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.

BEPREVE (NDA-022288)

(BEPOTASTINE BESILATE)

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

Download Data

Expand all

02/09/2018 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.1 Contamination of Tip and Solution

To minimize contaminating the dropper tip and solution, advise the patient not to touch the eyelids …

5.2 Contact Lens Wear

… BEPREVE should not be instilled while wearing contact lenses. Patient should remove contact lenses prior to instillation of BEPREVE, because benzalkonium chloride may be absorbed by soft contact lenses.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion; additions underlined:

Risk Summary

There are no available human data for the use of BEPREVE during pregnancy to inform any drug-associated risks.

Oral administration of bepotastine besilate to pregnant rats or rabbits during organogenesis or during the pre/postnatal period did not produce adverse embryofetal or offspring effects at clinically relevant systemic exposures. Maternal toxicity was observed in the rabbits at the lowest dose administered, 20 mg/kg/day (215 times the maximum recommended human ophthalmic dose, RHOD, on a mg/m2 basis)

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data

Animal Data

In embryofetal development studies, oral administration of bepotastine besilate to pregnant rabbits throughout organogenesis did not produce teratogenic effects at maternal doses up to 500 mg/kg/day (approximately 5400 times the maximum RHOD, on a mg/m2 basis). A maternal no observed adverse effect level (NOAEL) was not identified in this study due to spontaneous abortion observed at the lowest dose tested, 20 mg/kg/day (approximately 215 times higher than the maximum RHOD, on a mg/m2 basis). Oral administration of bepotastine besilate to pregnant rats throughout organogenesis produced skeletal anomalies at 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis), a dose that also produced maternal toxicity and lethality. No teratogenic effects were observed in rats at maternal doses up to 200 mg/kg/day (corresponding to an estimated blood plasma concentration 3300 times higher than that anticipated in humans at the maximum RHOD). A maternal NOAEL was observed at 10 mg/kg/day (54 times higher than the maximum RHOD, on a mg/m2 basis). Following a single 3 mg/kg oral dose in rats (16 times higher than the maximum RHOD, on a mg/m2 basis), the concentration of radio-labeled bepotastine besilate …

… In a pre/postnatal development study, oral administration of bepotastine besilate to rats during the perinatal and lactation periods produced an increase in stillbirths and decreased growth and development in offspring at a maternal dose of 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis). There were no observed adverse effects on offspring of rats treated with 100 mg/kg/day (540 times higher than the maximum RHOD, on a mg/m2 basis). Effects on parturition and maternal lethality were observed at 100 mg/kg/day and 1000 mg/kg/day, respectively. A maternal NOAEL was observed at 10 mg/kg/day (54 times higher than the maximum RHOD, on a mg/m2 basis).

8.2 Lactation

PLLR conversion; additions underlined:
Risk Summary

There are no data on the presence of BEPREVE in human milk, the effects on the breastfed infant or the effects on milk production.

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

Animal Data

Following a single 3 mg/kg oral dose (16 times the maximum RHOD, on a mg/m2 basis) of radiolabeled bepotastine besilate to nursing rats … at 48 hours after administration, the radioactivity concentration was below detection limits. The milk radioactivity concentration was higher than the maternal blood plasma radioactivity concentration at each time of measurement. It is not known whether bepotastine besilate would be present in maternal milk following topical ocular administration.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Sterility of Dropper Tip

Advise patients not to touch the dropper tip to any surface, as this may contaminate the solution and to keep the bottle tightly closed when not in use.