Icosapent Ethyl Capsules

Dosage Forms And Strengths

VASCEPA capsules are supplied in the following dosage form strengths:

• 0.5-gram amber-colored, oval, soft-gelatin capsules imprinted with V500.
• 1-gram amber-colored, oblong, soft-gelatin capsules imprinted with VASCEPA.

Storage And Handling

VASCEPA (icosapent ethyl) capsules are supplied as 0.5-gram amber-colored soft-gelatin capsules imprinted with V500 or as 1-gram amber-colored soft-gelatin capsules imprinted with VASCEPA.

Bottles of 240 (0.5-gram): NDC 52937-001-40.
Bottles of 120 (1-gram): NDC 52937-001-20.

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]. Keep out of reach of children.

Distributed by: Amarin Pharma Inc. Bedminster, NJ, USA. Manufactured for: Amarin Pharmaceuticals Ireland Limited Dublin, Ireland +1-855-VASCEPA (+1-855-827-2372). Revised: Aug 2016

No information provided.

Mechanism Of Action

Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.

Pharmacokinetics

After oral administration, VASCEPA is de-esterified during the absorption process and the active metabolite EPA is absorbed in the small intestine and enters the systemic circulation mainly via the thoracic duct lymphatic system. Peak plasma concentrations of EPA were reached approximately 5 hours following oral doses of VASCEPA.

VASCEPA was administered with or following a meal in all clinical studies; no food effect studies were performed. Take VASCEPA with or following a meal.

The mean volume of distribution at steady-state of EPA is approximately 88 liters. The majority of EPA circulating in plasma is incorporated in phospholipids, triglycerides and cholesteryl esters, and < 1% is present as the unesterified fatty acid. Greater than 99% of unesterified EPA is bound to plasma proteins.

EPA is mainly metabolized by the liver via beta-oxidation similar to dietary fatty acids. Beta oxidation splits the long carbon chain of EPA into acetyl Coenzyme A, which is converted into energy via the Krebs cycle. Cytochrome P450-mediated metabolism is a minor pathway of elimination of EPA. The total plasma clearance of EPA at steady state is 684 mL/hr. The plasma elimination half-life (t½) of EPA is approximately 89 hours. VASCEPA does not undergo renal excretion.

Drug-Drug Interactions

VASCEPA was studied at the 4 g/day dose level with the following medications which are typical substrates of cytochrome P450 enzymes, and no drug-drug interactions were observed:

Omeprazole: In a drug-drug interaction study with 28 healthy adult subjects, VASCEPA 4 g/day at steady-state did not significantly change the steady-state AUCτ or Cmax of omeprazole when co-administered at 40 mg/day to steady-state.

Rosiglitazone: In a drug-drug interaction study with 28 healthy adult subjects, VASCEPA 4 g/day at steady-state did not significantly change the single dose AUC or Cmax of rosiglitazone at 8 mg.

Warfarin: In a drug-drug interaction study with 25 healthy adult subjects, VASCEPA 4 g/day at steady-state did not significantly change the single dose AUC or Cmax of R-and S-warfarin or the anti-coagulation pharmacodynamics of warfarin when co-administered as racemic warfarin at 25 mg.

Atorvastatin: In a drug-drug interaction study of 26 healthy adult subjects, VASCEPA 4 g/day at steady-state did not significantly change the steady-state AUCτ or Cmax of atorvastatin, 2-hydroxyatorvastatin, or 4-hydroxyatorvastatin when co-administered with atorvastatin 80 mg/day to steady-state.

Specific Populations

Gender: When administered VASCEPA in clinical trials, plasma total EPA concentrations did not differ significantly between men and women.

Pediatric: The pharmacokinetics of VASCEPA has not been studied in pediatric patients.

Hepatic or Renal Impairment: VASCEPA has not been studied in patients with renal or hepatic impairment.

Clinical Studies

Severe Hypertriglyceridemia

The effects of VASCEPA 4 grams per day were assessed in a randomized, placebo-controlled, double-blind, parallel-group study of adult patients (76 on VASCEPA, 75 on placebo) with severe hypertriglyceridemia. Patients whose baseline TG levels were between 500 and 2,000 mg/dL were enrolled in this study for 12 weeks. The median baseline TG and LDL-C levels in these patients were 684 mg/dL and 86 mg/dL, respectively. Median baseline HDL-C level was 27 mg/dL. The randomized population in this study was mostly Caucasian (88%) and male (76%). The mean age was 53 years and the mean body mass index was 31 kg/m². Twenty-five percent of patients were on concomitant statin therapy, 28% were diabetics, and 39% of the patients had TG levels > 750 mg/dL.

The changes in the major lipoprotein lipid parameters for the groups receiving VASCEPA or placebo are shown in Table 2.

Table 2: Median Baseline and Percent Change from Baseline in Lipid Parameters in Patients with Severe Hypertriglyceridemia ( ≥ 500 mg/dL)

VASCEPA 4 grams per day reduced median TG, VLDL-C, and Apo B levels from baseline relative to placebo. The reduction in TG observed with VASCEPA was not associated with elevations in LDL-C levels relative to placebo.

The effect of VASCEPA on the risk of pancreatitis in patients with severe hypertriglyceridemia has not been determined. The effect of VASCEPA on cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Your pharmacist can provide more information about icosapent.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.01. Revision date: 2/12/2013.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions reported in at least 2% and at a greater rate than placebo for patients treated with VASCEPA based on pooled data across two clinical studies are listed in Table 1.

Table 1: Adverse Reactions Occurring at Incidence > 2% and Greater than Placebo in Double-Blind, Placebo-Controlled Trials*

An additional adverse reaction from clinical studies was oropharyngeal pain.

Read the entire FDA prescribing information for Vascepa (Icosapent Ethyl Capsules)

• Cholesterol

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.