Atenolol 50mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Atenolol 50mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Atenolol tablets, contain 50mg atenolol.
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Tablets
White round biconvex tablets with score line on one side and K logo on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
- Management of hypertension
- Management of angina pectoris
- Management of cardiac arrhythmias
- Myocardial infarction: early intervention in the acute phase.
4.2 Posology and method of administration
Adults:
Hypertension: One tablet daily. Most patients respond to 100 mg daily given orally as a single dose. Some patients, however, will respond to 50 mg given as a single daily dose. The effect will be fully established after one to two weeks. A further reduction in blood pressure may be achieved by combining atenolol with other antihypertensive agents. For example, co-administration of atenolol with a diuretic provides a highly effective and convenient antihypertensive therapy.
Angina: Most patients with angina pectoris will respond to 100 mg given orally once daily or 50 mg given twice daily. It is unlikely that additional benefit will be gained by increasing the dose.
Cardiac arrhythmias: 50-100 mg after having controlled the arrhythmias with intravenous atenolol.
Myocardial infarction: For patients suitable for treatment with intravenous adrenoceptor blockade and presenting within 12 hours of the onset of the chest pain, atenolol 5-10 mg should be given by slow intravenous injection (1 mg/minute) followed by atenolol 50 mg orally about 15 minutes, later provided no untoward effects occur from the intravenous dose. This should be followed by a further 50 mg orally 12 hours after the intravenous dose and then 12 hours later by 100 mg orally to be given once daily. If bradycardia and/or hypotension requiring treatment, or any other untoward effects occur, atenolol should be discontinued.
Elderly patients
Dosage requirements may be reduced, especially in patients with impaired renal function.
Children
There is no paediatric experience with atenolol and for this reason it is not recommended for use in children.
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 in patients who have a creatinine clearance greater than 35 ml/min/1.73 m2 (normal range is 100 to 150 ml/min/1.73 m2). For patients with a creatinine clearance of 15 to 35 ml/min/1.73 m2 (equivalent to serum creatinine of 300 to 600 pmol/litre) the oral dose should be 50 mg daily. For patients with a creatinine clearance of <15 ml/min/1.73 m2 (equivalent to serum creatinine of >600 pmol/litre) the oral dose should be 25 mg daily or 50 mg on alternate 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
Atenolol as with other P-adrenoceptor blocking drugs, should not be used in patients with any of the following conditions:
- known hypersensitivity to the substance or to any of the excipients,
- bradycardia,
- cardiogenic shock,
- hypotension,
- metabolic acidosis,
- severe peripheral arterial circulatory disturbances,
- second or third degree heart block,
- sick sinus syndrome,
- untreated phaeochromocytoma
- uncontrolled heart failure.
4.4 Special warnings and precautions for use
Atenolol as with other P-adrenoceptor blocking drugs:
-although contra-indicated in uncontrolled heart failure (see Contraindications), 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 P1 selective P adrenoceptor blocking drug. Consequently, its use may be considered although utmost caution must be exercised.
-although contra-indicated in severe peripheral arterial circulatory disturbances (see Contraindications), may also aggravate less severe peripheral arterial circulatory disturbances.
-due to its negative effect on conduction time, caution must be excercised 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 may be reduced.
-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 minimize the risk of myocardial depression. The patient may be protected against vagal reactions by intravenous administration of atropine.
-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 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 pi - adrenoceptor blocking drugs may have less effect on lung function than non-selective P-adrenoceptor blocking drugs, as with all P-adrenoceptor blocking drugs, these should be avoided in patients with reversible obstruction 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
Caution must be exercised when prescribing a p-adrenoceptor blocking drug with Class 1 anti arrhythmic agents such as disopyramide and amiodarone as they may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.
Combined use of P-adrenoceptor blocking drugs and calcium channel blocker with negative isotropic effects e.g. verapamil, diltiazem can lead to an exaggeration of these effects, particularly in patients with impaired ventricular function and/or sino-atrial or atrio-ventricular conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the P-adrenoceptor blocking drug 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.
P-adrenoceptor blocking drugs may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the P-adrenoceptor blocking drug should be withdrawn several days before discontinuing clonidine. If replacing clonidine by P-adrenoceptor blocking drug therapy, the introduction of P-adrenoceptor blocking drugs should be delayed for several days after clonidine administration has stopped.
Digitalis glycosides: in association with P-adrenoceptor blocking drugs, may increase atrioventricular conduction time.
Concomitant use of sympathomimetic agents, e.g. adrenaline (epinephrine), may counteract the effect of P-adrenoceptor blocking drugs.
Concomitant use with insulin and oral anti diabetic 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, eg. ibuprofen or indometacin, may decrease the hypotensive effects of P-adrenoceptor blocking drugs.
Anaesthesia: Caution must be exercised when using anaesthetic agents with atenolol. The anaesthetist should be informed and the choice of anaesthetic should be the agent with as little negative inotropicactivity as possible. Use of P-adrenoceptor blocking drugs 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
Pregnancy: Atenolol crosses the placental barrier and appears in the cord blood. No studies have been performed on the use of atenolol in the first trimester and the possibility of foetal injury cannot be excluded. Atenolol 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 associated with intrauterine 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 P-adrenoceptor blocking agents, in general, have been associated with a decrease in placental perfusion which may result in intra-uterine deaths, immature and premature deliveries.
Lactation: There is significant accumulation of atenolol in breast milk. Neonates born to mothers who are receiving atenolol at parturition or breastfeeding may be at risk of hypoglycaemia and bradycardia.
Caution should be exercised when atenolol is administered during pregnancy or to a nursing woman
4.7 Effects on ability to drive and use machines
The use of atenolol is unlikely to result in any impairment of the ability of patients to drive or operate machinery. However, it should be taken into account that occasionally dizziness or fatigue may occur.
4.8 Undesirable effects
Atenolol is well tolerated. In clinical studies, the undesired events reported are usually attributable to the pharmacological actions of atenolol
The following undesired events, listed by body system, have been reported. with the following frequencies: very common ( >10%), common (1-9.9%), uncommon (0.1-0.9%), 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 beta-blockers.
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, in susceptible 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 wellbeing of the patient is adversely affected by any of the above reactions.
4.9 Overdose
The symptoms of overdosage may include bradycardia, hypotension, acute cardiac insufficiency and bronchospasm.
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 to 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 to 10 mg/hour depending on response. If no response to glucagon occurs or if glucagon is unavailable, a P-adrenoceptor stimulant such as dobutamine 2.5 to 10 microgram/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 P-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
Pharmacotherapeutic group: Pi receptor antagonists, ATC code: C07AB03
Atenolol is a P-adrenoceptor blocking drug which is p1-selective (i.e. acts preferentially on p1-adrenergic receptors in the heart). Selectivity decreases with increasing dose. It is without intrinsic sympathomimetic and membrane stabilising activities, and, as with other P-adrenoceptor blocking drugs, has negative inotropic effects (and is therefore contra-indicated in uncontrolled heart failure). As with other P-adrenoceptor blocking drugs, its mode of action in the treatment of hypertension is unclear. It is probably the action of atenolol in reducing cardiac rate and contractility which makes it effective in eliminating or reducing the symptoms of patients with angina. It is unlikely that any additional ancillary properties possessed by S(-) atenolol, in comparison with the racemic mixture, will give rise to different therapeutic effects.
Atenolol is effective and well tolerated in most ethnic populations although the response may be less in black patients. Atenolol is compatible with diuretics, other antihypertensive agents and antianginal agents (see section 4.5. Interaction with other medicinal products).
Early intervention with atenolol in acute myocardial infarction reduces infarct size and decreases morbidity and mortality. Fewer patients with a threatened infarction progress to frank infarction; the incidence of ventricular arrhythmias is decreased and marked pain relief may result in reduced need of opiate analgesics. Early mortality is decreased. Atenolol is an additional treatment to standard coronary care.
5.2 Pharmacokinetic properties
Absorption of atenolol following oral dosing is consistent but incomplete (approximately 40 to 50%) with peak plasma concentrations occurring 2 to 4 hours after dosing. Atenolol blood levels are consistent and subject to little variability.
There is no significant hepatic metabolism of atenolol and more than 90% of that absorbed reaches the systemic circulation unaltered. The plasma half-life is about 6 hours but this may rise in severe renal impairment since the kidney is the major route of elimination. Atenolol penetrates tissues poorly due to its low lipid solubility and its concentration in brain tissue is low. Plasma protein binding is low (approximately 3%).
5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber additional to those already included in other sections of the SPC.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Maize starch
Heavy magnesium carbonate Gelatin
Magnesium stearate Sodium laurylsulphate
6.2 Incompatibilities
Not applicable
6.3 Shelf life
36 months
6.4 Special precautions for storage
Do not store above 25°C.
6.5 Nature and contents of container
Blister strips in cardboard outers comprising: PVC/Aluminium blister strips.
Pack size: 28 tablets.
6.6 Special precautions for disposal
No special requirements
MARKETING AUTHORISATION HOLDER
7
Pharma Roth GmbH Gustav-Stresemann-Ring 1, 65189 Wiesbaden/Germany
8 MARKETING AUTHORISATION NUMBER(S)
Pl 37235/0006
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/08/2008
10 DATE OF REVISION OF THE TEXT
04/05/2011