OMEGA-3-ACID ETHYL ESTERS (Page 3 of 4)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis Mutagenesis Impairment of Fertility

In a rat carcinogenicity study with oral gavage doses of 100, 600, and 2,000 mg/kg/day, males were treated with omega-3-acid ethyl esters for 101 weeks and females for 89 weeks without an increased incidence of tumors (up to 5 times human systemic exposures following an oral dose of 4 grams/day based on a body surface area comparison). Standard lifetime carcinogenicity bioassays were not conducted in mice.

Omega-3-acid ethyl esters were not mutagenic or clastogenic with or without metabolic activation in the bacterial mutagenesis (Ames) test with Salmonella typhimurium and Escherichia coli or in the chromosomal aberration assay in Chinese hamster V79 lung cells or human lymphocytes. Omega-3-acid ethyl esters were negative in the in vivo mouse micronucleus assay.

In a rat fertility study with oral doses of 100, 600, and 2,000 mg/kg/day, males were treated for 10 weeks prior to mating and females were treated for 2 weeks prior to mating and through lactation. No adverse effect on fertility was observed at 2,000 mg/kg/day (5 times the MRHD of 4 grams/day based on body surface area [mg/m2 ]).

14 CLINICAL STUDIES

14.1 Severe Hypertriglyceridemia

The effects of omega-3-acid ethyl esters 4 grams per day were assessed in 2 randomized, placebo-controlled, double-blind, parallel-group trials of 84 adult subjects (42 on omega-3-acid ethyl esters, 42 on placebo) with very high TG levels. Subjects whose baseline TG levels were between 500 and 2,000 mg/dL were enrolled in these 2 trials of 6 and 16 weeks’ duration. The median TG and LDL-C levels in these subjects were 792 mg/dL and 100 mg/dL, respectively. Median high-density lipoprotein cholesterol (HDL-C) level was 23.0 mg/dL.

The changes in the major lipoprotein lipid parameters for the groups receiving omega-3-acid ethyl esters or placebo are shown in Table 2.

Table 2. Median Baseline and Percent Change from Baseline in Lipid Parameters in Subjects with Severe Hypertriglyceridemia (≥500 mg/dL)
Parameter Omega-3- A cid E thyl E sters n = 42 Placebo n = 42 Difference
BL % Change BL % Change
TG 816 -44.9 788 +6.7 -51.6
Non-HDL-C 271 -13.8 292 -3.6 -10.2
TC 296 -9.7 314 -1.7 -8.0
VLDL-C 175 -41.7 175 -0.9 -40.8
HDL-C 22 +9.1 24 0.0 +9.1
LDL-C 89 +44.5 108 -4.8 +49.3

BL = Baseline (mg/dL); % Change = Median Percent Change from Baseline;
Difference = Omega-3-acid ethyl esters Median % Change – Placebo Median % Change.
TC = Total cholesterol. VLDL-C = Very-low-density lipoprotein (VLDL) cholesterol.

Omega-3-acid ethyl esters 4 grams per day reduced median TG, VLDL-C, and non-HDL-C levels and increased median HDL-C from baseline relative to placebo. Treatment with omega-3-acid ethyl esters to reduce very high TG levels may result in elevations in LDL-C and non-HDL-C in some individuals. Patients should be monitored to ensure that the LDL-C level does not increase excessively.

The effect of omega-3-acid ethyl esters on the risk of pancreatitis has not been determined.

The effect of omega-3-acid ethyl esters on cardiovascular mortality and morbidity has not been determined.

16 HOW SUPPLIED/STORAGE AND HANDLING

Omega-3-Acid Ethyl Esters Capsules USP are supplied as 1-gram, soft gelatin oblong capsules filled with a light yellow liquid and imprinted with CW 410 in white ink.

Supplied in bottles of 120 capsules.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze.

Keep this and all medication out of the reach of children.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Information for Patients

  • Omega-3-acid ethyl esters capsules should be used with caution in patients with known sensitivity or allergy to fish and/or shellfish [see Warnings and Precautions ( 5.2)] .
  • Advise patients that use of lipid-regulating agents does not reduce the importance of adhering to diet [see Dosage and Administration ( 2)] .
  • Advise patients not to alter omega-3-acid ethyl esters capsules in any way and to ingest intact capsules only [see Dosage and Administration ( 2)] .
  • Instruct patients to take omega-3-acid ethyl esters capsules as prescribed. If a dose is missed, advise patients to take it as soon as they remember. However, if they miss one day of omega-3-acid ethyl esters capsules, they should not double the dose when they take it.

Manufactured by:
Procaps S.A.
Barranquilla, ColombiaSouth America

PHARMACIST-DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT

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PATIENT INFORMATION Omega-3-Acid Ethyl Esters (oh-MAY-ga 3 AS-id eth-il es-ters) Capsules
What are omega-3-acid ethyl esters capsules ? Omega-3-acid ethyl esters capsules are a prescription medicine used along with a low-fat and low-cholesterol diet to lower very high triglyceride (fat) levels in adults.It is not known if omega-3-acid ethyl esters capsules change your risk of having inflammation of your pancreas (pancreatitis).It is not known if omega-3-acid ethyl esters capsules prevent you from having a heart attack or stroke.It is not known if omega-3-acid ethyl esters capsules are safe and effective in children.
Who should not take omega-3-acid ethyl esters capsules ? Do not take omega-3-acid ethyl esters capsules if you are allergic to omega-3-acid ethyl esters or any of the ingredients in omega-3-acid ethyl esters capsules. See the end of this leaflet for a complete list of ingredients in omega-3-acid ethyl esters capsules.
Before taking omega-3-acid ethyl esters capsules, tell your healthcare provider about all of your medical conditions, including if you:
  • have diabetes.
  • have a low thyroid problem (hypothyroidism).
  • have a liver problem.
  • have a pancreas problem.
  • have a certain heart rhythm problem called atrial fibrillation or flutter.
  • are allergic to fish or shellfish. It is not known if people who are allergic to fish or shellfish are also allergic to omega-3-acid ethyl esters capsules.
  • are pregnant or plan to become pregnant. It is not known if omega-3-acid ethyl esters capsules will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. Omega-3-acid ethyl esters can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take omega-3-acid ethyl esters capsules.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Omega-3-acid ethyl esters capsules can interact with certain other medicines that you are taking. Using omega-3-acid ethyl esters capsules with medicines that affect blood clotting (anticoagulants or blood thinners) may cause serious side effects.
How should I take omega-3-acid ethyl esters capsules ?
  • Take omega-3-acid ethyl esters capsules exactly as your healthcare provider tells you to take it.
  • You should not take more than 4 capsules of omega-3-acid ethyl esters capsules each day. Either take all 4 capsules at one time or 2 capsules two times a day.
  • Do not change your dose or stop omega-3-acid ethyl esters capsules without talking to your healthcare provider.
  • Take omega-3-acid ethyl esters capsules with food.
  • Take omega-3-acid ethyl esters capsules whole. Do not break, open, crush, dissolve, or chew omega-3-acid ethyl esters capsules before swallowing. If you cannot swallow omega-3-acid ethyl esters capsules whole, tell your healthcare provider. You may need a different medicine.
  • If you miss a dose of omega-3-acid ethyl esters capsules, take the missed dose as soon as you remember. If you miss one day of omega-3-acid ethyl esters capsules, do not double your dose the next time you take it.
  • Your healthcare provider may start you on a cholesterol-lowering diet before giving you omega-3-acid ethyl esters capsules. Stay on this diet while taking omega-3-acid ethyl esters capsules.
  • Your healthcare provider should do blood tests to check your triglyceride, bad cholesterol (LDL-C), and liver function (ALT and AST) levels while you take omega-3-acid ethyl esters capsules.
What are the possible side effects of omega-3-acid ethyl esters capsules ? Omega-3-acid ethyl esters capsules may cause serious side effects, including:
  • changes in certain blood tests. Omega-3-acid ethyl esters capsules may cause an increase in the results of blood tests used to check your liver function and your bad cholesterol levels.
  • increased risk of a heart rhythm problem in people who have a heart rhythm problem. Omega-3-acid ethyl esters capsules may cause an increase in the frequency of a heart rhythm problem (atrial fibrillation or flutter), especially in the first few months of taking omega-3-acid ethyl esters capsules, if you already have a heart rhythm problem.
The most common side effects of omega-3-acid ethyl esters capsules include:
  • burping
  • upset stomach
  • a change in your sense of taste
These are not all the possible side effects of omega-3-acid ethyl esters capsules. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store omega-3-acid ethyl esters capsules ?
  • Store omega-3-acid ethyl esters capsules at room temperature between 68°F to 77°F (20°C to 25°C).
  • Do not freeze omega-3-acid ethyl esters capsules.
  • Safely throw away medicine that is out of date or no longer needed.
Keep omega-3-acid ethyl esters capsules and all medicines out of the reach of children.
General information about the safe and effective use of omega-3-acid ethyl esters capsules. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use omega-3-acid ethyl esters capsules for a condition for which it was not prescribed. Do not give omega-3-acid ethyl esters capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about omega-3-acid ethyl esters capsules that is written for health professionals.
What are the ingredients in omega-3-acid ethyl esters capsules ? Active Ingredient: omega-3-acid ethyl esters, mostly EPA and DHAInactive Ingredients: alpha-tocopherol, caprylic and capric acid triglycerides (medium-chain triglycerides), gelatin, glycerin, and purified water. The capsule imprinting ink contains ammonium hydroxide, ethanol, ethyl acetate, isopropyl alcohol, polyethylene glycol, polyvinyl acetate phthalate, propylene glycol, purified water, and titanium dioxide.
Manufactured by:Procaps S.A.Barranquilla, ColombiaSouth America

This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: 11/2023

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