COMPOSITION: BUTOBLOC 400 mg: Each tablet contains acebutolol hydrochloride equivalent to acebutolol 400 mg.
PHARMACOLOGICAL CLASSIFICATION: A 5.2 Adrenolytics.
PHARMACOLOGICAL ACTION: Acebutolol is a cardioselective beta blocker which exerts its action by blocking the beta1-adrenoceptor. This action of acebutolol protects the heart against effort/emotion induced sympathetic increases in rate and force of contractions, thus preventing excessive rises in myocardial oxygen demand.
Acebutolol also has an effect in inhibiting the rise in serum free fatty acid concentration induced in man by isoprenaline. Acebutolol does not significantly alter serum glucose, triglyceride or cholesterol levels.
Acebutolol possesses antidysrhythmic action against sympathetically induced dysrhythmias.
It has been reported that acebutolol has some intrinsic sympathomimetic activity and membrane stabilising properties. Pharmacokinetics Acebutolol is well absorbed from the gastro-intestinal tract, but undergoes extensive first-pass metabolism in the liver.
Although the bioavailability of acebutolol is reported to be about 40%, the major metabolite diacetolol is active.
Following oral administration, peak plasma concentrations of acebutolol and diacetolol are reached in approximately 2 and 4 hours, respectively.
Acebutolol and diacetolol are widely distributed in the body, but they have low to moderate lipid solubility and penetration into the cerebrospinal fluid is poor. They cross the placenta and higher concentrations are achieved in breast milk than in maternal plasma.
The plasma elimination half-life for acebutolol and diacetolol is 3 to 4 hours and 8 to 13 hours respectively. Half-life values for acebutolol and diacetolol may be increased in the elderly and half-life values may be prolonged up to 32 hours in patients with severe renal impairment.
Acebutolol and diacetolol are excreted both in the urine and in the bile and may undergo enterohepatic recycling.
Acebutolol and diacetolol are removed by dialysis.
The management of angina pectoris.
The control of cardiac dysrhythmias excluding those due to conduction defects.
The management of mild to moderate hypertension.
CONTRA-INDICATIONS: Hypersensitivity to any of the ingredients.
Cardiogenic shock is an absolute contra-indication to beta-blockade and caution is required in all patients with blood pressure in the order of 100/60 mm Hg or below.
Patients with bronchospasm, asthma, or patients with a history of obstructive airway diseases.
Second and third degree heart block and sinus bradycardia and metabolic acidosis (e.g. in diabetics).
After prolonged fasting.
Special care should be taken in patients with a poor cardiac reserve. BUTOBLOC should be avoided in cardiac failure, unless or until signs of failure are controlled with digitalis or diuretics.
Uncontrolled cardiac failure, excluding that due to hypertrophic obstructive cardiomyopathy. Pregnancy and lactation: BUTOBLOC crosses the placental barrier. Administration to pregnant women has been associated with intra-uterine growth retardation. Administration to pregnant mothers shortly before giving birth, or during labour may result in the newborn infants being born hypotonic, collapsed and hypoglycaemic.
Acebutolol should not be used during breastfeeding as it accumulates in breast milk.
WARNINGS: Patients with a history of anaphylaxis to an antigen may be more reactive to repeated challenge antigen while taking beta blockers. Such patients may be unresponsive to the usual dose of adrenaline used to treat allergic reactions. Particular caution should be exercised with patients suffering from bradycardia of less than 50 pulse beats per minute, peripheral vascular disease and Raynaud's phenomenon.
Abrupt withdrawal of beta blockers may exacerbate angina and may lead to sudden death.
BUTOBLOC should not be used with verapamil or within several days of verapamil therapy (and vice versa).
Caution is advised with the administration of BUTOBLOC to elderly patients or to patients with renal or hepatic disease, especially in the presence of metabolic acidosis. Careful adjustment of dosage requirements may be necessary. Elderly patients may not respond to acebutolol as well as younger patients.
In the perioperative period it is generally unwise to reduce the dosage to which the patient is accustomed, as there may be danger of aggravation of angina pectoris or of hypertension. A patient's normal tachycardiac response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard.
DOSAGE AND DIRECTIONS FOR USE:
Angina Pectoris: Usual dosage is 400 mg orally daily at breakfast or 200 mg twice daily.
In severe forms up to 300 mg three times daily may be required; up to 1,2 g daily has been used. Cardiac dysrhythmias: The usual initial dose for cardiac arrhythmias is 200 mg twice daily but up to 1,2 g daily in divided doses has been required. Mild to Moderate Hypertension: The initial dosage is 400 mg (at breakfast) or 200 mg twice daily. If response is not adequate within two weeks, dosage should be increased up to 800 mg once daily (at breakfast) or up to 400 mg orally twice daily.
Up to 1,2 g daily in divided doses has been used with no serious untoward effects. BUTOBLOC may be used with other anti-hypertensive agents (e.g. thiazide diuretics, methyldopa, bethanidine, guanethidine, etc.) the dosage of which can normally be reduced. The concurrent use of BUTOBLOC with a thiazide diuretic is often worth consideration.
Reduced doses may be required in patients with impaired renal function; it is suggested that the dose be reduced by 50% when glomerular filtration rate is between 25 and 50 mL per minute and by 75% when glomerular filtration rate is below 25 mL per minute.
It is recommended that doses greater than 800 mg daily should be avoided in elderly patients.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-Effects: The most frequent and serious side-effects are related to the beta-adrenergic blocking activity. Among the most serious adverse events are heart failure, heart block, and bronchospasm. Troublesome subjective side-effects include fatigue and coldness of the extremities. Cardiovascular: Bradycardia and hypotension. Congestive heart failure or heart block may be precipitated in patients with underlying cardiac disorders. Respiratory: Bronchospasm may be precipitated in susceptible patients. Pneumonitis, pulmonary fibrosis, and pleurisy have also been reported, Central nervous system: Depression, hallucinations, confusion, and sleep disturbances. Coma and convulsions have been reported following beta blocker overdosage. Musculo-skeletal: Fatigue is a common side-effect. Paraesthesia, peripheral neuropathy, and myopathies have been reported. Gastro-intestinal: Nausea, vomiting, diarrhoea, constipation and abdominal cramping. Skin: Skin rash, pruritis and reversible alopecia. Haematological: Non thrombocytopenic purpura, thrombocytopenia, and less frequently agranulocytosis. Transient eosinophilia can occur. Metabolic: Plasma concentrations of very low density lipoprotein and triglyceride are consistently raised in patients taking beta blockers. Concentrations of high density lipoprotein are reduced. These effects may be less with beta1-cardioselective agents and beta blockers with intrinsic sympathomimetic activity. Ocular: Decreased tear production, blurred vision and soreness. Other: Other adverse events reported include a lupus-like syndrome, male impotence, sclerosing peritonitis, and retroperitoneal fibrosis. Severe peripheral vascular disease and even peripheral gangrene may be precipitated.
Adverse reactions are more common in patients who receive the medicine intravenously or in patients with renal decompensation. Special Precautions: Airway obstruction: asthma, chronic bronchitis and other chronic pulmonary diseases.
Bronchoconstriction may occur in patients suffering from asthma, bronchitis and other chronic and obstructive pulmonary diseases. Bradycardia: caution is required depending on the circumstances and the degree. Beta blockers which possess an intrinsic sympathomimetic effect, lower the heart rate less markedly and thus entail less risk of provoking excessive bradycardia. Bradycardia (usually less than 50-55 beats per minute) indicates that the dosage should not be further increased. Congestive cardiac failure: may be worsened; its presence may demand digitalisation. The combination of BUTOBLOC and digitalis can be considered despite the potentiation of negative chronotropic effect of the two medicines. Careful control of dosages and of the individual patient's response (and notably pulse rate) is essential in this situation. Diabetes: the sympathetically mediated responses to hypoglycaemia (sweating and tachycardia) are impaired by beta-blockade and the patient should be warned accordingly, The dosage of the hypoglycemic agent may need to be reduced. Abrupt discontinuation of therapy may cause exacerbation of angina pectoris in patients suffering from ischaemic heart disease. Discontinuation of therapy should be gradual (over a period of one to two weeks) and patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued. Beta blockers should be used with care where peripheral circulation is impaired i.e. Raynaud's disease. Peripheral gangrene may ensue with the use of BUTOBLOC.
Patients with phaeochromocytoma should not receive beta blockers without a concomitant alpha-adrenergic blocker.
BUTOBLOC may mask the symptoms of hyperthyroidism and hypoglycemia and may unmask myasthenia gravis .
Psoriasis may be aggravated.
INTERACTIONS: It can be dangerous to administer BUTOBLOC concomitantly with phenothiazines, hypoglycemic agents and Class 1 antiarrthymic agents such as disopyramide. Such interactions can have life-threatening consequences.
Caution should be exercised if BUTOBLOC is to be used along with catecholamine depleting agents such as reserpine.
If a beta-adrenoreceptor antagonist is used concurrently with clonidine the latter should not be withdrawn until several days after the former is discontinued as severe hypertension may occur.
Caution should also be exercised when transferring a patient from clonidine. The withdrawal of clonidine may result in the release of large amounts of catecholamines which may give rise to a hypertensive crisis. If beta-blockers are administered in these circumstances, the unopposed alpha receptor stimulation may potentiate this effect.
Beta blockers should be avoided in combination with cardiodepressant calcium-channel blockers such as verapamil and diltiazem. Concurrent administration has resulted in hypotension, bradycardia, conduction defects, and cardiac failure. These effects have occurred particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities.
Prior to anaesthesia, the anaesthetist's attention should be drawn to the fact that the patient is on BUTOBLOC therapy. If treatment is continued special care should be taken when using anaesthetic agents such as ether, cyclopropane and trichloroethylene.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: Overdosage may produce bradycardia and severe hypotension. Bronchospasm and heart failure may be produced in certain individuals.
Cases of mild overdosage should be observed for at least 4 hours, as apnoea and cardiovascular collapse may appear suddenly,
Gastric lavage should be performed if within 4 hours of suspected overdose. Repeated activated charcoal is necessary in severe overdoses.
In the event of excessive bradycardia or hypotension atropine sulphate, administered intravenously, should be given without delay. If the response is inadequate, glucagon may be given intravenously, Alternatively a slow intravenous injection of isoprenaline or dobutamine may be required to counteract beta-blockade, with constant monitoring until a response occurs.
Transvenous cardiac pacing may be required for severe bradycardia.
Heart failure is treated with digitalis and diuretics. Bronchospasm is treated with intravenous aminophylline and/or inhaled beta-2 stimulants e.g. salbutamol.
IDENTIFICATION: BUTOBLOC 400 mg: White, capsule-shaped, film-coated, biconvex tablets, scored on one side, other side plain.
PRESENTATION: BUTOBLOC 400 mg: White HDPE bottles containing 30, 100 and 500 tablets
STORAGE DIRECTIONS: Store below 25°C in a well-closed container. Protect from light.
KEEP OUT OF REACH OF CHILDREN
REGISTRATION NUMBER: BUTOBLOC 400 mg: 32/5.2/0053
NAME AND BUSINESS ADDRESS OF APPLICANT: Pharmacare Ltd
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 14 January 1999
New addition to this site: December 2005
Source: Pharmaceutical Industry