BETAGAN ® (levobunolol hydrochloride ophthalmic solution, USP) s terile

BETAGAN^® (levobunolol hydrochloride ophthalmic solution, USP) sterile is a noncardioselective beta-adrenoceptor blocking agent for ophthalmic use. The solution is colorless to slightly light yellow in appearance with an osmolality range of 250-360 mOsm/kg. The shelf life pH range is 5.5 to 7.5.

Chemical Name: (-)-(S)-5-[3-(tert-Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1(2H)-naphthalenone hydrochloride.

Structural Formula: levobunolol HCl

The structural formula for levobunolol HCl is a noncardioselective beta-adrenoceptor blocking agent for ophthalmic use. The solution is colorless to slightly light yellow in app...

Contains: Active: levobunolol HCl 0.5%. Preservative: benzalkonium chloride 0.004% Inactives: edetate disodium; polyvinyl alcohol 1.4%; potassium phosphate, monobasic; purified water; sodium chloride; sodium metabisulfite; sodium phosphate, dibasic; and hydrochloric acid or sodium hydroxide to adjust pH.

Levobunolol HCl is a noncardioselective beta-adrenoceptor blocking agent, equipotent at both beta₁ and beta₂ receptors. Levobunolol HCl is greater than 60 times more potent than its dextro isomer in its beta-blocking activity, yet equipotent in its potential for direct myocardial depression. Accordingly, the levo isomer, levobunolol HCl, is used. Levobunolol HCl does not have significant local anesthetic (membrane-stabilizing) or intrinsic sympathomimetic activity.

Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.

Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous.

BETAGAN^® (levobunolol hydrochloride ophthalmic solution, USP) has been shown to be an active agent in lowering elevated as well as normal intraocular pressure (IOP) whether or not accompanied by glaucoma. 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.

The onset of action with one drop of BETAGAN ^® can be detected within one hour after treatment, with maximum effect seen between 2 and 6 hours.

A significant decrease of IOP can be maintained for up to 24 hours following a single dose.

In controlled clinical studies of approximately two years duration, intraocular pressure was well-controlled in approximately 80% of subjects treated with BETAGAN ^® ophthalmic solution 0.5% twice daily (b.i.d.). The mean IOP decrease from baseline was between 7 mm Hg and 8 mm Hg. No significant effects on pupil size, tear production or corneal sensitivity were observed. BETAGAN ^® at the concentrations tested, when applied topically, decreased heart rate and blood pressure in some patients. The IOP-lowering effect of BETAGAN ^® was well maintained over the course of these studies.

In a three-month clinical study, a single daily application of 0.5% BETAGAN ^® ophthalmic solution controlled the IOP of 72% of subjects achieving an overall mean decrease in IOP of 7.0 mm Hg.

The primary mechanism of the ocular hypotensive action of levobunolol HCl in reducing IOP is most likely a decrease in aqueous humor production. BETAGAN ^® reduces IOP with little or no effect on pupil size or accommodation.

BETAGAN^® ophthalmic solution has been shown to be effective in lowering intraocular pressure and may be used in patients with chronic open-angle glaucoma or ocular hypertension.

BETAGAN^® ophthalmic solution is contraindicated in those individuals with bronchial asthma, or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease (see WARNINGS); sinus bradycardia; second and third degree atrioventricular block; overt cardiac failure (see WARNINGS); cardiogenic shock; or hypersensitivity to any component of these products.

As with other topically applied ophthalmic drugs, BETAGAN ^® may be absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported with topical application of beta-adrenergic blocking agents (see CONTRAINDICATIONS). Additionally, ophthalmic beta-blockers may impair compensatory tachycardia and increase risk of hypotension.

In clinical trials the use of BETAGAN ^® ophthalmic solution has been associated with transient ocular burning and stinging in up to 1 in 3 patients, and with blepharoconjunctivitis in up to 1 in 20 patients. Decreases in heart rate and blood pressure have been reported (see CONTRAINDICATIONS and WARNINGS).

The following adverse reactions have been reported rarely with the use of BETAGAN ^®: iridocyclitis, headache, transient ataxia, dizziness, lethargy, urticaria, and pruritus.

Decreased corneal sensitivity has been noted in a small number of patients. Although levobunolol has minimal membrane-stabilizing activity, there remains a possibility of decreased corneal sensitivity after prolonged use.

The following additional adverse reactions have been reported either with BETAGAN ^® ophthalmic solution or ophthalmic use of other beta-adrenergic receptor blocking agents:

BODY AS A WHOLE: Headache, asthenia, chest pain. CARDIOVASCULAR: Bradycardia, arrhythmia, hypotension, syncope, heart block, cerebral vascular accident, cerebral ischemia, congestive heart failure, palpitation, cardiac arrest. DIGESTIVE: Nausea, diarrhea. PSYCHIATRIC: Depression, confusion, increase in signs and symptoms of myasthenia gravis, paresthesia. SKIN: Hypersensitivity, including localized and generalized rash, alopecia, Stevens-Johnson Syndrome. RESPIRATORY: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), respiratory failure, dyspnea, nasal congestion. UROGENITAL: Impotence. ENDOCRINE: Masked symptoms of hypoglycemia in insulin-dependent diabetics (see WARNINGS). SPECIAL SENSES: Signs and symptoms of keratitis or eye allergy, blepharoptosis, visual disturbances including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis, and foreign body sensation in eye. 

Other reactions associated with the oral use of non-selective adrenergic receptor blocking agents should be considered potential effects with ophthalmic use of these agents.

No data are available regarding overdosage in humans. Should accidental ocular overdosage occur, flush eye(s) with water or normal saline. If accidentally ingested, efforts to decrease further absorption may be appropriate (gastric lavage). The most common signs and symptoms to be expected with overdosage with administration of a systemic beta-adrenergic blocking agent are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. Should these symptoms occur, discontinue BETAGAN ^® therapy and initiate appropriate supportive therapy. The following supportive measures should be considered:

1. Symptomatic bradycardia: Use atropine sulfate intravenously in a dosage of 0.25 mg to 2 mg to induce vagal blockade. If bradycardia persists, intravenous isoproterenol hydrochloride should be administered cautiously. In refractory cases the use of a transvenous cardiac pacemaker should be considered.

2. Hypotension: Use sympathomimetic pressor drug therapy, such as dopamine, dobutamine or levarterenol. In refractory cases the use of glucagon hydrochloride may be useful.

3. Bronchospasm: Use isoproterenol hydrochloride. Additional therapy with aminophylline may be considered.

4. Acute cardiac failure: Conventional therapy with digitalis, diuretics and oxygen should be instituted immediately. In refractory cases the use of intravenous aminophylline is suggested. This may be followed, if necessary, by glucagon hydrochloride which may be useful.

5. Heart block (second or third degree): Use isoproterenol hydrochloride or a transvenous cardiac pacemaker.

The recommended starting dose is one to two drops of BETAGAN ^® ophthalmic solution 0.5% in the affected eye(s) once a day. In patients with more severe or uncontrolled glaucoma, BETAGAN ^® 0.5% can be administered b.i.d. As with any new medication, careful monitoring of patients is advised.

Dosages above one drop of BETAGAN ^® 0.5% b.i.d. are not generally more effective. If the patient’s IOP is not at a satisfactory level on this regimen, concomitant therapy with other ophthalmic IOP-lowering agents can be instituted. Patients should not typically use two or more topical ophthalmic beta-adrenergic blocking agents simultaneously.

BETAGAN^® (levobunolol hydrochloride ophthalmic solution, USP) is supplied sterile in white low density polyethylene ophthalmic dispenser bottles and tips, with a yellow high density polystyrene cap, as follows:  

5 mL in 10 mL bottle    NDC 0023-4385-05
10 mL in 15 mL bottle  NDC 0023-4385-10
15 mL in 15 mL bottle  NDC 0023-4385-15

Storage: Protect from light. Store at 15°-25°C (59°-77°F).

Revised: 09/2021

© 2021 Allergan. All rights reserved.
All trademarks are the property of their respective owners.
Distributed by: Allergan, USA Inc., Madison NJ 07940

Allergan

NDC 0023-4384-05
Rx Only
BETAGAN
(levobunolol
hydrochloride
ophthalmic
solution, USP)
0.5%
sterile
5 mL

PRINCIPAL DISPLAY PANEL NDC 0023-4384-05 Rx Only BETAGAN (levobunolol hydrochloride ophthalmic solution, USP) 0.5% sterile 5 mL