various factors, including diet, physical activity, genetics, obesity (excessive body fat), diabetes (high sugar levels in the blood), and certain medications.

How Does the Omega-3-Acid Ethyl Esters 90 Work?

Omega-3-acid ethyl esters 90 work by influencing lipid metabolism, particularly triglycerides. The exact mechanism needs to be understood. The active ingredients in this medication are ethyl esters of Omega-3 fatty acids, primarily eicosapentaenoic acid and docosahexaenoic acid, which have several potential mechanisms of action:

• Triglyceride Synthesis Inhibition: EPA and DHA are poor substrates for the enzymes responsible for triglyceride (TG) synthesis in the liver. By incorporating these Omega-3 fatty acids, the synthesis of triglycerides may be reduced.

• Increased Beta-Oxidation: Omega-3 fatty acids may enhance mitochondrial and peroxisomal beta-oxidation in the liver, leading to increased metabolism of fatty acids.

• Decreased Lipogenesis: EPA and DHA may reduce fat formation (lipogenesis) within the liver.

What Are the Clinical Uses of the Omega-3-Acid Ethyl Esters 90?

Omega-3-acid ethyl esters 90 are clinically used to manage elevated triglyceride levels in the blood. It is used in the case of

• Hypertriglyceridemia: Omega-3-Acid Ethyl Esters 90 is prescribed to individuals with severe hypertriglyceridemia (very high levels of triglycerides) as an adjunct to diet. Increased triglyceride levels are associated with enhanced risk of cardiovascular disease.

What Is the Dosage of the Omega-3-Acid Ethyl Esters 90?

The dosage of Omega-3-acid ethyl esters 90 can vary and is typically prescribed based on individual patient needs and medical conditions. The suggested daily dosage for Omega-3-acid ethyl esters is 4 grams per day. This can be taken as a single four-gram dose (4 capsules) or two 2-gram doses (two capsules given twice daily).

How Are Omega-3-Acid Ethyl Esters 90 Administered?

• It is necessary to carefully assess triglyceride levels before initiating therapy. Identify potential underlying causes such as diabetes mellitus (high sugar in the blood), hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormones), or medications contributing to elevated triglyceride levels and manage accordingly.

• Patients should adhere to an appropriate lipid-lowering diet before starting Omega-3-acid ethyl esters, and this dietary regimen should be maintained during Omega-3-acid ethyl esters treatment. Omega-3-acid ethyl esters are typically administered with meals.

• It is important to swallow Omega-3-acid ethyl ester capsules whole without breaking, crushing, dissolving, or chewing them.

What Are the Side Effects of Omega-3-Acid Ethyl Esters 90?

Omega-3-acid ethyl esters 90 has the potential to cause significant side effects, including

• Elevated results in liver function blood tests (ALT or alanine aminotransferase and AST or aspartate aminotransferase) and increased levels of bad cholesterol (LDL-C).

• Increased occurrence of a heart rhythm issue (atrial fibrillation or flutter), particularly in the initial months of Omega-3-acid ethyl esters use.

Common side effects of Omega-3-acid ethyl esters comprise

• Burping.

• Upset stomach.

• Altered sense of taste.

If the patient experiences a bothersome or persistent side effect, consult the doctor.

What Are the Things to Inform the Doctor Before Taking Omega-3-Acid Ethyl Esters 90?

Before starting Omega-3-acid ethyl esters, inform the doctor if the patient has the following:

• Diabetes.

• Experience hypothyroidism (a low thyroid problem).

• Liver problem.

• Pancreas problem.

• A heart rhythm issue known as atrial fibrillation or flutter.

• Are allergic to fish or shellfish. It is unclear whether individuals with allergies to fish or shellfish also have allergies to Omega-3-acid ethyl esters.

• Inform about the pregnancy or desire to plan for it. The impact of Omega-3-acid ethyl esters on unborn babies is unknown.

• The patient should disclose the status of breastfeeding to the doctor. Omega-3-acid ethyl esters may pass into breast milk, and the decision to take Omega-3-acid ethyl esters or breastfeed should be made in consultation with the doctor.

Additionally:

• Share with the doctor all medicines one takes, including prescriptions, over-the-counter medications, vitamins, and herbal supplements.

• Be aware that Omega-3-acid ethyl esters may interact with certain medications, especially those affecting blood clotting (anticoagulants or blood thinners), potentially leading to serious side effects.

• Keep a list of all the medications to show to the doctor and pharmacist when starting new treatments.

Dietary Considerations

None. It is necessary to follow a balanced diet.

Missed Dose

Patients should follow the prescribed regimen for Omega-3-acid ethyl esters 90. If a dose is missed, the patient should take it as soon as they recall. However, if a day is skipped, the patients should avoid doubling the dose upon the next intake.

Overdose

In case of an overdose with Omega-3-acid ethyl esters 90, seek immediate medical attention or contact a poison control center. Symptoms of an overdose may include gastrointestinal discomfort, nausea, and an increased risk of bleeding. Following prescribed dosages is essential to preventing the potential adverse effects of excessive consumption.

Storage and Handling

For proper storage, keep Omega-3-acid ethyl esters 90 at 25 degrees Celsius (77 degrees Fahrenheit), with allowable excursions between 15 and 30 degrees Celsius (59 to 86 degrees Fahrenheit), as specified by the United States Pharmacopeia (USP) Controlled Room Temperature. Avoid freezing, and ensure the capsules are kept out of reach of children.

For Doctors

Chemical Taxonomy

Omega-3-acid ethyl esters, a lipid-regulating agent, are presented as a gel capsule filled with liquid for oral intake. Each 1-gram capsule of Omega-3-acid ethyl esters 90 contains a minimum of 900 mg (milligrams) of ethyl esters derived from Omega-3 fatty acids sourced from fish oils. These primarily consist of a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - about 375 mg). The empirical formula of EPA ethyl ester is C22H34O2, with a molecular weight of 330.51. The empirical formula of DHA ethyl ester is C24H36O2, with a molecular weight of 356.55. In addition to the active ingredients, Omega-3-acid ethyl ester 90 capsules contain 4 mg of alpha-tocopherol (in a soybean oil carrier), and the capsule shell is composed of gelatin, glycerol, and purified water.

Dosing Considerations:

• Usage Guidelines: Before initiating Omega-3-acid ethyl esters treatment, patients should adhere to an appropriate lipid-lowering diet, and this dietary regimen should be maintained throughout Omega-3-acid ethyl esters therapy. Before starting Omega-3-acid ethyl esters therapy, laboratory tests should confirm consistent abnormal lipid levels. Efforts should be directed toward managing serum lipids through proper diet, exercise, weight reduction for obese individuals, and addressing any underlying medical conditions such as diabetes mellitus and hypothyroidism contributing to lipid abnormalities. Medications that may worsen hypertriglyceridemia, such as beta-blockers, Thiazides, and Estrogens, should be stopped or changed whenever possible before considering triglyceride-lowering drug therapy.
• Usage Limitations: The impact of Omega-3-acid ethyl esters on the risk of pancreatitis (inflammation of the pancreas) remains undetermined. Additionally, the effects of Omega-3-acid ethyl esters on cardiovascular mortality and morbidity have not been established.

Warnings and Precautions

The associated warnings and precautions are:

Monitoring Laboratory Tests:

• In individuals with hepatic impairment, regularly checking alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels through periodic monitoring during Omega-3-acid ethyl esters therapy is recommended. Some patients may experience increases in ALT levels without a corresponding increase in AST levels.

• Additionally, LDL-C (low-density lipoprotein cholesterol) levels should be monitored regularly, as Omega-3-acid ethyl esters have been observed to increase LDL-C levels in certain patients. Periodic laboratory studies are advised to measure triglyceride levels throughout Omega-3-acid ethyl esters therapy.

Fish Allergy: Omega-3 fatty acids (EPA and DHA) are derived from various fish sources. It is uncertain whether individuals with fish or shellfish allergies have an elevated potential for an allergic reaction to Omega-3-acid ethyl esters. Exercise caution when administering Omega-3-acid ethyl esters to patients with a confirmed hypersensitivity to fish and shellfish.

Recurrent Atrial Fibrillation (AF) or Flutter:

• A double-blind, placebo-controlled trial was conducted involving 663 subjects with symptomatic paroxysmal AF or persistent AF, both conditions causing disturbances in heart rhythm. In that clinical trial, those randomized to Omega-3-acid ethyl esters exhibited a higher rate of recurrent AF or flutter than the placebo group. This was observed in subjects receiving eight grams per day for seven days and four grams daily after 23 weeks. The trial included individuals with no substantial structural heart disease, not on anti-arrhythmic therapy (rate control permitted), and in normal sinus rhythm at baseline.

• At 24 weeks, the paroxysmal AF stratum showed 47 percent of first recurrent symptomatic AF or flutter events on placebo and 53 percent on Omega-3-acid ethyl esters, with a primary endpoint hazard ratio (HR) of 1.19 (95 percent CI: 0.93, 1.35). In the persistent AF stratum, the corresponding figures were 35 percent on placebo and 52 percent on Omega-3-acid ethyl esters, with an HR of 1.63 (95 percent CI: 0.91, 2.18). The combined HR for both strata was 1.25 (95 percent CI: 1.00, 1.40). While the clinical significance of these results is uncertain, there is a potential link between Omega-3-acid ethyl esters and an increased incidence of symptomatic atrial fibrillation or flutter recurrences, particularly within the first two to three months of initiating therapy.

• It is important to note that the use of Omega-3-acid ethyl esters is not recommended for the treatment of AF or flutter.

What Are the Pharmacological Actions of Omega-3-Acid Ethyl Esters 90?

The pharmacological actions of Omega-3-acid ethyl esters 90 are:

• Pharmacodynamics: For Omega-3-acid ethyl esters 90, the pharmacodynamics involve influencing lipid metabolism, particularly triglycerides, through mechanisms such as inhibiting triglyceride synthesis and modulating fatty acid metabolism in the liver.

• Mechanism of Action: The precise mechanism of action of Omega-3-acid ethyl esters has yet to be fully understood. Possible mechanisms include the inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, enhanced mitochondrial and peroxisomal beta-oxidation in the liver, diminished lipogenesis in the liver, and increased activity of plasma lipoprotein lipase. Omega-3-acid ethyl esters might decrease triglyceride synthesis in the liver due to EPA and DHA being inefficient substrates for the enzymes involved in triglyceride synthesis. Additionally, EPA and DHA may hinder the esterification of other fatty acids.

• Pharmacokinetics: The pharmacokinetics of Omega-3-acid ethyl esters have not been studied in the pediatric population, and there is currently no data on absorption, metabolism, or elimination in this group. Regarding individuals with renal or hepatic impairment, Omega-3-acid ethyl esters have not been studied in this population, and information on their absorption, metabolism, and elimination in these conditions is unavailable.

Non-Clinical Toxicity:

Carcinogenesis, Mutagenesis, and Impairment of Fertility:

• In a rat study on carcinogenicity, males and females were treated with Omega-3-acid ethyl esters for extended periods without an increased incidence of tumors. The doses administered ranged up to five times the systemic exposures observed in humans following an oral dose of four grams per day, as determined by body surface area comparison. Standard lifetime carcinogenicity assessments were not conducted in mice.
• Omega-3-acid ethyl esters demonstrated non-mutagenic and non-clastogenic properties in various tests, including the bacterial mutagenesis (Ames) test and chromosomal aberration assays.
• Additionally, they were found to be negative in the in vivo mouse micronucleus assay.
• In a rat fertility study, treatment with Omega-3-acid ethyl esters did not adversely affect fertility at the highest dose tested (2,000 mg/kg/day (milligrams per kilogram daily), equivalent to five times the systemic exposure in humans after taking an oral dose of four grams per day, as assessed through body surface area comparison.

What Are the Contraindications of Omega-3-Acid Ethyl Esters 90?

Omega-3-acid ethyl esters should not be used in patients with a confirmed hypersensitivity, such as an anaphylactic reaction, to Omega-3-acid ethyl esters or any of its components.

What Are the Drug Interactions of Omega-3-Acid Ethyl Esters 90?

• Anticoagulants or Other Coagulation-Affecting Drugs: Certain Omega-3-acid trials showed a lengthening of bleeding time. However, the observed prolongation did not exceed normal thresholds and did not lead to clinically significant instances of bleeding. Comprehensive clinical trials have yet to assess the impact of Omega-3-acid ethyl esters in conjunction with anticoagulants. Patients undergoing Omega-3-acid ethyl esters treatment alongside anticoagulants or other coagulation-affecting drugs (such as anti-platelet agents) should undergo periodic monitoring.

Drug Interaction Studies

• Simvastatin: In a 14-day trial involving 24 healthy adults, simultaneous administration of Simvastatin 80 mg with Omega-3-acid ethyl esters (4 grams) did not alter the exposure levels (AUC (area under the curve) and C max (peak concentration)) of Simvastatin or its major metabolite.

• Atorvastatin: In a 14-day trial with 50 healthy adults, co-administration of Atorvastatin 80 mg of Omega-3-acid ethyl esters (4 grams) had no impact on AUC or C max for Atorvastatin and its metabolites.

• Rosuvastatin: In a 14-day trial with 48 healthy adults, simultaneous co-administration of Omega-3-acid ethyl esters (4 grams) with Rosuvastatin 40 mg did not alter the AUC or Cmax of Rosuvastatin.

Clinical Studies

In two randomized, placebo-controlled, double-blind trials involving 84 adult subjects with very high triglyceride levels (baseline levels between 500 and 2,000 mg/dL (milligrams per deciliter)), Omega-3-acid ethyl esters at a dosage of four grams per day were evaluated over six and 16 weeks. The subjects had a median baseline triglyceride level of 792 mg/dL and an LDL-C level of 100 mg/dL, with a median HDL-C level of 23.0 mg/dL.

Omega-3-acid ethyl esters at four grams per day reduced median TG, VLDL-C (very low-density lipoprotein cholesterol), non-HDL-C, and increased median HDL-C compared to baseline and placebo. However, it should be noted that treatment with Omega-3-acid ethyl esters to lower very high TG levels may lead to increases in LDL-C and non-HDL-C in certain individuals. Monitoring is recommended to ensure that LDL-C levels do not excessively rise. The impact of Omega-3-acid ethyl esters on the risk of pancreatitis (inflammation of the pancreas) and cardiovascular mortality and morbidity has not been determined.

Use in Specific Populations

• Pregnancy: Omega-3-acid ethyl esters are a pregnancy category C, which means no adequate and well-controlled studies in pregnant women exist for Omega-3-acid ethyl esters 90. The potential fetal harm or impact on reproductive capacity is unknown. Omega-3-acid ethyl esters 90 during pregnancy are advisable only if the potential benefits outweigh the potential risks to the fetus.

• Nursing Mothers: Studies with Omega-3-acid ethyl esters have shown excretion in human milk. The impact on nursing infants is unknown, and caution is advised when administering Omega-3-acid ethyl esters to nursing mothers. An animal study in lactating rats indicated higher drug levels in milk compared to plasma.

• Pediatric Use: The safety and efficacy of pediatric patients have not been determined.

• Geriatric Use: Clinical trials included a limited number of subjects over 65 years, and findings suggest that safety and efficacy in individuals older than 60 did not significantly differ from those younger than 60.