Vascepa (Page 3 of 3)

14.2 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)

% 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)
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)

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.

16 HOW SUPPLIED/STORAGE AND HANDLING

NDC: 63629-8247-1: 30 Capsules in a BOTTLE

NDC: 63629-8247-2: 60 Capsules in a BOTTLE

NDC: 63629-8247-3: 120 Capsules in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling before starting VASCEPA (Patient Information).

Inform patients that VASCEPA may increase their risk for atrial fibrillation or atrial flutter [see Warnings and Precautions (5.1)].

Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions to VASCEPA and advise them to discontinue VASCEPA and seek medical attention if any reactions occur [see Warnings and Precautions (5.2)].

Inform patients that VASCEPA may increase their risk for bleeding, especially if they are receiving other antithrombotic agents [see Warnings and Precautions (5.3)].

Advise patients to swallow VASCEPA capsules whole. Do not break open, crush, dissolve, or chew VASCEPA [see Dosage and Administration (2.2)].

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.

For more information about VASCEPA, go to www.VASCEPA.com or call 1-855-VASCEPA (1-855-827-2372).

AMARIN^®

VASCEPA^® (icosapent ethyl)

Distributed by:
Amarin Pharma, Inc.
Bridgewater, NJ, USA

Manufactured for:
Amarin Pharmaceuticals Ireland Limited Dublin, Ireland

VASCEPA is a registered trademark of the Amarin group of companies

©2021 Amarin Pharma, Inc. Bridgewater NJ 08807. All rights reserved

P00120N 09/2021

This Patient Information has been approved by the U.S. Food and Drug Administration	Revised: 09/2021
PATIENT INFORMATION VASCEPA® (vas-EE-puh) (icosapent ethyl) capsules
What is VASCEPA? VASCEPA is a prescription medicine used: along with certain medicines (statins) to reduce the risk of heart attack, stroke, and certain types of heart issues requiring hospitalization in adults with heart (cardiovascular) disease, or diabetes and 2 or more additional risk factors for heart disease. along with a low-fat and low-cholesterol diet to lower high levels of triglycerides (fats) in adults. It is not known if VASCEPA changes your risk of having inflammation of your pancreas (pancreatitis). It is not known if VASCEPA is safe and effective in children.
Do not take VASCEPA if you are allergic to icosapent ethyl or any of the ingredients in VASCEPA. See the end of this leaflet for a complete list of ingredients in VASCEPA.
Before taking VASCEPA, tell your doctor about all of your medical conditions, including if you: have diabetes. have a low thyroid problem (hypothyroidism). have a liver problem. have a pancreas problem. are allergic to fish or shellfish. It is not known if people who are allergic to fish or shellfish are also allergic to VASCEPA. are pregnant, or planning to become pregnant. It is not known if VASCEPA will harm your unborn baby. are breastfeeding or plan to breastfeed. VASCEPA can pass into your breast milk, and may harm your baby. Talk to your doctor about the best way to feed your baby if you take VASCEPA. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and dietary or herbal supplements. VASCEPA can interact with certain other medicines that you are taking. Especially tell your doctor if you take medicines that affect your blood clotting (anticoagulants or blood thinners).
How should I take VASCEPA? Take VASCEPA exactly as your doctor tells you to take it. Do not change your dose or stop taking VASCEPA without talking to your doctor. Do not take more capsules than what is prescribed by your doctor. If you are prescribed the 0.5-gram capsules, you should not take more than 8 capsules each day with food. If you are prescribed the 1-gram capsules, you should not take more than 4 capsules each day with food. Take VASCEPA capsules whole. Do not break, crush, dissolve, or chew VASCEPA capsules before swallowing. If you miss a dose of VASCEPA, take it as soon as you remember. However, if you miss one day of VASCEPA, do not double your dose when you take it. Your doctor may start you on a diet that is low in saturated fat, cholesterol, carbohydrates, and low in added sugars before giving you VASCEPA. Stay on this diet while taking VASCEPA. Your doctor may do blood tests to check your triglyceride and other lipid levels while you take VASCEPA.
What are the possible side effects of VASCEPA? VASCEPA may cause serious side effects, including: Heart rhythm problems (atrial fibrillation and atrial flutter). Heart rhythm problems which can be serious and cause hospitalization have happened in people who take VASCEPA, especially in people who have heart (cardiovascular) disease or diabetes with a risk factor for heart (cardiovascular) disease, or who have had heart rhythm problems in the past. Tell your doctor if you get any symptoms of heart rhythm problems such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, chest discomfort, or you faint. Possible allergic reactions if you are allergic to fish or shellfish. Stop taking VASCEPA and tell your doctor right away or get emergency medical help if you have any signs or symptoms of an allergic reaction. Bleeding. Serious bleeding can happen in people who take VASCEPA. Your risk of bleeding may increase if you are also taking a blood thinner medicine. If you have liver problems and are taking VASCEPA, your doctor should do blood tests during treatment. The most common side effects of VASCEPA include: Muscle and joint pain. Swelling of the hands, legs, or feet. Constipation Gout Heart rhythm problems (atrial fibrillation). These are not all the possible side effects of VASCEPA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store VASCEPA? Store VASCEPA at room temperature between 68° to 77° F (20° to 25° C). Safely throw away medicine that is out of date or no longer needed. Keep VASCEPA and all medicine out of the reach of children.
General information about the safe and effective use of VASCEPA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VASCEPA for a condition for which it was not prescribed. Do not give VASCEPA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about VASCEPA that is written for health professionals.
What are the ingredients in VASCEPA? Active ingredient: icosapent ethyl Inactive ingredients: tocopherol, gelatin, glycerin, maltitol, sorbitol, and purified water VASCEPA is a registered trademark of the Amarin group of companies. ©2021 Amarin Pharma, Inc. Bridgewater NJ, 08807 All rights reserved PP00120N Distributed by: Amarin Pharma Inc. Bridgewater, NJ, USA Manufactured for: Amarin Pharmaceuticals Ireland Limited Dublin, Ireland +1-855-VASCEPA (+1-855-827-2372) www.vascepa.com For more information, go to www.vascepa.com or call 1-855-VASCEPA (1-855-827-2372).

VASCEPA icosapent ethyl capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63629-8247(NDC:52937-001) Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ICOSAPENT ETHYL (ICOSAPENT) ICOSAPENT ETHYL 1000 mg

Inactive Ingredients Ingredient Name Strength TOCOPHEROL 2 mg GELATIN, UNSPECIFIED SORBITOL GLYCERIN MALTITOL WATER

Product Characteristics Color YELLOW (Amber) Score no score Shape OVAL (Oblong) Size 25mm Flavor Imprint Code Vascepa Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:63629-8247-1 30 CAPSULE in 1 BOTTLE None 2 NDC:63629-8247-2 60 CAPSULE in 1 BOTTLE None 3 NDC:63629-8247-3 120 CAPSULE in 1 BOTTLE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202057 10/01/2012

Labeler — Bryant Ranch Prepack (171714327)

Registrant — Bryant Ranch Prepack (171714327)

Establishment
Name	Address	ID/FEI	Operations
Bryant Ranch Prepack		171714327	REPACK (63629-8247), RELABEL (63629-8247)

Revised: 12/2021 Bryant Ranch Prepack