BETOPTIC S® Ophthalmic Suspension 0.25% contains betaxolol hydrochloride, a cardioselective beta-adrenergic receptor inhibitor, in a sterile resin suspension formulation. Betaxolol hydrochloride is a white, crystalline powder, with a molecular weight of 343.89. The chemical structure is presented below.

Empirical Formula:

C₁₈H₂₉NO₃•HCl

Chemical Name:

(±)-1-[p-[2-(cyclopropylmethoxy)ethyl]phenoxy]­3-(isopropylamino)-2-propanol hydrochloride.

Each mL of BETOPTIC S® Ophthalmic

Suspension 0.25% contains: Active: betaxolol HCl 2.8 mg equivalent to 2.5 mg of betaxolol base. Preservative: benzalkonium chloride 0.01%. Inactive(s): Mannitol, Poly(Styrene-Divinyl Benzene) sulfonic acid, Carbomer 934P, edetate disodium, hydrochloric acid or sodium hydroxide (to adjust pH) and purified water.

BETOPTIC S® Ophthalmic Suspension 0.25% has a pH of approximately 7.6 and an osmolality of approximately 290 mOsmol/kg.

Last updated on RxList: 7/14/2008

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

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

Dosage Forms And Strengths

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

BETOPTIC S® 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

Last updated on RxList: 7/14/2008

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® 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® 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.

Oral Beta-Adrenergic Receptor Inhibitors

Patients who are receiving a beta-adrenergic receptor inhibitor orally and BETOPTIC S® 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.

Last updated on RxList: 7/14/2008

Included as part of the PRECAUTIONS section.

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® 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® 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®, 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. [see Patient Counseling Information].

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® 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® Ophthalmic Suspension 0.25% is administered to nursing women.

Pediatric Use

Safety and IOP-lowering effect of

BETOPTIC S® 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.

Last updated on RxList: 7/14/2008

No information is available on overdosage of humans. The oral LD₅₀ of the drug ranged from 350-920 mg/kg in mice and 860-1050 mg/kg in rats. The symptoms which might be expected with an overdose of a systemically administered beta-1-adrenergic receptor inhibitor are bradycardia, hypotension and acute cardiac failure.

A topical overdose of BETOPTIC S® Ophthalmic Suspension 0.25% may be flushed from the eye(s) with warm tap water.

BETOPTIC S® 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.

Last updated on RxList: 7/14/2008

Mechanism of Action

Betaxolol HCl, a cardioselective (beta-1­adrenergic) receptor inhibitor, does not have significant membrane-stabilizing (local anesthetic) activity and is devoid of intrinsic sympathomimetic action. Orally administered beta-adrenergic receptor inhibitors reduce cardiac output in healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor antagonists may inhibit the sympathetic stimulatory effect necessary to maintain adequate cardiac function.

When instilled in the eye, BETOPTIC S® Ophthalmic Suspension 0.25% has the action of reducing elevated intraocular pressure, whether or not accompanied by glaucoma. Ophthalmic betaxolol has minimal effect on pulmonary and cardiovascular parameters.

Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Betaxolol has the action of reducing elevated as well as normal intraocular pressure and the mechanism of ocular hypotensive action appears to be a reduction of aqueous production as demonstrated by tonography and aqueous fluorophotometry.

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 intraocular pressure. In some patients, the intraocular pressure 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 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 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.

Clinical Studies

In controlled, double-masked studies, the magnitude and duration of the ocular hypotensive effect of BETOPTIC S® Ophthalmic Suspension 0.25% and BETOPTIC® Ophthalmic Solution 0.5% were clinically equivalent. BETOPTIC S® Suspension was significantly more comfortable than BETOPTIC® Solution.

Last updated on RxList: 7/14/2008

How to Use The DROP-TAINER®*Bottle

The DROP-TAINER® bottle is designed to assure the delivery of a precise dose of medication. Before using your DROP-TAINER® bottle, read the complete instructions carefully.

1. If you use other topically applied ophthalmic medications, they should be administered at least 10 minutes before BETOPTIC S®.
2. Wash hands before each use.
3. Before using the medication for the first time, be sure the Safety Seal on the bottle is unbroken.
4. Tear off the Safety Seal to break the seal.
5. Before each use, shake well and remove the screw cap.
6. Invert the bottle and hold the bottle between your thumb and middle finger, with the tips of the fingers pointing towards you.
7. Tilt your head back and position the bottle above the affected eye. DO NOT TOUCH THE EYE WITH THE TIP OF THE DROPPER.
8. With the opposite hand, place a finger under the eye. Gently pull down until a "V" pocket is made between your eye and lower lid.
9. With the hand holding the bottle, place your index finger on the bottom of the bottle. Push the bottom of the bottle to dispense one drop of medication. DO NOT SQUEEZE THE SIDES OF THE BOTTLE.
10. Repeat 6, 7, 8, and 9 with other eye if instructed to do so. 11. Replace screw cap by turning until firmly touching the bottle.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye(s) or surrounding structures. Patients should also be instructed that ocular solutions, if handled improperly, could become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye(s) and subsequent loss of vision may result from using contaminated solutions. physician's present multidose container.

Patients requiring concomitant topical ophthalmic medications should be instructed to administer these at least 10 minutes before instilling BETOPTIC S® Suspension.

Last updated on RxList: 7/14/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BETAXOLOL SUSPENSION - OPHTHALMIC

(bet-AX-oh-lol)

COMMON BRAND NAME(S): Betoptic S

USES: This medication is used alone or with other medications to treat high pressure inside the eye due to glaucoma (open-angle type) or other eye diseases (e.g., ocular hypertension). Lowering high pressure inside the eye helps to prevent blindness. Betaxolol belongs to a class of drugs known as beta blockers and works by decreasing the amount of fluid that is made within the eye.

HOW TO USE: To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

If you are wearing contact lenses, remove them before using eye drops. Wait at least 15 minutes before replacing your contact lenses.

Shake the bottle well before using. Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch, usually twice daily or as directed by your doctor. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed or if your dose is for more than 1 drop.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 10 minutes before using the other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day. It is important to continue using this medication even if you feel well. Most people with glaucoma or high pressure in the eyes do not feel sick.

SIDE EFFECTS: Temporary stinging/discomfort of the eye, watery/dry/itchy/red eyes, blurred vision, feeling as if something is in the eye, crusting of eyelashes, headache, trouble sleeping, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: eye pain/swelling/discharge, vision changes, increased eye sensitivity to light, swelling of the ankles/feet, tiredness, slow/irregular heartbeat, muscle weakness, mental/mood changes, hair loss.

Seek immediate medical attention if any of these rare but very serious side effects occur: trouble breathing, sudden unexplained weight gain, chest pain, weakness on one side of the body, slurred speech, confusion, persistent dizziness, fainting.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using betaxolol, tell your doctor or pharmacist if you are allergic to it; or to other beta blockers (e.g., timolol, metipranolol); or to the preservative in this product (benzalkonium chloride); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain types of heart rhythm problems (e.g., sinus bradycardia, second- or third-degree atrioventricular block), certain serious heart conditions (cardiogenic shock, severe heart failure).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, low blood sugar levels (hypoglycemia), overactive thyroid (hyperthyroidism), muscle weakness disorders (e.g., myasthenia gravis), breathing problems (e.g., asthma, chronic obstructive pulmonary disease-COPD), heart failure (treated, stable type), low blood flow to the brain (cerebrovascular insufficiency).

If you develop an eye infection or injury, or have eye surgery, check with your doctor about whether you should continue to use your current bottle of betaxolol. You may be advised to start using a new bottle.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or cause blurred vision; use caution engaging in activities requiring alertness or clear vision such as driving or using machinery. Limit alcoholic beverages.

If you have diabetes, this product may mask the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness/sweating, are unaffected by this drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain diabetes drugs (e.g., insulin, sulfonylureas such as glyburide), certain psychiatric drugs (e.g., venlafaxine, tricyclic antidepressants such as amitriptyline), drugs for high blood pressure (e.g., clonidine, reserpine, oral beta blockers such as propranolol, calcium channel blockers such as diltiazem), epinephrine.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. If this product is accidentally swallowed, you may experience symptoms such as trouble breathing, slow/irregular heartbeat.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.