Betaxolol hydrochloride is a β1-selective adrenergic blocking agent.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 121, 122
Ocular Hypertension and Glaucoma
In ophthalmology, topical betaxolol hydrochloride is used to reduce elevated intraocular pressure (IOP) in patients with chronic open-angle glaucoma1, 2, 8, 12, 18, 19, 20, 74, 93, 94, 121, 122 or ocular hypertension.1, 2, 9, 10, 11, 94, 121 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.121
Elevated IOP in patients with glaucoma can be reduced by medical treatment, laser therapy, and/or incisional glaucoma surgery; treatment with a topical ocular hypotensive agent frequently is the initial intervention for primary open-angle glaucoma.130 Selection of an initial ocular hypotensive agent is influenced by the extent of the required reduction in IOP, coexisting medical conditions, and the characteristics of the individual drugs (e.g., dosing frequency, adverse effect profile, cost).130, 132 With single-agent regimens, the reduction in IOP is approximately 25-33% with topical prostaglandin analogs; 20-25% with topical β-adrenergic blocking agents, α-adrenergic agonists, or miotic (parasympathomimetic) agents; 20-30% with oral carbonic anhydrase inhibitors; 18% with topical rho kinase inhibitors; and 15-20% with topical carbonic anhydrase inhibitors.130, 131 In the absence of other considerations (e.g., contraindications, cost considerations, intolerance, adverse effects, patient refusal), a prostaglandin analog frequently is considered for initial therapy because of the relatively greater activity, once-daily administration, and low frequency of systemic adverse effects with this drug class; however, ocular adverse effects can occur.130, 131, 132, 134
IOP should be reduced toward a target level that the clinician believes will slow disease progression and avoid visual field losses that would substantially reduce quality of life during the patient's lifetime.130, 132 The target level is an estimate and should be individualized based on such factors as the extent of optic nerve damage and/or visual field loss, the baseline IOP at which damage occurred, rate of progression, life expectancy, and other considerations.130, 132 Reducing the pretreatment IOP by 25% or more has been shown to slow progression of primary open-angle glaucoma.130, 131 The target IOP should be adjusted up or down as needed over the course of the disease.130, 131, 132 If the target IOP is not achieved with single-agent therapy, alternative or additional ocular hypotensive agents may be selected depending on the patient's response to the initial drug.130 Combination therapy with drugs from different therapeutic classes often is required to achieve adequate control of IOP.131, 133
Controlled studies of betaxolol 0.25% resin-formulated ophthalmic suspension versus the 0.5% ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension have demonstrated that the resin-formulated suspension is therapeutically equivalent (i.e., in terms of the magnitude and duration of the hypotensive effect) to the solution.121, 122, 126
Because betaxolol has little or no effect on pupil size,1, 2, 8, 9, 11, 12, 18, 121, 122 a miotic should be used concomitantly in patients with angle-closure glaucoma.1, 121
Like timolol, betaxolol reduces elevated IOP in patients with chronic open-angle glaucoma without producing the miosis and/or ciliary spasm that are associated with miotic agents.1, 2, 8, 9, 11, 12, 18 In addition, use of betaxolol in patients with central lenticular opacities can avoid the visual impairment caused by a constricted pupil.1, 2 Usual dosages of betaxolol appear to be as effective as usual dosages of timolol in reducing IOP in patients with chronic open-angle glaucoma;1, 2, 12, 18, 19, 74, 93 however, unlike timolol,1, 2, 18, 53, 54, 55, 58, 59, 60, 61, 74 betaxolol has been associated with minimal adverse pulmonary1, 2, 9, 12, 14, 18, 21, 96, 97, 110, 121, 122 or cardiovascular effects.1, 2, 8, 9, 11, 12, 14, 110, 121, 122 Several studies involving small numbers of patients indicate that topical betaxolol may be used safely in some patients with chronic open-angle glaucoma who have coexisting reactive airway disease (e.g., asthma, chronic bronchitis, chronic obstructive pulmonary disease),1, 2, 20, 21, 30, 97 including some who cannot tolerate nonselective β-blocking agents (e.g., timolol)20, 30 or in whom these nonselective agents are contraindicated;21 however, increased airway resistance and pulmonary distress have been reported following topical application of betaxolol to the eye1, 21, 95, 121, 122 and the drug should be used with caution in patients with evidence of reactive airway disease on pulmonary function testing or excessive restriction of pulmonary function.1, 113, 121, 122 (See Cautions: Systemic Effects.)
During prolonged therapy with topical betaxolol, the effect in reducing IOP is generally well maintained.1, 2, 8, 12 The reduction in mean IOP has been maintained for up to 4 years after initial stabilization with the drug in some patients.2, 104 Betaxolol has been used effectively and has been well tolerated in some patients with glaucoma who have undergone laser trabeculoplasty and have needed additional long-term ocular hypotensive therapy; in some aphakic patients; and in patients with glaucoma who wear hard or soft contact lenses.1, 2, 122
For systemic uses of betaxolol hydrochloride, see 24:24.
Betaxolol hydrochloride is applied topically to the eye as an ophthalmic solution1, 2, 7, 8, 9, 10, 11, 12, 14, 18, 19, 20, 21, 74, 93 or resin-formulated suspension.121, 122, 126 Care should be taken to avoid contamination of the dispensing container.1, 103, 121 (See Cautions: Precautions and Contraindications.) The resin-formulated suspension should be shaken well prior to use.121, 122
Patients receiving the resin-formulated suspension should be advised to administer any concomitant topical ophthalmic drugs at least 10 minutes before administering the suspension.121
Betaxolol hydrochloride ophthalmic solution and the resin-formulated suspension contain benzalkonium chloride, which may be absorbed by soft contact lenses.1, 121 Contact lenses should be removed prior to administration of each betaxolol dose, but may be reinserted 15 minutes after the dose.121
Although USP currently states that potency of betaxolol hydrochloride preparations should be expressed both in terms of the salt and the base (“active moiety”),123 dosage currently is expressed in terms of the base.1, 2, 121 (See Chemistry and Stability: Chemistry.)
For the treatment of open-angle glaucoma or ocular hypertension, the therapeutic regimen must be adjusted to the individual requirements and response of the patient as determined by tonometric readings before and during therapy.65
For the initial treatment of open-angle glaucoma1, 2, 8, 121, 122 or ocular hypertension in adults,1, 2, 9, 10, 11, 121, 122 the usual dosage of betaxolol is 1 or 2 drops of the 0.5% ophthalmic solution or 1 drop of the 0.25% resin-formulated ophthalmic suspension in the affected eye(s) twice daily.1, 2, 8, 10, 11, 121 When betaxolol is used for the treatment of open-angle glaucoma or ocular hypertension in pediatric patients, the usual dosage is 1 drop of the 0.25% resin-formulated suspension in the affected eye(s) twice daily.121
Because of diurnal variations, it has been suggested that intraocular pressure (IOP) be measured at different times during the day to determine if an adequate hypotensive effect is maintained in patients receiving twice-daily therapy.107 IOP may not stabilize for a few weeks after initiating betaxolol therapy in some patients.1
If the target IOP is not achieved, alternative or additional ocular hypotensive agents may be required.130, 131, 133 (See Uses: Ocular Hypertension and Glaucoma.)
Betaxolol hydrochloride ophthalmic solution and resin-formulated suspension are generally well tolerated following topical application to the eye.2, 8, 9, 11, 12, 14, 18, 93, 94, 98, 99
The most frequent adverse effect following instillation of either topical betaxolol 0.5% ophthalmic solution or 0.25% resin-formulated ophthalmic suspension is mild ocular stinging and discomfort,1, 2, 8, 18, 74, 94, 98, 121, 122, 126 which occurs in about 25% of patients receiving the solution and in about 11% of patients receiving the resin-formulated suspension; it is usually transient and well tolerated.1, 2, 121, 122 Tearing1, 2, 18, 121, 122, 126 occurs in less than 5% of patients receiving the solution or the resin-formulated suspension.2, 122, 126 Blurred vision,1, 121, 126 corneal punctate keratitis,1, 2, 121, 122, 126 itching and/or foreign body sensation,1, 121, 122, 126 erythema,1, 121, 122 inflammation,1, 121, 126 photophobia,1, 18, 121, 122, 126 ocular pain and/or discharge,1, 121, 126 and ocular dryness1, 121, 122, 126 have been reported rarely in patients receiving either the solution or resin-formulated suspension. Choroidal detachment following filtration procedures also has been reported with the administration of aqueous suppressant therapy.121 Decreased corneal sensitivity,1, 2, 11, 12, 18 corneal punctate staining,1, 8, 121 edema,1, 121 and anisocoria1, 121 have been reported rarely in patients receiving the solution. Decreased visual acuity1, 121 and crusting of the eyelashes1, 121 have been reported rarely in patients receiving the resin-formulated suspension. Allergic reactions121 also have been reported in patients receiving betaxolol.121
Use of betaxolol hydrochloride ophthalmic solution or resin-formulated suspension to date has been associated with a low potential for causing systemic effects.1, 2, 8, 9, 11, 12, 18, 22, 23, 24, 93, 94, 98, 99, 110, 121, 122 Generally, there has not been evidence of substantial adverse pulmonary1, 2, 9, 12, 14, 18, 21, 22, 23, 74, 93, 96, 97, 98, 110, 121, 122 or cardiovascular1, 2, 8, 9, 11, 12, 14, 21, 22, 23, 74, 93, 98, 99, 110, 121, 122 effects following topical application of the drug to the eye. Ophthalmic betaxolol has had minor effects on blood pressure1, 2, 8, 9, 22, 23, 93, 110, 121, 122 and heart rate;1, 2, 8, 9, 18, 21, 23, 93, 99, 110 slight decreases in mean systolic (about 6 mm Hg) and diastolic (about 7 mm Hg) blood pressures have been observed in some patients.18 However, one patient with a history of well-compensated congestive heart failure secondary to atrial fibrillation experienced bradycardia and worsening of the heart failure following initiation of therapy with betaxolol ophthalmic solution.119 Ophthalmic betaxolol has been used safely in some patients with chronic open-angle glaucoma and coexisting reactive airway disease (e.g., asthma, chronic bronchitis, chronic obstructive pulmonary disease);1, 2, 20, 21, 30, 96 however, increased airway resistance and pulmonary distress (characterized by dyspnea, bronchospasm, thickened bronchial secretions, asthma, and respiratory failure) have been reported in patients receiving ophthalmic betaxolol, although to a lesser degree than with timolol,1, 21, 95, 121, 122 and betaxolol should be used with caution in patients with evidence of reactive airway disease on pulmonary function testing or excessive restriction of pulmonary function.1, 113, 121, 122
Other adverse effects reported rarely in patients receiving ophthalmic betaxolol include bradycardia,1, 121 heart block,1, 121 congestive heart failure,1, 121 hives,1, 121 toxic epidermal necrolysis,1, 121 hair loss,1, 121 glossitis,1, 121 taste or smell perversion,121 insomnia,1, 2 dizziness,1, 121 vertigo,1, 121 headache,1, 121 lethargy,1, 121 mental depression,1, 120, 121 and an increase in manifestations of myasthenia gravis.1, 121
Precautions and Contraindications
Clinical studies to date have shown that topical ophthalmic betaxolol has a low potential for systemic effects;2, 8, 9, 11, 12, 18, 22, 23, 24, 93, 94, 98, 110 however, betaxolol may be absorbed systemically following topical application to the eye,1, 121 and the usual precautions associated with systemic use of β-adrenergic blocking agents should be considered when using topical betaxolol, especially in patients with excessive restriction of pulmonary function.1, 119, 121 Severe respiratory and cardiac reactions, including death resulting from bronchospasm in patients with asthma and, rarely, death associated with cardiac failure, have been reported in patients receiving topical (ocular) β-adrenergic blocking agents.1, 121 In addition, patients receiving topical betaxolol and a systemic β-adrenergic blocking agent concomitantly should be observed carefully for potential additive effects on intraocular pressure (IOP) and/or systemic effects of β-adrenergic blockade.1
Betaxolol hydrochloride ophthalmic preparations have been used successfully in patients with glaucoma or ocular hypertension and coexisting reactive airway disease; however, asthmatic attacks and pulmonary distress have been reported in these patients during betaxolol therapy.1, 121 Although pulmonary function test results in some such patients have not been adversely affected on rechallenge, the possibility of adverse pulmonary effects in patients sensitive to β-adrenergic blocking agents cannot be ruled out.1, 121
Betaxolol hydrochloride ophthalmic solution and resin-formulated suspension should be used with caution in patients with a history of cardiac failure or heart block, and the drug should be discontinued at the first sign or symptom of impending cardiac failure.1, 119, 121 Ophthalmic betaxolol should also be used with caution in patients subject to hypoglycemia or with diabetes mellitus, especially those with labile disease who are receiving insulin or oral hypoglycemic agents or those prone to hypoglycemia, since β-blocking agents may mask the signs and symptoms of hypoglycemia (e.g., tachycardia and blood pressure changes but not sweating).1, 88, 121 Patients having or suspected of developing thyrotoxicosis should be monitored closely during ophthalmic betaxolol therapy, since β-blocking agents may mask certain clinical signs and symptoms of hyperthyroidism (e.g., tachycardia) and abrupt withdrawal of these agents can precipitate thyroid storm.1, 121
β-Adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic manifestations (e.g., diplopia, ptosis, and generalized weakness).1, 121
The necessity of withdrawing β-blocking agents prior to major surgery is controversial.87, 100, 113, 121β-Blocking agents may reduce the ability of the heart to respond to reflex β-adrenergic stimuli, which may increase the risk of general anesthesia.1, 121 Severe, protracted hypotension has occurred during surgery in some patients who received β-adrenergic blocking agents, and difficulty in restarting and maintaining the heartbeat also has been reported.121 Therefore, the manufacturers state that gradual withdrawal of betaxolol prior to administration of general anesthesia should be considered.1, 121 If necessary during surgery, the effects of β-blocking agents may be reversed by sufficient doses of adrenergic agonists.121
Patients who have a history of atopy or of a severe anaphylactic reaction to a variety of allergens reportedly may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blocking agents and may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.1, 121
Since topical betaxolol alone has little or no effect on the size of the pupil,1, 2, 8, 9, 11, 12, 18, 93, 99, 121, 122 a miotic should be used concomitantly for the treatment of increased IOP in patients with angle-closure glaucoma.1, 121
Topical betaxolol should be used with caution in patients with vascular insufficiency because of the potential effects of β-blocking agents on blood pressure and pulse rate.121 If signs or symptoms suggestive of Raynaud phenomenon or reduced cerebral blood flow develop, alternative ocular hypotensive therapy should be considered.121
Bacterial keratitis has been reported with the use of multiple-dose containers of topical ophthalmic solutions.121 These containers were contaminated inadvertently by patients who, in most cases, had concurrent corneal disease or disruption of the ocular epithelial surface.121 Patients should be informed that improper handling of ophthalmic preparations can result in contamination of the preparation by common bacteria known to cause ocular infections and that they should avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.121 Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic preparations.121 Patients also should be advised to immediately contact their clinician for advice regarding continued use of the current multidose container if they experience an intercurrent ocular condition (e.g., trauma, infection) or require ocular surgery.121
Patients who wear contact lenses should be advised that betaxolol hydrochloride ophthalmic solution and the resin-formulated suspension contain benzalkonium chloride, which may be absorbed by soft contact lenses.1, 121 Contact lenses should be removed prior to each dose of betaxolol but may be reinserted 15 minutes after the dose.121
Patients receiving betaxolol hydrochloride resin-formulated suspension should be advised to use caution when driving or operating machinery since they may experience temporary blurring of vision following instillation of the suspension.121
The manufacturers state that betaxolol hydrochloride ophthalmic solution and the resin-formulated suspension are contraindicated in patients with sinus bradycardia,1, 18, 121 atrioventricular block greater than first-degree,1, 18, 121 cardiogenic shock,1, 18, 121 or overt cardiac failure1, 121 that is not adequately compensated (e.g., with cardiac glycosides and/or diuretics).104 Ophthalmic betaxolol is also contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulations.1, 121
Safety and efficacy of betaxolol 0.25% resin-formulated ophthalmic suspension in pediatric patients have been established in a 3-month, multicenter, double-masked, active-controlled clinical trial; adverse effects observed in this study were comparable to those observed in adults.121
The manufacturer states that safety and efficacy of betaxolol 0.5% ophthalmic solution in pediatric patients have not been established.1, 11
No overall differences in safety or efficacy have been observed between geriatric patients and younger adults.121
Mutagenicity and Carcinogenicity
In vitro and in vivo microbial and mammalian test systems using betaxolol have not revealed evidence of mutagenicity.1, 2, 34, 121, 122
Lifetime studies in mice using oral betaxolol dosages of 6, 20, or 60 mg/kg daily and in rats using oral dosages of 3, 12, or 48 mg/kg daily did not reveal evidence of carcinogenic potential.1, 2, 34, 121, 122 Higher dosages have not been studied.1, 121
Pregnancy, Fertility, and Lactation
Reproduction studies in rats using oral betaxolol dosages of 4, 40, or 400 mg/kg daily (more than 300, 3000, or 30,000 times the recommended human daily ocular dose, respectively) and in rabbits using oral dosages of 1, 4, 12, and 36 mg/kg daily have not revealed evidence of teratogenicity.1, 2, 34 There are no adequate and well-controlled studies to date using betaxolol hydrochloride ophthalmic solution or resin-formulated suspension in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.1, 121
Reproduction studies in male and female rats using oral betaxolol dosages of 4, 32, or 256 mg/kg daily did not reveal evidence of impaired fertility;34 however, increased postimplantation loss in rats and rabbits occurred at dosages greater than 128 and 12 mg/kg daily, respectively.1, 2, 121, 122
Since betaxolol is distributed into milk,83 the drug should be used with caution in nursing women.1, 121 Although betaxolol concentrations in milk may be up to 3 times those in maternal blood,108 it is unlikely that clinically important doses of the drug would be ingested by breast-fed infants during ophthalmic use of usual betaxolol dosages in the woman.113
Systemic Beta-Adrenergic Blocking Agents
The possibility of an additive effect on intraocular pressure (IOP) and/or systemic β-adrenergic blockade should be considered in patients receiving a systemic β-blocking agent and topical betaxolol concomitantly.1, 121
Concomitant use of β-adrenergic blocking agents with antiarrhythmics, including amiodarone, may have additive effects resulting in hypotension and/or marked bradycardia.121
Calcium-channel Blocking Agents
Concomitant use of β-adrenergic blocking agents with calcium-channel blocking agents may have additive effects resulting in hypotension and/or marked bradycardia.121
Concomitant use of β-adrenergic blocking agents with cardiac glycosides may have additive effects resulting in hypotension and/or marked bradycardia.121
The manufacturer states that when topical betaxolol is administered concomitantly with a catecholamine-depleting drug (e.g., reserpine), the patient should be observed closely for possible additive effects and the production of hypotension and/or bradycardia, which may result in vertigo, syncope, and/or postural hypotension.1, 121
The manufacturer states that since betaxolol is a β-adrenergic-blocking agent, caution should be exercised in patients receiving concomitant therapy with adrenergic psychotropic drugs.1, 121
There currently is no information available on overdosage of topical betaxolol in humans.1, 121 The oral LD50 of betaxolol ranged from 350-920 mg/kg in mice and 860-1050 mg/kg in rats.1, 121 In general, overdosage of betaxolol may be expected to produce effects associated with β-adrenergic blocking agents (e.g., bradycardia, hypotension, cardiac failure).1, 121
Treatment of betaxolol overdosage generally involves symptomatic and supportive care.121 In case of topical overdosage of betaxolol hydrochloride ophthalmic solution or resin-formulated suspension, the eye(s) should be flushed with adequate amounts84, 104 of warm tap water.1, 121
Betaxolol hydrochloride is a β1-selective adrenergic blocking agent.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 16, 17, 25, 45, 48, 83, 121, 122 The drug is one of the most potent2, 6, 13, 16, 17, 25, 45, 48, 122 and selective2, 13, 16, 17, 25, 48, 122β1-adrenergic blocking agents currently available. In vitro studies indicate that the β1-adrenergic blocking activity of betaxolol on a molar basis is approximately the same as that of propranolol,6, 13, 25 2-8 times that of metoprolol,6, 25 and 9 times that of atenolol.25 Betaxolol does not exhibit intrinsic β1-agonist activity13, 15, 17, 83 and does not have substantial membrane-stabilizing (local anesthetic) activity.1, 2, 8, 9, 13, 18, 25, 28, 83, 121, 122
Following topical application to the eye, betaxolol hydrochloride reduces both elevated1, 2, 8, 9, 11, 12, 14, 19, 93, 94, 121, 122 and normal1, 2, 7 intraocular pressure (IOP) in patients with8, 9, 10, 11, 14, 19, 93, 94, 121 or without1, 2, 7, 94, 121 glaucoma. Betaxolol reduces IOP without affecting pupillary size1, 2, 8, 9, 11, 12, 18, 93, 94, 99, 122 or accommodation.2, 8, 9, 11, 122 In patients with elevated IOP, topical betaxolol reduces mean IOP by about 20-35% from baseline.1, 8, 9, 10, 93, 122, 126 Iris color does not appear to substantially affect IOP response to the drug.7, 12, 104
The exact mechanism by which β-blockers, including betaxolol, reduce IOP has not been clearly defined.1, 2, 7, 65, 122 Fluorophotometric studies suggest that reduced aqueous humor formation is the principal effect.1, 2, 7, 65, 121, 122β-Adrenergic blocking agents may block endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes and subsequent formation of aqueous humor.64, 65, 115, 116, 117, 118
Betaxolol does not appear to affect tonographic aqueous outflow resistance.7, 19 The drug apparently does not influence tear secretion2, 8, 9, 12, 18, 93, 94, 122 nor does it adversely affect ocular motor function.2, 11 Changes in visual acuity have not been observed with topical betaxolol,2, 8, 9, 11, 12, 18, 93, 122 and the drug appears to have minimal local anesthetic effect on the cornea.1, 2, 8, 9, 11, 12, 18, 93, 94, 99, 121, 122
The IOP-lowering effect of ophthalmic betaxolol has been maintained for at least 4 years with continuous use of the drug in some patients.2, 104
Unlike timolol (a nonselective β-adrenergic blocking agent), betaxolol appears to have minimal systemic pulmonary1, 2, 9, 12, 14, 18, 21, 97, 98, 99, 110, 121, 122 or cardiovascular1, 8, 9, 11, 12, 14, 22, 23, 93, 98, 110, 121, 122 effects following topical application to the eye; however, adverse pulmonary effects (e.g., bronchoconstriction, increased airway resistance, pulmonary distress) have been reported rarely.1, 21, 95, 96, 121 In a crossover study in 9 patients with reactive airway disease who exhibited at least a 15% decrease in forced expiratory volume in one second (FEV1) following topical application of timolol 0.5% to the eye, timolol adversely affected pulmonary function as determined by changes in FEV1, forced vital capacity (FVC), and forced respiratory flow rate (FEF25-75) in all patients; however, betaxolol 1% solution (not commercially available in the US) adversely affected FEV1 in only one patient.21, 95, 96 Ophthalmic application of betaxolol generally has had little, if any, effect on blood pressure1, 2, 8, 9, 22, 110, 121, 122 and heart rate,1, 2, 8, 9, 18, 21, 23, 110, 121, 122 although slight decreases in mean systolic and diastolic blood pressures have been observed in some patients.12, 18 In a crossover study in healthy adults, no evidence of cardiovascular β-adrenergic blockade during exercise (i.e., effect on heart rate or blood pressure) was observed following topical application of betaxolol 1% to the eye; however, evidence of systemic cardiovascular effect was present following ophthalmic timolol 0.5%.1, 2, 22, 121, 122
Betaxolol does not appear to affect glucose metabolism89, 105 or the rate of recovery of blood glucose concentration following hypoglycemia.26, 85 Following oral administration of betaxolol, mean serum total cholesterol and triglyceride concentrations have increased slightly in some patients, while consistent changes have not occurred in others.101, 102 Following oral administration of betaxolol in hypertensive patients, mean serum total cholesterol and triglyceride concentrations have generally been unchanged101 or slightly increased;102 the drug does not appear to decrease serum high-density lipoprotein (HDL)-cholesterol concentrations.102
In all studies described in the pharmacokinetics section, betaxolol was administered as the hydrochloride salt; dosages and concentrations of the drug are expressed in terms of betaxolol. Data from animal studies demonstrate that topically (i.e., to the eye) administered betaxolol 0.25% resin-formulated suspension and the 0.5% solution are bioequivalent.122, 126
The extent of ocular and systemic absorption of betaxolol hydrochloride following topical application to the eye has not been elucidated.104
Following topical application to the eye of a 0.5% solution or a 0.25% resin-formulated suspension of betaxolol, reduction in intraocular pressure (IOP) is usually evident within 0.5-1 hour, reaches a maximum within about 2 hours, and persists for about 12 hours or longer.1, 2, 121 The effect of a single dose of betaxolol on IOP usually dissipates within 24 hours after instillation;8 however, as with other ophthalmic β-blocking agents, some reduction in IOP may persist for as long as 1 week after discontinuance of betaxolol.9, 11, 14 In patients with open-angle glaucoma, the maximal lowering of IOP occurs after approximately 1-2 weeks of twice-daily application of the drug.8, 18
Betaxolol is well absorbed following oral administration.21, 39, 40, 41, 42, 43, 45, 47, 49, 50, 83, 106 Following oral administration of a single 20-mg dose of betaxolol in healthy adults, peak blood concentrations of about 46 ng/mL occur within approximately 3-4 hours.46, 47 Following oral administration of betaxolol, β-adrenergic blocking activity (e.g., as measured by a decrease in exercise-induced heart rate)16, 17, 28, 32, 35, 36, 37, 39, 42, 43 and/or reduction in systolic blood pressure17, 28, 36, 39, 42, 50, 79 begins within 3-6 hours16, 28, 32, 37, 39, 42, 43 and generally persists for 24 hours or longer.16, 17, 28, 37, 39, 42, 43
Distribution of betaxolol into human ocular tissues and fluids has not been characterized to date.104
Following IV administration in animals, betaxolol hydrochloride is widely distributed, with highest concentrations attained in liver, kidneys, heart, and lungs;46 the drug is also rapidly distributed into the CNS.46 The apparent volume of distribution of betaxolol is reportedly about 4.9-9.8 L/kg in healthy adults.40, 41, 46, 92, 106
In vitro, betaxolol is approximately 45-60% bound to plasma proteins,45, 83, 109 mainly to albumin and, to a lesser extent, to α1-acid glycoprotein (α1-AGP).109 Betaxolol crosses the placenta.83, 108 In one study in several pregnant women, the median ratio of fetal cord to maternal plasma drug concentrations was 0.7.83, 108 No accumulation of betaxolol was observed in the fetus or in amniotic fluid.113 Betaxolol is distributed into milk in humans.83
The metabolic fate and elimination characteristics of betaxolol hydrochloride following topical application to the eye have not been described to date.104
Following oral or IV administration, the elimination half-life of betaxolol is about 15 hours (range: 11-21 hours) in healthy adults28, 32, 42, 46, 83, 92, 106 and about 20 hours (range: 10.5-29) in hypertensive patients.44, 50, 113 The half-life of betaxolol is prolonged in patients with renal or hepatic insufficiency,45, 113 and in geriatric patients.80
Systemically absorbed betaxolol is extensively metabolized to at least 5 metabolites.2, 13, 46 The principal metabolite is the carboxylic acid derivative formed by oxidative deamination.46 The drug also undergoes O -dealkylation, yielding an alcohol derivative, and subsequent oxidation to form another carboxylic acid derivative.46 Small amounts of hydroxybetaxolol are formed by hydroxylation at the α carbon of the benzene ring.46 Small amounts of a dihydroxy metabolite are also formed from hydroxybetaxolol and from the O -dealkylated derivative.46 Only hydroxybetaxolol has β-adrenergic blocking activity (approximately 50% that of betaxolol).46
Following oral administration of a single dose of betaxolol in healthy adults, about 80-90% of the dose is excreted in urine and 1-3% in feces within 7 days; approximately 16% of the dose is excreted in urine unchanged, 35% as the deaminated carboxylic acid derivative, 24% as the carboxylic acid derivative formed by O -dealkylation and subsequent oxidation, 1% as hydroxybetaxolol, and less than 1% each as the alcohol and dihydroxy derivatives.46 It is not known whether the drug and metabolites excreted in feces represent unabsorbed drug or were excreted via biliary elimination.46 In animals, small amounts of the drug and/or its metabolites are excreted in feces via biliary elimination.46
Renal clearance of betaxolol is reduced in patients with renal insufficiency; however, total body clearance of the drug in patients with renal or hepatic insufficiency is similar to that in healthy individuals.45, 113
Betaxolol is not appreciably removed by hemodialysis or peritoneal dialysis.45, 113
Betaxolol hydrochloride is a β1-selective adrenergic blocking agent.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 121, 122 Betaxolol occurs as a racemic mixture of the R - and S -enantiomers.125 Betaxolol is structurally related to metoprolol, differing only by the addition of a cyclopropyl group at the terminal carbon of the methoxyethyl side chain of metoprolol.6, 68, 114 The presence of large substituents in the para position is believed to account for the selective β1-adrenergic blocking effect of betaxolol.2, 6, 68, 122
Betaxolol hydrochloride occurs as a white, crystalline powder1, 2 and has solubilities of 350 mg/mL in water6 and greater than 100 mg/mL in alcohol104 at room temperature. The drug is lipophilic and has a pKa of 9.38.27
USP currently states that potency of betaxolol hydrochloride preparations should be expressed both in terms of the salt and the base (“active moiety”).123 Previously, potency was expressed only in terms of betaxolol base. Dosage currently continues to be expressed in terms of the base.1, 121 Therefore, care should be taken to avoid confusion between labeled potencies as the salt and base and dosage of betaxolol hydrochloride.124 Each 2.8 or 5.6 mg of betaxolol hydrochloride is equivalent to about 2.5 or 5 mg of betaxolol, respectively.1, 2, 121
Betaxolol hydrochloride ophthalmic solution is a sterile, isotonic solution of the drug in water for injection;1 hydrochloric acid and/or sodium hydroxide may be added to adjust pH.1 Betaxolol hydrochloride ophthalmic suspension is a sterile, isotonic, resin-formulated suspension of the drug in purified water; hydrochloric acid and/or sodium hydroxide may be added to adjust pH.121, 122 The commercially available ophthalmic solution and suspension also contain benzalkonium chloride as a preservative and edetate disodium; sodium chloride is added to the solution to adjust tonicity.1, 2, 121, 122
Betaxolol hydrochloride ophthalmic solution should be stored at 20-25°C and the resin-formulated suspension should be stored upright at 2-25°C.1, 121
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
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Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | 0.5% (of betaxolol)* | ||
Suspension | 0.25% (of betaxolol) | Betoptic S® |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Akorn, Inc. Betaxolol hydrochloride solution prescribing information. Lake Forest, IL; 2016 Jun.
2. Alcon Laboratories. Betoptic® product monograph. Ft. Worth, TX; 1985 Sep.
3. Weiner N. Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985:181-214.
4. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983:169.
5. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:1684.
6. Manoury P. Betaxolol: chemistry and biological profile in relation to its physicochemical properties. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:13-9.
7. Reiss GR, Brubaker RF. The mechanism of betaxolol, a new ocular hypotensive agent. Ophthalmology . 1983; 90:1369-72. [PubMed 6664677]
8. Berrospi R, Leibowitz HM. Betaxolol: a new β-adrenergic blocking agent for treatment of glaucoma. Arch Ophthalmol . 1982; 100:943-6. [PubMed 6124227]
9. Caldwell DR, Salisbury CR, Guzek JP. Effects of topical betaxolol in ocular hypertensive patients. Arch Ophthalmol . 1984; 102:539-40. [PubMed 6704008]
10. Smith JP, Weeks RH, Newland EF et al. Betaxolol and acetazolamide: combined ocular hypotensive effect. Arch Ophthalmol . 1984; 102:1794-5. [PubMed 6391442]
11. Radius RL. Use of betaxolol in the reduction of elevated intraocular pressure. Arch Ophthalmol . 1983; 101:898-900. [PubMed 6860201]
12. Levy NS, Boone L, Ellis E. A controlled comparison of betaxolol and timolol with long-term evaluation of safety and efficacy. Glaucoma . 1985; 7:54-62.
13. Cavero I, Lefèevre-Borg F, Manoury P et al. In vitro and in vivo pharmacological evaluation of betaxolol, a new, potent, and selective β1-adrenoceptor antagonist. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:31-42.
14. Levy NS, Boone L. Effect of 0.25% betaxolol v placebo. Glaucoma . 1983; 5:230-2.
15. Vareilles P, Silverstone D, Plazonnet B et al. Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit. Invest Ophthalmol Vis Sci . 1977; 16:987-96. [PubMed 21145]
16. Shanks RG. Comparison of betaxolol with other β-blocking drugs in healthy volunteers. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:133-41.
17. Cadigan PJ, London D, Pentecost BL. Effects of betaxolol, given in single doses by mouth, on pulse rate and blood pressure in normal subjects. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:101-7.
18. Berry DP Jr, Van Buskirk EM, Shields MB. Betaxolol and timolol: a comparison of efficacy and side effects. Arch Ophthalmol . 1984; 102:42-5. [PubMed 6367723]
19. Allen RC, Epstein DL. A double-masked clinical trial of betaxolol and timolol in glaucoma patients. Invest Ophthalmol Vis Sci . 1982; 22(Suppl):40.
20. Allen RC, Boys-Smith J. Betaxolol in patients with coexistant glaucoma and pulmonary disease. Invest Ophthalmol Vis Sci . 1984; 25(Suppl 3):305.
21. Schoene RB, Abuan T, Ward RL et al. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol . 1984; 97:86-92. [PubMed 6141730]
22. Atkins JM, Pugh BR Jr, Timewell RM. Cardiovascular effects of topical beta-blockers during exercise. Am J Ophthalmol . 1985; 99:173-5. [PubMed 3970121]
23. Hernandez y Hernandez H, Cervantes R, Frati A et al. Cardiovascular effects of topical glaucoma therapies in normal subjects. J Toxicol Cutaneous Ocul Toxicol . 1983; 2:99-106.
24. Bloom E, Richmond C, Alvarado J et al. Betaxolol vs. timolol: plasma radio-receptor assays to evaluate systemic complications of beta blocker therapy for glaucoma. Invest Ophthalmol . 1985; 26(Suppl):125.
25. Boudot JP, Cavero I, Féenard S et al. Preliminary studies on SL 75212, a new potent cardioselective β-adrenoceptor antagonist. Br J Pharmacol . 1979; 66:445P. [PubMedCentral][PubMed 43176]
26. Kilborn JR, Morselli PL, Saunders J et al. The effects of the new β-adrenoceptor blocker SL 75212 on the cardiovascular responses to insulin induced hypoglycaemia in man. Br J Clin Pharmacol . 1979; 8:409P. [PubMed 41561]
27. Davis BJ, Turner P. The spectrofluorimetric estimation and buccal absorption of SL 75212, a novel β-adrenoceptor antagonist. Br J Clin Pharmacol . 1979; 8:405P. [PubMed 41558]
28. Cadigan PJ, London DR, Pentecost BL et al. Cardiovascular effects of single oral doses of the new β-adrenoceptor blocking agent betaxolol (SL 75212) in healthy volunteers. Br J Clin Pharmacol . 1980; 9:569-75. [PubMedCentral][PubMed 6104498]
29. Salonen JT, Palminteri R. Comparison of two doses of betaxolol and placebo in hypertension: a randomized, double-blind cross-over trial. Eur J Clin Pharmacol . 1982; 23:491-4. [PubMed 6761136]
30. Vukich JA, Leef DL, Allen RC. Betaxolol in patients with coexistant chronic open angle glaucoma and pulmonary disease. Invest Ophthalmol . 1985; 26(Suppl):227.
31. DeSantis L, Chandler M. Cardiac beta blockade after ocular instillation of beta adrenergic blockers in alert cynomolgus monkeys: safety profile for betaxolol. Invest Ophthalmol . 1985; 26(Suppl):227.
32. Balnave K, Neill JD, Russell CJ et al. The duration of effect of SL 75212 on an exercise tachycardia. Br J Clin Pharmacol . 1980; 9:297P. [PubMed 6102471]
33. Fillastre JP, Godin M, Cazor JL et al. Renal effects of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:183-93.
34. Friedmann JC. Safety evaluation of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:43-50.
35. Palminteri R, Kaik G. Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol. Eur J Clin Pharmacol . 1983; 24:741-5. [PubMed 6136412]
36. Stroobandt R, Kesteloot H. Dose-related efficacy of betaxolol in patients with angina pectoris. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:257-60.
37. Kesteloot H, Missotten A, Coupez-Lopinot R et al. Effect of betaxolol on heart rate at rest and during exercise. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:155-9.
38. Saunders J, Gomeni R, Kilborn JR et al. A comparison between propranolol, practolol and betaxolol (SL 75212) on the circulatory and metabolic responses to insulin-induced hypoglycaemia. Eur J Clin Pharmacol . 1981; 21:177-84. [PubMed 6119203]
39. Bianchetti G, Chauvin M, Giudicelli JF et al. Comparison of the β-adrenoceptor blocking properties and pharmacokinetics of SL 75212 and propranolol in man. Br J Clin Pharmacol . 1979; 8:407-8P.
40. Bianchetti G, Blatrix C, Gomeni R et al. Pharmacokinetics of the new β-adrenoceptor blocker SL 75212 in man after repeated oral administration. Br J Clin Pharmacol . 1979; 8:408P. [PubMed 41560]
41. Bianchetti G, Gomeni R, Kilborn JR et al. Blood concentrations and pharmacodynamic effects of SL 75212, a new β-adrenoceptor antagonist, after oral and intravenous administration. Br J Clin Pharmacol . 1979; 8:403-4P.
42. Giudicelli JF, Richer C, Ganansia J et al. Betaxolol: β-adrenoceptor blocking effects and pharmacokinetics in man. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:89-99.
43. Balnave K, Neill JD, Russell CJ et al. Observations on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective β-adrenoceptor blocking drug. Br J Clin Pharmacol . 1981; 11:171-80. [PubMedCentral][PubMed 6111331]
44. Palminteri R, Assael BM, Bianchetti G et al. Betaxolol kinetics in hypertensive children with normal and abnormal renal function. Clin Pharmacol Ther . 1984; 35:141-7. [PubMed 6692644]
45. Morselli PL, Thiercelin JF, Padovani P et al. Comparative pharmacokinetics of several β-blockers in renal and hepatic insufficiency. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:233-41.
46. Ferrandes B, Durand A, Andrée-Fraisse J et al. Pharmacokinetics and metabolism of betaxolol in various animal species and man. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:51-64.
47. Thiercelin JF, Bianchetti G, Larribaud J et al. Effects of a meal and its composition on the bioavailability of betaxolol administered orally to healthy subjects. World Rev Nutr Diet . 1984; 43:183-6. [PubMed 6147938]
48. Warrington SJ, Taylor EA, Kilborn JR. Comparison of pharmacodynamic effects of betaxolol with atenolol, practolol, and propranolol given intravenously. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:109-22.
49. Warrington SJ, Turner P, Kilborn JR et al. Blood concentrations and pharmacodynamic effects of betaxolol (SL 75212) a new β-adrenoceptor antagonist after oral and intravenous administration. Br J Clin Pharmacol . 1980; 10:449-52. [PubMedCentral][PubMed 6108127]
50. Weiss Y, Boutonnet G, Chenard A et al. Antihypertensive action and kinetics of a single daily dose of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:267-75.
51. Wax MB, Molinoff PB. Distribution and properties of beta-adrenergic receptors in human iris/ciliary body. Invest Ophthalmol Vis Sci . 1984; 25(Suppl):305.
52. Boger WP. Timolol: short term “escape” and long term “drift.” Ann Ophthalmol . 1979; 11:1239-42. Editorial.
53. Van Buskirk EM. Adverse reactions from timolol administration. Ophthalmology . 1980; 87:447-50. [PubMed 7402590]
54. Williams T, Ginther WH. Hazard of ophthalmic timolol. N Engl J Med . 1982; 306:1485-6. [PubMed 7078595]
55. McMahon CD, Shaffer RN, Hoskins HD Jr et al. Adverse effects experienced by patients taking timolol. Am J Ophthalmol . 1979; 88:736-8. [PubMed 507146]
56. Harrison R. Betaxolol and timolol. Arch Ophthalmol . 1984; 102:1424. [PubMed 6148923]
57. Berry DP Jr, Shields MB, Van Buskirk M. Betaxolol and timolol. Arch Ophthalmol . 1984; 102:1424-5.
58. Jones FL Jr, Ekberg NL. Exacerbation of obstructive airway disease by timolol. JAMA . 1980; 244:2730. [PubMed 7441859]
59. Ahmad S. Cardiopulmonary effects of timolol eyedrops. Lancet . 1979; 2:1028. [PubMed 91770]
60. Zimmerman TJ, Leader BJ, Golob DS. Potential side effects of timolol therapy in the treatment of glaucoma. Ann Ophthalmol . 1981; 13:683-9. [PubMed 7020551]
61. Schoene RB, Martin TR, Charan NB et al. Timolol-induced bronchospasm in asthmatic bronchitis. JAMA . 1981; 245:1460-1. [PubMed 7206150]
62. Anon. Additions to Timoptic contraindications. FDA Drug Bull . 1981; 11:1. [PubMed 7215728]
63. Taylor P. Anticholinesterase agents. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985:110-27.
64. Remis LL, Epstein DL. Treatment of glaucoma. Ann Rev Med . 1984; 35:195-205. [PubMed 6426371]
65. Havener WH. Ocular pharmacology. 5th ed. St. Louis: The CV Mosby Company; 1983:18-43,261-417,635-72.
66. Henry JA, Mitchell SN. Effect of pH on human plasma protein binding of a series of β-adrenoceptor antagonists. Br J Clin Pharmacol . 1981; 11:119-20P.
67. Fraunfelder FT, Barker AF. Respiratory effects of timolol. N Engl J Med . 1984; 311:1441. [PubMed 6493304]
68. Machin PJ, Hurst DN, Bradshaw RN et al. β1-Selective adrenoceptor antagonists. 2: 4-ether-linked phenoxypropanolamines. J Med Chem . 1983; 26:1570-6. [PubMed 6138435]
69. Shell JW. Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol . 1982; 26:207-18. [PubMed 7041308]
70. Smith LH. β-Adrenergic blocking agents. 15: 1-substituted ureidophenoxy-3-amino-2-propanols. J Med Chem . 1977; 20:705-8. [PubMed 16137]
71. Smith LH. β-Adrenergic blocking agents. 16: 1-(acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols. J Med Chem . 1977; 20:1254-8. [PubMed 20502]
72. Smith LH, Tucker H. β-Adrenergic blocking agents. 17: 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols. J Med Chem . 1977; 20:1653-6. [PubMed 22750]
73. Engel G. Subclasses of beta-adrenoceptors—a quantitative estimation of beta1- and beta2-adrenoceptors in guinea pigs and human lung. Postgrad Med J . 1981; 57(Suppl 1):77-83. [PubMedCentral][PubMed 6272254]
74. Allen RC. Betaxolol in the treatment of glaucoma: multi-clinic trials. Ophthalmology . 1984; 91(Suppl):142.
75. Langer SZ, Galzin AM. β-Adrenoceptors and noradrenergic neurotransmission: effects of betaxolol on the stimulation-evoked release of3H-norepinephrine in isolated rat atria and rabbit hypothalamic slices. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:21-30.
76. Söonksen PH, Brown PM, Saunders J et al. Metabolic and cardiovascular effects of betaxolol during hypoglycemia and exercise in normal volunteers. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:143-54.
77. Libersa C, Carrée A, Bertrand M et al. Study of the acute hemodynamic effects of betaxolol in noncomplicated essential hypertension. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:171-8.
78. Harrison DC, Buchbinder M, Schroeder JS. Acute hemodynamic effects of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:179-81.
79. Pathée M, Steimer C, Cazor JL et al. Dose-response study of betaxolol in hypertension. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:287-96.
80. Bianchetti G, Padovani P, Thiercelin JF et al. Pharmacokinetic studies on betaxolol—evaluation of the effects of age, hypertension, presence of food, and concomitant administration of hydrochlorothiazide on the disposition of the drug. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:123-31.
81. Barrett AM. Therapeutic applications of β-adrenoceptor antagonists. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:65-72.
82. Bergis SK. Long-term efficacy and safety of betaxolol and propranolol in hypertensive patients. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:353-7.
83. Beresford R, Heel RC. Betaxolol: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in hypertension. Drugs . 1986; 31:6-28. [PubMed 2866947]
84. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore: Williams & Wilkins; 1984:I-6.
85. Gomeni R, Kilborn JR, Morselli PL et al. The action of the new β-adrenoceptor blocker SL 75212 on the metabolic response to insulin-induced hypoglycaemia in man. Br J Clin Pharmacol . 1979; 8:404P. [PubMed 41557]
86. Davies IB, Larribaud J, Thiercelin JF et al. Betaxolol does not modify hypoglycaemic actions on glibenclamide or metformin in normal subjects. Br J Clin Pharmacol . 1984; 17:622P.
87. Merck Sharp & Dohme. Timoptic® prescribing information. West Point, PA; 1985 Oct.
88. Jackson JE, Bressler R. Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 2. Drugs . 1981; 22:295-320. [PubMed 7030708]
89. Brüugmann U, Blasini R. Comparative effects of long-acting beta-adrenergic receptor blockers with and without cardioselectivity: double-blind, randomized, cross-over and placebo-controlled study with betaxolol and nadolol. Circulation . 1983; 68(Suppl III):406. [PubMed 6861316]
90. Saunders J, Prestwich SA, Avery AJ et al. The effect of non-selective and selective beta-1-blockade on the plasma potassium response to hypoglycaemia. Diabete Metab . 1981; 7:239-42. [PubMed 6120859]
91. Zimmerman TJ. Timolol maleate—a new glaucoma medication? Invest Ophthalmol Visual Sci . 1977; 16:687-8. Editorial.
92. Giudicelli JF, Chauvin M, Thuillez C et al. β-Adrenoceptor blocking effects and pharmacokinetics of betaxolol (SL-75212) in man. Br J Clin Pharmacol . 1980; 10:41-9. [PubMedCentral][PubMed 6104973]
93. Stewart RH, Kimbrough RL, Ward RL. Betaxolol vs timolol: a six-month double-blind comparison. Arch Ophthalmol . 1986; 104:46-8. [PubMed 3510612]
94. Feghali JG, Kaufman PL. Decreased intraocular pressure in the hypertensive human eye with betaxolol, a β1-adrenergic antagonist. Am J Ophthalmol . 1985; 100:777-82. [PubMed 2866715]
95. Spiritus EM, Casciari R. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol . 1985; 100:492-3. [PubMed 4037047]
96. Schoene RB, Abuan T, Ward RL et al. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol . 1985; 100:493-4.
97. Dunn TL, Gerber MJ, Shen AS et al. Timolol-induced bronchospasm: utility of betaxolol as an alternative ocular hypotensive agent in patients with asthma. Clin Res . 1985; 33:20A.
98. Allen RC. Betaxolol in the treatment of glaucoma: multiclinic trials. Ophthalmology . 1984; 91:142.
99. Weinreb RN, Ritch R, Kushner FH. Effect of adding betaxolol to dipivefrin therapy. Am J Ophthalmol . 1986; 101:196-8. [PubMed 3946535]
100. Martin DE, Kammerer WS. The hypertensive surgical patient: controversies in management. Surg Clin North Am . 1983; 63:1017-33. [PubMed 6138862]
101. Djian J. Clinical evaluation of betaxolol (Kerlone) as a once-daily treatment for hypertension in 4685 patients. Br J Clin Pract . 1985; 39:188-91. [PubMed 2866790]
102. Jaillard J, Rouffy J, Sauvanet JP. Long-term influence of betaxolol on plasma lipids and lipoproteins. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:221-31.
103. American Society of Health-System Pharmacists, Inc.. Medication teaching manual: a guide for patient counseling. 2nd ed. Bethesda, MD: American Society of Hospital Pharmacists; 1980:300.
104. Poe RD (Alcon Laboratories, Fort Worth, TX): Personal communication; 1986 May 14.
105. Frances Y, Luccioni R, Vague P et al. Effects of betaxolol, propranolol, and acebutolol on the glycoregulation after oral glucose tolerance test in hypertensive patients. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:213-20.
106. Bianchetti G, Blatrix C, Gomeni R et al. Pharmacokinetics of the new β-adrenoceptor blocking agent betaxolol (SL 75212) in man after repeated oral administration. Arzneimittelforschung . 1980; 30:1912-6. [PubMed 6109538]
107. Kitazawa Y, Horie T. Diurnal variation of intraocular pressure in primary open-angle glaucoma. Am J Ophthalmol . 1975; 79:557-66. [PubMed 1168023]
108. Buotroy M, Vert P, Bianchetti G et al. Betaxolol: pharmacokinetics and pharmacodynamic effects of a new cardioselective beta-blocker in pregnant women. Proceedings of World Conference on Clinical Pharmacology and Therapeutics. Washington, DC; 1983 July 31-August 5. Abstract No. N565.
109. Ganansia J, Bianchetti G, Bouchet JL et al. Protein binding of betaxolol in healthy volunteers and in patients with renal or hepatic disease. In: Aiache and Hirtz, eds. Proceedings of 2nd European Congress of Biopharmaceutics and Pharmacokinetics; Salamanca, Spain: 1984 April 24-27. Vol 3: Clinical Pharmacokinetics; 1984:440-7.
110. Dunn TL, Gerber MJ, Shen AS et al. The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects. Am Rev Respir Dis . 1986; 133:264-8. [PubMed 3946922]
111. Anon. Two new beta-blockers for glaucoma. Med Lett Drugs Ther . 1986; 28:45-8. [PubMed 2870417]
112. Anon. The autonomic nervous system and the eye. Lancet . 1985; 2:591-2. [PubMed 2863600]
113. Reviewers' comments (personal observations); 1986 Apr.
114. Durand A, Pauloin D, Bernard F et al. In vitro metabolism of betaxolol and metoprolol: influence of the structure. Proceedings of World Conference on Clinical Pharmacology and Therapeutics. Washington, DC; 1983 July 31-August 5. Abstract No. N568.
115. Neufeld AH. Epinephrine and timolol: how do these drugs lower intraocular pressure? Ann Ophthalmol . 1981; 13:1109-11.
116. Watanabe K, Chiou GCY. Action mechanism of timolol to lower the intraocular pressure in rabbits. Ophthalmic Res . 1983; 15:160-7. [PubMed 6314218]
117. Remis LL, Epstein DL. Treatment of glaucoma. Glaucoma . 1984; 35:195-205.
118. Schenker HI, Yablonski ME, Podos SM et al. Fluorophotometric study of epinephrine and timolol in human subjects. Arch Ophthalmol . 1981; 99:1212-6. [PubMed 7259595]
119. Ball S. Congestive heart failure from betaxolol. Arch Ophthalmol . 1987; 105:320. [PubMed 2881533]
120. Orlando RG. Clinical depression associated with betaxolol. Am J Ophthalmol . 1986; 102:275. [PubMed 3740190]
121. Alcon Laboratories. Betoptic® S (betaxolol hydrochloride) suspension prescribing information. Fort Worth, TX; 2018 Nov.
122. Alcon Laboratories. Betoptic® S (betaxolol hydrochloride) product monograph. Fort Worth, TX; 1990 Feb.
123. The United States pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1995:197-8.
124. The USP Drug Nomenclature Committee. Nomenclature policies and recommendations: I. Review and current proposals and decisions. Pharmacopeial Forum . 1991; 17:1509-11.
125. Alcon Laboratories. Betaxon® (levobetaxolol hydrochloride ophthalmic suspension) prescribing information (dated 2000 May). In Physicians' desk reference for ophthalmology. 30th ed. Montvale, NJ: Medical Economics Inc; 2002:206-8.
126. Weinreb RN, Caldwell DR, Goode SM et al. A double-masked three-month comparison between 0.25% betaxolol suspension and 0.5% betaxolol ophthalmic solution. Am J Ophthalmol . 1990; 110:189-92. [PubMed 2198812]
130. Prum BE Jr, Rosenberg LF, Gedde SJ et al. Primary open-angle glaucoma preferred practice pattern® guideline [published corrigendum appears in Ophthalmology . 2018; 125: 949]. San Francisco, CA: American Academy of Ophthalmology; 2015. From the American Academy of Ophthalmology website. [Web]
131. Liebmann JM, Lee JK. Current therapeutic options and treatments in development for the management of primary open-angle glaucoma. Am J Manag Care . 2017; 23(15 Suppl):S279-S292. [PubMed 29164845]
132. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA . 2014; 311:1901-11. [PubMed 24825645]
133. Gupta D, Chen PP. Glaucoma. Am Fam Physician . 2016; 93:668-74. [PubMed 27175839]
134. Inoue K. Managing adverse effects of glaucoma medications. Clin Ophthalmol . 2014; 8:903-13. [PubMed 24872675]