BRIMONIDINE TARTRATE

BRIMONIDINE TARTRATE — brimonidine tartrate solution/ drops
Somerset Therapeutics, LLC

1 INDICATIONS AND USAGE

Brimonidine tartrate ophthalmic solution 0.2% is indicated for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

The IOP lowering efficacy of Brimonidine tartrate ophthalmic solution diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored.

2 DOSAGE AND ADMINISTRATION

The recommended dose is one drop of Brimonidine tartrate ophthalmic solution 0.2% in the affected eye(s) three times daily, approximately 8 hours apart.

Brimonidine tartrate ophthalmic solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.

3 DOSAGE FORMS AND STRENGTHS

Solution containing 2 mg/mL brimonidine tartrate.

4 CONTRAINDICATIONS

4.1 Neonates and Infants (under the age of 2 years)

Brimonidine tartrate ophthalmic solution is contraindicated in neonates and infants (under the age of 2 years) [see Use in Specific Populations (8.4) ].

4.2 Hypersensitivity Reactions

Brimonidine tartrate ophthalmic solution is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past [see Adverse Reactions (6.1) and (6.2) ].

5 WARNINGS AND PRECAUTIONS

5.1 Potentiation of Vascular Insufficiency

Brimonidine tartrate ophthalmic solution may potentiate syndromes associated with vascular insufficiency.

Brimonidine tartrate ophthalmic solution should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.

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.

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 [see Patient Counseling Information (17)].

5.4 Use with Contact Lenses

The preservative in Brimonidine tartrate ophthalmic solution, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling Brimonidine tartrate ophthalmic solution to insert soft contact lenses.

6 ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling:

• 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) ]
• Neonates and Infants (under the age of 2 years) [see Contraindications (4.1) ]

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

• Adverse reactions occurring in approximately 10-30% of the subjects (in descending order): oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus.
• Adverse reactions occurring in approximately 3-9% of the subjects (in descending order): corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, conjunctival blanching, abnormal vision and muscular pain.
• Adverse reactions reported < 3% of the patients: lid crusting, conjunctival hemorrhage, abnormal taste, insomnia, conjunctival discharge, depression, hypertension, anxiety, palpitations/arrhythmias, nasal dryness and syncope.

6.2 Postmarketing Experience

The following reactions have been identified during postmarketing use of brimonidine tartrate ophthalmic solutions in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, or a combination of these factors, include:

• Bradycardia; conjunctivitis; hypersensitivity; hypotension; iritis; keratoconjunctivitis sicca; lacrimation increased; miosis; nausea; skin reactions (including erythema, eyelid pruritus, rash, and vasodilation); and tachycardia.
• Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence in infants receiving brimonidine tartrate ophthalmic solutions.

7 DRUG INTERACTIONS

7.1 Antihypertensives/Cardiac Glycosides

Because Brimonidine tartrate ophthalmic solution may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with Brimonidine tartrate ophthalmic solution is advised.

7.2 CNS Depressants

Although specific drug interaction studies have not been conducted with Brimonidine tartrate ophthalmic solution, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.

7.3 Tricyclic Antidepressants

Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with Brimonidine tartrate ophthalmic solution in humans can lead to resulting interference with the IOP lowering effect. Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

7.4 Monoamine Oxidase Inhibitors

Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B: Teratogenicity studies have been performed in animals.

Brimonidine tartrate was not teratogenic when given orally during gestation days 6 through 15 in rats and days 6 through 18 in rabbits. The highest doses of brimonidine tartrate in rats (2.5 mg/kg/day) and rabbits (5 mg/kg/day) achieved AUC exposure values 375-fold higher or 19-fold higher, respectively, than similar values estimated in humans treated with Brimonidine tartrate ophthalmic solution 0.2%, one drop in one eye, twice daily.

There are no adequate and well-controlled studies in pregnant women; however, in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent.

Because animal reproduction studies are not always predictive of human response, Brimonidine tartrate ophthalmic solution should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.