Atenolol Tablets Bp 100mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Atenolol Tablets BP 100mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Atenolol 100 mg
3 PHARMACEUTICAL FORM
Tablets
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Management of hypertension
Management of angina pectoris
Management of cardiac dysrhythmias
Myocardial infarction - early intervention in the acute phase
4.2 Posology and method of administration
Oral
Hypertension:
The usual dose is one 100 mg tablet daily. Some patients may respond to a dose of one 50 mg tablet daily. The therapeutic effect is fully established after administration for one to two weeks. Further reduction in blood pressure, if desired, can be achieved by combining atenolol with other antihypertensive agents.
Angina pectoris:
One 100 mg tablet once daily or one 50 mg tablet twice daily are taken. Additional benefit is unlikely to be gained by increasing the dose.
Cardiac dysrhythmias:
Having controlled the dysrhythmia with intravenous atenolol the maintenance oral dose is one 50mg tablet to one 100 mg tablet daily as a single dose.
Myocardial infarction:
Patients presenting within 12 hours of the onset of chest pains and suitable for beta blockade therapy:
5 to 10 mg of atenolol is administered by slow intravenous injection (1 mg/minute). If no adverse effects occur following the intravenous dose, then 15 minutes later one 50 mg tablet is administered orally followed by a further 50 mg tablet, 12 hours after the intravenous dose. Then 12 hours later one 100 mg tablet is given orally, once daily. If bradycardia and/or hypertension requiring treatment, or any other side effects, occur atenolol therapy should be discontinued.
Elderly patients:
Dosage requirements may be reduced, especially in those with impaired renal function.
Children:
Atenolol is not recommended for use in children as there is no paediatric experience with atenolol.
Renal failure:
Since atenolol is excreted via the kidneys dosage should be adjusted in cases of severe impairment of renal function. No significant accumulation of
atenolol occurs at a GFR greater than 35 ml/min/1.73m2 (normal range is 100150 ml/min/1.73m2). For patients with a creatinine clearance of 15-35
ml/min/1.73m2 (equivalent to serum creatinine of 300-600 pmol/litre) the oral dose should be one 50 mg tablet daily or one 100 mg tablet once every two days; the intravenous dose should be 10 mg once every two days. For patients
with a creatinine clearance of <15 ml/min/1.73m2 (equivalent to serum creatinine of <600 pmol/litre) the oral dose should be one 50 mg tablet on alternate days or one 100 mg tablet once every four days; the intravenous dose should be 10 mg once every four days.
Patients on haemodialysis should be given 50 mg orally after each dialysis. This should be done under hospital supervision as marked falls in blood pressure can occur.
4.3 Contraindications
Uncontrolled cardiac failure.
Cardiogenic shock.
Heart block - 2nd or 3rd degree atrioventricular (AV) block.
Bradycardia (heart rate less than 45 beats per minute).
Sick sinus syndrome.
Hypotension
Untreated phaeochromocytoma.
Severe peripheral arterial circulatory disturbances.
Metabolic acidosis.
Hypersensitivity to atenolol or any of the other ingredients of the product.
4.4 Special warnings and precautions for use
Atenolol as with other beta-blockers:
• Should not be withdrawn abruptly. The dosage should be withdrawn gradually over a period of 7-14 days, to facilitate a reduction in beta-blocker dosage. Patients should be followed during withdrawal, especially those with ischaemic heart disease.
• When a patient is scheduled for surgery, and a decision is made to discontinue beta-blocker therapy, this should be done at least 24 hours prior to the procedure. The risk-benefit assessment of stopping beta-blockade should be made for each patient. If treatment is continued, an anaesthetic with little negative inotropic activity should be selected to minimise the risk of myocardial depression. The patient may be protected against vagal reactions by intravenous administration of atropine.
• Although contraindicated in uncontrolled heart failure (see section 4.3), may be used in patients whose signs of heart failure have been controlled. Caution must be exercised in patients whose cardiac reserve is poor.
• May increase the number and duration of angina attacks in patients with Prinzmetal's angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. Atenolol is a beta1-selective beta-blocker; consequently, its use may be considered although utmost caution must be exercised.
• Although contraindicated in severe peripheral arterial circulatory disturbances (see section 4.3), may also aggravate less severe peripheral arterial circulatory disturbances.
• Due to its negative effect on conduction time, caution must be exercised if it is given to patients with first-degree heart block.
• May mask the symptoms of hypoglycaemia, in particular, tachycardia.
• May mask the signs of thyrotoxicosis.
• Will reduce heart rate as a result of its pharmacological action. In the rare instances when a treated patient develops symptoms which may be attributable to a slow heart rate and the pulse rate drops to less than 50-55 bpm at rest, the dose should be reduced.
• May cause a more severe reaction to a variety of allergens when given to patients with a history of anaphylactic reaction to such allergens. Such patients may be
unresponsive to the usual doses of adrenaline (epinephrine) used to treat the allergic reactions.
• May cause a hypersensitivity reaction including angioedema and urticaria.
• Should be used with caution in the elderly, starting with a lesser dose (see Section 4.2).
Since Atenolol is excreted via the kidneys, dosage should be reduced in patients with a creatinine clearance of below 35 ml/min/1.73 m2.
Although cardioselective (beta1) 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 reversible obstructive airways disease, unless there are compelling clinical reasons for their use. Where such reasons exist, Atenolol may be used with caution. Occasionally, some increase in airways resistance may occur in asthmatic patients however, and this may usually be reversed by commonly used dosage of bronchodilators such as salbutamol or isoprenaline. The label and patient information leaflet for this product state the following warning: “If you have ever had asthma or wheezing, you should not take this medicine unless you have discussed these symptoms with the prescribing doctor”.
As with other beta-blockers, in patients with a phaeochromocytoma, an alpha-blocker should be given concomitantly.
4.5 Interaction with other medicinal products and other forms of interaction
Combined use of beta-blockers and calcium channel blockers with negative inotropic effects, e.g. verapamil and diltiazem, can lead to an exaggeration of these effects particularly in patients with impaired ventricular function and/or sinoatrial or atrioventricular conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.
Concomitant therapy with dihydropyridines, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.
Digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time.
Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped. (See also prescribing information for clonidine.)
Class I anti-arrhythmic drugs (e.g. disopyramide) and amiodarone may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.
Concomitant use of sympathomimetic agents, e.g. adrenaline (epinephrine), may counteract the effect of beta-blockers.
Concomitant use with insulin and oral antidiabetic drugs may lead to the intensification of the blood sugar lowering effects of these drugs. Symptoms of hypoglycaemia, particularly tachycardia, may be masked (see section 4.4).
Concomitant use of prostaglandin synthetase-inhibiting drugs, e.g. ibuprofen and indometacin, may decrease the hypotensive effects of beta-blockers.
Caution must be exercised when using anaesthetic agents with Atenolol. The anaesthetist should be informed and the choice of anaesthetic should be an agent with as little negative inotropic activity as possible. Use of beta-blockers with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.
4.6 Pregnancy and lactation
Atenolol crosses the placental barrier and appears in the cord blood. Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveriesAtenolol has been used under close supervision for the treatment of hypertension in the third trimester. Administration of atenolol to pregnant women in the management of mild to moderate hypertension has been assoiated with intra-uterine growth retardation. The use of atenolol in women who are, or may become, pregnant requires that the anticipated benefit be weighed against the possible risks, particularly in the first and second trimesters since beta-blockers, in general, have been associated with a decrease in placental perfusion which may result in intra-uterine deaths, immature and premature deliveries.
There is significant accumulation of Atenolol in breast milk.
Neonates born to mothers who are receiving Atenolol at parturition or breast-feeding may be at risk of hypoglycaemia and bradycardia.
Caution should be exercised when Atenolol is administered during pregnancy or to a woman who is breast-feeding.
4.7 Effects on ability to drive and use machines
The use of atenolol is unlikely to result in any impairment of the ability to drive or undertake tasks which require a high degree of concentration. However it should be taken into account that occasionally dizziness or fatigue may occur.
4.8 Undesirable effects
Atenolol tablets are well tolerated and the adverse effects experienced are usually a result of its pharmacological action, as with other beta-blockers.
The following undesired events, listed by body system, have been reported with the following frequencies: very common ( 10%), common (1-9.9%), uncommon (0.10.9%), rare (0.01-0.09%), very rare (<0.01%) including isolated reports, not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Rare: Purpura, thrombocytopenia.
Psychiatric disorders:
Uncommon: Sleep disturbances of the type noted with other betablockers.
Rare: Mood changes, nightmares, confusion, psychoses and hallucinations.
Nervous system disorders:
Rare: Dizziness, headache, paraesthesia.
Eye disorders:
Rare: Dry eyes, visual disturbances.
Cardiac disorders:
Common: Bradycardia.
Rare: Heart failure deterioration, precipitation of heart block.
Vascular disorders:
Common: Cold extremities.
Rare: Postural hypotension which may be associated with syncope, intermittent claudication may be increased if already present, insusceptible patients Raynaud's phenomenon.
Respiratory, thoracic and mediastinal disorders:
Rare: Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints.
Gastrointestinal disorders:
Common: Gastrointestinal disturbances.
Rare: Dry mouth.
Hepato-biliary disorders:
Uncommon: Elevations of transaminase levels.
Rare: Hepatic toxicity including intrahepatic cholestasis.
Skin and subcutaneous tissue disorders:
Rare: Alopecia, psoriasiform skin reactions, exacerbation of psoriasis, skin rashes. Not known: Hypersensitivity reactions, including angioedema and urticaria.
Reproductive system and breast disorders:
Rare: Impotence.
General disorders and administration site conditions:
Common: Fatigue.
Investigations:
Very rare: An increase in ANA (Antinuclear Antibodies) has been observed, however the clinical relevance of this is not clear.
Discontinuance of the drug should be considered if, according to clinical judgement, the well-being of the patient is adversely affected by any of the above reactions.
4.9 Overdose
Signs of overdosage are bradycardia, severe hypotension, bronchospasm, and acute cardiac insufficiency.
General treatment should include: close supervision; treatment in an intensive care ward; the use of gastric lavage; activated charcoal and a laxative to prevent absorption of any drug still present in the gastrointestinal tract; the use of plasma or plasma substitutes to treat hypotension and shock. The possible uses of haemodialysis or
haemoperfusion may be considered. Excessive bradycardia can be countered with atropine 1-2 mg intravenously and/or a cardiac pacemaker. If necessary, this may be followed by a bolus dose of glucagon 10 mg intravenously. If required, this may be repeated or followed by an intravenous infusion of glucagon 1-10 mg/hour depending on response. If no response to glucagon occurs or if glucagon is unavailable, a beta-adrenoceptor stimulant such as dobutamine 2.5 to 10 micrograms/kg/minute by intravenous infusion may be given. Dobutamine, because of its positive inotropic effect could also be used to treat hypotension and acute cardiac insufficiency. It is likely that these doses would be inadequate to reverse the cardiac effects of beta-blocker blockade if a large overdose has been taken. The dose of dobutamine should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient. Bronchospasm can usually be reversed by bronchodilators.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Atenolol is a beta-adrenergic blocking agent and blocks the antagonistic effect of the sympathetic neurotransmitters by competing for the receptor binding sites.
Atenolol predominantly blocks the beta-1 receptors located in cardiac tissue and is said to be cardioselective.
In general, so-called cardioselective beta-blockers are relatively cardioselective; in lower doses they block beta-1 receptors but begin to block beta-2 receptors as the dose is increased.
Antianginal action of atenolol is probably due to reduced myocardial oxygen requirement.
Antiarrhythmic action of atenolol is due to blockade of adrenergic stimulation of cardiac pacemakers potentials.
Action of atenolol as an antihypertensive is unknown but it could be due to reduced cardiac output, decreased sympathetic outflow to peripheral vasculature and inhibition of renin release by the kidney.
Atenolol is administered prophylactically in myocardial reinfarction. It acts by reducing the severity of myocardial ischaemia by decreasing myocardial oxygen requirements, post infarction mortality may also be reduced through an antiarrhythmic action.
5.2 Pharmacokinetic properties
Following oral administration, atenolol is completely absorbed from the gastro-intestinal tract. It is not significantly metabolised and is eliminated unaltered by the kidneys. Biological half-life of atenolol is longer than would be anticipated from its plasma half-life of about 6 hours. Atenolol diffuses across the placenta and is excreted in breast milk. Small quantities cross the blood-brain barrier and it is only about 5% bound to plasma proteins.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Calcium Hydrogen Phosphate, Povidone, Starch 1500, Microcrystalline Cellulose, AC-DI-SOL SD 711, Magnesium Stearate, Hydroxypropylmethyl Cellulose 6 CP, Sunset yellow aluminium lake (E 110), Quinoline yellow aluminium lake (E 104), Titanium dioxide (E 171).
I.M.S and purified water.
6.2 Incompatibilities
None.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Protect from heat, light and moisture.
6.5 Nature and contents of container
Blister packaging (10 tablets/strip) in aluminium foil, subsequently packed in printed cardboard carton containing 30 tablets in each.
Calendar packs:
Blister packaging (14 tablets/strip) in aluminium foil, subsequently packed in printed cardboard carton containing 28 tablets in each.
6.6 Special precautions for disposal
Keep out of the reach of children.
7 MARKETING AUTHORISATION HOLDER
ZeCare Ltd.
Unit 5 Blenheim Court,
Brownfields,
Welwyn Garden City,
Hertfordshire AL71AN
8 MARKETING AUTHORISATION NUMBER(S)
PL 24581/0007
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION 18/03/2009
10 DATE OF REVISION OF THE TEXT
26/08/2010