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.

ASTEPRO (NDA-022203)

(AZELASTINE HYDROCHLORIDE)

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

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06/28/2021 (SUPPL-18)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions are underlined)

The safety and effectiveness of ASTEPRO have been established for seasonal allergic rhinitis in pediatric patients 2 to 17 years of age and perennial allergic rhinitis in pediatric patients 6 months of age to 11 years of age [see Clinical Studies (14)].

Use of ASTEPRO for seasonal allergic rhinitis in patients 2 to 17 years of age is supported by evidence from the following studies:

An adequate and well-controlled study of ASTEPRO in a 2-week randomized, multi-center, double-blind, placebo-controlled clinical trial of 834 adult and adolescent patients 12 years of age and older with seasonal allergic rhinitis
A randomized, double-blind, placebo-controlled trial in 486 pediatric patients 6 to 11 years of age with perennial allergic rhinitis with or without concomitant seasonal allergic rhinitis
A 4-week, randomized, open-label safety trial in 191 pediatric patients 6 months to 5 years of age; data from this study supported use for this indication in patients 2 to 5 years of age

Use of ASTEPRO for perennial allergic rhinitis in pediatric patients 6 months to 11 years of age is supported by evidence from a randomized, double-blind, placebo-controlled trial in 486 pediatric patients 6 to 11 years of age with perennial allergic rhinitis with or without concomitant seasonal allergic rhinitis.

09/06/2018 (SUPPL-15)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

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

Risk Summary

Limited data from postmarketing experience over decades of use with ASTEPRO in pregnant women have not identified any drug associated risks of miscarriage, birth defects, or other adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of fetal harm at oral doses approximately 4 times the clinical daily dose. Oral administration of azelastine hydrochloride to pregnant mice, rats, and rabbits, during the period of organogenesis, produced developmental toxicity that included structural abnormalities, decreased embryo-fetal survival, and decreased fetal body weights at doses 180 times and higher than the maximum recommended human daily intranasal dose (MRHDID) of 1.644 mg. However, the relevance of these findings in animals to pregnant women was considered questionable based upon the high animal to human dose multiple.

The estimated background risk of major birth defects and miscarriage for the indicated populations 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.

Data

Animal Data

In an embryo-fetal development study in mice dosed during the period of organogenesis, azelastine hydrochloride caused embryo-fetal death, structural abnormalities (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification, and decreased fetal weight at approximately 200 times the maximum recommended human daily intranasal dose (MRHDID) in adults (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day), which also caused maternal toxicity as evidenced by decreased maternal body weight. Neither fetal nor maternal effects occurred in mice at approximately 9 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 3 mg/kg/day).

In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 7 to 17, azelastine hydrochloride caused structural abnormalities (oligo-and brachydactylia), delayed ossification, and skeletal variations, in the absence of maternal toxicity, at approximately 180 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Azelastine hydrochloride caused embryo-fetal death and decreased fetal weight and severe maternal toxicity at approximately 410 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 10 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 2 mg/kg/day).

In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, azelastine hydrochloride caused abortion, delayed ossification and decreased fetal weight and severe maternal toxicity at approximately 360 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 4 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 0.3 mg/kg/day).

In a prenatal and postnatal development study in pregnant rats dosed from late in the gestation period and through the lactation period from gestation day 17 through lactation day 21, azelastine hydrochloride produced no adverse developmental effects on pups at maternal doses up to approximately 180 times the MRHDID (on mg/m2 basis at a maternal dose of 30 mg/kg/day).

8.2 Lactation

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

Risk Summary

There are no data on the presence of azelastine hydrochloride in human milk, the effects on the breastfed infant, or the effects on milk production following use of azelastine hydrochloride.

Because many drugs are excreted in human milk, caution should be exercised when ASTEPRO is administered to a nursing woman.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ASTEPRO and any potential adverse effects on the breastfed infant from ASTEPRO or from the underlying maternal condition.