Triklo Capsules

Triklo Capsules are indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia (HTG).

Usage Considerations: Patients should be placed on an appropriate lipid-lowering diet before receiving Triklo Capsules and should continue this diet during treatment with Triklo Capsules.

Laboratory studies should be done to ascertain that the lipid levels are consistently abnormal before instituting therapy with Triklo Capsules. 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 triglyceride-lowering drug therapy.

Limitations of Use:

The effect of Triklo Capsules on the risk for pancreatitis has not been determined.

The effect of Triklo Capsules on cardiovascular mortality and morbidity has not been determined.

• Assess triglyceride levels carefully before initiating therapy. Identify other causes (e.g., diabetes mellitus, hypothyroidism, or medications) of high triglyceride levels and manage as appropriate [see Indications and Usage (1)].
• Patients should be placed on an appropriate lipid-lowering diet before receiving Triklo Capsules, and should continue this diet during treatment with Triklo Capsules. In clinical studies, Triklo Capsules were administered with meals.

The daily dose of Triklo 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 Triklo Capsules whole. Do not break open, crush, dissolve, or chew Triklo Capsules.

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% and at a greater rate than placebo for subjects treated with omega-3-acid ethyl esters based on pooled data across 23 clinical trials are listed in Table 1.

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

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. 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.

Pregnancy

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

Animal Data: Triklo Capsules 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 grams/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 grams/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 grams/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 grams/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 the human systemic exposure following an oral dose of 4 grams/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 grams/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 grams/day based on a body surface area comparison).

Nursing Mothers

Studies with Triklo Capsules 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 Triklo Capsules are administered to a nursing mother. An animal study in lactating rats given oral gavage 14C-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 subjects older than 65 years were enrolled in the clinical trials of Triklo Capsules. Safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.

Triklo Capsules (omega-3-acid ethylesters capsules, USP) are supplied as 1 gram, transparent, soft-gelatin capsules filled with light-yellow oil and imprinted with "AN34".

They are available as follows:

Bottles of 60 capsules: NDC 70868-150-60
Bottles of 120 capsules: NDC 70868-150-12

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Do not freeze. Dispense in a tight, light-resistant container. Protect from light. Keep out of reach of children.

NDC 70868-150-60

Triklo Capsules
(omega-3-acid ethyl
esters capsules, USP)

1 gram*

Swallow
capsules whole.

KEY
therapeutics

Rx Only

60 Capsules