Generic Name: Levobunolol Hydrochloride
Class: beta-Adrenergic Blocking Agents
VA Class: OP101
Chemical Name: (-)-5-(3-tert-Butylamino-2-hydroxypropoxy)-1,2,3,4-tetrahydronaphthalen-1-one hydrochloride
Molecular Formula: C17H25NO3•ClH [Molecular Formula]
CAS Number: 27912-14-7[CAS number]
Introduction
Nonselective β-adrenergic blocking agent.2 3 9 11 12 13 14 15 16 17 20 21 22 23 27 28 a b c
Uses for Betagan
Ocular Hypertension and Glaucoma
Reduction of elevated IOP in patients with chronic open-angle glaucoma2 51 52 53 54 55 56 58 92 a b c or ocular hypertension.2 51 52 53 54 55 56 57 58 92 a b c
Used alone2 51 52 53 54 55 56 57 58 92 a b c or in conjunction wth a topical miotic (e.g., pilocarpine), topical dipivefrin, topical epinephrine, and/or a systemic carbonic anhydrase inhibitor.2 101 a b c
Betagan Dosage and Administration
Administration
Ophthalmic Administration
Apply topically to the eye as an ophthalmic solution.2 51 52 53 54 55 56 57 58 92 a b c
Avoid contamination of the solution container.80
Dosage
Available as levobunolol hydrochloride; dosage expressed in terms of the salt.a b c
Adults
Ocular Hypertension and Glaucoma
Ophthalmic Administration
Initially, 1 or 2 drops of a 0.5% ophthalmic solution in the affected eye(s) once daily2 51 52 53 54 55 56 58 92 93 a b c or, alternatively, 1 or 2 drops of a 0.25% ophthalmic solution twice daily.b c
May increase dosage, if necessary, to 1 drop of a 0.5% ophthalmic solution in the affected eye(s) twice daily in patients with more severe or uncontrolled glaucoma.a b c
Adjust dosage according to individual requirements and response as determined by tonometric readings of IOP before and during therapy.7 a b c
If further reduction of IOP is required, a topical miotic and/or a systemically administered carbonic anhydrase inhibitor may be added to the regimen.2 a b c
Prescribing Limits
Adults
Ocular Hypertension and Glaucoma
Ophthalmic Administration
Dosages >1 drop of a 0.5% ophthalmic solution twice daily generally have not been more effective.a b c
Cautions for Betagan
Contraindications
Cardiogenic shock or overt cardiac failure that is not adequately compensated.98 99 a b c (See Cardiac Failure under Cautions.)
Bronchial asthma, history of bronchial asthma, or severe COPD.a b c (See Respiratory Disease under Cautions.)
Sinus bradycardia52 a b c or AV block greater than first degree.18 a b c
Known hypersensitivity to levobunolol or any ingredient in the formulation.a b c
Warnings/Precautions
Warnings
Systemic Effects
Levobunolol may be absorbed systemically following topical application to the eye;2 a b c consider the usual precautions associated with systemic use of nonselective β-adrenergic blocking agents when using topical levobunolol.a b c
Cardiac Failure
Severe cardiac reactions, including death associated with cardiac failure, have been reported in patients receiving topical (ocular) levobunolol.a b c May precipitate more severe cardiac failure in patients with preexisting heart failure and may cause cardiac failure in patients without a history of heart failure.a b c (See Actions.)
Avoid use in patients with cardiogenic shock or with overt cardiac failurea b c that is not adequately compensated (e.g., treated with cardiac glycosides and/or diuretics).98 99 In patients without a history of cardiac failure, discontinue therapy at the first sign or symptom of cardiac failure.a b c
Respiratory Disease
Patients with mild or moderately severe COPD (e.g., chronic bronchitis, emphysema), bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma, in which levobunolol is contraindicated) generally should not receive β-adrenergic blocking agents.a b c (See Contraindications.) If levobunolol is required, use with caution in such patients since it may antagonize bronchodilation produced by endogenous and exogenous catecholamines.a b c
Use with caution in other patients with diminished pulmonary function.a b c
Major Surgery
Possible increased risks associated with general anesthesia (e.g., severe hypotension, difficulty restarting or maintaining heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.a b c
Need for withdrawal of β-adrenergic blocking agents prior to major surgery controversial; in some patients, gradual withdrawal of β-adrenergic blocking agents prior to elective surgery may be appropriate.60 93 a b c
Diabetes Mellitus
β-Adrenergic blocking agents may mask signs and symptoms of acute hypoglycemia; administer with caution in patients subject to spontaneous hypoglycemia and in diabetic patients (especially those with labile diabetes) who are receiving hypoglycemic agents.64 a b c
Thyrotoxicosis
β-Adrenergic blocking agents may mask signs of hyperthyroidism (e.g., tachycardia).a b c
Possible thyroid storm if β-adrenergic blocking agent is abruptly withdrawn; carefully monitor patients suspected of developing thyrotoxicosis.a b c
Sensitivity Reactions
History of Anaphylactic or Hypersensitivity Reactions
Patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-adrenergic blocking agents; such patients may be unresponsive to usual doses of epinephine used to treat anaphylactic reactions.a b c
Use with caution in patients with known hypersensitivity to other β-adrenergic blocking agents.a b c
Sulfite Sensitivity
Levobunolol hydrochloride ophthalmic solution contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.82 83 84 85 86 87 88 89 110 a b c d
General Precautions
Cerebrovascular Insufficiency
Caution advised in patients with cerebrovascular insufficiency due to the potential effects of β-adrenergic blocking agents on BP and pulse.a b c
Consider alternative therapy if signs or symptoms of reduced cerebral blood flow occur.a b c
Angle-closure Glaucoma
Levobunolol has little or no effect on pupil size.2 51 52 53 54 55 56 58 a b c Do not use alone in patients with angle-closure glaucoma; use only in combination with a miotic in these patients.7 98 104 105 106 107 108 a b c
Muscle Weakness
β-Adrenergic blocking agents reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, generalized weakness).a b c
Specific Populations
Pregnancy
Category C.a b c
Lactation
Not known whether levobunolol is distributed into milk following topical application to the eye.a b c Caution if used in nursing women.a b c
Pediatric Use
Safety and efficacy not established.a b c
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults.a b c
Common Adverse Effects
Ocular stinging2 52 53 58 a b c or burning2 51 52 53 58 a b c on instillation,2 51 52 53 58 a b c blepharoconjunctivitis.2 51 a b c
Interactions for Betagan
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
β-Adrenergic blocking agents, systemic or topical | Possible additive effects on IOP and/or systemic β-adrenergic blockadea b c | Caution recommended if used concomitantly with systemic β-adrenergic blocking agentsa b c Concomitant administration of ≥2 topical ophthalmic β-adrenergic blocking agents generally not recommendeda b c |
Calcium-channel blocking agents | Potential AV conduction disturbances, hypotension, and left ventricular failure a b c | Monitor for adverse cardiovascular effects during concomitant usea b c Avoid concomitant use in patients with impaired cardiac functiona b c |
Catecholamine-depleting drugs (e.g., reserpine) | Possible additive cardiovascular effects (e.g., hypotension, marked bradycardia); may be manifested as vertigo, syncope, or postural hypotensiona b c | Observe closelya b c |
Digitalis | Potential additive effect in prolonging AV conduction timea b c | |
Epinephrine | Possible mydriasisa b c | |
Ocular hypotensive agents (e.g., topical miotic and/or systemically administered carbonic anhydrase inhibitor) | Additive IOP-lowering effects2 a b c | Used to therapeutic advantage2 a b c |
Phenothiazines | Possible additive hypotensive effects caused by inhibition of phenothiazine and levobunolol metabolisma b c |
Betagan Pharmacokinetics
Absorption
Bioavailability
Some systemic absorption occurs following topical administration.2 51 52 53 54 55 56 58 92 a b c
Onset
Following topical application to the eye, reduction in IOP is usually evident within 1 hour and reaches a maximum within about 2–6 hours.55 57 111 a b c
Duration
Reduction in IOP may persist for up to 24 hours.55 57 111 a b c
Distribution
Extent
Following topical application in rabbits, rapidly distributed throughout ocular tissues and fluids (e.g., cornea, iris, ciliary body, aqueous humor).2
Levobunolol crosses the placenta in some animals;2 not known whether distributed into human milk.a b c
Elimination
Metabolism
Extensively metabolized in the liver36 38 39 40 41 42 43 46 47 98 99 principally to dihydrolevobunolol, an active metabolite.36 38 39 40 42 44 45 46 47 48 99 109
Elimination Route
Approximately 93% of topically applied dose is excreted in urine and feces in rabbits.2 99
Half-life
Following ophthalmic administration of racemic bunolol in rabbits: 60–90 min.98 109
Stability
Storage
Ophthalmic
Solution
Light-resistant containers at 15–30°C.a b c
ActionsActions
Nonselective β-adrenergic blocking agent that has some direct myocardial depressant activity2 3 10 11 12 13 14 15 16 17 19 20 21 22 23 27 28 a b c but does not have substantial local anesthetic activity2 23 a b c or intrinsic sympathomimetic activity.2 14 20 21 23 a b c
Reduces both elevated2 51 52 53 54 55 56 57 58 92 a b c and normal IOP2 a b c with little or no effect on pupillary size2 51 52 53 54 55 56 92 a b c or accommodation.a b c
Reduces IOP by about 25–40% from baseline in patients with elevated IOP.2 51 52 53 54 55 56 57 58 92 a b c
Exact mechanism of action not fully elucidated;2 7 8 29 34 50 59 a b c fluorophotometric studies suggest that reduced aqueous humor formation is the predominant effect.2 7 8 97 98 a b c
May block endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes and subsequent formation of aqueous humor.2 6 7 8 30 32 34 59
Does not appear to affect aqueous humor outflow facility.8 34 59
Tolerance may develop with prolonged use;98 99 however, IOP-lowering effect maintained for at least 2 years with continuous use in some patients.2
Advice to Patients
Importance of learning and adhering to proper administration techniques to avoid contamination of the product.80
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, bronchospastic disease).a b c
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.a b c
Importance of informing patients of other important precautionary information.a b c (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | 0.25% | Betagan (with benzalkonium chloride and sodium metabisulfite) | Allergan |
Levobunolol Hydrochloride Ophthalmic Solution | Apotex, Bausch & Lomb, Falcon | |||
0.5% | Betagan (with benzalkonium chloride and sodium metabisulfite) | Allergan | ||
Levobunolol Hydrochloride Ophthalmic Solution | Apotex, Bausch & Lomb, Falcon |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Betagan 0.5% Solution (ALLERGAN): 15/$94.99 or 45/$271.98
Levobunolol HCl 0.25% Solution (BAUSCH & LOMB): 10/$22.99 or 30/$45.97
Levobunolol HCl 0.5% Solution (BAUSCH & LOMB): 10/$47.99 or 30/$135.97
Levobunolol HCl 0.5% Solution (BAUSCH & LOMB): 15/$65.99 or 45/$175.97
Levobunolol HCl 0.5% Solution (BAUSCH & LOMB): 5/$29.99 or 15/$75.97
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
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