Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

VASCEPA (NDA-202057)

(ICOSAPENT ETHYL)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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12/13/2019 (SUPPL-35)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Atrial Fibrillation/Flutter

(new subsection added)

VASCEPA is associated with an increased risk of atrial fibrillation or atrial flutter requiring hospitalization. In a double-blind, placebo-controlled trial of 8,179 statin-treated subjects with established cardiovascular disease (CVD) or diabetes plus an additional risk factor for

CVD, adjudicated atrial fibrillation or atrial flutter requiring hospitalization for 24 or more hours occurred in 127 (3%) patients treated with VASCEPA compared to 84 (2%) patients receiving placebo [HR= 1.5 (95% CI 1.14, 1.98)]. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter.

5.2 Potential for Allergic Reactions in Patients with Fish Allergy

(additions underlined)

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. 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.

5.3 Bleeding

(new subsection added)

VASCEPA is associated with an increased risk of bleeding. In a double-blind, placebo- controlled cardiovascular outcomes trial of 8,179 patients, 482 (12%) patients receiving VASCEPA experienced a bleeding event compared to 404 (10%) patients receiving placebo. Serious bleeding events occurred in 111 (3%) of patients on VASCEPA vs. 85 (2%) of patients receiving placebo. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel, or warfarin.

6 Adverse Reactions

(additions underlined)

The following important adverse reactions are described below and elsewhere in the labeling:

Atrial Fibrillation or Atrial Flutter
Potential for Allergic Reactions in Patients with Fish Allergy
Bleeding

6.1 Clinical Trials Experience

(additions and/or revisions underlined)

…

Cardiovascular Outcomes Trial

In a double-blind, randomized, placebo-controlled cardiovascular outcomes trial, 8,179 statin-stabilized patients were randomized to receive VASCEPA or placebo and followed for a median of 4.9 years. The median age at baseline was 64 years, 29% were women, 90% White, 5% Asian, 2% were Black, and 4% identified as Hispanic ethnicity.

Common adverse reactions (incidence greater than or equal to3% on VASCEPA and greater than or equal to1% more frequent than placebo) included musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation.

Hypertriglyceridemia Trials

In two randomized, double-blind, placebo-controlled trials in patients with triglyceride levels between 200 and 2000 mg/dL treated for 12 weeks, adverse reactions reported with VASCEPA at an incidence greater than or equal to 1% more frequent than placebo based on pooled data included arthralgia and oropharyngeal pain.

6.2 Postmarketing Experience

(new subsection added)

Additional adverse reactions have been identified during post-approval use of VASCEPA. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Diarrhea
Blood triglycerides increased
Abdominal discomfort
Pain in the extremities

7 Drug Interactions

7.1 Increased Bleeding Risk with Anticoagulants and Antiplatelet Agents

(additions and/or revisions underlined)

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. Monitor patients receiving VASCEPA and concomitant anticoagulants and/or antiplatelet agents for bleeding.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label)

8.2 Lactation

(PLLR conversion)

Risk Summary

Published studies have detected omega-3 fatty acids, including EPA, in human milk. Lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. There are no data on the effects of omega-3 fatty acid ethyl esters on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VASCEPA and any potential adverse effects on the breastfed child from VASCEPA or from the underlying maternal condition.

8.5 Geriatric Use

(additions and/or revisions underlined)

Of the total number of patients in well-controlled clinical studies of VASCEPA, 45% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger groups. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

8.7 Hepatic Impairment

(new subsection added)

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

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(additions and revisions underlined)

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.

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 .

Inform patients that VASCEPA may increase their risk for bleeding, especially if they are receiving other antithrombotic agents .

Advise patients to swallow VASCEPA capsules whole. Do not break open, crush, dissolve, or chew VASCEPA.

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).

PATIENT INFORMATION

(additions and/or revisions underlined)

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.

…

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).

…

02/16/2017 (SUPPL-19)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION VASCEPA (vas-EE-puh) (icosapent ethyl) capsules

(Additions and/or revisions are underlined)

Before taking VASCEPA tell your doctor about all of your medical conditions, including if you:

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and dietary or herbal supplements.

• If you are prescribed the 0.5 gram capsules, you should not take more than 8 capsules each day.

• If you are prescribed the 1 gram capsules, you should not take more than 4 capsules per day.

These are not all the possible side effects of VASCEPA.

You can ask your pharmacist or healthcare provider for information about VASCEPA that is written for health professionals.