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GLOBAL ATENOLOL 50mg tablets are white, biconvex, round, 8.0 mm in diameter and identified APO above scoreline A50. Each tablet contains 50mg Atenolol and typically weighs 170 mg.
GLOBAL ATENOLOL 100mg tablets are white, biconvex, round, 9.50 mm in diameter and identified APO above scoreline A100. Each tablet contains 100 mg Atenolol and typically weighs 340 mg.
Atenolol is a competitive beta-adrenergic receptor blocking agent which is cardioselective (i.e. acts preferentially on beta-adrenergic receptors in the heart). It does not possess membrane stabilising or intrinsic sympathomimetic (partial agonist) activities. Atenolol is effective at reducing blood pressure and maintaining this reduction for at least 24 hours after a single oral dose. This encourages patient compliance. All clinical and physiological effects of beta blockade are no longer present 72 hours after cessation of therapy. Mechanisms for the antihypertensive effect appear to include:
(a) Competitive antagonism of catecholamines at cardiac beta-adrenergic receptors resulting in a reduced rate and force of myocardial contraction and a decreased cardiac output.
(b) Inhibition of renin release by the kidneys.
(c) Inhibition of central vasomotor centres.
The proposed mechanism of the anti-anginal effect is a reduction of myocardial oxygen requirements resulting from a decrease in cardiac output.
Approximately 50% of an oral dose of atenolol is absorbed from the gastro-intestinal tract the remainder being excreted unchanged in the faeces. Maximum plasma concentrations are reached within two to four hours after a single oral dose and doses of 50mg and 100mg produce mean peak plasma concentrations of approximately 300 and 700 ng/mL, respectively. The plasma half-life (t1/2) is 6-7 hours and atenolol is effective for at least 24 hours after a single oral dose. The apparent volume of distribution (Vd) in adults is 0.7 L/kg. Atenolol is 6-16% plasma protein bound and is extensively distributed to extravascular tissues, but only a small amount is found in the central nervous system. Approximately 10% of atenolol is metabolised in man. About 3% of the material recovered in the urine is the hydroxylated metabolite which has been shown in animal studies to have 10% of the pharmacological activity of atenolol. Approximately 47% and 53% of an oral dose is eliminated in the urine and faeces respectively.
(a) Control of hypertension
For mild to moderate hypertension, atenolol can either be used alone or in combination with other agents, usually a thiazide diuretic. For severe hypertension, atenolol may be used in combination with diuretics and/or vasodilator agents.
(b) Long term management of angina pectoris.
(c) Control of cardiac dysrhythmias
(d) Myocardial Infarction. Early intervention in the acute phase and long term prophylaxis after recovery
The initial dose of atenolol is 50mg daily administered as a single oral dose. This may be increased to 100mg once daily if an adequate response is not achieved within one to two weeks. Increasing the dose beyond 100 mg a day is unlikely to produce any additional benefit. If further lowering of the blood pressure is required another antihypertensive agent should be added to the regimen.
Initially, 50mg is given as a single oral dose but this may be increased to 100mg once daily if an optimal response is not achieved within one week.
Once the dysrhythmias have been brought under control by the use of intravenously administered atenolol, Global Atenolol may be used at 50-100mg daily as a single dose as maintenance therapy.
For patients who are suitable for treatment with beta-blockade, and who present within 12 hours of the onset of chest pain atenolol (5-10mg) should be given by slow intravenous injection followed by atenolol 50mg orally 15 minutes later if no adverse effect occurs following the intravenous dose. A further 50mg should be given orally 12 hours after the intravenous dose and 100mg orally 12 hours later again. For patients who present some days after suffering an acute myocardial infarction 100mg daily as an oral dose is recommended for long term prophylaxis.
Dosage should be adjusted in patients with severe renal impairment. For patients with a creatinine clearance of 15-35 ml/min/1.73m2 the maximum oral dose should be 50mg daily. For patients with a creatinine clearance of less than 15ml/min/1.73m2 the maximum oral dose should be 50mg every other day. Patients on haemodialysis should be given 50mg after each dialysis under hospital supervision as marked falls in blood pressure may occur.
Dosage may need to be reduced
There is no experience with the use of atenolol in children
Bronchial asthma or other obstructive lung disorders
Uncontrolled heart failure
Cardiogenic shock
Sick-sinus syndrome
Grade 2 and 3 A-V block and infranodal A-V block
Severe bradycardia
Severe peripheral arterial circulatory disturbances
Hypotension
Metabolic acidosis
Untreated phraeochromocytoma
Anaesthesia with agents that produce myocardial depression e.g. ether
Special caution should be exercised when administering atenolol to patients with a history of heart failure. In addition, the concurrent use of beta-blockers and digitalis over a period of time can, in some cases, lead to cardiac failure. At the first sign of impending failure patients should be fully digitalised and/or given a diuretic. If cardiac failure continues atenolol should be withdrawn.
Atenolol may increase the frequency and duration of angina attacks in patients suffering from Prinzmetal angina. Extreme caution must be exercised if treatment with atenolol is required for these patients.
Discontinuation of atenolol in patients with angina pectoris should be gradual with dosage reduction over two weeks, if possible, whilst maintaining the same frequency of administration. Abrupt discontinuation can lead to severe exacerbation of angina and/or to myocardial infarction or ventricular arrhythmias.
Not only is the use of atenolol contraindicated in severe peripheral arterial circulatory disturbances, but also it may aggravate less severe peripheral arterial circulatory disorders.
Caution is required if atenolol is administered to patients with first degree A-V block.
Atenolol should be administered with caution to diabetic patients receiving insulin or oral hypoglycaemic agents or to patients subject to spontaneous hypoglycaemia. Beta-blockers may modify the tachycardia of hypoglycaemia.
Monitoring of renal, hepatic and haematopoetic function should be performed at regular intervals during long term treatment.
Atenolol may increase the severity of allergic reactions in patients who have a history of anaphylactic reactions. Such patients may be unresponsive to the usual doses used to treat the allergic reactions.
Prior to patients undergoing elective surgery, atenolol should be withdrawn cautiously with at least 48 hours between the last dose and anaesthesia. In emergency surgery, untoward effects of beta-adrenergic receptor blockade may be reversed, if necessary, by sufficient doses of agonists such as isoprenaline.
Abrupt withdrawal of atenolol in patients with thyrotoxicosis may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm.
Category C
In pregnancy atenolol crosses the placental barrier and the possibility of
foetal injury during the first and second trimesters cannot be excluded.
Atenolol has been used under close supervision for the treatment of hypertension
during the third trimester for a limited number of women. Intrauterine growth
retardation has been associated with the use of atenolol for longer periods
during pregnancy. Atenolol should only be used during pregnancy if the benefits
justify the potential risk to the foetus.
Atenolol appears in breast milk of lactating women and if its use is considered essential mothers should be advised against breast-feeding. Bradycardia has been reported in an infant who ingested atenolol in breast milk.
Animal studies to investigate the mutagenic and carcinogenic potential of atenolol proved negative.
Use of atenolol is unlikely to impair the patient's ability to drive or operate machinery however dizziness and fatigue may occasionally occur.
Various skin rashes and/or dry eyes have been reported with beta-blockers including atenolol. In the extremely rare event of severe oculomucocutaneous syndrome, treatment should be discontinued immediately.
The most common adverse reactions reported are bradycardia (3%), dizziness (3%), vertigo (2%), fatigue (3%), diarrhoea (2%) and nausea (3%).
Other adverse effects encountered are :
Cardiovascular: congestive heart failure, severe bradycardia, A-V block, palpitations, lengthening of PR interval, chest pain, light-headedness and postural hypotension, Raynaud's phenomenon, claudication, leg pain and cold extremities and oedema.
Respiratory: dyspnoea, wheeziness, bronchospasm, cough.
Central Nervous System: dizziness, vertigo, faintness, ataxia, tiredness, fatigue, nervousness, lethargy, depression, drowsiness, vivid dreams, insomnia, parasthesias, headache, tinnitus.
Gastrointestinal: abdominal discomfort, indigestion, diarrhoea, anorexia, nausea.
Miscellaneous: skin rash, itchy and/or dry eyes, decreased exercise tolerance, epitaxis, flushes, impotence, decreased libido, sweating, general body aches.
β-blockers may exacerbate the rebound hypertension, which may follow the withdrawal of clonidine. If the two medicines are administered concomitantly atenolol should be withdrawn several days prior to discontinuing the use of clonidine. If replacing clonidine with atenolol, the introduction of the atenolol should be delayed until several days after the withdrawal of the clonidine.
Beta-blockers should be used with caution in combination with calcium channel blocking agents which have negative inotropic effects such as verapamil and diltiazem especially in patients with impaired ventricular function and/or SA or AV conduction abnormalities. In such patients the negative inotropic effects may be exaggerated.
Concomitant therapy with dihydropyridines e.g. nifedipine may increase the risk of hypotension. Cardiac failure may occur in patients with latent cardiac insufficiency.
When used with digitalis glycosides there may be an increase in atrioventricular conduction time.
The β-blocker effect may be counteracted by concomitant use of sympathomimetic agents e.g. adrenaline.
Concomitant use of prostaglandin synthetase inhibitors e.g. ibuprofen, indomethacin with atenolol may decrease the hypotensive effects.
Care should be taken in prescribing beta-blockers with Class 1 antidysrhythmic agents such as disopyramide, phenytoin, quinidine, procainamide and lignocaine. Dosages of these agents may need to be modified.
Patients receiving catecholamine-depleting drugs e.g. reserpine, guanethidine should be closely monitored because the added beta-adrenergic effect of atenolol may produce an excessive reduction of sympathetic activity. Atenolol should not be combined with other β-blockers
The expected symptoms of overdosage may include bradycardia, hypotension, acute cardiac failure, bronchospasm and hypoglycaemia.
Treatment should include close supervision, the use of gastric lavage, activated charcoal and a laxative to prevent absorption of any atenolol still present in the gastrointestinal tract, and the use of plasma or plasma substitutes to treat hypotension and shock. Haemodialysis or haemoperfusion may be considered.
The following therapeutic measures may also be required:
Bradycardia: Atropine 1-2mg intravenously or other anticholinergic agent.
Heart block (second or third degree): Isoprenaline by slow intravenous injection or transvenous cardiac pacemaker.
Congestive heart failure: Conventional therapy
Hypotension: (depending on associated factors). Adrenaline rather than isoprenaline may be useful in addition to atropine and digitalis.
Bronchospasm: aminophylline or isoprenaline.
Hypoglycaemia: intravenous glucose
Store below 30°C. Protect from heat, light and moisture.
Keep container tightly closed.
Prescription Only Medicine.
GLOBAL ATENOLOL 50mg tablets:
Bottles of 100, 500 and 1000 tablets.
Calendar packs of 30 and 300 tablets.
GLOBAL ATENOLOL 100mg tablets:
Bottles of 100, 500 and 1000 tablets.
Calendar packs of 30 and 150 tablets.
Tablets contain lactose.
GLOBAL PHARMACEUTICALS
9F Airborne Road
North Harbour Industrial Estate
Albany
PO Box 302-177
North Harbour Postal Centre
Auckland
Tel: (09) 415-7551
Fax: (09) 415-7553
15 March 1999