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.

ALPHAGAN (NDA-020490)

(BRIMONIDINE TARTRATE)

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

Download Data

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09/18/2025 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Contamination of Topical Ophthalmic Products After Use

Newly added subsection

Do not touch the tip of the dispensing container to the eye or surrounding structures. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Patient Counseling Information (17)].

6 Adverse Reactions

Additions and/or revisions underlined:

. . .

Contamination of Topical Ophthalmic Products After Use [see Warnings and Precautions (5.3)]
Neonates and Infants (Pediatric Patients Younger than 2 Years Old) [see Contraindications (4.1)]

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion:

Risk Summary

There are no adequate and well-controlled studies with ALPHAGAN in pregnant women. 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.

In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent (see Data). Because animal reproduction studies are not always predictive of human response, ALPHAGAN should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Data

Human Data

Limited available data from postmarketing safety reports and published literature with topical use of brimonidine ophthalmic solution in pregnant women are insufficient to inform a drug- associated risk of pregnancy-related adverse outcomes including miscarriage, stillbirth, congenital anomaly, and events experienced by offspring while breastfeeding.

Animal Data

Embryofetal studies were conducted in pregnant rabbits administered brimonidine tartrate by daily oral gavage on gestation days 6 to 18, to target the period of organogenesis. Brimonidine caused miscarriage at

5 mg/kg/day (12-fold the recommended human ophthalmic dose [RHOD] based on AUC. The no observed adverse effect level (NOAEL) for developmental toxicity in rabbits was 1 mg/kg/day (2.3-fold the RHOD based on AUC). No treatment-related malformations were observed in rabbits. Signs of maternal sedation and fatigue were observed at all dose levels; the lowest observed adverse effect level (LOAEL) for maternal toxicity was 5 mg/kg/day, based on the dose-response for these signs.

Embryofetal studies were conducted in pregnant rats administered brimonidine tartrate by daily oral gavage on gestation days 6 to 15, to target the period of organogenesis. The NOAEL for developmental toxicity was

2.5 mg/kg/day (236-fold the RHOD based on AUC). No treatment-related malformations were observed in rats. The LOAEL for maternal toxicity was 2.5 mg/kg/day, based on signs of sedation and fatigue. The maternal NOAEL was 1.0 mg/kg/day (71-fold the RHOD based on AUC).

After pregnant rats received a single oral dose of 14C-brimonidine tartrate, brimonidine and metabolites crossed the placenta and were detectable in fetal blood and organs.

8.2 Lactation

PLLR conversion:

Risk Summary

It is not known whether brimonidine tartrate is excreted in human milk. In animal studies, brimonidine tartrate has been shown to cross the blood-brain barrier and is excreted into breast milk after oral administration to lactating rats (see Data). Because of the potential for serious adverse reactions, including central nervous system depression and apnea, from ALPHAGAN in nursing infants, ALPHAGAN is not recommended for use during lactation.

Data

Animal Data

After a single oral dose of 14C-labeled brimonidine tartrate to lactating rats, brimonidine and metabolites were detected in milk. After male and female rats received a single oral dose of 14C-brimonidine tartrate, brimonidine crossed the blood-brain barrier. Radiolabel was detected in the cerebellum, cerebrum, and spinal cord.

Other

Pregnancy and Lactation Labeling Rule (PLLR) conversion