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Levobunolol

Pronunciation

(lee voe BYOO noe lole)

Index Terms

  • l-Bunolol Hydrochloride
  • Levobunolol Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Ophthalmic, as hydrochloride:

Betagan: 0.5% (5 mL [DSC], 10 mL, 15 mL [DSC])

Generic: 0.25% (5 mL [DSC], 10 mL [DSC]); 0.5% (5 mL, 10 mL, 15 mL)

Brand Names: U.S.

  • Betagan

Pharmacologic Category

  • Beta-Adrenergic Blocker, Nonselective
  • Ophthalmic Agent, Antiglaucoma

Pharmacology

Blocks both beta1- and beta2-adrenergic receptors and reduces intraocular pressure by reducing aqueous humor production or possibly increases the outflow of aqueous humor.

Onset of Action

Within 1 hour; Peak effect: 2 to 6 hours

Duration of Action

Up to 24 hours

Use: Labeled Indications

Elevated intraocular pressure: Treatment of elevated intraocular pressure in patients with ocular hypertension or chronic open-angle glaucoma

Contraindications

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

Documentation of allergenic cross-reactivity for ophthalmic beta-adrenergic blocking agents is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Elevated intraocular pressure: Ophthalmic: Instill 1 to 2 drops into affected eye(s) once daily; may increase to 1 drop twice daily in patients with severe or uncontrolled glaucoma. Doses >1 drop twice daily are generally not more effective.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Administration

For topical ophthalmic use only. Wash hands before and after use. Some solutions contain benzalkonium chloride; remove contact lens prior to administration. Wait 15 minutes before reinserting. Do not touch tip of applicator to eye or other surfaces. Do not administer 2 or more ophthalmic beta-adrenergic blocking agents simultaneously.

Storage

Store at 15°C to 25°C (59°F to 77°F). Protect from light.

Drug Interactions

Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Consider therapy modification

Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy

Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination

Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Monitor therapy

Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Consider therapy modification

Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification

Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification

Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination

Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Consider therapy modification

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy

Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy

Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy

Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Avoid combination

Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Monitor therapy

NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy

Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy

Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Consider therapy modification

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Adverse Reactions

>10%: Ophthalmic: Burning sensation of eyes (≤33%), stinging of eyes (≤33%)

1% to 10%: Ophthalmic: Blepharoconjunctivitis (5%)

Frequency not defined:

Cardiovascular: Bradycardia, cardiac arrhythmia, cardiac failure, cerebral ischemia, cerebrovascular accident, chest pain, heart block, hypotension, palpitations, syncope

Central nervous system: Ataxia (transient), confusion, depression, dizziness, exacerbation of myasthenia gravis, foreign body sensation of eye, headache, lethargy, paresthesia

Dermatologic: Alopecia, pruritus, skin rash, Stevens-Johnson syndrome, urticaria

Endocrine & metabolic: Hypoglycemia (masked)

Gastrointestinal: Diarrhea, nausea

Genitourinary: Impotence

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Weakness

Ophthalmic: Blepharoptosis, decreased corneal sensitivity, diplopia, iridocyclitis, keratitis, ocular allergy, visual disturbance

Respiratory: Bronchospasm, dyspnea, nasal congestion, respiratory failure

Warnings/Precautions

Concerns related to adverse events:

• Anaphylactic reactions: Instill with caution in patients with history of severe anaphylaxis to a variety of 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.

• Choroidal detachment: Beta-blockade and/or other aqueous suppressive therapy has been associated with choroidal detachment following filtration procedures.

Disease-related concerns:

• Cerebrovascular disease: Use with caution in cerebrovascular insufficiency; consider alternative therapy for patients with signs/symptoms of decreased cerebral blood flow after therapy initiation.

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

• Heart failure: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition; may lead to heart failure in patients without a history of heart failure (discontinue use at first sign or symptoms of heart failure). Use is contraindicated in overt heart failure. In a scientific statement from the AHA, 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 or other myasthenic symptoms (eg, diplopia, ptosis, generalized weakness).

• Peripheral vascular disease and Raynaud disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease or Raynaud disease. Use with caution and monitor for progression of arterial obstruction.

• Respiratory disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring. Severe respiratory reactions, including fatalities due to bronchospasm in patients with asthma, have been reported with ophthalmic use. Use is contraindicated in bronchial asthma or history of bronchial asthma and severe COPD.

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

Concurrent drug therapy issues:

• 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 may contain benzalkonium chloride, which may be absorbed by soft contact lenses. Remove lens prior to administration and wait 15 minutes before reinserting.

Dosage form specific issues:

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

• Appropriate use: Should not be used alone in angle-closure glaucoma (has no effect on pupillary constriction). Concomitant use of 2 topical beta-blockers is not recommended. Multidose vials have been associated with development of bacterial keratitis; avoid contamination.

• Surgery: May block systemic effects of beta agonists (eg, epinephrine, norepinephrine); notify anesthesiologist if patient is receiving ophthalmic beta-blocker therapy. Patients undergoing planned major surgery should be gradually tapered off therapy (if possible) prior to procedure. If necessary during surgery, effects of beta-blocker therapy may be reversed by adrenergic agonists.

Monitoring Parameters

Intraocular pressure, heart rate, funduscopic exam, visual field testing

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. The same adverse effects observed with systemic administration of beta-blockers may occur following ophthalmic use of levobunolol. If ophthalmic agents are needed for the treatment of glaucoma during pregnancy, the minimum effective dose should be used in combination with punctual occlusion to decrease potential exposure to the fetus (Johnson 2001; Salim 2014; Samples 1988).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience burning or stinging. Have patient report immediately to prescriber vision changes, eye pain, severe eye irritation, muscle weakness, severe dizziness, passing out, bradycardia, shortness of breath, excessive weight gain, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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