BRIMONIDINE TARTRATE

Brimonidine Tartrate Ophthalmic Solution, 0.15%, sterile, is a relatively selective alpha-2 adrenergic receptor agonist for topical ophthalmic use. The structural formula of brimonidine tartrate is: 5-bromo-6-(2-imidazolin-2-ylamino) quinoxaline D-tartrate; MW= 442.22 In solution, brimonidine tartrate ophthalmic solution has a clear, greenish-yellow color. It has an osmolality of 250 to 350 mOsmol/kg and a pH of 6.6 to 7.4 (0.15%). Brimonidine tartrate appears as white to slightly yellowish powder and is soluble in both water (0.6 mg/mL) and in the product vehicle (1.4 mg/mL) at pH 7.7. Each mL of Brimonidine Tartrate Ophthalmic Solution contains the active ingredient brimonidine tartrate 0.15% (1.5 mg/mL) with the inactive ingredients boric acid; calcium chloride dihydrate; carboxymethylcellulose sodium; magnesium chloride; potassium chloride; sodium borate; sodium chloride; sodium chlorite (0.08 mg/mL) as a preservative; water for injection; and hydrochloric acid and/or sodium hydroxide to adjust pH. structure.jpg

Brimonidine tartrate ophthalmic solution, 0.15% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Brimonidine tartrate ophthalmic solution is an alpha adrenergic agonist indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. ( 1 )

The recommended dosage is one drop of brimonidine tartrate ophthalmic solution 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. One drop in the affected eye(s) three times daily, approximately 8 hours apart. ( 2 )

Neonates and infants (pediatric patients younger than 2 years old). ( 4.1 ) Hypersensitivity Reactions. ( 4.2 ) 4.1 Neonates and Infants (Pediatric Patients Younger than 2 Years Old) Brimonidine tartrate ophthalmic solution is contraindicated in neonates and infants (pediatric patients younger than 2 years old) [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.

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 (Pediatric Patients Younger than 2 Years Old) [see Contraindications ( 4.1 )] Most common adverse reactions occurring in approximately 5% to 20% of patients receiving brimonidine ophthalmic solution (0.1% to 0.2%) included allergic conjunctivitis, burning sensation, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, hypertension, ocular allergic reaction, oral dryness, and visual disturbance. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions occurring in approximately 10% to 20% of the subjects receiving brimonidine ophthalmic solution (0.1% to 0.2%) included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritus. Adverse reactions occurring in approximately 5% to 9% included: burning sensation, conjunctival folliculosis, hypertension, ocular allergic reaction, oral dryness, and visual disturbance. Adverse reactions occurring in approximately 1% to 4% of the subjects receiving brimonidine ophthalmic solution (0.1% to 0.2%) included: abnormal taste, allergic reaction, asthenia, blepharitis, blepharoconjunctivitis, blurred vision, bronchitis, cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, 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 (primarily colds and respiratory infections), insomnia, keratitis, lid disorder, 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 reactions were reported in less than 1% of subjects: corneal erosion, hordeolum, nasal dryness, and taste perversion. 6.2 Postmarketing Experience The following reactions have been identified during postapproval use of brimonidine tartrate ophthalmic solutions. 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, depression, hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, skin reactions (including erythema, eyelid pruritus, rash, and vasodilation), syncope, and tachycardia. Apnea, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic solutions.

Antihypertensives/cardiac glycosides may lower blood pressure. ( 7.1 ) Use with CNS depressants may result in an additive or potentiating effect. ( 7.2 ) Tricyclic antidepressants may potentially blunt the hypotensive effect of systemic clonidine. ( 7.3 ) Monoamine oxidase inhibitors may result in increased hypotension. ( 7.4 ) 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.

Storage: Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room temperature]. KEEP THIS AND ALL DRUGS OUT OF REACH OF CHILDREN