WARNINGS AND PRECAUTIONS
General
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 ophthalmic 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 following systemic or ophthalmic administration of timolol maleate [see Contraindications (4) ].
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 failure.
In patients without a history of cardiac failure, continued depression of the myocardium with beta-adrenergic receptor inhibitors over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, Timolol GFS should be discontinued.
Bronchospasm and Obstructive Pulmonary Disease
Bronchospasm may occur. 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, in which Timolol GFS is contraindicated [see Contraindications (4) ]) should, in general, not receive beta-adrenergic receptor inhibitors, including Timolol GFS.
Surgical Anesthesia
The necessity or desirability of withdrawal of beta-adrenergic receptor inhibitors prior to 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 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.
Diabetes Mellitus
Beta-adrenergic receptor inhibitors should be administered with caution in diabetic patients subject to hypoglycemia who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor inhibitors may mask the signs and symptoms of acute hypoglycemia.
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 that might precipitate a thyroid storm.
Cerebrovascular Insufficiency
Because of potential effects of beta-adrenergic receptor inhibitors on blood pressure and pulse, these agents should be used with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of therapy with Timolol GFS, alternative therapy should be considered.
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) ].
Choroidal Detachment
Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant (e.g., timolol) therapy.
Angle-Closure Glaucoma
In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This may require constricting the pupil. Timolol GFS has little or no effect on the pupil and should not be used alone in the treatment of angle-closure glaucoma.
Atopy/Anaphylaxis
While taking beta receptor inhibitors, patients with a history of atopy or a history of severe anaphylactic reactions 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.
Muscle Weakness
Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been reported to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.
USE IN SPECIFIC POPULATIONS
Pregnancy
Teratogenic effects
Pregnancy Category C: Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose) demonstrated no evidence of fetal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1,000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the maximum recommended human ophthalmic dose, in this case without apparent maternotoxicity.
There are no adequate and well-controlled studies in pregnant women. Timolol GFS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
Timolol maleate has been detected in human milk following oral and ophthalmic drug administration. Because of the potential for serious adverse reactions in nursing infants from Timolol GFS, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and IOP-lowering effect of Timolol GFS 0.25% and 0.5% has been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-controlled trial.
Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and younger patients.
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