As an adjunct to diet and exercise, Amarin's lipid-regulating agent Vascepa (icosapent ethyl capsules) is indicated to reduce triglyceride levels in adult patients with severe hypertriglyceridemia, or very high triglyceride (TG) levels greater than or equal to 500 milligrams per deciliter (mg/dL).
As an adjunct to diet and exercise, Amarin’s lipid-regulating agent Vascepa (icosapent ethyl capsules) is indicated to reduce triglyceride levels in adult patients with severe hypertriglyceridemia, or very high triglyceride (TG) levels greater than or equal to 500 milligrams per deciliter (mg/dL).
Approved by the FDA in July 2012, Vascepa has “demonstrated a statistically significant placebo-adjusted reduction in levels of triglycerides without elevation in levels of very low-density lipoprotein cholesterol (VLDL-C), commonly referred to as 'bad cholesterol,’ ” Amarin Chairman and CEO Joseph Zakrzewski said in a press release.
Approximately 4 million people in the United States have severe hypertriglyceridemia, which is typically correlated with an increased risk of cardiovascular disease and often caused or exacerbated by uncontrolled diabetes mellitus and obesity.
Pharmacology and Pharmacokinetics
The full prescribing information of Vascepa notes potential mechanisms of action include “increased beta-oxidation; inhibition of acetyl Coenzyme A (acyl-CoA):1,2-diacylglycerol acyltransferase (DGAT); decreased lipogensesis in the liver; and increased plasma lipoprotein lipase activity.”
Following oral administration, Vascepa is de-esterified and active metabolite omega-3 fatty acid eicosapentaenoic acid (EPA) is absorbed in the small intestine and incorporated in phospholipids, triglycerides and cholesteryl esters after it enters plasma through the thoracic duct lymphatic system. Peak plasma concentrations are reached about five hours later.
Similar to dietary fatty acids, EPA is mainly metabolized by the liver through beta-oxidation — a process that splits the acid’s long carbon chain into acyl-CoA, which is converted into energy. The plasma elimination half-life of EPA is 89 hours.
Dosage and Administration
Prior to receiving Vascepa, patients should engage in a lipid-lowering diet and physical activity, and then maintain those core lifestyle improvements throughout dose administration.
Attempts should be made to control medical problems that can contribute to abnormal lipid levels — such as diabetes mellitus, hypothyroidism and alcohol intake — and medications known to exacerbate hypertriglyceridemia — such as beta blockers, thiazides and estrogens — should be discontinued or changed before Vascepa administration.
Vascepa is supplied as 1-gram amber-colored, soft-gelatin capsules imprinted with “VASCEPA.” Each capsule contains 1 gram of icosapent ethyl, an ethyl ester of EPA. The daily dose of Vascepa is four grams per day in the form of two capsules swallowed whole and taken with food.
In a 12-week placebo-controlled, double-blind study of 151 patients with baseline TG levels between 500 mg/dL and 2,000 mg/dL, a 4-gram daily dose of Vascepa was shown to reduce median TG, VLDL-C and Apolipoprotein B levels from baseline compared to placebo patients.
The effect of Vascepa on the risk for pancreatitis and cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia was not determined in the study.
Contraindications, Warnings and Precautions
Vascepa is contraindicated in patients with hypersensitivity to icosapent ethyl, and alanine aminotransferase and aspartate aminotransferase levels should be periodically monitored in patients with hepatic impairment.
Though icosapent ethyl is an ethyl ester of EPA, which is obtained from fish oil, it is unknown whether patients who are allergic to fish or shellfish have an increased risk of allergic reaction to Vascepa.
The most commonly reported adverse reaction to Vascepa is arthralgia, though an additional adverse reaction found in clinical studies was oropharyngeal pain.