BETIMOL

WARNINGS As with other topically applied ophthalmic drugs, Betimol ® is absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely, death in association with cardiac failure have been reported following systemic or topical administration of beta-adrenergic blocking agents. Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe cardiac failure. In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. Betimol ® should be discontinued at the first sign or symptom of cardiac failure. Obstructive Pulmonary Disease Patients with chronic obstructive pulmonary disease (e.g. chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma which are contraindications) should in general not receive beta-blocking agents. Major Surgery The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to a major surgery is controversial. Beta-adrenergic receptor blockade impairs 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 blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic receptor blocking agents is recommended. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of beta-adrenergic agonists. Diabetes Mellitus Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia. Thyrotoxicosis Beta-adrenergic blocking agents 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 blocking agents which might precipitate a thyroid storm.

ADVERSE REACTIONS The most frequently reported ocular event in clinical trials was burning/stinging on instillation and was comparable between Betimol ® and timolol maleate (approximately one in eight patients). The following adverse events were associated with use of Betimol ® in frequencies of more than 5% in two controlled, double-masked clinical studies in which 184 patients received 0.25% or 0.5% Betimol ® : OCULAR: Dry eyes, itching, foreign body sensation, discomfort in the eye, eyelid erythema, conjunctival injection, and headache. BODY AS A WHOLE: Headache. The following side effects were reported in frequencies of 1 to 5%: OCULAR: Eye pain, epiphora, photophobia, blurred or abnormal vision, corneal fluorescein staining, keratitis, blepharitis and cataract. BODY AS A WHOLE: Allergic reaction, asthenia, common cold and pain in extremities. CARDIOVASCULAR: Hypertension. DIGESTIVE: Nausea. METABOLIC/NUTRITIONAL: Peripheral edema. NERVOUS SYSTEM/PSYCHIATRY: Dizziness and dry mouth. RESPIRATORY: Respiratory infection and sinusitis. In addition, the following adverse reactions have been reported with ophthalmic use of beta blockers: OCULAR: Conjunctivitis, blepharoptosis, decreased corneal sensitivity, visual disturbances including refractive changes, diplopia and retinal vascular disorder. BODY AS A WHOLE: Chest pain. CARDIOVASCULAR: Arrhythmia, palpitation, bradycardia, hypotension, syncope, heart block, cerebral vascular accident, cerebral ischemia, cardiac failure and cardiac arrest. DIGESTIVE: Diarrhea. ENDOCRINE: Masked symptoms of hypoglycemia in insulin dependent diabetics (See WARNINGS ). NERVOUS SYSTEM/PSYCHIATRY: Depression, impotence, increase in signs and symptoms of myasthenia gravis and paresthesia. RESPIRATORY: Dyspnea, bronchospasm, respiratory failure and nasal congestion. SKIN: Alopecia, hypersensitivity including localized and generalized rash, urticaria.