Name of the medicinal product

Betoptic S

Qualitative and quantitative composition

Dosage Forms And Strengths

Bottle filled with 2.5, 5, 10, and 15 mL of 0.25% sterile ophthalmic suspension

BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% is supplied as follows: 2.5, 5, 10 and 15 mL in plastic ophthalmic DROP-TAINER® dispensers. Tamper evidence is provided with a shrink band around the closure and neck area of the DROP-TAINER package.

2.5 mL: NDC 0065-0246-20

5 mL: NDC 0065-0246-05

10 mL: NDC 0065-0246-10

15 mL: NDC 0065-0246-15

Storage and Handling

Store upright at 2°- 25°C (36°- 77°F). Shake well before using.

Alcon Laboratories, Inc. Fort Worth, Texas 76134. FDA Rev date: 5/8/2008

Therapeutic indications

BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% is indicated for the treatment of elevated intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension.

Dosage (Posology) and method of administration

Instill one drop of BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% in the affected eye twice daily. It may be used alone or in combination with other intraocular pressure lowering medications.

Contraindications

BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Suspension is contraindicated in patients with:

sinus bradycardia
greater than a first degree atrioventricular block
cardiogenic shock
patients with overt cardiac failure
hypersensitivity to any component of this product.

Special warnings and precautions for use

WARNINGS

Included as part of the PRECAUTIONS section.

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 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 with topical application of beta-adrenergic receptor inhibitors.

Cardiac Failure

BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Suspension 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® (betaxolol hydrochloride ophthalmic suspension) should be discontinued at the first signs of cardiac failure.

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.

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.

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).

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.

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 re-challenges 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.

Atopy/Anaphylaxis

While taking beta 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.

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.

Cerebrovascular 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 cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of therapy with BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) , 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..

Choroidal Detachment

Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant therapy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Lifetime studies with betaxolol HCl have been completed in mice at oral doses of 6, 20 or 60 mg/kg/day and in rats at 3, 12 or 48 mg/kg/day; betaxolol HCl demonstrated no carcinogenic effect. Higher dose levels were not tested. In a variety of in vitro and in vivo bacterial and mammalian cell assays, betaxolol HCl was nonmutagenic.

Use In Specific Populations

Pregnancy

Teratogenic effects

Pregnancy Category C: Reproduction, teratology, and peri- and postnatal studies have been conducted with orally administered betaxolol HCl in rats and rabbits. There was evidence of drug related postimplantation loss in rabbits and rats at dose levels above 12 mg/kg and 128 mg/kg, respectively. Betaxolol HCl was not shown to be teratogenic, however, and there were no other adverse effects on reproduction at subtoxic dose levels. There are no adequate and well-controlled studies in pregnant women. BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether betaxolol HCl is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% is administered to nursing women.

Pediatric Use

Safety and IOP-lowering effect of

BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% 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.

Interaction with other medicinal products and other forms of interaction

SIDE EFFECTS

Clinical Studies 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® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% 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® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% 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 formations, edema and anisocoria.

DRUG INTERACTIONS

Oral Beta-Adrenergic Receptor Inhibitors

Patients who are receiving a beta-adrenergic receptor inhibitor orally and BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% should be observed for a potential additive effect either on the intraocular pressure 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.

Fertility, pregnancy and lactation

Teratogenic effects

Pregnancy Category C: Reproduction, teratology, and peri- and postnatal studies have been conducted with orally administered betaxolol HCl in rats and rabbits. There was evidence of drug related postimplantation loss in rabbits and rats at dose levels above 12 mg/kg and 128 mg/kg, respectively. Betaxolol HCl was not shown to be teratogenic, however, and there were no other adverse effects on reproduction at subtoxic dose levels. There are no adequate and well-controlled studies in pregnant women. BETOPTIC S® (betaxolol hydrochloride ophthalmic suspension) Ophthalmic Suspension 0.25% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Undesirable effects