Acebutolol

Acebutolol: Drug information
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Sectral® may be confused with Factrel®, Seconal®, Septra®

U.S. BRAND NAMES — Sectral®

PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class II
Beta Blocker With Intrinsic Sympathomimetic Activity

DOSING: ADULTS
Angina, ventricular arrhythmia: Oral: 400 mg/day in 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): 400 mg/day in divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day

DOSING: ELDERLY — Oral: Initial: 200-400 mg/day; dose reduction due to age-related decrease in Clcr will be necessary; do not exceed 800 mg/day.

DOSING: RENAL IMPAIRMENT
Clcr 25-49 mL/minute: Reduce dose by 50%.

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

DOSING: HEPATIC IMPAIRMENT — Use with caution.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, as hydrochloride: 200 mg, 400 mg
Sectral®: 200 mg, 400 mg

DOSAGE FORMS: CONCISE
Capsule, as hydrochloride: 200 mg, 400 mg
Sectral®: 200 mg, 400 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — To discontinue therapy, taper dose gradually over a period of 2 weeks. May be administered without regard to meals.

USE — Treatment of hypertension; management of ventricular arrhythmias

USE - UNLABELED / INVESTIGATIONAL — Treatment of chronic stable angina

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, 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): Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD. Use with caution in these patients. Observe closely 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. Raynaud's disease: Use with caution in these patients with Raynaud's disease; may precipitate symptoms of Raynaud's. 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. Thyrotoxicosis: Beta-blockade may mask signs of hyperthyroidism (eg, tachycardia). Abrupt discontinuation may also induce a thyroid storm.

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. Pediatrics: Safety and efficacy have not been established in children.

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.

METABOLISM / TRANSPORT EFFECTS — Inhibits CYP2D6 (weak)

DRUG INTERACTIONS
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 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. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. 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

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. 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

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

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

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

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. 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 decrease the metabolism 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. This is true at higher beta-blockers doses where cardioselectivity is lost. 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) (manufacturer); D (2nd and 3rd trimesters - expert analysis)

PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acebutolol and its metabolite cross the human placenta. The neonatal half-life of acebutolol is 6-14 hours and diacetolol is 24-30 hours. Decreased birth weight, blood pressure, and heart rate have been observed in neonates following maternal use of acebutolol during pregnancy. Neonatal hypoglycemia has also been reported. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Monitoring of the newborn is recommended.

LACTATION — Enters breast milk/not recommended (AAP recommends "use with caution")

BREAST-FEEDING CONSIDERATIONS — Acebutolol and its metabolites are found in human breast milk; the milk/plasma ratio is 7.1 for acebutolol and 12.2 for diacetolol. Hypotension, bradycardia, and tachypnea have been reported in nursing infants.

DIETARY CONSIDERATIONS — May be taken without regard to meals.

PRICING — (data from 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): $124.99

MONITORING PARAMETERS — Blood glucose; blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG

CANADIAN BRAND NAMES — Apo-Acebutolol®; Gen-Acebutolol; Monitan®; Novo-Acebutolol; Nu-Acebutolol; Rhotral; Rhoxal-acebutolol; Sandoz-Acebutolol; Sectral®

INTERNATIONAL BRAND NAMES — Abutol (PL); ACB (NZ); Acebutolol (PL); Acecor (PL); Acepin (TW); Acetanol (JP); Beloc (CN); Butobloc (ZA); Cetolol (PL); Diasectral (DK, FI); Flebutol (VE); Grifobutol (CN); Prent (CH, DE, IT, PT); 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, 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%

Protein binding: ~26%

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

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

PATIENT INFORMATION — Do not discontinue abruptly. Consult pharmacist or prescriber before taking with other adrenergic drugs (eg, cold medications). Take at the same time each day. May be taken without regard to meals. Use with caution while driving or performing tasks requiring alertness. Notify prescriber if CHF symptoms become worse or if other side effects occur. May mask signs of hypoglycemia in diabetics.