Action And Clinical Pharmacology: Betaxolol is a cardioselective (beta-1-adrenergic) receptor blocking agent. It does not have significant membrane-stabilizing (local anesthetic) activity and is devoid of intrinsic sympathomimetic action.
Ocular: When instilled in the eye, betaxolol reduces elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma. When used as a solution, the onset of action occurs within 30 minutes and the maximal effect is usually attained approximately 2 hours after instillation. Although the time of onset of action, and time of maximal effect for the suspension have not been determined, controlled double masked studies show that the magnitude and duration of the ocular hypotensive effect of betaxolol 0.5% solution and betaxolol 0.25% suspension were clinically equivalent.
A single dose provides a 12-hour reduction in intraocular pressure (IOP) and twice daily administration maintains the IOP below 22 mm Hg in most patients.
Betaxolol has no effect on pupil size or accommodation.
Systemic: Ophthalmic betaxolol is virtually devoid of systemic effects. Following oral administration, the elimination half-life of betaxolol is 14 to 22 hours, and it is metabolized mainly to inactive substances which are excreted in the urine. Although betaxolol is absorbed systemically, ophthalmic doses do not ordinarily produce pharmacologically active tissue levels and thus, despite its cardioselective beta blocking activity, it has minimal, if any, effect on heart rate or blood pressure.
Betaxolol has a low affinity for b2-adrenergic receptors, and ophthalmic doses have no significant effect on pulmonary function as measured by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC. Ophthalmic doses do not inhibit the effect of isoproterenol, a beta-adrenergic stimulant, on pulmonary function. Therefore, ophthalmic betaxolol may be used in the treatment of patients with glaucoma or ocular hypertension who have coexisting reactive airway disease.
Indications And Clinical Uses: For lowering intraocular pressure in the treatment of ocular hypertension or chronic open angle glaucoma. May be used alone or in combination with other IOP-lowering medication.
Contra-Indications: Hypersensitivity to any component of this product.
Although ophthalmic betaxolol has minimal systemic effects, as with all beta-adrenergic blocking agents, it should not be used in patients with sinus bradycardia, atrioventricular block greater than first degree, cardiogenic shock, or patients with overt cardiac failure.
Precautions: General: Patients who are receiving a beta-adrenergic blocking agent orally and ophthalmic betaxolol should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta blockade.
Although ophthalmic betaxolol has demonstrated a low potential for systemic effects, it should be used with caution in patients with bradycardia, and those with diabetes (especially labile diabetes) because of possible masking of hypoglycemia. Consideration should be given to the gradual withdrawal of all beta-adrenergic blocking agents in patients suspected of developing thyrotoxicosis, and also prior to general anesthesia, because of the reduced ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli (see Drug Interactions).
Betaxolol, a cardioselective beta-blocker, has produced only minimal effects in patients with reactive airway disease; however, caution should be exercised in the treatment of patients with excessive restriction of pulmonary function.
In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle by constriction of the pupil with a miotic agent. Betaxolol has no effect on the pupil; therefore, ophthalmic betaxolol should be used with a miotic to reduce elevated intraocular pressure in angle-closure glaucoma.
As with the use of other antiglaucoma drugs, diminished responsiveness to ophthalmic betaxolol after prolonged therapy has been reported in some patients. However, in one long-term study in which 250 patients treated with betaxolol ophthalmic solution have been followed for up to 3 years, no significant difference in mean intraocular pressure has been observed after initial stabilization.
Drug Interactions: Although ophthalmic betaxolol used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with epinephrine has been reported occasionally.
Close observation of the patient is recommended when a beta-blocker is administered to patients receiving oral beta-adrenergic blocking drugs, or catecholamine-depleting drugs such as reserpine, because of possible additive effects. Caution should be exercised in patients using concomitant adrenergic psychotropic drugs.
Pregnancy: There have been no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly indicated.
Lactation: It is not known whether betaxolol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ophthalmic betaxolol is administered to nursing women.
Children: Clinical studies to establish the safety and efficacy in children have not been performed.
Adverse Reactions: The following adverse reactions have been reported in clinical trials of up to 3 years of patient experience with betaxolol ophthalmic preparations.
Ocular: Betaxolol has been well tolerated. Discomfort of short duration may be experienced by some patients upon instillation and occasional tearing has been reported. Instances of decreased corneal sensitivity, erythema, itching sensation, corneal punctate staining, keratitis, anisocoria and photophobia have been reported. Based on comparative studies, there is an increased incidence of blurred vision upon instillation of Betoptic S compared with Betoptic.
Systemic: Systemic reactions following topical administration of betaxolol have been reported rarely (e.g., CNS: insomnia and depressive neurosis).
Symptoms And Treatment Of Overdose: Symptoms: No data are available on overdosage of humans. However, anticipated symptoms include symptomatic bradycardia, hypotension, bronchospasm, acute cardiac failure and heart block (second or third degree).
A 10 mL container of 0.5% betaxolol ophthalmic solution would contain 50 mg of betaxolol. Betaxolol at 40 mg twice daily is reported to be an effective and safe systemic dosage for hypertension. Thus, an individual would ingest an amount of betaxolol from one container which is less than the maximum daily oral dose of betaxolol.
Since the oral LD50 in animals ranged from 350 to 1 050 mg/kg, a 10 kg child would only receive 5 mg/kg if the child ingested 10 mL of 0.5 % betaxolol ophthalmic solution. An acute toxic response is thus extremely remote.
Treatment: Should an overdosage occur, the following is suggested:
Ocular: Flush eye with lukewarm tap water.
Systemic: Gastric lavage.
Symptomatic bradycardia: Use atropine sulfate i.v. in a dosage of 0.25 mg to 2 mg to induce vagal blockage. If bradycardia persists, i.v. isoproterenol HCl should be administered cautiously. In refractory cases the use of a transvenous cardiac pacemaker may be considered.
Hypotension: Use sympathomimetic pressor drug therapy, such as dopamine, dobutamine or levarterenol. In refractory cases, the use of glucagon HCL has been reported to be useful.
Bronchospasm: Use isoproterenol HCl. Additional therapy with aminophylline may be considered.
Acute cardiac failure: Conventional therapy with digitalis, diuretics, and oxygen should be instituted immediately. In refractory cases the use of i.v. aminophylline is suggested. This may be followed if necessary by glucagon HCl which has been reported to be useful.
Heart block (second or third degree): use isoproterenol HCl or a transvenous cardiac pacemaker.
Dosage And Administration: The usual dose is 1 drop of betaxolol ophthalmic suspension in the affected eye(s) twice daily. In some patients, the intraocular pressure lowering response may require a few weeks to stabilize. Clinical follow-up should include a determination of the intraocular pressure during the first month of treatment. Thereafter, intraocular pressures should be determined on an individual basis at the judgment of the physician.
When a patient is transferred from a single antiglaucoma agent, continue the agent already used and add 1 drop of betaxolol in the affected eye(s) twice a day. On the following day, discontinue the previous antiglaucoma agent completely and continue with betaxolol ophthalmic solution or suspension.
Because of diurnal variations of intraocular pressure in individual patients, satisfactory response to twice a day therapy is best determined by measuring intraocular pressure at different times during the day. Intraocular pressure of less than 22 mm Hg may not be optimal for control of glaucoma in each patient; therefore, therapy should be individualized.
If the intraocular pressure of the patient is not adequately controlled on this regimen, concomitant therapy with pilocarpine, other miotics, epinephrine or systemically administered carbonic anhydrase inhibitors can be instituted.
When a patient is transferred from several concomitantly administered antiglaucoma agents, individualization is required. Adjustment should involve one agent at a time made at intervals of not less than 1 week. A recommended approach is to continue the agents being used and add 1 drop of betaxolol ophthalmic suspension in the affected eye(s) twice a day. On the following day, discontinue one of the other antiglaucoma agents. The remaining antiglaucoma agents may be decreased or discontinued according to the patient’s response to treatment. The physician may be able to discontinue some or all of the other antiglaucoma agents.
Special Instructions: Patients should be instructed to avoid contamination of the dropper tip.
The Betoptic S suspension must be well shaken before use.
Availability And Storage: Each mL of sterile, isotonic, aqueous suspension contains: betaxolol 0.25% (0.28% betaxolol HCl) with benzalkonium chloride (as preservative), mannitol, poly (styrene- divinyl benzene) sulfonic acid, carbomer 934P, edetate disodium, hydrochloric acid and/or sodium hydroxide (to adjust pH) and purified water. Drop-Tainer dispensers of 5 and 10 mL. Store at room temperature.
BETOPTIC® S Alcon Betaxolol HCl Antiglaucoma Agent