Betoptic S Drug Information

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.

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.

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.

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.

Oral Beta-Adrenergic Receptor Inhibitors Patients who are receiving a beta-adrenergic receptor inhibitor

orally and BETOPTIC S should be observed for a potential additive effect either on the IOP or on the known systemic effects of beta blockade.

Catecholamine-Depleting Drugs Close observation of the patient is recommended when a beta-adrenergic

receptor inhibitor is administered to patients receiving catecholamine-depleting drugs, such as reserpine, because of possible additive effects and the production of hypotension and/or bradycardia, which may result in vertigo, syncope, or postural hypotension.

Concomitant Adrenergic Psychotropic Drugs Betaxolol is an adrenergic receptor inhibitor; therefore, caution

should be exercised in patients using concomitant adrenergic psychotropic drugs.

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.

Pregnancy Risk Summary There are no adequate and well-controlled studies of BETOPTIC S administration in pregnant women to inform a drug-associated risk. There are limited data with the use of betaxolol eye drops in pregnant women. Epidemiological studies have not revealed malformative effects but show a risk for intrauterine growth retardation when beta-blockers are administered by the oral route.

In animal reproductive studies, no drug-induced maternal toxicity or teratogenicity was observed at clinically relevant doses (see Data). Because animal reproductive studies are not always predictive of human response, BETOPTIC S should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In a rat embryo-fetal development (EFD) study, 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 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.

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.

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. Sinus bradycardia, second or third degree atrioventricular (AV) block, overt cardiac failure, and cardiogenic shock.

No information is available on overdosage in humans. The oral LD 50 of the drug ranged from 350 to 920 mg/kg in mice and 860 to 1,050 mg/kg in rats. The symptoms which might be expected with an overdose of a systemically administered beta-adrenergic receptor inhibitor are bradycardia, hypotension, bronchospasm, and acute cardiac failure.

A topical overdose of BETOPTIC S may be flushed from the eye(s) with warm tap water. If overdose occurs, treatment should be symptomatic and supportive.