It is not known whether omega-3-acid ethyl esters are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LOVAZA is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

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

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

In the event of an overdose, the patient should be treated symptomatically, and general supportive care measures instituted, as required.

LOVAZA, a lipid-regulating agent, is supplied as a liquid-filled gel capsule for oral administration. Each 1-gram capsule of LOVAZA contains at least 900 mg of the ethyl esters of omega-3 fatty acids 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 CHO, 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 CHO, and the molecular weight of DHA ethyl ester is 356.55. The structural formula of DHA ethyl ester is:

LOVAZA capsules also contain the following inactive ingredients: 4 mg α-tocopherol (in a carrier of soybean oil), and gelatin, glycerol, and purified water (components of the capsule shell).

The mechanism of action of LOVAZA is not completely understood. Potential mechanisms of action include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal β-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity. LOVAZA may reduce the synthesis of triglycerides in the liver because EPA and DHA are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit esterification of other fatty acids.

In healthy volunteers and in patients with hypertriglyceridemia, EPA and DHA were absorbed when administered as ethyl esters orally. Omega-3-acids administered as ethyl esters (LOVAZA) induced significant, dose-dependent increases in serum phospholipid EPA content, though increases in DHA content were less marked and not dose-dependent when administered as ethyl esters.

Uptake of EPA and DHA into serum phospholipids in subjects treated with LOVAZA was independent of age (<49 years versus ≥49 years).

Females tended to have more uptake of EPA into serum phospholipids than males. The clinical significance of this is unknown.

Pharmacokinetics of LOVAZA in pediatric patients have not been established [see Use in Specific Populations (8.4)].

LOVAZA has not been studied in patients with renal or hepatic impairment.

In a 14-day study of 24 healthy adult subjects, daily co-administration of simvastatin 80 mg with LOVAZA 4 grams did not affect the extent (AUC) or rate (C) of exposure to simvastatin or the major active metabolite, beta-hydroxy simvastatin at steady state.

In a 14-day study of 50 healthy adult subjects, daily co-administration of atorvastatin 80 mg with LOVAZA 4 grams did not affect AUC or C of exposure to atorvastatin, 2-hydroxyatorvastatin, or 4