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.

CORLANOR (NDA-206143)

(IVABRADINE HYDROCHLORIDE)

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

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08/04/2021 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Atrial Fibrillation

(Additions and/or revisions underlined)

Corlanor increases the risk of atrial fibrillation. In the Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial (SHIFT), the rate of atrial fibrillation was 5.0% per patient-year in patients treated with Corlanor and 3.9% per patient-year in patients treated with placebo [see Clinical Studies (14)]. Regularly monitor cardiac rhythm. Discontinue Corlanor if atrial fibrillation develops.

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

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.

Adult Patients with Heart Failure

In SHIFT, safety was evaluated in 3,260 patients treated with Corlanor and 3,278 patients given placebo. The median duration of Corlanor exposure was 21.5 months.

05/13/2019 (SUPPL-7)

Approved Drug Label (PDF)

4 Contraindications

Clinically significant hypotension replaces Blood pressure less than 90/50 mmHg.

Clinically significant bradycardia replaces Resting heart rate less than 60bpm prior to treatment.

5 Warnings and Precautions

5.1 Fetal Toxicity

Additions and/or revisions underlined:

… Advise females of reproductive potential to use …

5.3 Bradycardia and Conduction Disturbances

Subsection now broken into two sections, with the Adult title above existing information:

Adult Patients

Bradycardia, sinus arrest, and heart block …

Newly added Pediatric section:

Pediatric Patients

Bradycardia and first-degree heart block were observed in pediatric patients treated with Corlanor. Asymptomatic and symptomatic bradycardia were observed in 6.8% and 4.1% of pediatric patients treated with Corlanor, respectively. In the placebo treatment arm, 2.4% of pediatric patients had asymptomatic bradycardia, but none had symptomatic bradycardia. Bradycardia was managed through dose titration but did not result in study drug discontinuation.

6 Adverse Reactions

6.1 Clinical Trials Experience

Subsection now broken into two sections, with the Adult title above existing information:

Adult Patients with Heart Failure

In the Systolic Heart failure treatment …

Newly added Pediatric section:

Pediatric Patients with Heart Failure

The safety of Corlanor in pediatric patients 6 months to less than 18 years of age is based on a clinical trial in symptomatic heart failure patients with dilated cardiomyopathy and elevated heart rate. This trial provides experience in 73 patients treated with Corlanor for a median duration of 397 days, and 42 patients given placebo. Bradycardia (symptomatic and asymptomatic) occurred at rates similar to those in adults. Phosphenes were observed in pediatric patients treated with Corlanor.

6.2 Postmarketing Experience

Adverse reactions listed are in Adults only.

7 Drug Interactions

Additions and/or revisions underlined:

7.3 Pacemakers in Adults

… targeting a heart rate of 50 to 60 beats per minute in adults.

8 Use in Specific Populations

8.4 Pediatric Use

Newly added information; please refer to label for complete information.

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

MEDICATION GUIDE

Medication guide has been reformatted and revised; please refer to label for complete information.

PATIENT COUNSELING INFORMATION

Newly added bulleted information:

Oral Solution

Advise parents/caregivers on preparation and administration instructions including the use of a calibrated oral syringe and a medicine cup (provided by the pharmacy) to avoid dosing errors.

Advise parents/caregivers that the oral solution should not be administered by the child. Advise parents/caregivers to not double up doses (e.g., if patient spits out the drug or caregiver forgets to give the drug at the prescribed time). Advise parents/caregivers to throw away the unused product remaining in the cup immediately after drawing up the prescribed dose in the syringe.

01/10/2017 (SUPPL-2)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Bradycardia and Conduction Disturbances

(Additions and/or revisions are underlined)

…Bradycardia may increase the risk of QT prolongation which may lead to severe ventricular arrhythmias, including torsade de pointes, especially in patients with risk factors such as use of QTc prolonging drugs…

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

…The following adverse reactions have been identified during post-approval use of Corlanor: syncope, hypotension, torsade de pointes, ventricular fibrillation, ventricular tachycardia…

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

MEDICATION GUIDE

(Additions and/or revisions are underlined)

What is the most important information I should know about Corlanor?

Increased risk of irregular or rapid heartbeat (atrial fibrillation or heart rhythm problems). Tell your doctor if you have symptoms of an irregular or rapid heartbeat, such as feeling that your heart is pounding or racing (palpitations), chest pressure, or worsened shortness of breath, near fainting or fainting.