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Acebutolol

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
Chemical Name: (±)-N-[3-Acetyl-4-[2-hydroxy-3-[(1-meth ylethyl)amino]propoxy]phenyl]butanamide monohydrochloride
Molecular Formula: C18H28N2O4• HCl
CAS Number: 34381-68-5
Brands: Sectral

Medically reviewed by Drugs.com on Feb 15, 2021. Written by ASHP.

Introduction

A short-acting β1-selective adrenergic blocking agent (β-blocker).

Uses for Acebutolol

Hypertension

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

β-Blockers generally not preferred for first-line therapy of hypertension according to current evidence-based hypertension guidelines, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics). A 2017 ACC/AHA multidisciplinary hypertension guideline states that β-blockers used for ischemic heart disease that are also effective in lowering BP include bisoprolol, carvedilol, metoprolol succinate, metoprolol tartrate, nadolol, propranolol, and timolol.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

The 2017 ACC/AHA hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers. However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.

Cardiac Arrhythmias

Treatment of frequent ventricular premature complexes (VPCs), including uniform and multiform VPCs and/or coupled VPCs, and R-on-T complexes in patients with primary arrhythmias or arrhythmias secondary to various cardiac disorders (e.g., CAD, acute MI, valvular disease).

Management of various supraventricular tachyarrhythmias.

Angina

Management of chronic stable angina pectoris.

Acute MI

Secondary prevention following acute MI to reduce the risk of reinfarction and mortality.

Acebutolol Dosage and Administration

General

  • Individualize dosage according to patient response.

  • β-Adrenergic blocking selectivity diminishes as dosage is increased.

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

  • When substituting another β-blocker for acebutolol, initiate at a comparable dosage without interruption of β-blocker therapy.

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic). Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.

Administration

Acebutolol hydrochloride is administered orally. Also been administered IV, but a parenteral dosage form is currently not commercially available in the US.

Oral Administration

Hypertension

Usually administer as a single daily dose; however, for 24-hour BP control, some patients may require administration of the daily dose in 2 divided doses.

Ventricular Arrhythmias

Twice-daily dosing of the drug appears to be more effective than once-daily dosing for the suppression and prevention of frequent VPCs.

Angina

Once-daily administration may be as effective as divided doses; however, further studies are needed.

Dosage

Available as acebutolol hydrochloride; dosage expressed in terms of acebutolol.

Adults

Hypertension
Oral

Initially, 200–400 mg daily. Manufacturer and some clinicians state usual maintenance dosage is 400–800 mg daily, but some patients may achieve adequate BP control with dosages as low as 200 mg daily.

Increase dosage up to 1.2 g daily in 2 divided doses in patients with more severe hypertension or if adequate reduction of BP does not occur; alternatively, add another hypotensive agent (e.g., thiazide diuretic).

Some experts state usual dosage range is 200–800 mg daily, administered in 2 divided doses.

Ventricular Arrhythmias
Oral

Initially, 200 mg twice daily. Increase gradually until optimum effect is achieved. Usual maintenance dosage is 600–1200 mg daily.

Angina
Oral

Initially, 200 mg twice daily. Increase dosage gradually until optimum effect is achieved. Usual maintenance dosage is 800 mg or less daily, but patients with severe angina may require higher dosages.

Adjust dosage of β-blockers according to clinical response and to maintain a resting heart rate of 55–60 bpm.

Prescribing Limits

Adults

Hypertension
Oral

Maximum 1.2 g daily.

Special Populations

Renal Impairment

Active metabolite (diacetolol) eliminated principally by the kidneys; dosage and/or frequency of administration must be modified in response to the degree of renal impairment.

Dosage Reductions in Patients with Renal Impairment

Reduction in Usual Daily Dosage

Clcr (mL/min)

50%

25–49 mL/minute

75%

<25 mL/minute

Acebutolol and diacetolol removed by hemodialysis; individualize dosage carefully in patients with severe renal impairment who undergo chronic intermittent hemodialysis.

Geriatric Patients

Consider reduction in maintenance dosage. Avoid dosages >800 mg daily.

Cautions for Acebutolol

Contraindications

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

Warnings/Precautions

Warnings

Heart Failure

Possible precipitation of heart failure.

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).

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.

Abrupt Withdrawal of Therapy

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

Peripheral Vascular Disease

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

Bronchospastic Disease

Possible bronchoconstriction.

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.

Major Surgery

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. Use with caution in patients undergoing major surgery involving general anesthesia; anesthetics used should not cause myocardial depression.

Diabetes and Hypoglycemia

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.

Use with caution in patients with diabetes mellitus.

Thyrotoxicosis

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

Sensitivity Reactions

Anaphylactic 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. Such patients may be unresponsive to usual doses of epinephrine.

Specific Populations

Pregnancy

Category B.

Lactation

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

Pediatric Use

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

Geriatric Use

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

Hepatic Impairment

Use with caution. 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.

Renal Impairment

Use with caution; dosage should be reduced based on the degree of renal impairment. (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.

Interactions for Acebutolol

Specific Drugs

Drug

Interaction

Comments

α-Adrenergic agonists

Possible exaggerated hypertensive reactions

Warn patients of potential hazard

Calcium-channel blockers

Potential additive depressant effects on SA or AV nodal conduction

Cardiac glycosides (digoxin)

Potential additive depressant effects on SA or AV nodal conduction

Pharmacokinetic interaction unlikely

Diuretics

Possible increased hypotensive effect

Careful dosage adjustment recommended

Glyburide

Possible decreased hypoglycemic action in type II diabetic patients, presumably by decreasing insulin secretion

Hydralazine

Pharmacokinetic interaction unlikely

Hydrochlorothiazide

Pharmacokinetic interaction unlikely

Hypotensive agents

Possible increased hypotensive effect

Careful dosage adjustment recommended

NSAIAs

Potential blunting of hypotensive effects

Oral contraceptives

Pharmacokinetic interaction unlikely

Reserpine

Possible additive pharmacologic effects

Observe closely for evidence of marked bradycardia or hypotension (e.g., vertigo, presyncope or syncope, or orthostatic changes in BP without compensatory tachycardia)

Sulfinpyrazone

Pharmacokinetic interaction unlikely

Sympathomimetic agents

Antagonism of β1-adrenergic stimulating effects (e.g., bronchodilation)

Increased dosage of β-adrenergic agonist bronchodilators may be required

Tolbutamide

Interaction unlikely

Warfarin

Interaction unlikely

Acebutolol Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration; undergoes extensive first-pass metabolism in the liver.

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 individuals or patients with hypertension or arrhythmias.

Absolute bioavailability is approximately 35–50%.

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.

Onset

Effect on resting, reflex, or exercise-induced heart rate and systolic BP begins within 1–1.5 hours, in healthy or hypertensive individuals.

Duration

Effect may persist for up to 24 hours or longer.

Special Populations

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

Distribution

Extent

Acebutolol and diacetolol readily cross the placenta and can accumulate in the fetus.

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

Plasma Protein Binding

Approximately 11–25% (acebutolol) and 6–9% (diacetolol). Approximately 50% bound to erythrocytes.

Elimination

Metabolism

Rapidly and extensively metabolized in the liver to metabolites (acetolol and diacetolol).

Elimination Route

Acebutolol and its metabolites are excreted in feces and urine.

Half-life

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

Special Populations

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

Stability

Storage

Oral

Capsules

Tight containers at room temperature (approximately 25°C).

Protect from light.

Actions

  • Pharmacologic effects result from both the unchanged drug and diacetolol, which is equipotent to acebutolol.

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

  • Decreases exercise-induced heart rate, inhibits reflex orthostatic tachycardia, and may decrease or leave unchanged cardiac output at rest or during exercise. Decreases systolic and diastolic BP at rest and during exercise.

  • Precise mechanism of hypotensive action has not been determined. May reduce BP by blocking peripheral (especially cardiac) adrenergic receptors (decreasing cardiac output), by decreasing sympathetic outflow from the CNS, and/or by suppressing renin release.

  • Exhibits antiarrhythmic activity; considered a class II antiarrhythmic agent.

  • Can produce nervous system effects, although the frequency and/or severity of such effects may be less than those observed with some other β-blockers.

  • Unlike some β-blockers, does not consistently suppress plasma renin activity (PRA).

  • May increase airway resistance and decrease ventilatory capacity, especially in patients with asthma and/or COPD or when high dosages are used.

  • Does not appear to substantially affect glucose metabolism; however, the drug may potentiate insulin-induced hypoglycemia in diabetic patients receiving oral hypoglycemic agents. (See Interactions.)

Advice to Patients

  • Importance of taking acebutolol exactly as prescribed.

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

  • 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.

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

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

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

Acebutolol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg (of acebutolol)*

Acebutolol Hydrochloride Capsules

Sectral

Promius

400 mg (of acebutolol)*

Acebutolol Hydrochloride Capsules

Sectral

Promius

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 25, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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