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Kerlone

Generic Name: Betaxolol Hydrochloride
Class: beta-Adrenergic Blocking Agents
VA Class: CV100
Chemical Name: 2-Propanol, 1-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)-3-((1-methylethyl) amino)-, hydrochloride
Molecular Formula: C18H29NO3•ClH
CAS Number: 63659-19-8

Introduction

A β1-selective adrenergic blocking agent.1 2 3 4 5 6 7 8 9 10 24 25

Uses for Kerlone

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 28

Slideshow: 2014 Update: First Time Brand-to-Generic Switches

One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, ischemic heart disease, and/or diabetes mellitus.37

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.37

Kerlone Dosage and Administration

General

  • Individualize dosage according to patient response and tolerance.1 28 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.)

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

Hypertension
Oral

Initially, 5–10 mg once daily.1 28 30 37 Increase dosage gradually up to 20 mg daily.1 2 3 16 30 37

Prescribing Limits

Adults

Hypertension
Oral

Maximum 40 mg daily.1 28

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

Cautions for Kerlone

Contraindications

  • Known hypersensitivity to betaxolol.1

  • Patients with sinus bradycardia, heart block greater than first degree, cardiogenic shock, or overt cardiac failure.1

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation of CHF.1

Avoid use in patients with decompensated CHF; may use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).1

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.1

Abrupt WIthdrawal of Therapy

Abrupt discontinuance of therapy is not recommended as it may exacerbate angina symptoms or precipitate MI in patients with CAD.1

Gradually decrease dosage over a period of about 2 weeks and monitor patients carefully; advise patients to temporarily limit their physical activity during withdrawal of therapy.1

If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly and initiate appropriate measures for the management of unstable angina pectoris.1

Bronchospastic Disease

Possible bronchoconstriction.1

Generally should not be used in patients with bronchospastic disease, but may be used with caution in such patients who do not respond to or cannot tolerate alternative treatment.1

Administer the lowest effective dosage (5–10 mg once daily); a bronchodilator (e.g., a β2-adrenergic agonist) should be available.1

Major Surgery

Possible risks associated with general anesthesia (e.g., severe hypotension, difficulty maintaining heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.1 Use with caution in patients undergoing major surgery involving general anesthesia.1 Use particular care if anesthetics that depress the myocardium (e.g., cyclopropane, ether, trichloroethylene) are used.1

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., may mask tachycardia but not sweating or dizziness).1

Use with caution in patients with diabetes mellitus receiving hypoglycemic drugs.1

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.1 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.1

Sensitivity Reactions

Anaphylactic Reactions

Possible increased reactivity to repeated, accidental, diagnostic, or therapeutic challenges with a variety of allergens while taking β-blocking agents.1 Such patients may be unresponsive to usual doses of epinephrine.1

General Precautions

Intraocular Pressure

Possible reduction in intraocular pressure.1 May interfere with glaucoma screening test; withdrawal of therapy may cause return to increased intraocular pressure.1 (See Interactions.)

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Possible increased incidence of bradycardia in patients >65 years of age compared with younger adults.1 Bradycardia (possibly dose related) may respond to dosage reduction.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Although elimination half-life may be increased, clearance may remain unchanged, resulting in little change in the AUC.1 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Clearance may be decreased.1 Dosage adjustment may be needed based on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Bradycardia, edema, headache, dizziness, fatigue, lethargy, insomnia, nervousness, bizarre dreams, impotence, dyspnea, pharyngitis, rhinitis, upper respiratory infection, dyspepsia, nausea, diarrhea, chest pain, arthralgia, rash.1

Interactions for Kerlone

Specific Drugs

Drug

Interaction

Comments

β-Adrenergic blocking agents (opthalmic solution)

Possible additive effects on intraocular pressure or systemic β blockade1

Calcium-channel blocking agents

Potential hypotension, AV conduction disturbances, and left ventricular failure1

Avoid concomitant use in patients with impaired cardiac function1

Chlorthalidone

Pharmacokinetic interaction unlikely1

Cimetidine

Pharmacokinetic interaction unlikely1

Clonidine

β-Adrenergic blockade may exacerbate rebound hypertension following discontinuance of clonidinea

Discontinue β-blockers several days before initiating gradual withdrawal of clonidine1

If replacing clonidine, delay initiation of the β-blocker for several days after stopping clonidinea

Hydrochlorothiazide

Pharmacokinetic interaction unlikely1

Nifedipine

Pharmacokinetic interaction unlikely1

Reserpine

Additive effects1

Monitor for signs of hypotension and bradycardia (e.g., vertigo, syncope, postural hypotension)1

Warfarin

No potentiation of anticoagulant effect1

Kerlone Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration usually attained within 1.5–6 hours.1

Absolute bioavailability is 89%.1

Onset

Reductions in BP and heart rate observed within 24 hours after 5- to 40-mg doses (given once daily); these effects usually are maximal within 1 or 2 weeks.1

Food

Food or alcohol does not appear to affect absorption.1

Distribution

Extent

Distributed into milk.1

Plasma Protein Binding

Approximately 50%.1

Elimination

Metabolism

Metabolized in the liver.1

Elimination Route

Excreted in the urine as metabolites and unchanged drug.1

Half-life

14–22 hours.1

Special Populations

Clearance varies with the degree of renal impairment.1

In patients with hepatic impairment, half-life was increased by 33%, but clearance was unchanged.1

In geriatric patients, elimination may be reduced.1

Stability

Storage

Oral

Tablets

15–25°C.1

Actions

  • Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium.1 Blocks β2-adrenergic receptors within the bronchial and vascular smooth muscle only at high doses.1

  • Decreases resting and exercise-stimulated heart rate, cardiac output, cardiac work, and reflex orthostatic tachycardia and inhibits isoproterenol-induced tachycardia.1

  • One of the most potent2 6 11 14 15 17 19 20 25 and selective2 11 14 15 17 20 25 β1-adrenergic blocking agents currently available.

  • No intrinsic sympathomimetic activity1 11 13 15 22 and little or no membrane-stabilizing effect on the heart.1 2 8 9 11 16 17 18 22 24 25

  • Reduces BP by decreasing cardiac output, decreasing sympathetic outflow from the CNS, and/or suppressing renin release.1

Advice to Patients

  • Importance of taking betaxolol exactly as prescribed.1

  • Importance of not interrupting or discontinuing therapy without consulting clinician; patients should temporarily limit their physical activity when discontinuing therapy.1

  • Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure (e.g., weight gain, increased shortness of breath) or if any difficulty in breathing occurs.1

  • In patients with heart failure, importance of informing clinician of signs or symptoms of exacerbation (e.g., weight gain, difficulty in breathing).1

  • Importance of patients informing anesthesiologist or dentist that they are receiving betaxolol therapy prior to undergoing major surgery.1

  • Importance of informing patients with diabetes that the drug may mask signs and symptoms of hypoglycemia, including increased heart rate.1

  • Importance of avoiding some activities (e.g., operating machinery, driving a motor vehicle) until effects on the individual are known.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Betaxolol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

10 mg*

Betaxolol Hydrochloride Tablets

Amide

Kerlone

Sanofi-Synthelabo

20 mg*

Betaxolol Hydrochloride Tablets

Amide

Kerlone

Sanofi-Synthelabo

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Betaxolol HCl 10MG Tablets (KVK TECH): 30/$44.99 or 90/$113.97

Kerlone 10MG Tablets (SANOFI-AVENTIS U.S.): 30/$50.99 or 90/$134.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sanofi-Synthelabo. Kerlone (betaxolol hydrochloride) tablets prescribing information. New York, NY; 2003 Mar.

2. Alcon Laboratories. Betoptic product monograph. In: Barnhart ER, publisher. Physicians’ desk reference for ophthalmology. 19th ed. Oradell, NJ: Medical Economics Company Inc; 1991:211-2.

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]

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a. AHFS Drug Information 2004. McEvoy GK, ed. Clonidine. American Society of Health-System Pharmacists; 2004:1648-55.

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