Drugs Details

Drugs Info of Vascepa
Drugs Details
  • Drugs Type  : Multum
  • Date : 9th Feb 2015 09:33 pm
  • Brand Name : Vascepa
  • Generic Name : icosapent (Pronunciation: eye KOE sa pent)
Descriptions

VASCEPA, a lipid-regulating agent, is supplied as a 1-gram amber-colored, liquid-filled soft gelatin capsule for oral administration.

Each VASCEPA capsule contains 1 gram of icosapent ethyl. Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). The empirical formula of icosapent ethyl is C22H34O2 and the molecular weight is 330.51. The chemical name for icosapent ethyl is ethyl all-cis-5,8,11,14,17-icosapentaenoate with the following chemical structure:

 

VASCEPA® (icosapent ethyl) Structural Formula Illustration

VASCEPA 1-gram capsules also contain the following inactive ingredients: tocopherol, gelatin, glycerin, maltitol, sorbitol, and purified water.

What are the possible side effects of icosapent (Vascepa)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Common side effects may include:

  • joint pain; or
  • sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at...

Read All Potential Side Effects and See Pictures of Vascepa »


This monograph has been modified to include the generic and brand name in many instances.

 

Indications

VASCEPA® (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe ( ≥ 500 mg/dL) hypertriglyceridemia.

Usage Considerations

Patients should be placed on an appropriate lipid-lowering diet and exercise regimen before receiving VASCEPA and should continue this diet and exercise regimen with VASCEPA.

Attempts should be made to control any medical problems such as diabetes mellitus, hypothyroidism, and alcohol intake that may contribute to lipid abnormalities. Medications known to exacerbate hypertriglyceridemia (such as beta blockers, thiazides, estrogens) should be discontinued or changed, if possible, prior to consideration of TG-lowering drug therapy.

Limitations of Use

The effect of VASCEPA on the risk for 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.

Dosage Administration

Assess lipid levels 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].

Patients should engage in appropriate nutritional intake and physical activity before receiving VASCEPA, which should continue during treatment with VASCEPA.

The daily dose of VASCEPA is 4 grams per day taken as 2 capsules twice daily with food.

Patients should be advised to swallow VASCEPA capsules whole. Do not break open, crush, dissolve, or chew VASCEPA.

How Supplied

Dosage Forms And Strengths

VASCEPA capsules are supplied as 1-gram amber-colored soft-gelatin capsules imprinted with VASCEPA.

Storage And Handling

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

Bottles of 120: 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 by: Banner Pharmacaps Tilburg, The Netherlands or Catalent Pharma Solutions, LLC St. Petersburg, FL, USA. Manufactured for: Amarin Pharmaceuticals Ireland Limited Dublin, Ireland +1-855-VASCEPA (+1-855-827-2372). Revised: Nov 2011


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

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*

Adverse Reaction Placebo
(N=309)
VASCEPA
(N=622)
n % n %
Arthralgia 3 1 14 2.3
*Studies included patients with triglycerides values of 200 to 2000 mg/dL.

An additional adverse reaction from clinical studies was oropharyngeal pain.

Read the Vascepa (icosapent ethyl capsules) Side Effects Center for a complete guide to possible side effects

Interactions

Anticoagulants

Some published studies with omega-3 fatty acids have demonstrated prolongation of bleeding time. The prolongation of bleeding time reported in those studies has not exceeded normal limits and did not produce clinically significant bleeding episodes. Patients receiving treatment with VASCEPA and other drugs affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.

Drug Abuse And Dependence

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

Read the Vascepa Drug Interactions Center for a complete guide to possible interactions

Learn More »


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Monitoring: Laboratory Tests

In patients with hepatic impairment, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored periodically during therapy with VASCEPA.

Fish Allergy

VASCEPA contains ethyl esters of the omega-3 fatty acid, eicosapentaenoic acid (EPA), obtained from the oil of fish. It is not known whether patients with allergies to fish and/or shellfish are at increased risk of an allergic reaction to VASCEPA. VASCEPA should be used with caution in patients with known hypersensitivity to fish and/or shellfish.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a 2-year rat carcinogenicity study with oral gavage doses of 0.09, 0.27, and 0.91 g/kg/day icosapent ethyl, respectively, males did not exhibit drug-related neoplasms. Hemangiomas and hemangiosarcomas of the mesenteric lymph node, the site of drug absorption, were observed in females at clinically relevant exposures based on body surface area comparisons across species relative to the maximum clinical dose of 4 g/day. Overall incidence of hemangiomas and hemangiosarcomas in all vascular tissues did not increase with treatment.

In a 6-month carcinogenicity study in Tg.rasH2 transgenic mice with oral gavage doses of 0.5, 1, 2, and 4.6 g/kg/day icosapent ethyl, drug-related incidences of benign squamous cell papilloma in the skin and subcutis of the tail was observed in high dose male mice. The papillomas were considered to develop secondary to chronic irritation of the proximal tail associated with fecal excretion of oil and therefore not clinically relevant. Drug-related neoplasms were not observed in female mice.

Icosapent ethyl was not mutagenic with or without metabolic activation in the bacterial mutagenesis (Ames) assay or in the in vivo mouse micronucleus assay. A chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells was positive for clastogenicity with and without metabolic activation.

In an oral gavage rat fertility study, ethyl-EPA, administered at doses of 0.3, 1, and 3 g/kg/day to male rats for 9 weeks before mating and to female rats for 14 days before mating through day 7 of gestation, increased anogenital distance in female pups and increased cervical ribs were observed at 3 g/kg/day (7 times human systemic exposure with 4 g/day clinical dose based on a body surface area comparison).

Use In Specific Populations

Pregnancy

Pregnancy Category C

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

In pregnant rats given oral gavage doses of 0.3, 1 and 2 g/kg/day icosapent ethyl from gestation through organogenesis all drug treated groups had visceral or skeletal abnormalities including: 13th reduced ribs, additional liver lobes, testes medially displaced and/or not descended at human systemic exposures following a maximum oral dose of 4 g/day based on body surface comparisons. Variations including incomplete or abnormal ossification of various skeletal bones were observed in the 2 g/kg/day group at 5 times human systemic exposure following an oral dose of 4 g/day based on body surface area comparison.

In a multigenerational developmental study in pregnant rats given oral gavage doses of 0.3, 1, 3 g/kg/day ethyl-EPA from gestation day 7-17, an increased incidence of absent optic nerves and unilateral testes atrophy were observed at ≥ 0.3 g/kg/day at human systemic exposure following an oral dose of 4 g/day based on body surface area comparisons across species. Additional variations consisting of early incisor eruption and increased percent cervical ribs were observed at the same exposures. Pups from high dose treated dams exhibited decreased copulation rates, delayed estrus, decreased implantations and decreased surviving fetuses (F2) suggesting multigenerational effects of ethyl-EPA at 7 times human systemic exposure following 4 g/day dose based on body surface area comparisons across species.

In pregnant rabbits given oral gavage doses of 0.1, 0.3, and 1 g/kg/day from gestation through organogenesis there were increased dead fetuses at 1 g/kg/day secondary to maternal toxicity (significantly decreased food consumption and body weight loss).

In pregnant rats given ethyl-EPA from gestation day 17 through lactation day 20 at 0.3, 1, 3 g/kg/day complete litter loss was observed in 2/23 litters at the low dose and 1/23 mid-dose dams by post-natal day 4 at human exposures based on a maximum dose of 4 g/day comparing body surface areas across species.

Nursing Mothers

Studies with omega-3-acid ethyl esters 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 VASCEPA is 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

Of the total number of subjects in clinical studies of VASCEPA, 33% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.


This monograph has been modified to include the generic and brand name in many instances.

OverDose

No information provided.

ContrainDications

VASCEPA is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to VASCEPA or any of its components.
This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

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

Absorption

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.

Distribution

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.

Metabolism and Excretion

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 (t1/2) 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)

Parameter VASCEPA 4 g/day
N=76
Placebo
N=75
Difference (95% Confidence Interval)
Baseline % Change Baseline % Change
TG (mg/dL) 680 -27 703 10 -33* (-47, -22)
LDL-C (mg/dL) 91 -5 86 -3 -2 (-13, +8)
Non-HDL-C (mg/dL) 225 -8 229 8 -18 (-25, -11)
TC (mg/dL) 254 -7 256 8 -16 (-22, -11)
HDL-C (mg/dL) 27 -4 27 0 -4 (-9, +2)
VLDL-C (mg/dL) 123 -20 124 14 -29** (-43, -14)
Apo B (mg/dL) 121 -4 118 4 -9**(-14, -3)
% Change= Median Percent Change from Baseline
Difference= Median of [VASCEPA % Change – Placebo % Change] (Hodges-Lehmann Estimate) p-values from Wilcoxon rank-sum test
*p-value < 0.001 (primary efficacy endpoint)
**p-value < 0.05 (key secondary efficacy endpoints determined to be statistically significant according to the pre-specified multiple comparison procedure)

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.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

VASCEPA should be used with caution in patients with known sensitivity or allergy to fish and/or shellfish [see WARNINGS AND PRECAUTIONS].

Patients should be advised that use of lipid-regulating agents does not reduce the importance of appropriate nutritional intake and physical activity [see DOSAGE AND ADMINISTRATION].

Patients should be advised not to alter VASCEPA capsules in any way and to ingest intact capsules only [see DOSAGE AND ADMINISTRATION].

Instruct patients to take VASCEPA as prescribed. If a dose is missed, patients should take it as soon as they remember. However if they miss one day of VASCEPA, they should not double the dose when they take it.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

No Information Available!

Consumer Overview Side Effect

No Information Available!

Consumer Overview Missed Dose

No Information Available!

Patient Detailed Side Effect

Brand Names: Vascepa

Generic Name: icosapent (Pronunciation: eye KOE sa pent)

  • What is icosapent (Vascepa)?
  • What are the possible side effects of icosapent (Vascepa)?
  • What is the most important information I should know about icosapent (Vascepa)?
  • What should I discuss with my healthcare provider before taking icosapent (Vascepa)?
  • How should I take icosapent (Vascepa)?
  • What happens if I miss a dose (Vascepa)?
  • What happens if I overdose (Vascepa)?
  • What should I avoid while taking icosapent (Vascepa)?
  • What other drugs will affect icosapent (Vascepa)?
  • Where can I get more information?

What is icosapent (Vascepa)?

Icosapent works in the liver and bloodstream to reduce very low-density triglycerides.

Icosapent is used together with a low-fat and low-cholesterol diet to reduce triglycerides (fats) in adults with severely high triglycerides.

It is not known whether icosapent will lower your risk of developing heart disease or pancreatitis (inflammation of your pancreas).

Icosapent may also be used for purposes not listed in this medication guide.

What are the possible side effects of icosapent (Vascepa)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Common side effects may include:

  • joint pain; or
  • sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Vascepa (icosapent ethyl capsules) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about icosapent (Vascepa)?

Icosapent is used together with a low-fat diet and other treatments to lower total cholesterol in people with severe high cholesterol.

Before you take icosapent, tell your doctor if you have liver disease, diabetes, a thyroid disorder, pancreas problems, a bleeding or blood-clotting disorder, an allergy to fish or shellfish, or if you drink large quantities of alcohol.

Icosapent is only part of a treatment program that may also include diet, exercise, and weight control. Follow your doctor's instructions very closely.

Side Effects Centers
  • Vascepa

Patient Detailed How Take

What should I discuss with my healthcare provider before taking icosapent (Vascepa)?

You should not use icosapent if you are allergic to it.

To make sure icosapent is safe for you, tell your doctor if you have:

  • liver disease;
  • diabetes;
  • a thyroid disorder;
  • problems with your pancreas;
  • a bleeding or blood-clotting disorder;
  • if you are allergic to fish or shellfish; or
  • if you drink large amounts of alcohol.

FDA pregnancy category C. It is not known whether icosapent will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Icosapent can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give this medication to anyone under 18 years old without medical advice.

How should I take icosapent (Vascepa)?

Icosapent is usually taken 2 times per day. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You should not take more than 4 icosapent capsules per day.

Take with food.

Do not crush, chew, break, dissolve, or open an icosapent capsule. Swallow it whole.

While using icosapent, you may need frequent blood tests at your doctor's office.

Icosapent is only part of a treatment program that may also include diet, exercise, and weight control. Follow your doctor's instructions very closely.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Vascepa

Patient Detailed Avoid Taking

What happens if I miss a dose (Vascepa)?

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.

What happens if I overdose (Vascepa)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking icosapent (Vascepa)?

Avoid eating foods that are high in fat or cholesterol. Icosapent will not be as effective in lowering your cholesterol if you do not follow a cholesterol lowering diet plan.

Avoid drinking alcohol while you are taking icosapent.

What other drugs will affect icosapent (Vascepa)?

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with icosapent, especially:

  • argatroban, bivalirudin, dabigatran, fondaparinux, lepirudin, rivaroxaban;
  • abciximab, eptifibatide, tirofiban;
  • dalteparin, enoxaparin, tinzaparin;
  • anagrelide, cilostazol, clopidogrel, dipyridamole, eltrombopag, oprelvekin, prasugrel, romiplostim, ticagrelor, ticlopidine;
  • alteplase, reteplase, tenecteplase, urokinase;
  • a beta-blocker--atenolol, carvedilol, labetalol, metoprolol, nadolol, nebivolol, propranolol, sotalol, others;
  • birth control pills or hormone replacement therapy;
  • a blood thinner such as warfarin, Coumadin; or
  • a diuretic or "water pill."

This list is not complete. Other drugs may interact with icosapent, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Where can I get more information?

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.

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