Levobetaxolol (Ophthalmic)


VA CLASSIFICATION
Primary: OP110

Commonly used brand name(s): Betaxon.

Another commonly used name is
L-betaxolol .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antiglaucoma agent, ophthalmic —

Antihypertensive, ocular—

Indications

Accepted

Glaucoma, open-angle (treatment)
Hypertension, ocular (treatment)—Levobetaxolol is indicated for use in the treatment of ocular hypertension and chronic open-angle glaucoma{01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    343.89{01}


pH
    Between 5.5 and 7.5{01}.

Mechanism of action/Effect:

Levobetaxolol is a cardioselective beta-1–adrenergic antagonist. It appears to lower elevated intraocular pressure by reducing aqueous humor production, as demonstrated by tonography and aqueous fluorophotometry{01}.


Other actions/effects:

Topically applied levobetaxolol exerts a minor effect on heart rate and blood pressure{01}.

Levobetaxolol does not have significant membrane-stabilizing (local anesthetic) activity.{01} It also does not have intrinsic sympathomimetic action.{01}

Absorption:

Systemic absorption has occurred to some degree with other beta adrenergic blocking agents{01}.

Half-life:

Approximately 20 hours{01}.

Onset of action:

Approximately 30 minutes, after topical administration{01}.

Time to peak plasma concentration—

Approximately 3 hours, after topical administration{01}.

Peak plasma concentration—

Mean of 0.5 nanograms/milliliter{01}.

Time to peak effect:

Approximately 2 hours after topical administration{01}.

Duration of action:

Approximately 12 hours, after a single topical dose{01}.


Precautions to Consider

Carcinogenicity

The racemate betaxolol was not carcinogenic in lifetime studies of rats given oral doses of 3 mg/kg, 12 mg/kg and 48 mg/kg per day and in mice given oral daily doses of 6 mg/kg, 20 mg/kg, and 60 mg/kg per day{01}.

Mutagenicity

Levobetaxolol did not exhibit mutagenicity in the Ames assay, nor in the chromosomal aberration, mouse lymphoma, and cell transformation assays in vitro. Potential mutagenicity was observed in the sister chromatid exchange assay in Chinese Hamster Ovarian cell in vitro when in the presence of metabolic activation systems{01}.

Pregnancy/Reproduction
Fertility—
Drug-related postimplantation loss was observed in rabbits given levobetaxolol 12 mg/kg/day{01}

Pregnancy—
Adequate and well-controlled studies have not been done in humans.{01}

Sternebrae malformations were observed in rabbits given levobetaxolol 4 mg/kg/day. No other reproduction-related adverse effects have been observed in studies of levobetaxolol at sub-toxic dosing levels involving rabbits and rats. {01}

FDA Pregnancy Category C{01}.

Breast-feeding

It is not known whether levobetaxolol is distributed into human breast milk{01}.

Pediatrics

No information is available on the relationship of age to the effects of levobetaxolol in pediatric patients{01}.


Geriatrics


Studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of levobetaxolol in the elderly.

Surgical

Gradual withdrawal of beta-adrenergic blocking agents such as levobetaxolol should be considered prior to surgical anesthesia so as to avoid attenuation of the cardiac response to beta-adrenergically mediated sympathetic reflex stimuli{01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Beta-adrenergic blocking agents, systemic    (ophthalmic levobetaxolol has exhibited a minor effect upon heart rate and blood pressure during clinical studies; however, concomitant use of these medications may result in cumulative systemic effects associated with beta-adrenergic blockade, or additional effects on intraocular pressure{01}.)


» Catecholamine-depleting agents, such as reserpine    (if significant systemic absorption of ophthalmic beta-adrenergic blocking agents should occur, concomitant use of these medications may result in cumulative systemic effects associated with beta-adrenergic blockade; bradycardia and hypotension may occur{01}.)


Psychotropic agents, adrenergic{01}    (because levobetaxolol is an adrenergic-blocking agent, caution is recommended in patients using adrenergic psychotropic agents{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypersensitivity to levobetaxolol or any other ingredient in the formulation{01} or
» Sinus bradycardia{01} or
» Second or third degree atrioventricular block{01} or
» Overt cardiac failure{01} or
» Cardiogenic shock{01}
Risk-benefit should be considered when the following medical problems exist
» Anaphylactic reactions, severe, history of{01} or
» Atopy, history of{01}    (risk of developing unresponsiveness to usual doses of epinephrine used to treat anaphylactic reactions{01})


» Cardiac failure, history of{01} or
Heart block, history of{01}    (in clinical studies, levobetaxolol has been shown to have a minor effect on heart rate and blood pressure; treatment should be discontinued at the first signs of cardiac failure{01})


» Diabetes mellitus{01} or
» Hypoglycemia{01}    (ophthalmic beta-adrenergic receptor blocking agents may mask or suppress some of the signs and symptoms of acute hypoglycemia in patients with diabetes{01})


Glaucoma, angle-closure{01}    (when used to reduce elevated intraocular pressure, levobetaxolol must be used with a miotic agent because if it is used alone, it is expected to have little or no effect on the pupil{01})


Myasthenic conditions    (potentiation of muscle weakness associated with myasthenic conditions has been reported after beta-adrenergic receptor blockade{01})


» Pulmonary function impairment{01}    (acute asthmatic attacks and pulmonary distress have been reported during treatment with ophthalmic beta-adrenergic receptor blocking agents{01})


Surgery, major    (gradual withdrawal of beta-adrenergic receptor blocking agents may be indicated prior to induction of general anesthesia due to the potential for impairment of the cardiac response to beta-adrenergically mediated sympathetic reflex stimuli{01})


» Thyrotoxicosis{01}    (certain signs and symptoms of hyperthyroidism, such as tachycardia, may be masked by beta-adrenergic blocking agents; abrupt withdrawal may precipitate a thyroid storm{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Intraocular pressure    (should be monitored regularly to assure that an adequate response to treatment has been achieved and maintained over time{01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Bradycardia (slow or irregular heartbeat)
    
breast abscess (breast pain)
    
cataracts ( blurred or decreased vision)
    
cystitis (bloody or cloudy urine; difficult, burning, or painful urination)
    
diabetes mellitus (fatigue; increased hunger; increased thirst; increased urination)
    
gout (ankle, knee, or great toe joint pain; ankle, knee, or great toe joint swelling; lower back or side pain)
    
heart block ( slow or irregular heartbeat)
    
hypercholesterolemia
    
hyperlipidemia
    
hypertension (headache; pounding in ears ; dizziness; blurred vision)
    
hypertonia (muscle tightness; muscle stiffness )
    
hypotension (confusion; faintness or lightheadedness)
    
hypothyroidism (dry, puffy skin; loss of appetite; weight gain; tiredness)
    
infection (fever or chills)
    
injury, accidental
    
otitis media (earache; ringing or buzzing in ears)
    
psoriasis ( red, scaling, or crusted skin)
    
pulmonary distress including bronchitis, dyspnea, pneumonia, rhinitis, and sinusitis (difficult or labored breathing; shortness of breath ; cough, mucus-producing; tightness in chest ; pain or tenderness around eyes or cheekbones; runny or stuffy nose; wheezing)
    
tachycardia (fast, pounding, or irregular heartbeat)
    
tinnitus (ringing or buzzing in the ears){01}
    
vascular anomaly
    
vertigo (dizziness; feeling of constant movement)
    
vitreous disorders

{01}

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Ocular discomfort, transient upon administration of medication (eye pain)
{01}
Incidence less frequent
    
Alopecia (thinning or loss of hair)
    
anxiety (feeling very anxious or nervous)
    
arthritis (pain, swelling, or redness of joints; stiffness of joints)
    
blurred vision (transient)
    
constipation
    
dermatitis (blistering, crusting, irritation, itching, or reddening of skin; dry, scaly skin)
    
dizziness
    
dyspepsia (belching; acid or sour stomach; heartburn; indigestion)
    
ear pain
    
headache
    
pharyngitis (dryness or soreness of throat; cough; difficulty swallowing; hoarseness)
    
taste perversion (change in taste){01}
    
tendinitis ( inflammation, pain, or swelling in muscles){01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
There is no information available regarding overdosage of levobetaxolol in humans. The symptoms associated with a systemically administered overdose of a beta-adrenergic receptor blocking agent might be expected in the event of an ophthalmic overdose.{01}

The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Bradycardia {01}
    
cardiac failure, acute {01}
    
hypotension {01}


Treatment of overdose


Supportive care:
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Levobetaxolol (Ophthalmic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to levobetaxolol or any other ingredient in the formulation
Other medications, especially catecholamine depleting agents (for example, reserpine) or systemic beta-adrenergic receptor blocking agents
Other medical problems, especially cardiogenic shock; diabetes mellitus; history of atopy, cardiac failure, or severe anaphylactic reactions; hypoglycemia; overt cardiac failure; pulmonary function impairment; second- or third-degree atrioventricular block; sinus bradycardia; or thyrotoxicosis{01}

Proper use of this medication
» Removing contact lenses before using medication

Shaking medication well before using
»
Proper administration technique
Washing hands before using medication; using correct technique to instill medication in eye(s)

Washing hands again immediately after using medication

Preventing contamination: Not touching dropper to any surface; keeping container tightly closed

» Proper dosing
Applying as soon as possible; if almost time for next dose, skipping missed dose and going back to regular dosing schedule; not doubling doses

Proper storage

Precautions while using this medication
» Regular visits to physician to check progress

» Caution if having any kind of surgery (including dental surgery) or emergency treatment

» Caution when driving a car or using machinery because of possible blurred vision or dizziness

» Diabetic patients: May mask some signs of hypoglycemia


Side/adverse effects
Signs of potential side effects, especially bradycardia; breast abscess; cataracts; cystitis; diabetes mellitus; gout; heart block; hypercholesterolemia; hyperlipidemia; hypertension; hypertonia; hypotension; hypothyroidism; infection; accidental injury; otitis media; psoriasis; pulmonary distress, including bronchitis, dyspnea, pneumonia, rhinitis, and sinusitis; tachycardia; tinnitus; vascular anomaly; vertigo; and vitreous disorders


General Dosing Information
Patients with angle-closure glaucoma require the concurrent use of a miotic agent with a pressure reduction agent in order to reopen the angle. Levobetaxolol is expected to exert little effect on the pupil; concomitant use of a miotic agent is therefore necessary whenever levobetaxolol is used to treat the elevated pressures associated with angle-closure glaucoma {01}.

Levobetaxolol is intended for ophthalmic use only. It should not be used orally or for injection.


Ophthalmic Dosage Forms

LEVOBETAXOLOL HYDROCHLORIDE OPHTHALMIC SUSPENSION

Usual Adult Dose
Open-angle glaucoma or
Ocular hypertension
Topical, to the conjunctiva, 1 drop into the affected eye, two times a day{01}


Usual Pediatric Dose
Safety and efficacy have not been established for the use of levobetaxolol in children{01}

Usual Geriatric Dose
See Usual adult dose.

Strength(s) usually available
U.S.—


0.5% (levobetaxolol hydrochloride 5.6 mg, equivalent to 5.0 mg of levobetaxolol free base per mL) (Rx) [Betaxon (benzalkonium chloride 0.01%) (mannitol ) (poly (styrene-divinyl benzene) sulfonic acid ) (Carbomer 974P) (boric acid) (N-lauroylsarcosine) ( edetate disodium) (hydrochloric acid or tromethamine to adjust pH) (purified water){01}]

Packaging and storage:
Store upright between 4°C and 25°C (39°F and 77°F). Protect from light.{01}

Auxiliary labeling:
   • For the eye
   • Protect from light.
   • Shake well before using.



Developed: 05/11/2000



References
  1. Product Information: Betaxon®, levobetaxolol hydrochloride ophthalmic suspension. Alcon Laboratories, Fort Worth, TX reviewed 4/2000.
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