FDA

Betaxolol Hydrochloride

Approved 22 Oct 1999OralTablet

The FDA lists this product in 8 strengths and forms.

Indications

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

Contraindications

Betaxolol is contraindicated in patients with known hypersensitivity to the drug. Betaxolol is contraindicated in patients with sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. (see Warnings ).

Warnings and precautions

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 betaxolol 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 betaxolol 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 β 1 -selectivity (cardioselectivity), low doses of betaxolol may be used with caution in patients with bronchospastic disease who do not respond to or cannot tolerate alternative treatment. Since β 1 -selectivity is not absolute and is inversely related to dose, the lowest possible dose of betaxolol should be used (5 to 10 mg once daily) and a bronchodilator should be made available.

At a glance

Brand name: Betaxolol Hydrochloride
Route: Oral
Dosage form: Tablet
Applicant: Epic Pharma
Status: Prescription
FDA approval: 22 Oct 1999
Application: ANDA075541-002

Warnings and precautions

Interactions

Drug Interactions The following drugs have been coadministered with betaxolol and have not altered its pharmacokinetics: cimetidine, nifedipine, chlorthalidone, and hydrochlorothiazide. Concomitant administration of betaxolol with the oral anticoagulant warfarin has been shown not to potentiate the anticoagulant effect of warfarin. Catecholamine-depleting drugs (eg, reserpine) may have an additive effect when given with beta-blocking agents.

Patients treated with a beta-adrenergic receptor blocking agent plus a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. Should it be decided to discontinue therapy in patients receiving beta-blockers and clonidine concurrently, the beta-blocker should be discontinued slowly over several days before the gradual withdrawal of clonidine.

Literature reports suggest that oral calcium antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function. Hypotension, AV conduction disturbances, and left ventricular failure have been reported in some patients receiving beta-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen.

Hypotension was more likely to occur if the calcium antagonist were a dihydropyridine derivative, eg, nifedipine, while left ventricular failure and AV conduction disturbances, including complete heart block, were more likely to occur with either verapamil or diltiazem. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with beta blockers. Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects. Disopyramide has been associated with severe bradycardia, asystole and heart failure when administered with beta blockers. Particular care should be taken when using anesthetic agents which depress the myocardium, such as ether, cyclopropane, and trichloroethylene (see Warnings, Major surgery ).

Adverse reactions

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. Betaxolol, 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: Dose Range Body System/Adverse Reaction Betaxolol (N=509) 5-40 mg q.d.* (%) Propranolol (N=73) 40-160 mg b.i.d.

(%) Atenolol (N=75) 25-100 mg q.d. (%) Placebo (N=109) (%) Cardiovascular Bradycardia (heart rate <50 BPM) Symptomatic bradycardia Edema 8.1 0.8 1.8 4.1 1.4 0 12.0 0 0 0 0

1.8 Central Nervous System Headache Dizziness Fatigue Lethargy 6.5 4.5 2.9 2.8 4.1 11.0 9.6 4.1 5.3 2.7 4.0 2.7 15.6 5.5 0

0.9Psychiatric Insomnia Nervousness

Bizarre dreams Depression 1.2 0.8 1.0 0.8 8.2 1.4 2.7 2.7 2.7 2.7 1.3 4.0 0 0 0 0 Autonomic Impotence 1.2† 0 0 0 Respiratory Dyspnea Pharyngitis Rhinitis Upper respiratory infection 2.4 2.0 1.4 2.6 2.7 0 0 0 1.3 4.0 4.0 0 0.9 0.9 0.9

5.5 Gastrointestinal Dyspepsia Nausea Diarrhea 4.7 1.6 2.0 6.8 1.4 6.8 2.7 4.0 8.0 0.9 0

0.9Musculoskeletal

Chest pain Arthralgia 2.4 3.1 1.4 0 2.7 4.0 0.9

1.8Skin Rash 1.2 0 0

0 *Five patients received 80 mg q.d. †N=336 males; impotence is a known possible adverse effect of this pharmacological class. 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 4-52-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: Dose Range Body System/Adverse Reaction Betaxolol (N=155) 20-40 mg q.d. (%) Atenolol (N=81) 100 mg q.d. (%) Placebo (N=60) (%) Cardiovascular Bradycardia (heartrate <50 BPM) Symptomatic bradycardia Palpitation Edema Cold extremities 5.8 1.9 1.9 1.3 1.9 5.0 2.5 3.7 1.2 0 0 0 1.7 0 0 Central Nervous System Headache Dizziness Fatigue Asthenia Insomnia Paresthesia 14.8 14.8 9.7 7.1 5.0 1.9 9.9 17.3 18.5 0 3.7 2.5 23.3 15.0 0 16.7 3.3 0 Gastrointestinal Nausea Dyspepsia Diarrhea 5.8 3.9 1.9 1.2 7.4 3.7 0 3.3 0 Musculoskeletal Chest pain Joint pain Myalgia 7.1 5.2 3.2 6.2 4.9 3.7 5.0 1.7

3.3 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.

Betaxolol Hydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Betaxolol Hydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

0.9Psychiatric Insomnia Nervousness

0.9Musculoskeletal

1.8Skin Rash 1.2 0 0

Composition

Strengths and forms

Official product information