BERTOCIL

A cardioselective beta-1-adrenergic antagonist with no partial agonist activity.

For the management of hypertension.

Betaxolol is a competitive, beta-selective (cardioselective) adrenergic antagonist.

Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure.

Activation of beta-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen.

Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen.

They are routinely prescribed in patients with ischemic heart disease.

In addition, beta-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.

Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.

of an oral dose is complete.

There is a small and consistent first-pass effect resulting in an absolute bioavailability of 89% ± 5% that is unaffected by the concomitant ingestion of food or alcohol.

Primarily hepatic.

Approximately 15% of the dose administered is excreted as unchanged drug, the remainder being metabolites whose contribution to the clinical effect is negligible.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

LD 50 s are 350-400 mg betaxolol/kg in mice and 860-980 mg/kg in rats.

Predicted symptoms of overdose include bradycardia, congestive heart failure, hypotension, bronchospasm, and hypoglycemia.

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.

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.

(betaxolol hydrochloride ophthalmic suspension), 0.25% is supplied as follows: 10 mL and 15 mL in plastic ophthalmic dispensers.

Tamper evidence is provided with a shrink band around the closure and neck area of the package. 10 mL NDC 0078-0729-10 15 mL NDC 0078-0729-15 Storage and Handling Store upright at 2°C to 25°C (36°F to 77°F).

Shake well before using.

After opening, BETOPTIC S can be used until the expiration date on the bottle.

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.

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.

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.

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.

Safety and IOP lowering effect of BETOPTIC S has been demonstrated in pediatric patients in a 3 month, multicenter, double-masked, active-controlled trial.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.