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.

QOLIANA (NDA-021764)

(BRIMONIDINE TARTRATE)

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

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11/21/2025 (SUPPL-12)

Approved Drug Label (PDF)

4 Contraindications

Newly added subsection:

4.1 Neonates and Infants (Pediatric Patients Younger than 2 Years Old)

Brimonidine tartrate ophthalmic solution, 0.15% is contraindicated in neonates and infants (pediatric patients younger than 2 years old) [see Use in Specific Populations (8.4)].

4.2 Hypersensitivity Reactions

Subsection title revised

Brimonidine tartrate ophthalmic solution, 0.15% is contraindicated in patients with hypersensitivity to any component of this product [see Adverse Reactions (6.1) and (6.2)].

5 Warnings and Precautions

Newly added subsection:

5.2 Severe Cardiovascular Disease

Although brimonidine tartrate ophthalmic solution had minimal effect on the blood pressure of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease.

Newly added subsection:

5.3 Contamination of Topical Ophthalmic Products After Use

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.

6 Adverse Reactions

Additions and/or revisions underlined:

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

Neonates and Infants (Pediatric Patients Younger than 2 Years Old) [see Contraindications (4.1)]
Potentiation of Vascular Insufficiency [see Warnings and Precautions (5.1)]
Severe Cardiovascular Disease [see Warnings and Precautions (5.2)]
Contamination of Topical Ophthalmic Products After Use [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

. . .

Adverse reactions occurring in approximately 10 to 20% of the subjects included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritis.

Adverse reactions occurring in approximately 5 to 9% of the subjects included: burning sensation, conjunctival folliculosis, hypertension, ocular allergic reaction, oral dryness, and visual disturbance.

Adverse reactions occurring in approximately 1 to 4% of subjects included: allergic reaction, arthralgia, arthritis, asthenia, blepharitis, blepharoconjunctivitis, blurred vision, bronchitis, cataract, chest pain, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, diabetes mellitus, dyspepsia, dyspnea, epiphora, eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, fatigue, flu syndrome, follicular conjunctivitis, foreign body sensation, gastrointestinal disorder, headache, hypercholesterolemia, hypotension, infection, insomnia, joint disorder, keratitis, lid disorder, osteoporosis, pharyngitis, photophobia, rash, rhinitis, sinus infection, sinusitis, somnolence, stinging, superficial punctate keratopathy, tearing, visual field defect, vitreous detachment, vitreous disorder, vitreous floaters, and worsened visual acuity.

The following adverse reactions were reported in less than 1% of subjects: corneal erosion, nasal dryness, and taste perversion.

6.2 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been identified during postapproval use of brimonidine tartrate ophthalmic solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Bradycardia, iritis, miosis, skin reactions (including erythema, eyelid pruritis, rash, and vasodilation), and tachycardia.
Apnea, bradycardia, hypotension, hypothermia, hypotonia, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic solutions.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion:

Risk Summary

There are no adequate and well-controlled studies with brimonidine tartrate ophthalmic solution, 0.15% 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, brimonidine tartrate ophthalmic solution, 0.15% 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 tartrate 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 experiences 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 (approximately 50-times 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 (approximately 6-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 (approximately 750-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 mg/kg/day (180-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 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 brimonidine tartrate ophthalmic solution, 0.15% in nursing infants, brimonidine tartrate ophthalmic solution, 0.15% 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.

8.4 Pediatric Use

Additions and/or revisions underlined:

Brimonidine tartrate ophthalmic solution, 0.15% is contraindicated in pediatric patients younger than 2 years old [see Contraindications (4.1)]. During postmarketing surveillance, apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine.

In a well-controlled clinical study conducted in pediatric glaucoma patients aged 2 to 7 years old, the most commonly observed adverse events with brimonidine tartrate ophthalmic solution 0.2% dosed three-times- daily were somnolence (50% to 83% in pediatric patients aged 2 to 6 years old) and decreased alertness. In pediatric patients aged 7 years and older (>20 kg), somnolence appears to occur less frequently (25%).

Approximately 16% of pediatric patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Handling the Container

Instruct patients that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.3)]. Always replace the cap after using. If solution changes color or becomes cloudy, do not use. Do not use the product after the expiration date marked on the bottle.

When to Seek Physician Advice

Advise patients that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container.

Use with Other Ophthalmic Drugs

Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

Potential for Decreased Mental Alertness

As with other drugs in this class, brimonidine tartrate ophthalmic solution, 0.15% may cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness.