Acebutolol Hydrochloride

A short-acting β1-selective adrenergic blocking agent (β-blocker).1 2 17 18 113

Contraindications

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

Warnings/Precautions

Warnings

Possible precipitation of heart failure.1

Avoid use in patients with decompensated heart failure; 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

Possible exacerbated angina symptoms or precipitation of MI in patients with CAD.1 Abrupt discontinuance of therapy is not recommended.1 276 Gradually decrease dosage over a period of about 2 weeks; monitor patients carefully and advise to temporarily limit their physical activity.1 276 If exacerbation of angina occurs, reinstitute therapy promptly and initiate appropriate measures for the management of unstable angina pectoris.1

Possible reduction in cardiac output and precipitation or aggravation of symptoms of arterial insufficiency.1 Use with caution; observe for evidence of disease progression.1

Possible bronchoconstriction.1

Use with caution in patients with bronchospastic disease; administer the lowest effective dosage (initially in divided doses). A bronchodilator (e.g., a β2-adrenergic agonist, theophylline) should be available for immediate use, if necessary.1

Possible risks associated with general anesthesia (e.g., severe hypotension, maintenance of 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; anesthetics used should not cause myocardial depression.1

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, BP changes, tremor, feelings of anxiety, but not sweating or dizziness) and increased insulin-induced hypoglycemia.1

Use with caution in patients with diabetes mellitus.1

Signs of hyperthyroidism (e.g., tachycardia) may be masked.1 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.1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

Patients with a history of anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blocking agents.1 Such patients may be unresponsive to usual doses of epinephrine.1

Specific Populations

Category B.1

Distributed into milk in higher concentrations than in maternal plasma.1 2 105 Use not recommended by manufacturer.1

Safety and efficacy not established in children <12 years of age.1 268

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger adults.1 However, reduction of maintenance dosage may be necessary,1 2 since bioavailability of acebutolol and diacetolol (active metabolite) may be increased compared with that in younger adults.1 2 122 (See Geriatric Patients under Dosage and Administration.)

Use with caution.1 2 Cirrhosis does not appear to substantially affect the pharmacokinetics of acebutolol or diacetolol; however, the effects of hepatic impairment on elimination of the drug have not been fully evaluated.128

Use with caution; dosage should be reduced based on the degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Fatigue, dizziness, headache, dyspnea, constipation, diarrhea, dyspepsia, nausea, flatulence, insomnia, increased micturition, chest pain, edema, depression, abnormal dreams, rash, arthralgia, myalgia, cough, rhinitis, abnormal vision.1

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration;1 2 4 11 91 109 undergoes extensive first-pass metabolism in the liver.1 2 97 99 109 122 124

Peak plasma acebutolol and diacetolol concentrations occur within 2–2.5 hours (range: 1–4 hours) and 4 hours (range: 2.4–5 hours), respectively, in healthy individuals1 2 94 95 97 98 99 126 135 or patients with hypertension91 or arrhythmias.2 90 137

Absolute bioavailability is approximately 35–50%.1 4 94 97 102

Food

Food may slightly decrease the rate of absorption and peak plasma concentrations of acebutolol and its major metabolite (diacetolol), but the extent of absorption is not substantially affected.1 2 101

Onset

Effect on resting, reflex, or exercise-induced heart rate and systolic BP begins within 1–1.5 hours,1 3 21 91 100 in healthy1 21 98 100 or hypertensive91 individuals.

Duration

Effect may persist for up to 24 hours or longer.1 3 91 98 100

Special Populations

In geriatric patients, peak plasma concentrations and AUCs of acebutolol and diacetolol are increased twofold compared with those observed in younger patients.1 2 122

Distribution

Extent

Acebutolol and diacetolol readily cross the placenta1 2 105 106 107 and can accumulate in the fetus.105 106 107

Acebutolol and diacetolol are distributed into milk at concentrations higher than those in maternal plasma. (See Lactation under Cautions.)1 2 105 106

Plasma Protein Binding

Approximately 11–25% (acebutolol) and 6–9% (diacetolol).2 93 103 Approximately 50% bound to erythrocytes.4 125

Elimination

Metabolism

Rapidly and extensively metabolized in the liver2 110 113 to metabolites (acetolol and diacetolol).2 4 6 99 108 109 110 113

Elimination Route

Acebutolol and its metabolites are excreted in feces and urine.1 87 92 109 111 123

Half-life

About 3 hours in the initial distribution phase (t½α) 95 and about 11 hours (range: 6–12 hours) in the terminal phase (t½β).95 125 About 7.5 (range: 7–11 hours) and 3 hours, respectively, for diacetolol and acetolol following a single oral dose.101 108 125

Special Populations

Renal impairment may reduce clearances of acebutolol and diacetolol.125 Acebutolol and diacetolol are removed by hemodialysis.1 125 127

Storage

Oral

Tight containers1 253 at room temperature (approximately 25°C).1 2 3

Protect from light.1 305

• Importance of taking acebutolol exactly as prescribed.1

• Importance of not interrupting or discontinuing therapy without consulting clinician; patients should temporarily limit physical activity when discontinuing therapy.1 276

• 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 acebutolol therapy prior to undergoing major surgery.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.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.)