ing concomitant adrenergic psychotropic drugs. 7.4 calcium antagonists, antiarrhythmics and digitalis the concomitant use of a beta-adrenergic receptor inhibitor with calcium antagonists, antiarrhythmics (including amiodarone) or digitalis may have additive effects resulting in hypotension and/or marked bradycardia.

e 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)] .

ons 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.

ing concomitant adrenergic psychotropic drugs. 7.4 calcium antagonists, antiarrhythmics and digitalis the concomitant use of a beta-adrenergic receptor inhibitor with calcium antagonists, antiarrhythmics (including amiodarone) or digitalis may have additive effects resulting in hypotension and/or marked bradycardia.

dy, oral administration of 4, 40, or 400 mg/kg/day betaxolol on gestational days 6 through 18, the period of organogenesis, resulted in marked embryo-fetal lethality, increased incidence of skeletal and visceral abnormalities, and decreased fetal weights at the maternally toxic dose of 400 mg/kg/day (7785 times higher than the maximum recommended human ophthalmic dose [mrhod] of 0.0083 mg/kg/day, on a mg/m 2 basis). the no-observed-adverse-effect-level (noael) for maternal or embryo-fetal toxicity was 40 mg/kg/day (778 times higher than the mrhod, on a mg/m 2 basis). in a rabbit efd study, oral administration of 1, 4, 12, and 36 mg/kg/day betaxolol on gestational days 6 through 18, the period of organogenesis, resulted in a marked increase in embryo-fetal lethality at 36 mg/kg/day (1400 times higher than the mrhod, on a mg/m 2 basis). no maternal toxicity was reported in this study. in a perinatal and postnatal development study in rats, oral administration of 4, 32, and 256 mg/kg/day betaxolol during late gestation through lactation resulted in a marked decrease in offspring survival within 4 days postpartum at the highest dose (4982 times higher than the mrhod, on a mg/m 2 basis). in surviving f 1 offspring, growth/development and reproductive function were also affected. the noael was 32 mg/kg/day (623 times higher than the mrhod, on a mg/m 2 basis). in a prenatal and postnatal development study in rats, an oral betaxolol dose of 150 mg/kg/day (2920 times higher than the mrhod, on mg/m 2 basis) administered throughout the entire gestation period and lactation, resulted in maternal and developmental toxicity in f 1 offspring, including decreased offspring survival, body weight and growth/development and functional deficits in surviving offspring. no noael for developmental or maternal toxicity was established in this study. oral administration of 4, 32, and 256 mg/kg/day betoxolol to rats prior to mating and through late gestation, or until weaning, produced embryo-fetal lethality, neonatal mortality, decreased mean fetal weight, growth/development and functional deficits in surviving offspring at 256 mg/kg/day (4982 times higher than the mrhod, on a mg/m 2 basis). at 32 mg/kg/day (623 higher than the mrhod, on a mg/m 2 basis), decreased mean fetal weight on gestation day 20, and pup weight at birth and on day 4 postpartum were observed. at 4 mg/kg/day (78 times higher than the mrhod, on a mg/m 2 basis), a slight decrease in mean fetal weight was observed on gestation day 20. 8.2 lactation risk summary beta-blockers are excreted in breast milk following oral administration, having the potential to cause serious undesirable effects in the infant of the nursing mother. it is not known whether measurable levels of betaxolol would be present in maternal milk following topical ocular administration. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for betoptic s, and any potential adverse effects on the breast-fed child from betoptic s. 8.4 pediatric use safety and iop lowering effect of betoptic s has been demonstrated in pediatric patients in a 3 month, multicenter, double-masked, active-controlled trial. 8.5 geriatric use no overall differences in safety or effectiveness have been observed between elderly and younger patients.

40, or 400 mg/kg/day betaxolol on gestational days 6 through 18, the period of organogenesis, resulted in marked embryo-fetal lethality, increased incidence of skeletal and visceral abnormalities, and decreased fetal weights at the maternally toxic dose of 400 mg/kg/day (7785 times higher than the maximum recommended human ophthalmic dose [mrhod] of 0.0083 mg/kg/day, on a mg/m 2 basis). the no-observed-adverse-effect-level (noael) for maternal or embryo-fetal toxicity was 40 mg/kg/day (778 times higher than the mrhod, on a mg/m 2 basis). in a rabbit efd study, oral administration of 1, 4, 12, and 36 mg/kg/day betaxolol on gestational days 6 through 18, the period of organogenesis, resulted in a marked increase in embryo-fetal lethality at 36 mg/kg/day (1400 times higher than the mrhod, on a mg/m 2 basis). no maternal toxicity was reported in this study. in a perinatal and postnatal development study in rats, oral administration of 4, 32, and 256 mg/kg/day betaxolol during late gestation through lactation resulted in a marked decrease in offspring survival within 4 days postpartum at the highest dose (4982 times higher than the mrhod, on a mg/m 2 basis). in surviving f 1 offspring, growth/development and reproductive function were also affected. the noael was 32 mg/kg/day (623 times higher than the mrhod, on a mg/m 2 basis). in a prenatal and postnatal development study in rats, an oral betaxolol dose of 150 mg/kg/day (2920 times higher than the mrhod, on mg/m 2 basis) administered throughout the entire gestation period and lactation, resulted in maternal and developmental toxicity in f 1 offspring, including decreased offspring survival, body weight and growth/development and functional deficits in surviving offspring. no noael for developmental or maternal toxicity was established in this study. oral administration of 4, 32, and 256 mg/kg/day betoxolol to rats prior to mating and through late gestation, or until weaning, produced embryo-fetal lethality, neonatal mortality, decreased mean fetal weight, growth/development and functional deficits in surviving offspring at 256 mg/kg/day (4982 times higher than the mrhod, on a mg/m 2 basis). at 32 mg/kg/day (623 higher than the mrhod, on a mg/m 2 basis), decreased mean fetal weight on gestation day 20, and pup weight at birth and on day 4 postpartum were observed. at 4 mg/kg/day (78 times higher than the mrhod, on a mg/m 2 basis), a slight decrease in mean fetal weight was observed on gestation day 20.

as normal iop and the mechanism of ocular hypotensive action appears to be a reduction of aqueous production as demonstrated by tonography and aqueous fluorophotometry. 12.2 pharmacodynamics the onset of action with betaxolol can generally be noted within 30 minutes and the maximum effect can usually be detected 2 hours after topical administration. a single dose provides a 12-hour reduction in iop. in some patients, the iop lowering responses to betoptic s may require a few weeks to stabilize. as with any new medication, careful monitoring of patients is advised. ophthalmic betaxolol solution at 1% (one drop in each eye) was compared to placebo in a crossover study challenging nine patients with reactive airway disease. betaxolol hcl had no significant effect on pulmonary function as measured by forced expiratory volume in 1 second (fev1), forced vital capacity (fvc), fev1/fvc, and was not significantly different from placebo. the action of isoproterenol, a beta stimulant, administered at the end of the study was not inhibited by ophthalmic betaxolol. no evidence of cardiovascular beta-adrenergic blockade during exercise was observed with betaxolol in a double-masked, crossover study in 24 normal subjects comparing ophthalmic betaxolol and placebo for effects on blood pressure and heart rate.

ld be exercised in operating machinery or driving a motor vehicle. contact lens wear the preservative in betoptic s, benzalkonium chloride, may be absorbed by soft contact lenses. remove contact lenses during instillation of betopic s. contact lenses may be reinserted 15 minutes after instillation. distributed by: novartis pharmaceuticals corporation east hanover, new jersey 07936 © novartis t2021-95