Omega-3 Fatty Acids 30 mg, Vitamin E 400 IU, Wheat Germ Oil 100 mg Tablets

The mechanism of action of omega-3-acid ethyl esters 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. Omega-3-acid ethyl esters may reduce the synthesis of TG 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.

Absorption — In healthy volunteers and in subjects with hypertriglyceridemia, EPA and DHA were absorbed when administered as ethyl esters orally. Omega-3-acids administered as ethyl esters (omega-3-acid ethyl esters capsules) 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.

Specific Populations — Age:Uptake of EPA and DHA into serum phospholipids in subjects treated with omega-3-acid ethyl esters was independent of age (younger than 49 years versus 49 years and older).

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

Pediatric Patients:Pharmacokinetics of omega-3-acid ethyl esters have not been studied.

Patients with Renal or Hepatic Impairment:omega-3-acid ethyl esters has not been studied in patients with renal or hepatic impairment.

Drug Interaction Studies — Simvastatin:In a 14-day trial of 24 healthy adult subjects, daily coadministration of simvastatin 80 mg with omega-3-acid ethyl esters 4 grams did not affect the extent (AUC) or rate (C max) of exposure to simvastatin or the major active metabolite, beta-hydroxy simvastatin, at steady state.

Atorvastatin:In a 14-day trial of 50 healthy adult subjects, daily coadministration of atorvastatin 80 mg with omega-3-acid ethyl esters 4 grams did not affect AUC or Cmax of exposure to atorvastatin, 2-hydroxyatorvastatin, or 4-hydroxyatorvastatin at steady state.

Rosuvastatin:In a 14-day trial of 48 healthy adult subjects, daily coadministration of rosuvastatin 40 mg with omega-3-acid ethyl esters 4 grams did not affect AUC or C maxof exposure to rosuvastatin at steady state.

In vitro studies using human liver microsomes indicated that clinically significant cytochrome P450-mediated inhibition by EPA/DHA combinations are not expected in humans.

Vitamin E encompasses fat-soluble compounds with antioxidant activity. Alpha-tocopherol is the form recognized as meeting human requirements; biological activity differs among tocopherols and tocotrienols.

Vitamin E forms are absorbed in the small intestine and taken up by the liver. Hepatic alpha-tocopherol transfer protein preferentially returns alpha-tocopherol to the circulation, while the liver metabolizes and excretes other forms. This selective handling means different vitamin E forms should not be assigned identical pharmacokinetic values.