No

Antiarrhythmic Agent, Class II; Beta Blocker (with Intrinsic Sympathomimetic Activity)

Treatment of hypertension, ventricular arrhythmias, angina

B (per manufacturer); D (in 2nd and 3rd trimesters, based on expert analysis)

Hypersensitivity to beta-blocking agents; uncompensated congestive heart failure; cardiogenic shock; bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker); sinus node dysfunction; pregnancy (2nd and 3rd trimesters)

Abrupt withdrawal of drug should be avoided. May result in an exaggerated cardiac responsiveness such as tachycardia, hypertension, ischemia, angina, myocardial infarction, and sudden death. It is recommended that patients be gradually tapered off beta-blockers (over a 2-week period) rather than via abrupt discontinuation. Although acebutolol primarily blocks beta₁-receptors, high doses can result in beta₂-receptor blockage. Use with caution in diabetic patients. Beta-blockers may impair glucose tolerance, potentiate hypoglycemia, and/or mask symptoms of hypoglycemia in a diabetic patient. Use with caution in bronchospastic lung disease and renal dysfunction (especially the elderly). Beta-blockers with intrinsic sympathomimetic activity do not appear to be of benefit in congestive heart failure and should be avoided. See Usual Dosage - Renal/Hepatic Impairment.

>10%: Central nervous system: Fatigue (11%)

1% to 10%:

Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, congestive heart failure

Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyperesthesia, hypoesthesia, impotence

Dermatologic: Rash (2%), pruritus

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

Genitourinary: Micturition frequency (3%), dysuria, nocturia, impotence (2%)

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

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

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

<1% (Limited to important or life-threatening symptoms): Increased transaminases, increased bilirubin, increased alkaline phosphatase, hepatotoxic reaction, ventricular arrhythmias, AV block, facial edema, xerostomia, anorexia, impotence, urinary retention, cold extremities, systemic lupus erythematosus, palpitations, exacerbate pre-existing renal insufficiency

Case reports: Pleurisy, pulmonary granulomas, pneumonitis, lichen planus, lupus erythematosus, drug-induced lupus-like syndrome

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

Symptoms of intoxication include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia, and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia; atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol); CNS effects include convulsions, coma, and respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs

Treatment includes symptomatic treatment of seizures, hypotension, hyperkalemia and hypoglycemia; bradycardia and hypotension resistant to atropine, isoproterenol or pacing may respond to glucagon; wide QRS defects caused by the membrane-depressant poisoning may respond to hypertonic sodium bicarbonate; repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful.

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

Clonidine: Hypertensive crisis after or during withdrawal of either agent.

Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.

Glucagon: Acebutolol may blunt the hyperglycemic action of glucagon.

Insulin and oral hypoglycemics: Acebutolol masks the tachycardia from hypoglycemia.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.

Store at room temperature (~25°C/77°F); protect from light and dispense in a light-resistant, tight container

Competitively blocks beta₁-adrenergic receptors with little or no effect on beta₂-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity

Onset: 1-2 hours

Duration: 12-24 hours

Absorption: Oral: Well absorbed (40%)

Protein binding: 5% to 15%

Metabolism: Extensive first-pass

Half-life: 6-7 hours average

Time to peak: 2-4 hours

Elimination: ~55% of dose excreted via bile into feces and 35% excreted into urine

Oral:

Hypertension: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day

Ventricular arrhythmias: Initial: 400 mg/day; maintenance: 600-1200 mg/day in divided doses

Elderly: Initial: 200-400 mg/day; dose reduction due to age related decrease in Cl_cr will be necessary; do not exceed 800 mg/day

Dosing adjustment in renal impairment:

Cl_cr 25-49 mL/minute/1.73 m²: Reduce dose by 50%.

Cl_cr <25 mL/minute/1.73 m²: Reduce dose by 75%.

Dosing adjustment in hepatic impairment: Use with caution.

May be administered without regard to meals

To discontinue therapy, taper dose gradually

Blood pressure, orthostatic hypotension, heart rate, CNS effects, EKG

triglycerides, potassium, uric acid, cholesterol (S), glucose; HDL, thyroxine (S)

This drug possesses intrinsic sympathomimetic activity. While beta-blockers with intrinsic sympathomimetic activity induce fewer side effects, the cardiovascular benefits listed below are less clear than for beta-blockers without intrinsic sympathomimetic activity.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). Acebutolol exhibits ISA. To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.

Drowsiness/fatigue is common; may cause insomnia, depression, abnormal dreams, and polyuria

Additive hypotensive and/or sedative effects may be seen with concurrent use of antipsychotics, antidepressants, or benzodiazepines

No information available to require special precautions

Noncardioselective beta-blockers (ie, propranolol, nadolol) enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. This has not been reported for acebutolol, a cardioselective beta-blocker. Therefore, local anesthetic with vasoconstrictor can be safely used in patients medicated with acebutolol. Many nonsteroidal anti-inflammatory drugs such as ibuprofen and indomethacin can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.

Take exactly as directed; do not increase, decrease, or adjust dosage without consulting prescriber. Take pulse daily, prior to medication, and follow prescriber's instruction about holding medication. Do not take with antacids. Do not use alcohol and OTC medications such as cold remedies without consulting prescriber. If diabetic, monitor serum sugars closely (may alter glucose tolerance or mask signs of hypoglycemia). May cause fatigue, dizziness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when changing position from lying or sitting to standing or when climbing stairs); or alteration in sexual performance (reversible). Report chest pain or palpitations, unresolved swelling of extremities or unusual weight gain, difficulty breathing or new cough, skin rash, unresolved fatigue, unresolved constipation or diarrhea, unusual muscle weakness, or CNS disturbances. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.

Advise against abrupt withdrawal; monitor blood pressure, orthostatic hypotension, heart rate, CNS effects, EKG, and CVP

Capsule, as hydrochloride: 200 mg, 400 mg

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Jean P, Arditti J, Jouglard J, et al, "Acute Acebutolol Poisoning," Therapie, 1984, 39(1):49-50.

Kligman EW and Higbee MD, "Drug Therapy for Hypertension in the Elderly," J Fam Pract, 1989, 28(1):81-7.

Levison SP, "Treating Hypertension in the Elderly," Clin Geriatr Med, 1988, 4(1):1-12.

Nicolas F, Villers D, Rozo L, et al, "Severe Self Poisoning With Acebutolol in Association With Alcohol," Crit Care Med, 1987, 15(2):173-4.

Sangster B, de Wildt D, and van Dijk A, "A Case of Acebutolol Intoxication," Clin Toxicol, 1983, 20(1):69-77.

Schmutz JL, Houet C, Trechot P, et al, "Sweating and Beta-Adrenoceptor Antagonists," Dermatology, 1995, 190(1):86.

Tanner LA, Bosco LA, and Zimmerman HJ, "Hepatic Toxicity After Acebutolol Therapy," Ann Intern Med, 1989, 111(6):533-4.

Vestal RE, Wood AJ, and Shand DG, "Reduced Beta-Adrenoceptor Sensitivity in the Elderly," Clin Pharmacol Ther, 1979, 26(2):181-6.

Wong DG, Spence JD, Lamki L, et al, "Effect of Nonsteroidal Anti-inflammatory Drugs on Control of Hypertension of Beta-Blockers and Diuretics," Lancet, 1986, 1(8488):997-1001.

Wynn RL, "Dental Nonsteroidal Anti-inflammatory Drugs and Prostaglandin-Based Drug Interactions, Part Two," Gen Dent, 1992, 40(2):104, 106, 108.

Wynn RL, "Epinephrine Interactions With Beta-Blockers," Gen Dent, 1994, 42(1):16, 18.

Yin FC, Raizes, GS, Guarnieri T, et al, "Age-Associated Decrease in Ventricular Response to Haemodynamic Stress During Beta-Adrenergic Blockade," Br Heart J, 1978, 40(12):1349-55.