Atenolol 100mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Atenolol 100mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains 100 mg Atenolol Ph. Eur.
3 PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Atenolol 100mg tablets are indicated for the management of:
1. Hypertension
2. Angina pectoris
3. Cardiac arrhythmias
4. Acute myocardial infarction, as early intervention.
4.2 Posology and method of administration
Adults:
Hypertension:
The majority of patients respond to a single oral dose of 100mg daily though some patients respond to 50mg, the effect being established fully after one to two weeks. A further reduction in blood pressure may be obtained by combining atenolol tablets with other antihypertensive therapy such as diuretics.
Angina:
The majority of patients respond to a single oral dose of 100mg daily or to 50mg given twice daily. Increasing the dose above 100mg daily is unlikely to confer additional benefit.
Cardiac arrhythmias:
The initial dose for control of arrhythmias by intravenous application of atenolol is 2.5mg. This dose may be administered in intervals of 5 minutes until the recommended effect is observed or until the maximum dose of 0.15mg per kg of body weight has been reached, respectively. When the arrhythmia has been controlled with intravenous atenolol, the recommended oral maintenance dose of Atenolol tablets is a single daily dose of 50 - 100mg.
Myocardial Infarction:
In those patients who are considered suitable for beta-blocker therapy (presenting for treatment within 12 hours of the onset of chest pain), appropriate intravenous beta-blocker therapy should be supplemented 15 minutes later by a single oral dose of 50mg atenolol tablet providing intravenous therapy has been well tolerated. A further oral dose of 50mg Atenolol tablet should be given 12 hours later followed by 100mg after another 12 hours then 100mg once daily. Atenolol tablets should be stopped immediately on the occurrence of any untoward events.
Method of administration
For oral administration only.
Use in children
Not recommended.
Use in elderly
Elderly patients may require a lower dose, especially those with impaired renal function.
Renal failure
As atenolol tablets are excreted by the kidneys, the dose should be reduced in patients with a creatinine clearance of 35ml/min/1.73m2 or less. The daily oral dose should be 50mg for patients with a creatinine clearance between 15 and 35ml/min/1.73m2 and 25mg for patients with a creatinine clearance of less than 15ml/min/1.73m2, or 50mg on alternate days. Patients on haemodialysis should receive a single oral dose of 50mg after each dialysis. This should be given under supervision in hospital as it may cause a marked fall in blood pressure.
4.3 Contraindications
Atenolol tablets must not be given to patients with a known hypersensitivity to atenolol or any of the excipients. Beta-blocking drugs including atenolol tablets should not be given to patients with bradycardia, cardiogenic shock, hypotension, second or third degree heart block, sick sinus syndrome uncontrolled heart failure, severe peripheral arterial circulatory disturbances, untreated phaeochromocytoma or metabolic acidosis.
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 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 sever 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 creatine 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 Fertility, pregnancy and lactation
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 intra-uterine growth retardation.
The use of Atenolol in women who are, or may become, pregnant requires 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 breastfeeding 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
Atenolol tablets are unlikely to impair patients ability to drive or operate machinery unless fatigue or dizziness occur, about which the patient should be warned.
4.8 Undesirable effects
Atenolol tablets are 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 date).
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 judgment, the well-being of the patient is adversely affected by any of the above reactions.
4.9 Overdose
Overdosage may be indicated by bradycardia, hypotension, acute heart failure and bronchospasm. Treatment should be supportive, carried out in an intensive care unit, and include gastric lavage, activated charcoal and a laxative to reduce absorption of any drug remaining in the gut and to encourage sink conditions for back diffusion. Hypotension and shock may require treatment with plasma or plasma substitutes. Haemoperfusion and haemodialysis should be considered.
Bronchospasm is usually reversed by giving bronchodilators. Bradycardia may be treated with 1 - 2mg intravenous atropine or a pacemaker and followed, if necessary, by an intravenous bolus of 10mg glucagon repeated as required or followed by an intravenous infusion of glucagon 1 - 10mg/hr depending on response. If there is no response to glucagon or if it is unavailable, a beta stimulant should be given by intravenous infusion, such as dobutamine 2.5 to 10pg/kg/minute. Dobutamine may also be used to treat hypotension and acute heart failure because of its positive inotropic effect. If a large overdose has been taken, it is unlikely that these doses of dobutamine would be sufficient to reverse the cardiac effects of beta-blockade and they should be increased according to the response of the patient in order to achieve the desired clinical condition.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Atenolol is a hydrophilic beta1-selective adrenoreceptor blocking drug, that is, it acts preferentially on beta1-adrenoreceptors in the heart, but selectivity decreases with increasing dose. It does not have intrinsic sympathomimetic activity or membrane stabilising activity. Like other beta-adrenoreceptor blocking drugs, its antihypertensive mode of action is unclear and it is negatively inotropic and so is contra-indicated in uncontrolled heart failure. Its reduction of heart rate and myocardial contractility is probably responsible for its anti-anginal activity. It is unlikely that the S- form has any therapeutic effects not possessed by the racemic mixture.
It is effective and well tolerated by most races but may be less effective in black patients. It is compatible with diuretics, other antihypertensive agents and anti-anginal agents (see Warnings and Interactions).
Infarct size, morbidity, mortality, the number of patients progressing to frank infarction and the incidence of ventricular arrhythmias are all reduced by early treatment with Atenolol Tablets after acute myocardial infarction. The reduction in pain may reduce the need for opiate analgesia. Atenolol tablets are an additional treatment to standard coronary care.
5.2 Pharmacokinetic properties
When given by mouth, absorption of atenolol is consistent but incomplete with only about 40 - 50% being absorbed. Hepatic metabolism is insignificant and more than 90% reaches the systemic circulation. Plasma concentrations peak 24 hours after dosing, are consistent and subject to little variation. The plasma elimination half life is about 6 hours but this is increased in severe renal failure as the kidney is the main route of elimination. Plasma protein binding is about 3 %.
Atenolol penetrates tissues poorly and brain tissue levels are low due to its low lipid solubility.
5.3 Preclinical safety data
Oral atenolol is well tolerated in animals. Oral daily doses of 5 mg/kg in rats and 15 mg/kg in dogs were tolerated in long term toxicity studies without evidence of significant changes. Doses of 200 mg/kg in rats and 300 mg/kg in dogs were associated with an increase in heart and spleen weight.
In animal tests atenolol has shown no mutagenic, carcinogenic or teratogenic potential and does not impair fertility.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
|
Lactose monohydrate |
Ph. |
Eur. |
|
Microcrystalline cellulose |
Ph. |
Eur. |
|
Sodium starch glycollate |
Ph. |
Eur |
|
Maize starch |
Ph. |
Eur. |
|
Magnesium stearate |
Ph. |
Eur. |
6.2 Incompatibilities
None
6.3
Shelf life
30 months.
Special precautions for storage
6.4
Atenolol tablets should be stored below 25 °C and protected from light and moisture.
6.5 Nature and contents of container
Blister strip comprising aluminium foil on one side and PVC on the other. The strips are packed in cartons to contain 28 or 50 tablets.
6.6 Special precautions for disposal
None
7 MARKETING AUTHORISATION HOLDER
M & A Pharmachem Ltd Wigan Road, Westhoughton Bolton, Lancashire BL5 2AL
8 MARKETING AUTHORISATION NUMBER(S)
PL 04077/0227
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
09/01/2004
10 DATE OF REVISION OF THE TEXT
14/05/2013