Betaxolol (ophthalmic)

Oral beta-adrenergic receptor inhibitors may have additive effects. (7.1 ) Catecholamine-depleting drugs may have additive effects. ( 7.2 ) Concomitant adrenergic psychotropic drugs may have additive effects. ( 7.3 )

7.1 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.

7.2 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.

7.3 Concomitant Adrenergic Psychotropic Drugs Betaxolol is an adrenergic receptor inhibitor; therefore, caution should be exercised in patients using 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.

8.1 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 [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…