Levobunolol

As with other topically applied ophthalmic drugs, BETAGAN® (levobunolol) 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).

Cardiac Failure

Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure.

In Patients Without a History of Cardiac Failure

Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, BETAGAN® (levobunolol) ophthalmic solution should be discontinued.

Obstructive Pulmonary Disease

PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (e.g., CHRONIC BRONCHITIS, EMPHYSEMA) OF MILD OR MODERATE SEVERITY, BRONCHOSPASTIC DISEASE OR A HISTORY OF BRONCHOSPASTIC DISEASE (OTHER THAN BRONCHIAL ASTHMA OR A HISTORY OF BRONCHIAL ASTHMA, IN WHICH BETAGAN® IS CONTRAINDICATED, See CONTRAINDICATIONS), SHOULD IN GENERAL NOT RECEIVE BETA BLOCKERS, INCLUDING BETAGAN® (levobunolol) . However, if BETAGAN® (levobunolol) is deemed necessary in such patients, then it should be administered cautiously since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta 2 receptors.

Major Surgery

The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs 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 blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic receptor blocking agents may be appropriate.

If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of such agonists as isoproterenol, dopamine, dobutamine or levarterenol (See OVERDOSAGE).

Diabetes Mellitus

Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.

Thyrotoxicosis

Beta-adrenergic blocking agents 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 blocking agents, which might precipitate a thyroid storm.

These products contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have any of these serious side effects:

• severe swelling, itching, burning, redness, pain, or discomfort in or around your eye;
• drainage, crusting, or oozing of your eyes or eyelids;
• bronchospasm (wheezing, chest tightness, trouble breathing);
• slow heart rate, weak pulse, fainting, slow breathing (breathing may stop);
• feeling short of breath, even with mild exertion;
• swelling, rapid weight gain; or
• severe blistering, peeling, and red skin rash.

Less serious side effects may include:

• mild burning, stinging, itching, or discomfort of your eyes;
• blurred vision;
• mildly swollen or puffy eyes;
• headache, dizziness, spinning sensation;
• depression, confusion, tired feeling;
• muscle weakness;
• mild skin rash or itching; or
• nausea, diarrhea.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Your pharmacist can provide more information about levobunolol ophthalmic.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Do not use this medication if you are allergic to levobunolol, or if you have asthma, or severe chronic obstructive pulmonary disease (COPD), slow heartbeats, or a heart condition called "AV block."

Before using this medication, tell your doctor if you have breathing problems such as bronchitis or emphysema, a history of heart disease or congestive heart failure, diabetes, history of stroke, blood clot, or circulation problems, a thyroid disorder, or a muscle disorder such as myasthenia gravis.

Do not allow the dropper to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

Levobunolol ophthalmic is sometimes given together with other eye medications. Do not use any other eye medication unless your doctor has prescribed it for you. If you use another eye medication, use it at least 10 minutes before or after using levobunolol ophthalmic. Do not use the medications at the same time.

Levobunolol ophthalmic can cause blurred vision. Be careful if you drive or do anything that requires you to be able to see clearly.

Do not use this medication while you are wearing contact lenses. Levobunolol ophthalmic may contain a preservative that can be absorbed by soft contact lenses. Wait at least 15 minutes after using levobunolol before putting your contact lenses in.

• If you have an allergy to levobunolol or any other part of levobunolol.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Asthma or other lung or breathing problems that cause shortness of breath or wheezing, heart failure (weak heart), certain types of abnormal heartbeats called heart block or sick sinus syndrome, or a slow heartbeat.
• If you have COPD (chronic obstructive pulmonary disease).
• If you are using another drug like this one.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take levobunolol with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Change in eyesight, eye pain, or very bad eye irritation.
• Muscle weakness.
• Slow heartbeat.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Very bad dizziness or passing out.

• l-Bunolol Hydrochloride
• Levobunolol Hydrochloride

Hypersensitivity to levobunolol or any component of the formulation; bronchial asthma, severe COPD, sinus bradycardia, second- or third-degree AV block, overt cardiac failure, cardiogenic shock

Glaucoma (open-angle, chronic), intraocular hypertension: Ophthalmic:

0.25% solution: Instill 1-2 drops into affected eye(s) twice daily

0.5% solution: Instill 1-2 drops into affected eye(s) once daily; may increase to 1 drop twice daily in patients with severe or uncontrolled glaucoma; Maximum dose: Doses >1 drop twice daily (0.5%) are generally not more effective.

Concerns related to adverse events:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

Disease-related concerns:

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.

• Cerebrovascular insufficiency: Due to a possible effect on blood pressure and pulse, use with caution in patients with cerebrovascular insufficiency.

• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.

• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.

• Heart failure (HF): Use with caution in patients with compensated HF and monitor for a worsening HF (diminished myocardial contractility may lead to more severe failure); patients without a history of HF should discontinue use with the first symptoms of heart failure. In a scientific statement from the American Heart Association, levobunolol has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may worsen disease.

• Peripheral vascular disease (PVD): Use with caution in patients with PVD (including Raynaud's).

• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.

• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt beta-adrenergic blocker withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.

Concurrent drug therapy issues:

• Beta-blockers: Concomitant use with other topical beta-blockers should generally be avoided; monitor for increased effects (systemic or intraocular) with concomitant use of a systemic beta-blocker.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Contact lens wearers: Some products contain benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration.

• Elderly: Use with caution in the elderly with other disease states or syndromes that may be affected by a beta-blocker (CHF, COPD, etc); systemic absorption may occur with ophthalmic administration; monitor closely.

Dosage form specific issues:

• Metabisulfite: Ophthalmic solutions contain metabisulfite, which may cause allergic reactions in some individuals.

Other warnings/precautions:

• Absorption: Systemic absorption of levobunolol and adverse effects may occur with ophthalmic use, including respiratory and cardiovascular effects (including bradycardia and/or hypotension). Beta-blocker therapy should not be withdrawn abruptly in order to avoid acute tachycardia, hypertension, and/or ischemia. Patients undergoing major surgery should be gradually tapered off therapy prior to procedure.

• Appropriate use: Should not be used alone in angle-closure glaucoma (has no effect on pupillary constriction).

Commonly reported side effects of levobunolol ophthalmic include: burning sensation of eyes. See below for a comprehensive list of adverse effects.

Applies to levobunolol ophthalmic: ophthalmic solution

General

The most commonly reported side effects were ocular burning/stinging, blepharoconjunctivitis, eye irritation, and eye pain.[Ref]

Ocular

Very common (10% or more): Eye irritation, eye pain
Common (1% to 10%): Blepharitis, conjunctivitis
Rare (less than 0.1%): Iridocyclitis
Frequency not reported: Conjunctival/ocular hyperemia, allergic conjunctivitis, decreased corneal reflex, keratitis, blurred vision, punctate keratitis, eye/eyelids pruritus, eye/eyelid edema, eye discharge, increased lacrimation, dry eye, choroidal detachment following filtration surgery, corneal erosion, diplopia, ptosis, corneal calcification, decreased corneal sensitivity, blepharoptosis[Ref]

Respiratory

Frequency not reported: Asthma, dyspnea, throat irritation, nasal discomfort, bronchospasm (predominantly in patients with pre-existing bronchospastic disease), cough, respiratory failure, nasal congestion[Ref]

Cardiovascular

Frequency not reported: Raynaud's phenomenon, syncope, bradycardia, atrioventricular block, palpitations, hypotension, arrhythmia, cardiac arrest, cardiac failure, chest pain, congestive heart failure, cold hands and feet[Ref]

Hypersensitivity

Frequency not reported: Anaphylactic reaction, systemic allergic reactions including angioedema[Ref]

Nervous system

Rare (less than 0.1%): Transient ataxia
Frequency not reported: Confusion, dizziness, somnolence, lethargy, headache, memory loss, cerebral ischemia, cerebrovascular accident, increases in signs and symptoms of myasthenia gravis, paresthesia, dysgeusia[Ref]

Gastrointestinal

Frequency not reported: Nausea, abdominal pain, diarrhea, dry mouth, dyspepsia, vomiting[Ref]

Genitourinary

Frequency not reported: Decreased libido, sexual dysfunction, impotence[Ref]

Musculoskeletal

Frequency not reported: Myalgia[Ref]

Psychiatric

Frequency not reported: Depression, insomnia, nightmares[Ref]

Other

Frequency not reported: Edema, fatigue, asthenia[Ref]

Dermatologic

Frequency not reported: Stevens-Johnson syndrome, urticaria, contact dermatitis (including allergic contact dermatitis), rash, skin exfoliation, lichenoid keratosis, pruritus, erythema of eyelid, eyelid eczema, alopecia, psoriasiform rash, exacerbation of psoriasis[Ref]

Metabolic

Frequency not reported: Hypoglycemia, masked symptoms of hypoglycemia in insulin-dependent diabetics[Ref]

Some side effects of levobunolol ophthalmic may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.