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.

PERFOROMIST (NDA-022007)

(FORMOTEROL FUMARATE)

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

Download Data

Expand all

05/29/2019 (SUPPL-15)

Approved Drug Label (PDF)

4 Contraindications

(additions underlined)

Use of a LABA, including PERFOROMIST, without an inhaled corticosteroid is contraindicated in patients with asthma. PERFOROMIST is not indicated for the treatment of asthma.

5 Warnings and Precautions

5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death

(additions underlined)

The safety and efficacy of PERFOROMIST in patients with asthma have not been established. PERFOROMIST is not indicated for the treatment of asthma.

Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.

A 28-week, placebo-controlled US study comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs. 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34).

…

Available data do not suggest an increased risk of death with use of LABA in patients with COPD.

6 Adverse Reactions

(additions underlined)

Long-acting beta2-adrenergic agonists, such as PERFOROMIST, as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of asthma-related events. PERFOROMIST is not indicated for the treatment of asthma.

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

PATIENT COUNSELING INFORMATION

(additions underlined)

…

Serious Asthma-Related Events

Inform patients that long-acting beta agonist, such as PERFOROMIST, when used as monotherapy [without an inhaled corticosteroid], increase the risk of serious asthma-related events, including asthma-related death. PERFOROMIST is not indicated for the treatment of asthma.

…

PATIENT INFORMATION

( Medication Guide replaced with a Patient Package Insert, please refer to label for more information)

11/30/2017 (SUPPL-12)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

(Additions and/or revisions are underlined)

The following adverse reactions have been reported during post-approval use of PERFOROMIST Inhalation Solution…

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

Risk Summary

There are limited available data with PERFOROMIST Inhalation Solution use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Beta-agonists may interfere with uterine contractility. In animal reproduction studies, oral administration of formoterol fumarate to pregnant rats and rabbits caused increased fetal malformations (rats and rabbits), decreased fetal weight (rats), and increased neonatal mortality (rats) following administration of doses that produced exposures approximately 730 to 29,000 times the MRHD on a mg/m2 or AUC basis. These adverse effects generally occurred at large multiples of the MRHD when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No effects were observed in a study with rats that received formoterol fumarate by the inhalation route at an exposure approximately 300 times the MRHD.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Labor or delivery

There are no adequate and well-controlled human studies that have studied the effects of PERFOROMIST Inhalation Solution during labor and delivery. Because of the potential for beta-agonists interference with uterine contractility, use of PERFOROMIST Inhalation Solution during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Data

Animal Data

In embryofetal development studies with pregnant rats and rabbits dosed throughout the period of organogenesis, formoterol fumarate did not cause malformations in either species. However, for pregnant rats dosed throughout organogenesis, formoterol fumarate caused delayed fetal ossification at an exposure approximately 50 times the MRHD (on a mcg/m2 basis with maternal oral doses of 200 mcg/kg and higher) and decreased fetal weight at an exposure approximately 1,500 times the MRHD (on a mcg/m2 basis with maternal oral doses of 6,000 mcg/kg and above). In a pre- and post-natal development study with rats dosed during the late stage of pregnancy, formoterol fumarate caused stillbirth and neonatal mortality at an exposure approximately 1,500 times the MRHD (on a mcg/m2 basis with maternal oral doses of 6,000 mcg/kg and above). However, no effects were observed in this study at an exposure approximately 50 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 200 mcg/kg).

In embryofetal development studies, conducted by another testing laboratory, with pregnant rats and rabbits dosed throughout the period of organogenesis, formoterol fumarate was teratogenic in both species. Umbilical hernia, a malformation, was observed in rat fetuses at exposures approximately 730 times the MRHD (on a mcg/m2 basis with maternal oral doses of 3,000 mcg/kg/day and above). Brachygnathia, a skeletal malformation, was observed in rat fetuses at an exposure approximately 3,600 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 15,000 mcg/kg/day). In another study with rats, no teratogenic effects were observed with exposures up to approximately 300 times the MRHD (on a mcg/m2 basis with a maternal inhalation dose of 1,200 mcg/kg/day). Subcapsular cysts on the liver were observed in rabbit fetuses at an exposure approximately 29,000 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 60,000 mcg/kg/day). No teratogenic effects were observed with exposures up to approximately 1,700 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 3,500 mcg/kg).

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

Risk Summary

There are no well-controlled human studies of the use of PERFOROMIST Inhalation Solution in nursing mothers. It is not known whether formoterol fumarate is excreted in human milk, or whether there are effects on the breastfed infant or on the milk production.

In reproductive studies in rats formoterol was excreted in the milk.

The developmental and health benefits of breastfeeding should be considered along with the mother`s clinical need for PERFOROMIST Inhalation Solution and any potential adverse effects on the breastfed child from PERFOROMIST Inhalation Solution or from the underlying maternal condition.

Data

In a pharmacokinetic study in rats formoterol was excreted in the milk. The amount of radioactive labelled 3H- formoterol fumarate was less than 2% of that in the maternal plasma.