SEBUTOL

A cardioselective beta-adrenergic antagonist with little effect on the bronchial receptors.

The drug has stabilizing and quinidine-like effects on cardiac rhythm as well as weak inherent sympathomimetic action.

For the management of hypertension and ventricular premature beats in adults.

Acebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range.

In general, beta-blockers reduce the work the heart has to do and allow it to beat more regularly.

Acebutolol has less antagonistic effects on peripheral vascular ß2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists.

Low doses of acebutolol produce less evidence of bronchoconstriction than nonselective agents like propranolol but more than atenolol.

Well absorbed from the

Gl tract with an absolute bioavailability of approximately 40% for the parent compound.

Subject to extensive first-pass hepatic biotransformation (primarily to diacetolol).

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.

The plasma elimination half-life is approximately 3-4 hours.

The half-life of its metabolite, diacetolol, is 8-13 hours.

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Symptoms of overdose include extreme bradycardia, advanced atrioventricular block, intraventricular conduction defects, hypotension, severe congestive heart failure, seizures, and in susceptible patients, bronchospasm, and hypoglycemia.

Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by β-adrenergic receptor blockade may precipitate more severe failure.

Although β-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If cardiac failure persists, therapy with acebutolol should be withdrawn.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 Without a History of Cardiac Failure In patients with aortic or mitral valve disease or compromised left ventricular function, continued depression of the myocardium with β-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.

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal Following abrupt cessation of therapy with certain β-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 two weeks. (If therapy with an alternative β-blocker is desired, the patient may be transferred directly to comparable doses of another agent without interruption of β-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 β-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.

Bronchospastic Disease PATIENTS WITH BRONCHOSPASTIC DISEASE

SHOULD, IN GENERAL, NOT RECEIVE A β-BLOCKER.

Because of its relative β1-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 β1-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 theophylline or a β2-stimulant, should be made available in advance with instructions concerning its use.

WARNINGS, Major Surgery 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.

Diabetes and

Hypoglycemia β-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.

Thyrotoxicosis β-adrenergic blockade may mask certain clinical signs (tachycardia) of hyperthyroidism.

Abrupt withdrawal of β-blockade may precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom acebutolol therapy is to be withdrawn should be monitored closely.

HCl, USP is contraindicated in: 1) persistently severe bradycardia; 2) second.

• and third-degree heart block; 3) overt cardiac failure; and 4) cardiogenic shock See WARNINGS.

The initial dosage of acebutolol 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 to 800 mg per day, although some patients have been maintained on as little as 200 mg per 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.

The usual initial dose of acebutolol 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 to 1200 mg per day. If treatment is to be discontinued, the dosage should be reduced gradually over a period of about two weeks.

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.

Acebutolol hydrochloride capsules, USP are available as follows: 200 mg: Hard gelatin capsules with bright orange opaque body printed radially “669” with black ink and lavender opaque cap printed radially “Amneal” with black ink.

Bottles of 100 NDC 65162-669-10 Bottles of 500 NDC 65162-669-50 400 mg: Hard gelatin capsules with bright orange opaque body printed radially “670” with black ink and lavender opaque cap printed radially “Amneal” with black ink.

Bottles of 30 NDC 65162-670-03 Bottles of 100 NDC 65162-670-10 Bottles of 500 NDC 65162-670-50 Store at 20° to 25°C (68° to 77°F) .

Protect from light.

Keep tightly closed.

Dispense in a tight, light-resistant container.

Distributed by

Amneal Pharmaceuticals Bridgewater, NJ 08807 Rev. 01-2016-02.