Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

TRILIPIX (NDA-022224)

(CHOLINE FENOFIBRATE)

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

Download Data

Expand all

06/03/2021 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Hepatotoxicity

(Newly added section)

Serious drug-induced liver injury (DILI), including liver transplantation and death, have been reported postmarketing with Trilipix. DILI has been reported within the first few weeks of treatment or after several months of therapy and in some cases has reversed with discontinuation of Trilipix treatment. Patients with DILI have experienced signs and symptoms including dark urine, abnormal stool, jaundice, malaise, abdominal pain, myalgia, weight loss, pruritus, and nausea. Many patients had concurrent elevations of total bilirubin, serum alanine transaminase (ALT), and aspartate transaminase (AST). DILI has been characterized as hepatocellular, chronic active, and cholestatic hepatitis, and cirrhosis has occurred in association with chronic active hepatitis.

In clinical trials, Trilipix at a dose of 135 mg daily has been associated with increases in serum AST or ALT. The incidence of increases in transaminases observed with fenofibrate therapy may be dose related [see Adverse Reactions (6.1)].

Trilipix is contraindicated in patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities [see Contraindications (4)]. Monitor patient’s liver function, including serum ALT, AST, and total bilirubin, at baseline and periodically for the duration of therapy with Trilipix. Discontinue Trilipix if signs or symptoms of liver injury develop or if elevated enzyme levels persist (ALT or AST > 3 times the upper limit of normal, or if accompanied by elevation of bilirubin). Do not restart Trilipix in these patients if there is no alternative explanation for the liver injury.

5.3 Myopathy and Rhabdomyolysis

(Section title revised)

6 Adverse Reactions

(Newly added information)

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

Mortality and coronary heart disease morbidity [see Warnings and Precautions (5.1)]
Hepatoxicity [see Warnings and Precautions (5.2)]
Pancreatitis [see Warnings and Precautions (5.7)]
Hypersensitivity reactions [see Warnings and Precautions (5.9)]
Venothromboembolic disease [see Warnings and Precautions (5.10)]

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during postapproval use of fenofibrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: rhabdomyolysis, pancreatitis, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, increased total bilirubin, anemia, asthenia, severely depressed HDL- cholesterol levels, and interstitial lung disease.

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

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Patients should be advised:

to inform their physician of symptoms of liver injury (e.g., jaundice, abdominal pain, nausea, malaise, dark urine, abnormal stool, pruritus); any muscle pain, tenderness, or weakness; or any other new symptoms.

03/28/2019 (SUPPL-15)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Addition of and interstitial lung disease to adverse reactions identified during postapproval use of fenofibrate.

11/07/2018 (SUPPL-14)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

8.2 Lactation

PLLR conversion. Extensive additions and/or revisions in the 2 subsections. Please refer to label for complete information.

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

PATIENT COUNSELING INFORMATION

Addition of the following:

not to use Trilipix if there is a known hypersensitivity to fenofibrate or fenofibric acid.

that if they are taking coumarin anticoagulants, Trilipix may increase their anti-coagulant effect, and increased monitoring may be necessary.

to return to their physician’s office for routine monitoring.

not to breastfeed during treatment with Trilipix and for 5 days after the final dose.

05/18/2018 (SUPPL-13)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.9 Hypersensitivity Reactions

(subsection revised, additions underlined)

Acute Hypersensitivity

Anaphylaxis and angioedema have been reported postmarketing with fenofibrate. In some cases, reactions were life-threatening and required emergency treatment. If a patient develops signs or symptoms of an acute hypersensitivity reaction, advise them to seek immediate medical attention and discontinue fenofibrate.

Delayed Hypersensitivity

Severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported postmarketing, occurring days to weeks after initiation of fenofibrate. The cases of DRESS were associated with cutaneous reactions (such as rash or exfoliative dermatitis) and a combination of eosinophilia, fever, systemic organ involvement (renal, hepatic, or respiratory). Discontinue fenofibrate and treat patients appropriately if SCAR is suspected.

6 Adverse Reactions

6.1 Clinical Trials Experience

(additions underlined)

…

Urticaria was seen in 1.1 vs. 0%, and rash in 1.4 vs. 0.8% of fenofibrate and placebo patients respectively in controlled trials.

…

6.2 Postmarketing Experience

(additions underlined)

The following adverse reactions have been identified during postapproval use of fenofibrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: rhabdomyolysis, pancreatitis, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, anemia, asthenia, and severely depressed HDL-cholesterol levels.

Photosensitivity reactions to fenofibrate have occurred days to months after initiation; in some of these cases, patients reported a prior photosensitivity reaction to ketoprofen.