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.

ARCAPTA NEOHALER (NDA-022383)

(INDACATEROL MALEATE)

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

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07/30/2021 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Avoid Excessive Use of ARCAPTA NEOHALER and Avoid Use with Other Long-Acting Beta2-Adrenergic Agonists

Additions underlined

As with other inhaled beta2-adrenergic drugs, ARCAPTA NEOHALER should not be used more often, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

5.4 Hypersensitivity Reactions, including Anaphylaxis

Additions underlined

Immediate hypersensitivity reactions may occur after administration of ARCAPTA NEOHALER. If signs suggesting allergic reactions (in particular, difficulties in breathing or swallowing, swelling of tongue, lips and face, urticaria, skin rash, anaphylaxis) occur, ARCAPTA NEOHALER should be discontinued immediately and alternative therapy instituted.

6 Adverse Reactions

Additions underlined

The following clinically significant adverse reactions are described in greater detail elsewhere in the labeling:

Serious Asthma-Related Events – Hospitalizations, Intubations, Death [see Warnings and Precautions (5.1)]
Paradoxical Bronchospasm [see Warnings and Precautions (5.5)]
Hypersensitivity Reactions, including Anaphylaxis [see Contraindications (4), Warnings and Precautions (5.4)]
Cardiovascular Effects [see Warnings and Precautions (5.6)]

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion

Risk Summary

There are no adequate and well-controlled studies with ARCAPTA NEOHALER in pregnant women. Women should be advised to contact their physician if they become pregnant while taking ARCAPTA NEOHALER.

In animal reproduction studies, there was no evidence of fetal harm or structural abnormalities following subcutaneous administration of indacaterol maleate to pregnant Wistar rats and New Zealand White rabbits during the period of organogenesis at exposures approximately 180 and 410 times the maximum recommended human dose (MRHD of 75 mcg), respectively, on an exposure area under the curve (AUC) basis (see Data).

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% to 4% and 15% to 20%, respectively.

Clinical Considerations

Labor or Delivery

There are no adequate and well-controlled human studies that have investigated effects of ARCAPTA NEOHALER during labor and delivery. Because beta-agonist may potentially interfere with uterine contractility, ARCAPTA NEOHALER should be used during labor only if the potential benefit justifies the potential risk.

Data

Animal Data

In embryo-fetal development studies, pregnant Wistar rats received indacaterol maleate, during the period of organogenesis from Gestation Days 6 to 17, at exposures up to 180 times the MRHD (on an AUC basis with maternal subcutaneous doses up to 1 mg/kg/day) and pregnant New Zealand White rabbits received indacaterol maleate, during the period of organogenesis from Gestation Days 7 to 20, at exposures up to 1000 times the MRHD (on an AUC basis with maternal subcutaneous doses up to 3 mg/kg/day). Indacaterol maleate produced no evidence of fetal harm or structural abnormalities in rats and rabbits at exposures up to 180 and 410 times, respectively, the MRHD. Rabbit fetuses were observed with increased incidences of full supernumerary rib, a structural variation at an exposure approximately 1000 times the MRHD.

In a pre- and postnatal development study, pregnant Wistar rats received indacaterol maleate, throughout the period of organogenesis and lactation from Gestation Day 6 through Lactation Day 20, at doses up to 130 times the MRHD (on a mg/m2 basis with maternal subcutaneous doses up to 1 mg/kg/day). F1 pups received subcutaneous doses of indacaterol maleate up to 1 mg/kg/day from postpartum Days 4 through 20. There was no evidence of maternal toxicity with doses up to 130 times the MRHD. There were no effects on the physical or behavioral development of F1 pups with doses up to 40 times the MRHD (on a mg/m2 basis with maternal and F1 pup subcutaneous doses up to 0.3 mg/kg/day). There was a decrease in the number of F1 pregnant animals at a dose approximately 130 times the MRHD (on a mg/m2 basis with maternal and F1 pup subcutaneous doses of 1 mg/kg/day); however, there were no effects on mating or other parameters of reproductive performance.

8.2 Lactation

PLLR conversion

Risk Summary

There is no data on the presence of indacaterol in human milk, effect on the breastfed infant, or the effects on milk production. Indacaterol is present in the milk of lactating rats (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ARCAPTA NEOHALER and any potential adverse effects on the breastfed child from ARCAPTA NEOHALER or from the underlying maternal condition.

Data

Animal Data

Indacaterol and its metabolites were detected in the milk within 1 hour following a single subcutaneous dose of 650 mcg radiolabeled indacaterol maleate administered to lactating rats postpartum days 8 and 9.

05/29/2019 (SUPPL-7)

Approved Drug Label (PDF)

4 Contraindications

(additions underlined)

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

ARCAPTA NEOHALER is contraindicated in patients with a history of hypersensitivity to indacaterol or to any of the ingredients.

5 Warnings and Precautions

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

(additions underlined)

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

Use of long-acting betaR2R-adreneric agonists (LABA), such as indacaterol, the active ingredient in ARCAPTA NEOHALER, 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.

…

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 betaR2R-adrenergic agonists, such as ARCAPTA NEOHALER, as monotherapy (without inhaled corticosteroids) for asthma increase the risk of asthma-related events. ARCAPTA NEOHALER is not indicated for the treatment of asthma.

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

PATIENT COUNSELING INFORMATION

17.1 Serious Asthma-Related Events

(additions underlined)

Patients should be informed that LABA, such as ARCAPTA NEOHALER, when used as monotherapy [without an inhaled corticosteroid], increase the risk of serious asthma-related events, including asthma-related death. ARCAPTA NEOHALER 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)