Brimonidine and Timolol

COMBIGAN ® is indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP. The IOP-lowering of COMBIGAN dosed twice a day was slightly less than that seen with the concomitant administration of 0.5% timolol maleate ophthalmic solution dosed twice a day and 0.2% brimonidine tartrate ophthalmic solution dosed three times per day. COMBIGAN is a combination of brimonidine tartrate, an alpha-adrenergic receptor agonist, and timolol maleate, a beta-adrenergic receptor inhibitor, indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP.

COMBIGAN is comprised of two components: brimonidine tartrate and timolol. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. COMBIGAN is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor. Both brimonidine and timolol have a rapid onset of action, with peak ocular hypotensive effect seen at two hours post-dosing for brimonidine and one to two hours for timolol.

The recommended dosage is one drop in the affected eye(s) twice daily approximately 12 hours apart. 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), twice daily approximately 12 hours apart.

Bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease. Sinus bradycardia, atrioventricular block, overt cardiac failure, cardiogenic shock. Neonates and infants (pediatric patients younger than 2 years old). Hypersensitivity to any component of this product.

Potential for Severe Respiratory or Cardiac Reactions. Cardiac Failure. Obstructive Pulmonary Disease. Potentiation of Vascular Insufficiency. Increased Reactivity to Allergens. Potentiation of Muscle Weakness. Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus. Masking of Thyrotoxicosis. Ocular Hypersensitivity

6 A DVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Potential for Severe Respiratory or Cardiac Reactions Cardiac Failure Potentiation of Vascular Insufficiency Increased Reactivity to Allergens Potentiation of Muscle Weakness Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus Masking of Thyrotoxicosis Ocular Hypersensitivity Contamination of Topical Ophthalmic Products after Use Impairment of Beta-adrenergically Mediated Reflexes During Surgery Most common adverse reactions occurring in approximately 5% to 15% of patients included allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging.

7 D RUG INTERACTIONS Antihypertensives/cardiac glycosides may lower blood pressure. Concomitant use with systemic beta-blockers may potentiate systemic beta blockade. Oral or intravenous calcium antagonists may cause atrioventricular conduction disturbances, left ventricular failure, and hypotension. Catecholamine-depleting drugs may have additive effects and produce hypotension and/or marked bradycardia. Use with CNS depressants may result in an additive or potentiating effect. Digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time. CYP2D6 inhibitors may potentiate systemic beta-blockade. Tricyclic antidepressants may potentially blunt the hypotensive effect of systemic clonidine. Monoamine oxidase inhibitors may result in increased hypotension.

Store at 15°C to 25°C (59°F to 77°F). Protect from light.