✅ Uses & Indications
1 INDICATIONS AND USAGE Omega-3-acid ethyl esters capsules are indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (greater than or equal to 500 mg/dL) hypertriglyceridemia. Usage Considerations: Patients should be placed on an appropriate lipid-lowering diet before receiving omega-3-acid ethyl esters and should continue this diet during treatment with omega-3-acid ethyl esters capsules. Laboratory studies should be done to ascertain that the lipid levels are consistently abnormal before instituting therapy with omega-3-acid ethyl esters. Every attempt should be made to control serum lipids with appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that are contributing to the lipid abnormalities. Medications known to exacerbate hypertriglyceridemia (such as beta blockers, thiazides, estrogens) should be discontinued or changed, if possible, prior to consideration of TG-lowering drug therapy. Limitations of Use: The effect of omega-3-acid ethyl esters capsules on the risk for pancreatitis has not been determined. The effect of omega-3-acid ethyl esters on cardiovascular mortality and morbidity has not been determined. Omega-3-acid ethyl esters capsules are a combination of ethyl esters of omega 3 fatty acids, principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. (1) Limitations of Use: The effect of omega-3-acid ethyl esters on the risk for pancreatitis has not been determined. (1) The effect of omega-3-acid ethyl esters on cardiovascular mortality and morbidity has not been determined. (1)
📏 Dosage & Administration
2 DOSAGE AND ADMINISTRATION Assess TG levels carefully before initiating therapy. Identify other causes (e.g., diabetes mellitus, hypothyroidism, medications) of high TG levels and manage as appropriate [see Indications and Usage (1)] . Patients should be placed on an appropriate lipid-lowering diet before receiving omega-3-acid ethyl esters capsules, and should continue this diet during treatment with omega-3-acid ethyl esters. In clinical studies, omega-3-acid ethyl esters capsules was administered with meals. The daily dose of omega-3-acid ethyl esters capsules is 4 grams per day. The daily dose may be taken as a single 4-gram dose (4 capsules) or as two 2-gram doses (2 capsules given twice daily). Patients should be advised to swallow omega-3-acid ethyl esters capsules whole. Do not break open, crush, dissolve, or chew omega-3-acid ethyl esters capsules. The daily dose of omega-3-acid ethyl esters capsules is 4 grams per day taken as a single 4-gram dose (4 capsules) or as two 2-gram doses (2 capsules given twice daily). (2) Patients should be advised to swallow omega-3-acid ethyl esters capsules whole. Do not break open, crush, dissolve, or chew omega-3-acid ethyl esters capsules. (2)
💊 Side Effects
6 ADVERSE REACTIONS The most common adverse reactions (incidence >3% and greater than placebo) were eructation, dyspepsia, and taste perversion. To report SUSPECTED ADVERSE REACTIONS, contact Camber Pharmaceuticals Inc., at 1-866-495-8330 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions reported in at least 3% of subjects treated with omega-3-acid ethyl esters and at a greater rate than placebo based on pooled data across 23 clinical trials are listed in Table 1. Table 1. Adverse Reactions Occurring at Incidence ≥ 3% and Greater than Placebo in Clinical Trials of Omega-3-acid ethyl esters capsules Adverse Reactions a Omega-3-acid ethyl esters (n = 655) Placebo (n = 370) n % n % Eructation 29 4 5 1 Dyspepsia 22 3 6 2 Taste perversion 27 4 1 <1 a Trials included subjects with hypertriglyceridemia and severe hypertriglyceridemia. Additional adverse reactions from clinical trials are listed below: Digestive System Constipation, gastrointestinal disorder, and vomiting. Metabolic and Nutritional Disorders Increased ALT and increased AST. Skin Pruritus and rash. 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the events described below have been identified during post-approval use of omega-3-acid ethyl esters capsules. Because these events are reported voluntarily from a population of unknown size, it is not possible to reliably estimate their frequency or to always establish a causal relationship to drug exposure. The following events have been reported: anaphylactic reaction, hemorrhagic diathesis, urticaria.
⚠️ Warnings & Precautions
5 WARNINGS AND PRECAUTIONS In patients with hepatic impairment, monitor ALT and AST levels periodically during therapy. (5.1) Omega-3-acid ethyl esters capsules may increase levels of low-density lipoprotein (LDL). Monitor LDL levels periodically during therapy. (5.1) Use with caution in patients with known hypersensitivity to fish and/or shellfish. (5.2) There is a possible association between omega-3-acid ethyl esters and more frequent recurrences of symptomatic atrial fibrillation or flutter in patients with paroxysmal or persistent atrial fibrillation, particularly within the first months of initiating therapy. (5.3) 5.1 Monitoring: Laboratory Tests In patients with hepatic impairment, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored periodically during therapy with omega-3-acid ethyl esters capsules. In some patients, increases in ALT levels without a concurrent increase in AST levels were observed. In some patients, omega-3-acid ethyl esters increases low-density lipoprotein cholesterol (LDL-C) levels. LDL-C levels should be monitored periodically during therapy with omega-3-acid ethyl esters. Laboratory studies should be performed periodically to measure the patient’s TG levels during therapy with omega-3-acid ethyl esters. 5.2 Fish Allergy Omega-3-acid ethyl esters contains ethyl esters of omega-3 fatty acids (EPA and DHA) obtained from the oil of several fish sources. It is not known whether patients with allergies to fish and/or shellfish, are at increased risk of an allergic reaction to omega-3-acid ethyl esters. Omega-3-acid ethyl esters should be used with caution in patients with known hypersensitivity to fish and/or shellfish. 5.3 Recurrent Atrial Fibrillation (AF) or Flutter In a double-blind, placebo-controlled trial of 663 subjects with symptomatic paroxysmal AF (n = 542) or persistent AF (n = 121), recurrent AF or flutter was observed in subjects randomized to omega-3-acid ethyl esters who received 8 grams/day for 7 days and 4 grams/day thereafter for 23 weeks at a higher rate relative to placebo. Subjects in this trial had median baseline TG levels of 127 mg/dL, had no substantial structural heart disease, were taking no anti-arrhythmic therapy (rate control permitted), and were in normal sinus rhythm at baseline. At 24 weeks, in the paroxysmal AF stratum, there were 129 (47%) first recurrent symptomatic AF or flutter events on placebo and 141 (53%) on omega-3-acid ethyl esters (primary endpoint, HR: 1.19; 95% CI: 0.93, 1.35). In the persistent AF stratum, there were 19 (35%) events on placebo and 34 (52%) events on omega-3-acid ethyl esters (HR: 1.63; 95% CI: 0.91, 2.18). For both strata combined, the HR was 1.25; 95% CI: 1.00, 1.40. Although the clinical significance of these results is uncertain, there is a possible association between omega-3-acid ethyl esters and more frequent recurrences of symptomatic AF or flutter in patients with paroxysmal or persistent AF, particularly within the first 2 to 3 months of initiating therapy. Omega-3-acid ethyl esters capsules are not indicated for the treatment of AF or flutter.
🔄 Drug Interactions
7 DRUG INTERACTIONS Omega-3-acids may prolong bleeding time. Patients taking omega-3-acid ethyl esters capsules and an anticoagulant or other drug affecting coagulation (e.g., anti-platelet agents) should be monitored periodically. (7.1) 7.1 Anticoagulants or Other Drugs Affecting Coagulation Some trials with omega-3-acids demonstrated prolongation of bleeding time. The prolongation of bleeding time reported in these trials has not exceeded normal limits and did not produce clinically significant bleeding episodes. Clinical trials have not been done to thoroughly examine the effect of omega-3-acid ethyl esters and concomitant anticoagulants. Patients receiving treatment with omega-3-acid ethyl esters and an anticoagulant or other drug affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.
🚫 Contraindications
4 CONTRAINDICATIONS Omega-3-acid ethyl esters capsules are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters or any of its components. Omega-3-acid ethyl esters capsules are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters or any of its components.
📦 Storage & Handling
16 HOW SUPPLIED/STORAGE AND HANDLING Omega-3-acid ethyl esters capsules, USP are supplied as 1 gram clear, transparent oblong capsules containing clear to light yellow colored solution imprinted with ‘AT 132’ with white ink. NDC: 72162-1310-2: 120 Capsules in a BOTTLE Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light. Keep out of reach of children. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504