Betaxolol Hydrochloride

Betaxolol Hydrochloride Ophthalmic Solution contains betaxolol hydrochloride, a cardioselective beta-adrenergic receptor blocking agent, in a sterile isotonic solution. Betaxolol hydrochloride is a white, crystalline powder, soluble in water, with a molecular weight of 343.89. The chemical structure is presented below:

Each mL of Betaxolol Hydrochloride Ophthalmic Solution (0.5%) contains: Active: 5.6 mg betaxolol hydrochloride equivalent to betaxolol base 5 mg. Preservative: Benzalkonium Chloride 0.1%. Inactives: Edetate Disodium, Sodium Chloride, Hydrochloric Acid and/or Sodium Hydroxide (to adjust pH), and Purified Water.

Do not touch dropper tip to any surface as this may contaminate the solution.

Kerlone (betaxolol hydrochloride) is indicated in the management of hypertension. It may be used alone or concomitantly with other antihypertensive agents, particularly thiazide-type diuretics.

Most adverse reactions have been mild and transient and are typical of beta-adrenergic blocking agents, eg, bradycardia, fatigue, dyspnea, and lethargy. Withdrawal of therapy in U.S. and European controlled clinical trials has been necessary in about 3.5% of patients, principally because of bradycardia, fatigue, dizziness, headache, and impotence.

Frequency estimates of adverse events were derived from controlled studies in which adverse reactions were volunteered and elicited in U.S studies and volunteered and/or elicited in European studies.

In the U.S., the placebo-controlled hypertension studies lasted for 4 weeks, while the active-controlled hypertension studies had a 22- to 24- week double-blind phase. The following doses were studied: betaxolol-5, 10, 20, and 40 mg once daily; atenolol-25, 50, and 100 mg once daily; and propranolol-40, 80, and 160 mg b.i.d.

Kerlone (betaxolol hydrochloride) , like other beta-blockers, has been associated with the development of antinuclear antibodies (ANA) (e.g., lupus erythematosus). In controlled clinical studies, conversion of ANA from negative to positive occurred in 5.3% of the patients treated with betaxolol, 6.3% of the patients treated with atenolol, 4.9% of the patients treated with propranolol, and 3.2% of the patients treated with placebo.

Betaxolol adverse events reported with a 2% or greater frequency, and selected events with lower frequency, in U.S. controlled studies are:

Of the above adverse reactions associated with the use of betaxolol, only bradycardia was clearly dose related, but there was a suggestion of dose relatedness for fatigue, lethargy, and dyspepsia.

In Europe, the placebo-controlled study lasted for 4 weeks, while the comparative studies had a 4- to 52-week double-blind phase. The following doses were studied: betaxolol 20 and 40 mg once daily and atenolol 100 mg once daily.

From European controlled hypertension clinical trials, the following adverse events reported by 2% or more patients and selected events with lower frequency are presented:

The only adverse event whose frequency clearly rose with increasing dose was bradycardia. Elderly patients were especially susceptible to bradycardia, which in some cases responded to dose-reduction (see PRECAUTIONS).

The following selected (potentially important) adverse events have been reported at an incidence of less than 2% in U.S. controlled and open, long-term clinical studies, European controlled clinical trials, or in marketing experience. It is not known whether a causal relationship exists between betaxolol and these events; they are listed to alert the physician to a possible relationship:

Autonomic: flushing, salivation, sweating.

Body as a whole: allergy, fever, malaise, pain, rigors.

Cardiovascular: angina pectoris, arrhythmia, atrioventricular block, heart failure, hypertension, hypotension, myocardial infarction, thrombosis, syncope.

Central and peripheral nervous system: ataxia, neuralgia, neuropathy, numbness, speech disorder, stupor, tremor, twitching.

Gastrointestinal: anorexia, constipation, dry mouth, increased appetite, mouth ulceration, rectal disorders, vomiting, dysphagia.

Hearing and Vestibular: earache, labyrinth disorders, tinnitus, deafness.

Hematologic: anemia, leucocytosis, lymphadenopathy, purpura, thrombocytopenia.

Liver and biliary: increased AST, increased ALT.

Metabolic and nutritional: acidosis, diabetes, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipemia, hyperuricemia, hypokalemia, weight gain, weight loss, thirst, increased LDH.

Musculoskeletal: arthropathy, neck pain, muscle cramps, tendonitis.

Psychiatric:abnormal thinking, amnesia, impaired concentration, confusion, emotional lability, hallucinations, decreased libido.

Reproductive disorders: Female: breast pain, breast fibroadenosis, menstrual disorder; Male: Peyronie's disease, prostatitis.

Respiratory: bronchitis, bronchospasm, cough, epistaxis, flu, pneumonia, sinusitis.

Skin: alopecia, eczema, erythematous rash, hypertrichosis, pruritus, skin disorders.

Special senses: abnormal taste, taste loss.

Urinary system: cystitis, dysuria, micturition disorder, oliguria, proteinuria, abnormal renal function, renal pain.

Vascular:cerebrovascular disorder, intermittent claudication, leg cramps, peripheral ischemia, thrombophlebitis.

Vision: abnormal lacrimation, abnormal vision, blepharitis, ocular hemorrhage, conjunctivitis, dry eyes, iritis, cataract, scotoma.

Potential adverse effects: Although not reported in clinical studies with betaxolol, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and may be considered potential adverse effects of betaxolol:

Central nervous system: Reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability with slightly clouded sensorium, and decreased performance on neuropsychometric tests.

Allergic: Fever combined with aching and sore throat, laryngospasm, respiratory distress.

Hematologic: Agranulocytosis, thrombocytopenic purpura, and nonthrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis.

Metabolic: Hypoglycemia.

Miscellaneous: Raynaud's phenomena. There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small, and in most cases, the symptoms have cleared when treatment was withdrawn. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy.

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Kerlone (betaxolol hydrochloride) during investigational use and extensive foreign experience. However, dry eyes have been reported.

Cardiac failure

Sympathetic stimulation may be a vital component supporting circulatory function in congestive heart failure, and beta-adrenergic receptor blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe heart failure. In hypertensive patients who have congestive heart failure controlled by digitalis and diuretics, beta-blockers should be administered cautiously. Both digitalis and beta-adrenergic receptor blocking agents slow AV conduction.

In patients without a history of cardiac failure

Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. Therefore at the first sign or symptom of cardiac failure, discontinuation of Kerlone (betaxolol hydrochloride) should be considered. In some cases beta-blocker therapy can be continued while cardiac failure is treated with cardiac glycosides, diuretics, and other agents, as appropriate.

Exacerbation of angina pectoris upon withdrawal

Abrupt cessation of therapy with certain beta-blocking agents in patients with coronary artery disease has been followed by exacerbations of angina pectoris and, in some cases, myocardial infarction has been reported. Therefore, such patients should be warned against interruption of therapy without the physician's advice. Even in the absence of overt angina pectoris, when discontinuation of Kerlone (betaxolol hydrochloride) is planned, the patient should be carefully observed and therapy should be reinstituted, at least temporarily, if withdrawal symptoms occur.

Bronchospastic diseases

PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD NOT IN GENERAL RECEIVE BETA-BLOCKERS. Because of its relative β1 selectivity (cardioselectivity), low doses of Kerlone (betaxolol hydrochloride) may be used with caution in patients with bronchospastic disease who do not respond to or cannot tolerate alternative treatment. Since β1 selectivity is not absolute and is inversely related to dose, the lowest possible dose of Kerlone (betaxolol hydrochloride) should be used (5 to 10 mg once daily) and a bronchodilator should be made available. If dosage must be increased, divided dosage should be considered to avoid the higher peak blood levels associated with once-daily dosing.

Anesthesia and major surgery

The necessity, or desirability, of withdrawal of a beta-blocking therapy prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. While this might be of benefit in preventing arrhythmic response, the risk of excessive myocardial depression during general anesthesia may be increased and difficulty in restarting and maintaining the heart beat has been reported with beta-blockers. If treatment is continued, particular care should be taken when using anesthetic agents which depress the myocardium, such as ether, cyclopropane, and trichloroethylene, and it is prudent to use the lowest possible dose of Kerlone (betaxolol hydrochloride) . Kerlone (betaxolol hydrochloride) , like other beta-blockers, is a competitive inhibitor of beta-receptor agonists and its effect on the heart can be reversed by cautious administration of such agents (eg, dobutamine or isoproterenol-see OVERDOSAGE). Manifestations of excessive vagal tone (eg, profound bradycardia, hypotension) may be corrected with atropine 1 to 3 mg IV in divided doses.

Diabetes and hypoglycemia

Beta-blockers should be used with caution in diabetic patients. Beta-blockers may mask tachycardia occurring with hypoglycemia (patients should be warned of this), although other manifestations such as dizziness and sweating may not be significantly affected. Unlike nonselective beta-blockers, Kerlone (betaxolol hydrochloride) does not prolong insulin-induced hypoglycemia.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism (eg, tachycardia). Abrupt withdrawal of beta-blockade might precipitate a thyroid storm; therefore, patients known or suspected of being thyrotoxic from whom Kerlone (betaxolol hydrochloride) is to be withdrawn should be monitored closely (see DOSAGE AND ADMINISTRATION: Cessation of therapy).

Kerlone (betaxolol hydrochloride) should not be given to patients with untreated pheochromocytoma.

General

• Individualize dosage according to patient response and tolerance.1 30

• If long-term therapy is discontinued, reduce dosage gradually over a period of about 2 weeks.1 (See Abrupt Withdrawal of Therapy under Cautions.)

BP Monitoring and Treatment Goals

• Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

• When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

• Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501

Administration

Oral Administration

Administer orally;1 absorption does not appear to be affected by food or alcohol.1

Dosage

Available as betaxolol hydrochloride; dosage expressed in terms of the salt.1 Commercially available tablets containing 10 or 20 mg of betaxolol hydrochloride contain 8.94 or 17.88 mg of betaxolol, respectively.1

Adults

Initially, 5–10 mg once daily, either alone or in combination with a diuretic.1 30 600 May double dosage after 7–14 days up to 20 mg daily.1 2 3 16 30 500 600

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Prescribing Limits

Adults

Maximum 40 mg daily.1

Special Populations

Hepatic Impairment

Dosage reductions are not routinely necessary.1 Use with caution; monitor patients carefully.1

Renal Impairment

Initially, 5 mg once daily in those with severe impairment or undergoing dialysis.1 Increase dosage in increments of 5 mg daily, no more frequently than at 2-week intervals, up to a maximum of 20 mg daily.1

Geriatric Patients

Initially, 5 mg daily.1

Bronchospastic Disease

Use the lowest possible dosage (5–10 mg once daily).1

If dosage must be increased, consider divided administration of the daily dose to avoid the higher peak plasma concentrations associated with once-daily dosing.1

Storage

Oral

15–25°C.1

Your pharmacist can provide more information about betaxolol ophthalmic.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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You should not take this medication if you are allergic to betaxolol or if you have a serious heart problem such as heart block, sick sinus syndrome, or slow heart rate, or severe or uncontrolled heart failure or pheochromocytoma.

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before taking betaxolol, tell your doctor if you have:

• angina (chest pain), congestive heart failure, coronary artery disease;
• asthma, bronchitis, emphysema;
• diabetes;
• low blood pressure;
• depression;
• liver or kidney disease;
• a thyroid disorder;
• psoriasis;
• myasthenia gravis; or
• problems with circulation (such as Raynaud's syndrome).

FDA pregnancy category C. It is not known whether betaxolol is harmful to an unborn baby. Betaxolol may cause heart or lung problems in a newborn if the mother takes the medication during pregnancy. Before taking betaxolol, tell your doctor if you are pregnant or plan to become pregnant during treatment.

Betaxolol can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Betaxolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking betaxolol.