Betaxolol

1 INDICATIONS AND USAGE BETOPTIC S ® (betaxolol hydrochloride ophthalmic suspension) 0.25% is indicated for the treatment of elevated intraocular pressure (IOP) in patients with chronic open-angle glaucoma or ocular hypertension. BETOPTIC S is a beta-adrenergic receptor inhibitor indicated for the treatment of elevated intraocular pressure (IOP) in patients with chronic open-angle glaucoma or ocular hypertension. ( 1 )

2 DOSAGE AND ADMINISTRATION Instill one drop of BETOPTIC S in the affected eye(s) twice daily. Shake well before using. BETOPTIC S may be used alone or in combination with other IOP lowering medications. Advise patients requiring concomitant topical ophthalmic medications to administer these at least 10 minutes before instilling BETOPTIC S. Instill one drop in the affected eye(s) twice daily. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Ophthalmic suspension containing 2.5 mg/mL of betaxolol as base (0.25%) in 10 mL and 15 mL bottles. Ophthalmic suspension: 2.5 mg/mL of betaxolol as base (0.25%). ( 3 )

4 CONTRAINDICATIONS BETOPTIC S is contraindicated in patients with: sinus bradycardia greater than a first degree atrioventricular (AV) block cardiogenic shock patients with overt cardiac failure hypersensitivity to any component of this product Hypersensitivity to any component of this product. ( 4 ) Sinus bradycardia, second or third degree atrioventricular (AV) block, overt cardiac failure, and cardiogenic shock. ( 4 )

5 WARNINGS AND PRECAUTIONS Systemic Absorption : Same adverse reactions found with systemic administration of beta-adrenergic receptor inhibitors may occur with topical ophthalmic administration. ( 5.1 ) Cardiac Failure : Discontinue treatment at the first signs of cardiac failure. ( 5.2 ) Diabetes Mellitus : Beta-adrenergic receptor inhibitors may mask the signs and symptoms of acute hypoglycemia. Administer with caution in diabetic patients subject to hypoglycemia. ( 5.3 ) Thyrotoxicosis : Beta-adrenergic receptor inhibitors may mask certain clinical signs (e.g., tachycardia) or hyperthyroidism. ( 5.4 ) 5.1 Systemic Absorption As with many topically applied ophthalmic drugs, this drug is absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic receptor inhibitors may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and death due to cardiac failure, have been reported with topical application of beta-adrenergic receptor inhibitors. 5.2 Cardiac Failure BETOPTIC S has been shown to have a minor effect on heart rate and blood pressure in clinical studies. Caution should be used in treating patients with a history of cardiac failure or heart block. Treatment with BETOPTIC S should be discontinued at the first signs of cardiac failure. 5.3 Diabetes Mellitus Beta-adrenergic receptor inhibitors should be administered with caution in patients subject to hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor inhibitors may mask the signs and symptoms of acute hypoglycemia. 5.4 Thyrotoxicosis Beta-adrenergic receptor inhibitors may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic receptor inhibitors, which might precipitate a thyroid storm. 5.5 Muscle Weakness Beta-adrenergic receptor inhibitors have been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). 5.6 Surgical Anesthesia The necessity or desirability of withdrawal of beta-adrenergic receptor inhibitors prior to major surgery is controversial. Beta-adrenergic receptor inhibitors impair the ability of the heart to respond to beta adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor inhibitors have experienced protracted, severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. In patients undergoing elective surgery, consider gradual withdrawal of beta-adrenergic receptor inhibitors. If necessary during surgery, the effects of beta-adrenergic receptor inhibitors may be reversed by sufficient doses of adrenergic agonists. 5.7 Bronchospasm and Obstructive Pulmonary Disease Caution should be exercised in the treatment of glaucoma patients with excessive restriction of pulmonary function. There have been reports of asthmatic attacks and pulmonary distress during betaxolol treatment. Although rechallenges of some such patients with ophthalmic betaxolol has not adversely affected pulmonary function test results, the possibility of adverse pulmonary effects in patients sensitive to beta-adrenergic receptor inhibitors cannot be ruled out. 5.8 Atopy/Anaphylaxis While taking beta-adrenergic receptor inhibitors, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions. 5.9 Angle-Closure Glaucoma In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle. This may require constricting the pupil. Betaxolol has little or no effect on the pupil and should not be used alone in the treatment of angle-closure glaucoma. 5.10 Vascular Insufficiency Because of potential effects of beta-adrenergic receptor inhibitors on blood pressure and pulse, these inhibitors should be used with caution in patients with vascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow or Raynaud’s phenomenon develop following initiation of therapy with BETOPTIC S, alternative therapy should be considered. 5.11 Bacterial Keratitis Bacterial keratitis may occur with use of multiple dose containers of topical ophthalmic products when these containers are inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. Instruct patients on appropriate instillation techniques [see Patient Counseling Information (17)] . 5.12 Choroidal Detachment Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant therapy. 5.13 Contact Lens Wear The preservative in BETOPTIC S, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of BETOPTIC S but may be reinserted 15 minutes after instillation [see Patient Counseling Information (17)] .

6 ADVERSE REACTIONS The most frequent adverse reaction is transient ocular discomfort. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or 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. In clinical trials, the most frequent adverse reaction associated with the use of BETOPTIC S has been transient ocular discomfort. The following other adverse reactions have been reported in small numbers of patients: Ocular: blurred vision, corneal punctate keratitis, foreign body sensation, photophobia, tearing, itching, dryness of eyes, erythema, inflammation, discharge, ocular pain, decreased visual acuity, and crusty lashes. Systemic Adverse Reactions Include : Cardiovascular: Bradycardia, heart block, and congestive failure. Pulmonary: Pulmonary distress characterized by dyspnea, bronchospasm, thickened bronchial secretions, asthma, and respiratory failure. Central Nervous System: Insomnia, dizziness, vertigo, headaches, depression, lethargy, and increase in signs, and symptoms of myasthenia gravis. Other: Hives, toxic epidermal necrolysis, hair loss and glossitis. Perversions of taste and smell have been reported. In a 3-month, double-masked, active-controlled, multicenter study in pediatric patients, the adverse reaction profile of BETOPTIC S was comparable to that seen in adult patients. 6.2 Additional Potential Adverse Reactions Associated With Betaxolol Additional medical events reported with other formulations of betaxolol include allergic reactions, decreased corneal sensitivity, corneal punctate staining which may appear in dendritic formation, edema, and anisocoria.

16 HOW SUPPLIED/STORAGE AND HANDLING BETOPTIC S (betaxolol hydrochloride ophthalmic suspension), 0.25% is supplied as follows: 10 mL and 15 mL in plastic ophthalmic dispensers. Tamper evidence is provided with a shrink band around the closure and neck area of the package. 10 mL NDC 0078-0729-10 15 mL NDC 0078-0729-15 Storage and Handling Store upright at 2°C to 25°C (36°F to 77°F). Shake well before using. After opening, BETOPTIC S can be used until the expiration date on the bottle.