ACEBUTOLOL

Posology The dose and treatment duration should be based on the individual response and should be adequately monitored by the treating physician. If long-term treatment will be discontinued, withdrawal of treatment by betablockers should be achieved by gradual dosage reduction.

Hypertension:

The usual initial daily dose is 400 mg. Based on pharmacokinetic studies it is recommended to administer the entire dose at once in the morning. In exceptional cases, the daily dose can be divided into two separate doses of 200 mg administered in the morning and evening.

If response is not adequate within two weeks, dosage may be increased up to 400 mg orally twice daily; in some patients 1200 mg orally daily, given as 800 mg at breakfast and 400 mg 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 antihypertensive agent .

Angina pectoris:

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

Cardiac Arrhythmias:

When given orally, an initial dose of 200 mg is recommended. The daily dose requirement for long term anti arrhythmic activity should lie between 400 and 1200 mg 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 antiarrhythmic effect to become apparent.

Renal impairment:

Dosage in patients with renal impairment should be based on creatinine clearance. Creatinine clearance 25-50 ml / min, the dose should be reduced in 50%. 4).

Elderly:

There are no specific dosage recommendations for the elderly with normal glomerular filtration rate. 4) Paediatric population Paediatric dose has not been established. The safety and efficacy of Acebutolol in children has not been established.

No data are available Method of administration Oral use For all indications, it is advised that the lowest recommended dosage be used initially. Acebutolol tablets are swallowed with a glass of water and not chewed or crushed.

Summary of safety profile 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 “antinuclear 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), Not known (cannot be estimated from the available data) 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.

4).

Tabulated list of adverse reactions:

Very common Antinuclear antibody Uncommon Lupus like syndrome Immune system disorders Rare Although antinuclear factor titres have increased in some patients, the incidence of associated clinical syndromes is rare and, if present, an immediate discontinuation of treatment is required.

Renal impairment:

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

The dosage frequency should not exceed once daily in patients with renal impairment. 2). Monitoring for heart rate could further guide on the appropriate dose in clinical practice, and should be reduced if excessive bradycardia appears (< 50-55 beats/min at rest).

Asthma and chronic obstructive pulmonary disease:

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 nonselective 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. Acebutolol can only be administered to mild forms of bronchospastic disease or bronchial asthma, but the initial dose is low. Respiratory function tests are recommended before starting treatment.

If bronchospasm occurs during treatment, beta-mimetic bronchodilators may be used.

Bradycardia:

Betablockers may induce bradycardia. In such cases (< 50-55 beats/min at rest), the dosage should be reduced. 3).

Heart failure:

In treatment-compensated heart failure, acebutolol should be given at very low, gradually increasing doses and under strict medical supervision if necessary.

1 or to beta blockers. Cardiogenic shock is an absolute contraindication. Extreme caution is required in patients with blood pressures of the order of 100/60 mmHg or below. Acebutolol is also contraindicated in patients with - Asthma and chronic obstructive pulmonary disease in their severe forms, - Second and third degree heart block, - Prinzmetal angina - Sick sinus syndrome - Marked bradycardia (< 45 – 50 bpm) - Raynaud's phenomenon and peripheral arterial disease in their severe forms, - Decompensated heart failure - Metabolic acidosis - Severe peripheral circulatory disorders - Untreated phaeochromocytoma.

6).