Acebutolol

Acebutolol

Copyright 1978-2011 Lexicomp, Inc. All rights reserved.
(For additional information see “Acebutolol: Patient drug information”)

Brand Names: U.S. Sectral®
Brand Names: Canada Apo-Acebutolol®; Mylan-Acebutolol; Mylan-Acebutolol (Type S); Novo-Acebutolol; Nu-Acebutolol; Rhotral; Sandoz-Acebutolol; Sectral®; Teva-Acebutolol
Pharmacologic Category Antiarrhythmic Agent, Class II; Beta Blocker With Intrinsic Sympathomimetic Activity
Dosing: Adult
Angina, ventricular arrhythmia: Oral: 400 mg/day in 2 divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day

Hypertension: Oral: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day; usual dose range (JNC 7): 200-800 mg/day in 2 divided doses

Chronic stable angina (unlabeled use): Oral: Usual dose: 400-1200 mg/day in 2 divided doses (Gibbons, 2002); low doses (ie, 400 mg/day) may also be given as once daily (Pina, 1988)

Dosing: Geriatric Refer to adult dosing. Consider dose reduction due to age-related increase in bioavailability; do not exceed 800 mg/day. In the management of hypertension, consider lower initial dose (eg, 200-400 mg/day) and titrate to response (Aronow, 2011).
Dosing: Renal Impairment
Clcr 25-49 mL/minute: Reduce dose by 50%.

Clcr <25 mL/minute: Reduce dose by 75%.

Dosing: Hepatic Impairment There are no dosage adjustments provided in manufacturer’s labeling;use with caution.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral, as hydrochloride: 200 mg, 400 mg

Sectral®: 200 mg, 400 mg

Generic Equivalent Available: U.S. Yes
Administration May be administered without regard to meals.
Use Treatment of hypertension; management of ventricular arrhythmias
Use – Unlabeled/Investigational Treatment of chronic stable angina (Note: Not recommended for patients with prior MI)
Medication Safety Issues
Sound-alike/look-alike issues:
Sectral® may be confused with Seconal®, Septra®

Adverse Reactions Significant
>10%: Central nervous system: Fatigue (11%)

1% to 10%:

Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, CHF

Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyper-/hypoesthesia

Dermatologic: Rash (2%), pruritus

Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), abdominal pain, vomiting

Genitourinary: Micturition frequency (3%), dysuria, impotence, nocturia

Neuromuscular & skeletal: Myalgia (2%), back pain, joint pain

Ocular: Abnormal vision (2%), conjunctivitis, dry eyes, eye pain

Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing

Postmarketing and/or case reports: Alkaline phosphatase increased, anorexia, AV block, bilirubin increased, cold extremities, drug-induced lupus-like syndrome, exacerbate pre-existing renal insufficiency, facial edema, hepatotoxic reaction, lichen planus, palpitation, pleurisy, pneumonitis, pulmonary granulomas, systemic lupus erythematosus, transaminases increased, urinary retention, ventricular arrhythmia, xerostomia

Potential adverse effects (based on experience with other beta-blocking agents) include agranulocytosis, allergic reactions, alopecia (reversible), catatonia, claudication, depression (reversible), disorientation, emotional lability, erythematous rash, ischemic colitis, laryngospasm, mesenteric artery thrombosis, Peyronie’s disease, purpura, respiratory distress, short-term memory loss, slightly clouded sensorium, thrombocytopenia

Contraindications Overt cardiac failure; cardiogenic shock; persistently-severe bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker)
Warnings/Precautions
Concerns related to adverse events:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

Disease-related concerns:

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; for patients with bronchospastic disease who do not respond to or cannot tolerate other therapies, initial low doses of acebutolol may be employed and used cautiously with close monitoring. Ensure patient has an inhaled beta2-agonist immediately available.

• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.

• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.

• Heart failure (HF): Beta-blockers with intrinsic sympathomimetic activity (eg, acebutolol) are likely to worsen survival in patients with HF and should be avoided. Beta-blockers shown to improve survival in clinical trials should be used in these patients.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Mesenteric vascular disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with mesenteric vascular disease. Use with caution in these patients. Observe closely for progression of arterial obstruction.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis.

• Peripheral vascular disease (PVD) and Raynaud’s disease: May precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud’s disease. Use with caution and monitor for progression of arterial obstruction.

• Pheochromocytoma (untreated): Adequate alpha1-receptor blockade is required prior to use of any beta-blocker.

• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.

• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.

• Renal impairment: Use with caution in patients with renal impairment, especially the elderly. Elimination of the metabolite, diacetolol, is reduced resulting in a two- to threefold increase in its half-life.

• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may precipitate thyroid storm. Alterations in thyroid function tests may be observed.

Concurrent drug therapy issues:

• Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur.

• Cardiac glycosides: Use with caution in patients receiving digoxin; bradycardia or heart block can occur.

• Inhaled anesthetic agents: Use with caution in patients receiving inhaled anesthetic agents known to depress myocardial contractility.

Special populations:

• Elderly: Use reduced doses in elderly patients; concentrations of acebutolol and diacetolol are significantly higher in the elderly. Dose should not exceed 800 mg/day.

Other warnings/precautions:

• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.

• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.

Metabolism/Transport Effects Inhibits CYP2D6 (weak)
Drug Interactions
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification

Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification

Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification

Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy

Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy

Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy

Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy

Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Risk D: Consider therapy modification

Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy

Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Risk X: Avoid combination

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy

Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy

Lidocaine: Beta-Blockers may increase the serum concentration of Lidocaine. Risk C: Monitor therapy

Lidocaine (Systemic): Beta-Blockers may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy

Lidocaine (Topical): Beta-Blockers may decrease the metabolism of Lidocaine (Topical). Risk C: Monitor therapy

MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy

Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy

Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy

Propoxyphene: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy

Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions
Food: Peak serum acebutolol levels may be slightly decreased if taken with food.

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid yohimbe, ginseng (may worsen hypertension).

Pregnancy Risk Factor B (show table)
Pregnancy Implications Adverse effects were not observed in animal reproduction studies; therefore, acebutolol is classified as pregnancy category C. Acebutolol and diacetolol (active metabolite) cross the placenta. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blockers during pregnancy. Intrauterine growth restriction (IUGR), small placentas, as well as fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. The plasma elimination half-life of acebutolol is longer in pregnant women at term. Acebutolol has been evaluated for the treatment of hypertension in pregnancy, but other agents may be more appropriate for use.
Lactation Enters breast milk/not recommended (AAP recommends “use with caution”; AAP 2001 update pending)
Breast-Feeding Considerations Acebutolol and diacetolol (active metabolite) are excreted into breast milk. Bradycardia, hypotension, and tachypnea (transient) were observed in a nursing infant. Breast-feeding is not recommended by the manufacturer.
Dietary Considerations May be taken without regard to meals.
Pricing: U.S. (www.drugstore.com)
Capsules (Acebutolol HCl)

200 mg (100): $54.98

400 mg (30): $21.99

Capsules (Sectral)

200 mg (60): $179.98

400 mg (30): $125.00

Monitoring Parameters Blood glucose (especially in patients with diabetes mellitus); blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG
International Brand Names ACB (NZ); Acecor (CZ); Acepin (TW); Acetanol (JP); Beloc (CN); Butobloc (ZA); Diasectral (DK, FI); Flebutol (VE); Grifobutol (CN); Prent (CH, DE, IT, PT, TR); Rhodiasectral (AR); Sectral (AE, AT, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CY, CZ, EG, ES, FR, GB, GY, HK, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KW, LB, LU, LY, NL, OM, PL, QA, SA, SG, SR, SY, TT, TW, YE, ZA); Sectral LP (FR); Sincer (TW); Wesfalin (AR)
Mechanism of Action Competitively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity
Pharmacodynamics/Kinetics
Onset of action: 1-2 hours

Duration: 12-24 hours

Absorption: Oral: 40%

Distribution: Vd: 1.2 L/kg

Protein binding: ~26%

Metabolism: Extensive first-pass effect to equipotent and cardioselective diacetolol metabolite

Bioavailability: Acebutolol: 40%

Half-life elimination: Parent drug: 3-4 hours; Metabolite: 8-13 hours

Time to peak: 2-4 hours

Excretion: Feces (50% to 60%); urine (30% to 40%); diacetolol eliminated primarily in the urine

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