Omtryg

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of omega-3-acid ethyl esters in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of omega-3-acid ethyl esters in the elderly.

Pregnancy

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to fish or shellfish, history of—Use with caution. May increase risk of having an allergic reaction.

• Atrial fibrillation or flutter (heart rhythm problem), or history of—Use with caution. May cause this condition to occur again.

• Diabetes or
• Hypothyroidism (underactive thyroid)—May increase risk for hypertriglyceridemia.

• Liver problems—Your doctor may want to monitor you more closely for unwanted effects.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bleeding gums
• cough
• coughing up blood
• difficulty with breathing or swallowing
• dizziness
• fast or irregular heartbeat
• headache
• hives, itching, or skin rash
• increased menstrual flow or vaginal bleeding
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red or black, tarry stools
• red or dark brown urine
• sweating
• tightness in the chest
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• bad, unusual, or unpleasant (after) taste
• belching
• bloated or full feeling
• change in taste
• excess air or gas in the stomach
• heartburn
• indigestion
• stomach discomfort, upset, or pain

• Diarrhea
• difficulty having a bowel movement (stool)
• loss of appetite
• nausea or vomiting
• passing of gas
• stomach fullness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Monitoring: Laboratory Tests

In patients with hepatic impairment, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored periodically during therapy with Omtryg. In some patients, increases in ALT levels without a concurrent increase in AST levels were observed.

In some patients, Omtryg increases LDL-cholesterol levels. LDL-cholesterol levels should be monitored periodically during therapy with Omtryg.

Fish Allergy

Omtryg 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 Omtryg. Omtryg should be used with caution in patients with known hypersensitivity to fish and/or shellfish.

Recurrent Atrial Fibrillation (AF) or Flutter

In a double-blind, placebo-controlled trial of 663 patients with symptomatic paroxysmal AF (n=542) or persistent AF (n=121), recurrent AF or flutter was observed in patients randomized to omega-3-acid ethyl esters who received 8 capsules/day for 7 days and 4 capsules/day thereafter for 23 weeks at a higher rate relative to placebo. Patients in this trial had median baseline triglycerides 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 atrial fibrillation or flutter in patients with paroxysmal or persistent atrial fibrillation, particularly within the first 2 to 3 months of initiating therapy.

Omtryg is not indicated for the treatment of AF or flutter.

Anticoagulants or Other Drugs Affecting Coagulation

Some studies with omega-3-acids demonstrated prolongation of bleeding time. The prolongation of bleeding time reported in these studies has not exceeded normal limits and did not produce clinically significant bleeding episodes. Clinical studies have not been done to thoroughly examine the effect of Omtryg and concomitant anticoagulants. Patients receiving treatment with Omtryg and an anticoagulant or other drug affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.

Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. It is unknown whether Omtryg can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Omtryg should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.

Animal Data: Omega-3-acid ethyl esters have been shown to have an embryocidal effect in pregnant rats when given in doses resulting in exposures 7 times the recommended human dose of 4 capsules/day based on a body surface area comparison.

In female rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day beginning 2 weeks prior to mating and continuing through gestation and lactation, no adverse effects were observed in the high dose group (5 times human systemic exposure following an oral dose of 4 capsules/day based on body surface area comparison).

In pregnant rats given oral gavage doses of 1,000, 3,000, and 6,000 mg/kg/day from gestation day 6 through 15, no adverse effects were observed (14 times human systemic exposure following an oral dose of 4 capsules/day based on a body surface area comparison).

In pregnant rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day from gestation day 14 through lactation day 21, no adverse effects were seen at 2,000 mg/kg/day (5 times the human systemic exposure following an oral dose of 4 capsules/day based on a body surface area comparison). However, decreased live births (20% reduction) and decreased survival to postnatal day 4 (40% reduction) were observed in a dose-ranging study using higher doses of 3,000 mg/kg/day (7 times human systemic exposure following an oral dose of 4 capsules/day based on a body surface area comparison).

In pregnant rabbits given oral gavage doses of 375, 750, and 1,500 mg/kg/day from gestation day 7 through 19, no findings were observed in the fetuses in groups given 375 mg/kg/day (2 times human systemic exposure following an oral dose of 4 capsules/day based on a body surface area comparison). However, at higher doses, evidence of maternal toxicity was observed (4 times human systemic exposure following an oral dose of 4 capsules /day based on a body surface area comparison).

Nursing Mothers

Studies with omega-3-acid ethyl esters have demonstrated excretion in human milk. The effect of this excretion on the infant of a nursing mother is unknown; caution should be exercised when Omtryg is administered to a nursing mother. An animal study in lactating rats given oral gavage 14 C-ethyl EPA demonstrated that drug levels were 6 to 14 times higher in milk than in plasma.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

A limited number of patients older than 65 years were enrolled in the clinical studies of omega‑3‑acid ethyl esters. Safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.

Omtryg does not have any known drug abuse or withdrawal effects.

Omtryg, a lipid-regulating agent, is supplied as a liquid-filled gel capsule for oral administration. Each Omtryg capsule contains 1.2 grams of omega-3-acid ethyl esters type A, USP, liquid concentrate consisting of at least 900 mg omega-3-acid ethyl esters sourced from fish oils. These are predominantly a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - approximately 375 mg).

The empirical formula of EPA ethyl ester is C22H34O2, and the molecular weight of EPA ethyl ester is 330.51. The structural formula of EPA ethyl ester is:

The empirical formula of DHA ethyl ester is C24H36O2, and the molecular weight of DHA ethyl ester is 356.55. The structural formula of DHA ethyl ester is:

Omtryg capsules also contain the following inactive ingredients: 4.6 mg α-tocopherol (in a carrier of sunflower oil), gelatin, glycerol, and purified water (components of the capsule shell).

Bottle Label

NDC 61112-001-01          Rx Only

Omtryg™
(omega-3-acid ethyl esters)
Capsules, USP

1.2 grams*

120 Capsules

TRYGG
Pharma

*Each capsule contains 1.2 grams of
omega-3-acid ethyl esters type A, USP, liquid
concentrate consisting of at least 900 mg
omega-3-acid ethyl esters.

Each Capsule Provides:
Eicosapentaenoic acid (EPA) ethyl ester: 465 mg
Docosahexaenoic acid (DHA) ethyl ester: 375 mg

Usual Dosage:
See accompanying prescribing information.
Swallow capsules whole.
Do not break open, crush, dissolve or chew.

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

Dispense in a tight, light-resistant container.

Manufactured by:
Swiss Caps AG
Husenstrasse 35
Kirchberg
Switzerland, 9533

Manufactured for:
Trygg Pharma, Inc.
1001 North 19th St.
Suite 1200
Arlington, VA 22209

89918-01
REV.02
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