Beta blocker agents, selective - ATC code: C07AB04

acebutolol hydrochloride

Each tablet contains 443.40mg of the active substance Acebutolol hydrochloride (equivalent to 400mg of base). Also contains 21.20mg of lactose monohydrate.

Tablet White to off-white, circular, biconvex, film-coated tablets with bevel edges, one face impressed 'SECTRAL 400 or ACB 400. Plain reverse

The management of hypertension, angina pectoris and the control of tachyarrhythmias.

Hypertension: Initial dosage of 400mg orally once daily at breakfast or 200mg orally twice daily. If response is not adequate within two weeks, dosage may be increased up to 400mg orally twice daily; in some patients 1200mg orally daily, given as 800mg at breakfast and 400mg in the evening may be required. A further reduction in blood pressure may be obtained by the concurrent administration of a thiazide diuretic or other anti-hypertensive agent (except Rauwolfia and its alkaloids).

Angina pectoris: Initial dosage of 400mg orally once daily at breakfast or 200mg twice daily. In severe forms up to 300mg three times daily may be required. Up to 1200mg daily has been used.

Cardiac Arrhythmias: When given orally, an initial dose of 200mg is recommended. The daily dose requirement for long term anti arrhythmic activity should lie between 400 and 1200mg daily. The dose can be gauged by response, and better control may be achieved by divided doses rather than single doses. It may take up to three hours for maximal anti-arrhythmic effect to become apparent.

Paediatric dose has not been established.

There are no specific dosage recommendations for the elderly with normal glomerular filtration rate. Dose reduction is necessary if moderate to severe renal impairment is present.

Cardiogenic shock is an absolute contraindication. Extreme caution is required in patients with blood pressures of the order of 100/60 mmHg or below.

SECTRAL is also contraindicated in patients with second and third degree heart block, sick sinus syndrome, marked bradycardia (< 45 – 50 bpm) and uncontrolled heart failure, metabolic acidosis, severe peripheral circulatory disorders, hypersensitivity to Acebutolol, any of the excipients or to beta blockers, and untreated phaeochromocytoma.

Renal impairment is not contraindicated to the use of Sectral which has both renal and non-renal excretory pathways. Some caution should be exercised when administering high doses to patients with severe renal failure as accumulation could possibly occur in these circumstances.

The dosage frequency should not exceed once daily in patients with renal impairment. As a guide, the dosage should be reduced by 50% when glomerular filtration rates are between 25-50ml/min and by 75% when they are below 25ml/min.

Drug-induced bronchospasm is usually at least partially reversible by the use of a suitable agonist.

Although cardio-selective beta blockers may have less effect on lung function than non-selective beta blockers as with all beta blockers these should be avoided in patients with obstructive airways disease unless there are compelling clinical reasons for their use. Where such reasons exist, cardio-selective β-blockers should be used with the utmost care.

Beta-blockers may induce bradycardia. In such cases, the dosage should be reduced. They may be used with patients with controlled heart failure.

Use with caution in patients with Prinzmetal's angina.

Beta-blockers may aggravate peripheral circulatory disorders. They may mask signs of thyrotoxicosis and hypoglycaemia. They should only be used in patients with phaeochromocytoma with concomitant alpha-adrenoreceptor therapy.

Patients with known psoriasis should take beta-blockers only after careful consideration.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.

Withdrawal of treatment by beta-blockers should be achieved by gradual dosage reduction: this is especially important in patients with ischaemic heart disease.

When it has been decided to interrupt beta-blockade prior to surgery, therapy should be discontinued for at least 24 hours. Continuation of the therapy reduces the risk of arrhythmias but the risk of hypotension may be increased. If treatment is continued, caution should be observed with certain anaesthetic drugs. The patient may be protected against vagal reactions by intravenous administration of atropine

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sectral should not be used with Verapamil or within several days of Verapamil therapy (and vice versa). Use with great care with any other calcium antagonists, particularly Diltiazem

Class 1 anti-arrthythmic drugs (such as disopyramide) and amiodarone may increase atrial conduction time and induce negative inotropic effects when used concomitantly with beta-blockers.

In patients with labile and insulin-dependent diabetes, the dosage of the hypoglycaemic agent may need to be reduced. However beta-blockers have also been known to blunt the effect of glibenclamide. Beta-adrenergic blockade may also prevent the appearance of signs of hypoglycaemia.

Cross reactions due to displacement of other drugs from plasma protein binding sites are unlikely due to the low degree of plasma protein binding exhibited by Acebutolol and Diacetolol.

If a beta-blocker is used concurrently with clonidine the latter should not be withdrawn until several days after the former is discontinued.

Acebutolol may antagonize the effect of sympathomimetic and xanthine bronchodilators.

Concurrent use of digoxin and beta-blockers may occasionally induce serious bradycardia. The anti-hypertensive effects of beta-blockers may be attenuated by non-steroidal anti-inflammatory agents.

Concomitant administration of tricyclic antidepressants, barbiturates and phenothiazines as well as other anti-hypertensive agents may increase the blood pressure lowering effects of beta-blockers.

There is a theoretical risk that concurrent administration of monoamine oxidase inhibitors and high doses of beta-blockers, even if they are cardio-selective can produce hypertension. Sectral therapy should be brought to the attention of the anaesthetist prior to general anaesthesia. If treatment is continued, special care should be taken when using anaesthetic agents such as ether, cyclopropane and trichlorethylene.

Adverse reactions associated with acebutolol during controlled clinical trials in patients with hypertension, angina pectoris or arrhythmia (1002 patients exposed to acebutolol) are presented by system organ class and by decreasing order of frequency.

The frequency of the events “anti-nuclear antibody” and “lupus like syndrome” was found from 1440 patients suffering from hypertension, angina pectoris or arrhythmia and exposed to acebutolol in open or double blind studies performed in the United States.

Frequencies are defined as: very common (1/10), common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000).

When the exact frequency of the event was not reported, the frequency category assigned is “not known” (ADRs with *).

Adverse reactions reported from post-marketing experience are also listed. These adverse reactions are derived from spontaneous reports and therefore, the frequency of these adverse reactions is “not known” (cannot be estimated from the available data).

The most frequent and serious adverse reactions of acebutolol are related to the beta-adrenergic blocking activity. The most frequent reported clinical adverse reactions are fatigue and gastrointestinal disorders. Among the most serious adverse reactions are cardiac failure, atrioventricular block and bronchospasm. Abrupt withdrawal as for all beta-blockers may exacerbate angina pectoris and precaution is especially required in patients with ischaemic heart disease.

sanofi-aventis

(POM)

15 February 2012