Acebutolol
- Dosing Information
- The initial dosage of acebutolol hydrochloride capsules in uncomplicated mild-to-moderate hypertension is 400 mg. This can be given as a single daily dose, but in occasional patients twice daily dosing may be required for adequate 24-hour blood-pressure control. An optimal response is usually achieved with dosages of 400 to 800 mg/day, although some patients have been maintained on as little as 200 mg/day. Patients with more severe hypertension or who have demonstrated inadequate control may respond to a total of 1200 mg daily (administered b.i.d.), or to the addition of a second antihypertensive agent. Beta-1 selectivity diminishes as dosage is increased.
- Dosing Information
- The usual initial dosage of acebutolol hydrochloride capsules is 400 mg daily given as 200 mg b.i.d. Dosage should be increased gradually until an optimal clinical response is obtained, generally at 600 to 1200 mg/day. If treatment is to be discontinued, the dosage should be reduced gradually over a period of about 2 weeks.
- Dosing information
- Older patients have an approximately 2-fold increase in bioavailability and may require lower maintenance doses. Doses above 800 mg/day should be avoided in the elderly.
- Dosing Information
- Monotherapy: 600 to 1600 mg/day.
- Acebutolol 100 mg + oral nifedipine 10 mg.
- Dosing Information
- Acebutolol 200 mg PO q12h + digoxin initial dose of 1 mg PO/IV followed by 0.25 mg/day (maintenance).
- Dosing information
- 200 milligrams mg/day.
- Second-degree AV heart block
- Third-degree AV heart block
- Overt cardiac failure
- Cardiogenic shock
Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt cardiac failure, acebutolol can be used with caution in patients with a history of heart failure who are controlled with digitalis and/or diuretics. Both digitalis and acebutolol impair AV conduction. If cardiac failure persists, therapy with acebutolol should be withdrawn.
In patients with aortic valve disease or mitral valve disease or compromised left ventricular function, continued depression of the myocardium with beta-blocking agents over a period of time may lead to cardiac failure. At the first signs of failure, patients should be digitalized and/or be given a diuretic and the response observed closely. If cardiac failure continues despite adequate digitalization and/or diuretic, acebutolol therapy should be withdrawn.
Following abrupt cessation of therapy with certain beta-blocking agents in patients with coronary artery disease, exacerbation of angina pectoris and, in some cases, myocardial infarction and death have been reported. Therefore, such patients should be cautioned against interruption of therapy without a physician's advice. Even in the absence of overt ischemic heart disease, when discontinuation of acebutolol is planned, the patient should be carefully observed, and should be advised to limit physical activity to a minimum while acebutolol is gradually withdrawn over a period of about 2 weeks. (If therapy with an alternative beta-blocker is desired, the patient may be transferred directly to comparable doses of another agent without interruption of beta-blocking therapy.) If an exacerbation of angina pectoris occurs, antianginal therapy should be restarted immediately in full doses and the patient hospitalized until his condition stabilizes.
Treatment with beta-antagonists reduces cardiac output and can precipitate or aggravate the symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease. Caution should be exercised with such patients, and they should be observed closely for evidence of progression of arterial obstruction.
PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE A BETA-BLOCKER. Because of its relative 1-selectivity, however, low doses of acebutolol may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate, alternative treatment. Since 1-selectivity is not absolute and is dose dependent, the lowest possible dose of acebutolol should be used initially, preferably in divided doses to avoid the higher plasma levels associated with the longer dose-interval. A bronchodilator, such as a theophylline or a 2-stimulant, should be made available in advance with instructions concerning its use.
Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
Beta-blockers may potentiate insulin-induced hypoglycemia and mask some of its manifestations such as tachycardia; however, dizziness and sweating are usually not significantly affected. Diabetic patients should be warned of the possibility of masked hypoglycemia.
Beta-adrenergic blockade may mask certain clinical signs (tachycardia) of hyperthyroidism. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom acebutolol therapy is to be withdrawn should be monitored closely.
While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
The following table shows the frequency of treatment-related side effects derived from controlled clinical trials in patients with hypertension, angina pectoris, and arrhythmia. These patients received acebutolol, propranolol, or hydrochlorothiazide as monotherapy, or placebo.
The following selected (potentially important) side effects were seen in up to 2% of acebutolol patients:
- Cardiovascular: Hypotension, bradycardia, heart failure.
- Central Nervous System: Anxiety, hyperesthesia, hypoesthesia, impotence.
- Dermatological: Pruritus.
- Gastrointestinal: Vomiting, abdominal pain.
- Genitourinary: Dysuria, nocturia.
- Liver and Biliary System: A small number of cases of liver abnormalities (increased SGOT, SGPT, LDH) have been reported in association with acebutolol therapy. In some cases increased bilirubin or alkaline phosphatase, fever, malaise, dark urine, anorexia, nausea, headache, and/or other symptoms have been reported. In some of the reported cases, the symptoms and signs were confirmed by rechallenge with acebutolol. The abnormalities were reversible upon cessation of acebutolol therapy.
- Musculoskeletal: Back pain, joint pain.
- Respiratory: Pharyngitis, wheezing.
- Special Senses: Conjunctivitis, dry eye, eye pain.
- Autoimmune: In extremely rare instances, systemic lupus erythematosus has been reported.
The incidence of drug-related adverse effects (volunteered and solicited) according to acebutolol dose is shown below. (Data from 266 hypertensive patients treated for 3 months on a constant dose.)
In addition, certain adverse effects not listed above have been reported with other beta-blocking agents and should also be considered as potential adverse effects of acebutolol.
- Central Nervous System: Reversible mental depression progressing to catatonia (an acute syndrome characterized by disorientation for time and place), short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance (neuropsychometrics).
- Cardiovascular: Intensification of AV block.
- Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.
- Hematologic: Agranulocytosis, nonthrombocytopenic purpura  and thrombocytopenic purpura.
- Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.
- Miscellaneous: Reversible alopecia and Peyronie's disease.
The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with acebutolol during investigational use and extensive foreign clinical experience.
Acebutolol, like other beta-blockers, has been associated with the development of antinuclear antibodies (ANA). In prospective clinical trials, patients receiving acebutolol had a dose-dependent increase in the development of positive ANA titers and the overall incidence was higher than that observed with propranolol. Symptoms (generally persistent arthralgias and myalgias) related to this laboratory abnormality were infrequent (less than 1% with both drugs). Symptoms and ANA titers were reversible upon discontinuation of treatment.
- Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported.
- No significant interactions with:
- Digoxin
- Hydrochlorothiazide
- Hydralazine
- Sulfinpyrazone
- Oral contraceptives
- Tolbutamide
- Warfarin
- Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Studies in humans have shown that both acebutolol and diacetolol cross the placenta. Neonates of mothers who have received acebutolol during pregnancy have reduced birth weight, decreased blood pressure, and decreased heart rate. In the newborn the elimination half-life of acebutolol was 6 to 14 hours, while the half-life of diacetolol was 24 to 30 hours for the first 24 hours after birth, followed by a half-life of 12 to 16 hours. Adequate facilities for monitoring these infants at birth should be available.
- Empty stomach by emesis or lavage.
- Bradycardia: IV atropine (1 mg to 3 mg in divided doses). If antivagal response is inadequate, administer isoproterenol cautiously since larger than usual doses of isoproterenol may be required.
- Persistent hypotension in spite of correction of bradycardia: Administer vasopressor (e.g., epinephrine, norepinephrine, dopamine, or dobutamine) with frequent monitoring of blood pressure and heart rate.
- Bronchospasm: A theophylline derivative, such as aminophylline and/or parenteral 2-stimulant, such as terbutaline.
- Cardiac failure: Digitalize the patient and/or administer a diuretic. It has been reported that glucagon is useful in this situation.
Acebutolol is dialyzable.
Acebutolol hydrochloride, USP is a white or slightly off-white powder freely soluble in water, and less soluble in alcohol. Chemically it is defined as the hydrochloride salt of () N-propoxy]phenyl] butanamide.
The 1-selectivity of acebutolol has also been demonstrated on the basis of the following vascular and bronchial effects:
Acebutolol has less antagonistic effects on peripheral vascular 2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists.
In single-dose studies in asthmatics examining effects of various beta-blockers on pulmonary function, low doses of acebutolol produce less evidence of bronchoconstriction and less reduction of 2 agonist, bronchodilating effects, than nonselective agents like propranolol but more than atenolol.
ISA has been observed with acebutolol in man, as shown by a slightly smaller (about three beats per minute) decrease in resting heart rate when compared to equivalent beta-blocking doses of propranolol, metoprolol or atenolol. Chronic therapy with acebutolol induced no significant alteration in the blood lipid profile.
Acebutolol has been shown to delay AV conduction time and to increase the refractoriness of the AV node without significantly affecting sinus node recovery time, atrial refractory period, or the HV conduction time. The membrane-stabilizing effect of acebutolol is not manifest at the doses used clinically.
Significant reductions in resting and exercise heart rates and systolic blood pressures have been observed 1.5 hours after acebutolol administration with maximal effects occurring between 3 and 8 hours postdosing in normal volunteers. Acebutolol has demonstrated a significant effect on exercise-induced tachycardia 24 to 30 hours after drug administration.
There are significant correlations between plasma levels of acebutolol and both the reduction in resting heart rate and the percent of beta-blockade of exercise-induced tachycardia. The antihypertensive effect of acebutolol has been shown in double-blind controlled studies to be superior to placebo and similar to propranolol and hydrochlorothiazide. In addition, patients responding to acebutolol administered twice daily had a similar response whether the dosage regimen was changed to once daily administration or continued on a b.i.d. regimen. Most patients responded to 400 to 800 mg/day in divided doses.
The antiarrhythmic effect of acebutolol was compared with placebo, propranolol, and quinidine. Compared with placebo, acebutolol significantly reduced mean total ventricular ectopic beats (VEB), paired VEB, multiform VEB, R-on-T beats, and ventricular tachycardia (VT). Both acebutolol and propranolol significantly reduced mean total and paired VEB and VT. Acebutolol and quinidine significantly reduced resting total and complex VEB; the antiarrhythmic efficacy of acebutolol was also observed during exercise.
The plasma elimination half-life of acebutolol is approximately 3 to 4 hours, while that of its metabolite, diacetolol, is 8 to 13 hours. The time to reach peak concentration for acebutolol is 2.5 hours and for diacetolol, after oral administration of acebutolol hydrochloride, 3.5 hours.
Within the single oral dose range of 200 mg to 400 mg, the kinetics are dose proportional. However, this linearity is not seen at higher doses, probably due to saturation of hepatic biotransformation sites. In addition, after multiple dosing the lack of linearity is also seen by AUC increases of approximately 100% as compared to single oral dosing. Elimination via renal excretion is approximately 30% to 40% and by non-renal mechanisms 50% to 60%, which includes excretion into the bile and direct passage through the intestinal wall.
Acebutolol hydrochloride has a low binding affinity for plasma proteins (about 26%). Acebutolol and its metabolite, diacetolol, are relatively hydrophilic and, therefore, only minimal quantities have been detected in the cerebrospinal fluid (CSF).
Drug interaction studies with tolbutamide and warfarin indicated no influence on the therapeutic effects of these compounds. Digoxin and hydrochlorothiazide plasma levels were not affected by concomitant acebutolol administration. The kinetics of acebutolol were not significantly altered by concomitant administration of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives.
In patients with renal impairment, there is no effect on the elimination half-life of acebutolol, but there is decreased elimination of the metabolite, diacetolol, resulting in a 2- to 3-fold increase in its half-life. For this reason, the drug should be administered with caution in patients with renal insufficiency. Acebutolol and its major metabolite are dialyzable.
Acebutolol crosses the placental barrier, and is secreted in breast milk.
In geriatric patients, the bioavailability of acebutolol and its metabolite is increased, approximately 2-fold, probably due to decreases in the first-pass metabolism and renal function in the elderly.
- Reduction in the resting heart rate and decrease in exercise-induced tachycardia
- Reduction in cardiac output at rest and after exercise
- Reduction of systolic blood pressure and diastolic blood pressure at rest and postexercise
- Inhibition of isoproterenol-induced tachycardia.
- 200 mg, opaque purple and orange capsule marked "RP 700" and "Sectral 200" NDC 67857-700-01, in bottles of 100 capsules.
- 400 mg, opaque brown and orange capsule marked "RP 701" and "Sectral 400"
NDC 67857-701-01, in bottles of 100 capsules.
- Protect from light
- Dispense in a light-resistant, tight container
- Use carton to protect contents from light
Patients should also be warned of possible severe hypertensive reactions from concomitant use of alpha-adrenergic stimulants, such as the nasal decongestants commonly used in OTC cold preparations and nasal drops.
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-  Kaul S, Hecht HS, Seidman R, Hopkins J, Singh BN (1984). "Comparative effects of oral acebutolol and propranolol at rest and during exercise in ischemic heart disease: double-blind placebo crossover study utilizing radionuclide ventriculography". Am Heart J. 108 (3 Pt 1): 46974. PMID 6382987.CS1 maint: Multiple names: authors list (link)
-  Pfisterer M, Muller-Brand J, Burkart F (1982). "Combined acebutolol/nifedipine therapy in patients with chronic coronary artery disease: additional improvement of ischemia-induced left ventricular dysfunction". Am J Cardiol. 49 (5): 125966. PMID 7064850.CS1 maint: Multiple names: authors list (link)
-  Kowey PR, Dalessandro DA, Herbertson R, Briggs B, Wertan MA, Rials SJ;  et al. (1997). "Effectiveness of digitalis with or without acebutolol in preventing atrial arrhythmias after coronary artery surgery". Am J Cardiol. 79 (8): 11147. PMID 9114777.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
-  Cohen TJ, Cayenne S, Black M, Doolittle S, Ibrahim B, Quan W (1999). "The effects of intrinsic sympathomimetic activity on beta-blocker efficacy for treatment of neurocardiogenic syncope". J Invasive Cardiol. 11 (7): 45760. PMID 10745573.CS1 maint: Multiple names: authors list (link)