Atenolol 25mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Atenolol 25 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Atenolol 25 mg
For excipients, see Section 6.1
3 PHARMACEUTICAL FORM
Tablet
Plain, white, round, flat tablets 8mm in diameter, scored on one side
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
1. The management of hypertension
2. The management of angina pectoris
3. The management of cardiac dysrhythmias
4. The management of myocardial infarction: early intervention in the acute phase and long-term prophylaxis after recovery from myocardial infarction.
4.2 Posology and method of administration
For oral administration.
Adults:
Hypertension:
One tablet daily. Most patients respond to 100 mg daily given 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.
Dysrhythmias:
Having controlled the dysrhythmias with intravenous atenolol a suitable maintenance dosage is 50 mg - 100 mg daily, given as a single dose.
Myocardial infarction:
15 minutes after the administration of the intravenous dose an oral dose of 50 mg may be given provided that no untoward effects occur from the intravenous dose. This should be followed by a further 50mg orally 12 hours after the intravenous dose and then 12 hours later by 100 mg orally to be given once daily for up to ten days. If bradycardia and/or hypotension require treatment, or any other untoward effects occur, Atenolol should be discontinued.
Renal failure:
Atenolol is excreted via the kidneys, dosage adjustment should therefore be considered in patients with severe impairment of renal function. As a guide, for patients with a serum creatinine of 300 - 600 pmol/L, the atenolol oral dose should be 50 mg daily or 100 mg once every two days, for patients with a serum creatinine of > 600 pmol/L, the oral dose of Atenolol should be 50 mg on alternate days or 100 mg once every four days.
Patients on haemodialysis should be given 50mg atenolol orally following each dialysis. Because of the possibility of marked falls in blood pressure, this should be carried out under hospital supervision.
Elderly
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.
4.3 Contraindications
As with other beta-adrenoceptor blocking drugs, atenolol should not be used in the following circumstances:
- patients with second degree or third degree heart block.
- patients with severe bradycardia.
- uncontrolled or digitalis/diuretic-refractory heart failure.
- patients with cardiogenic shock.
- patients with sick sinus syndrome.
- patients with untreated phaeochromocytoma.
- patients with hypersensitivity to atenolol or to any other ingredients of the preparation.
- patients with severe peripheral circulatory disturbances.
- patients with metabolic acidosis.
- patients with hypotension.
4.4 Special warnings and precautions for use
Sudden withdrawal of Beta-adrenoceptor blocking agents in patients with ischaemic heart disease may result in the appearance of anginal attacks of increased frequency or severity or deterioration in cardiac state. Discontinuation of therapy should be gradual.
Anaesthesia:
Care should be taken when using anaesthetic agents with Atenolol. The anaesthetist should be informed to enable the necessary precautions to be taken.
If a beta-blocker is withdrawn prior to surgery it should be discontinued for at least 24 hours.
Atenolol should only be used with caution in patients with controlled congestive cardiac failure. Evidence of development of this condition should be regarded as a signal to discontinue therapy.
Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with asthma or a history of obstructive airways disease, unless no alternative treatment is available. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken.
The initial treatment of severe malignant hypertension should be so designed as to avoid sudden reduction in diastolic blood pressure with impairment of autoregulatory mechanisms.
Patients with psoriasis should take beta-blockers only after careful consideration.
Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.
Atenolol 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 betal selective beta adrenoceptor blocking drug; consequently, its use may be considered although utmost caution must be exercised.
Although contraindicated in severe peripheral arterial circulatory disturbances, atenolol may also aggravate less severe peripheral arterial circulatory disturbances.
Due to atenolol’s negative effect on conduction time, caution must be exercised if it is given to patients with first degree heart block.
4.5 Interaction with other medicinal products and other forms of interaction
- The beta-blocker should only be used with great caution in patients who are receiving concomitant myocardial depressants such as chloroform, lignocaine, procainamide, Beta-adrenoceptor stimulants such as isoprenaline, or verapamil or alpha-adrenoceptor stimulants such as noradrenaline, adrenaline (which reverse the hypotensive effects and increase the vasoconstrictor activities).
- Neurone blocking agents such as Guanethidine, Reserpine, diuretics and other antihypertensive agents, including the vasodilator group, will have an additive effect on the hypotensive action of the drug.
- The Beta-blocker may mask the symptoms of thyrotoxicosis.
- Caution should be exercised when transferring patients from Clonidine to beta-adrenoceptor blocking drugs. If the Beta-blocker and Clonidine are given concurrently, the Clonidine should not be discontinued until several days after withdrawal of the Beta-blocker.
- Combined use of beta-adrenoceptor blocking drugs and calcium channel blockers with negative inotropic 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 beta-adrenoceptor blocking drug nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.
- Digitalis glycosides, in association with beta-adrenoceptor blocking drugs, may increase atrio-ventricular conduction time.
- Caution must be exercised when prescribing a beta-adrenoceptor blocking drug with Class 1 antiarrhythmic agents such as disopyramide.
- Beta-blockers may have hypoglycaemic or hyperglycaemic actions and may decrease or increase the patients requirements for insulin or oral antidiabetic agents. Beta-blockers may mask some of the symptoms of hypoglycaemia.
- Plasma concentrations of beta-adrenoceptor blocking drugs may be increased by cimetidine, which is believed to impair beta-blocker metabolism.
- Reduction in first-pass metabolism of oral beta-adrenoceptor blocking drugs may occur in patients also receiving hydralazine.
- Plasma clearance of beta-adrenoceptor blocking drugs can be affected by alcohol intake.
- Concomitant use of prostaglandin synthetase inhibiting drugs, e.g. ibuprofen or indomethacin, may decrease the hypotensive effects of beta-adrenoceptor blocking drugs.
- Plasma concentrations of some beta-adrenoceptor blocking drugs may be reduced by barbiturates.
- Concomitant use of phenothiazines and beta-adrenoceptor blocking drugs may cause increased plasma concentrations and bioavailability and reduced metabolism.
Fertility, pregnancy and lactation
4.6
Atenolol should not be given during pregnancy and lactation unless it is considered essential by the physician.
Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in the foetus and the neonate in the postnatal period.
As most beta-blockers will pass into breast milk to a variable extent, breast feeding is not recommended during treatment with atenolol.
Atenolol has been used effectively under close supervision for the treatment of hypertension associated with pregnancy. Animal studies do not suggest a teratogenic effect with the drug. There is an accumulation of Atenolol in breast milk. However, detrimental effects in the baby during breast feeding have not been reported.
4.7 Effects on ability to drive and use machines
Atenolol may occasionally produce drowsiness, dizziness, light-headedness and blurred vision. Patients should observe caution while driving or performing other tasks requiring alertness.
4.8 Undesirable effects
Atenolol is generally well-tolerated and side effects associated with it are infrequent and generally mild. These can include: coldness of the extremities and muscular fatigue may occur and, in isolated cases, bradycardia. Sleep disturbances which are associated with some other beta-blocking preparations are rare.
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when treatment is withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Cessation of therapy with a beta-blocker should be gradual.
Beta-adrenergic blocking drugs can cause dry mouth and gastrointestinal disturbances including nausea and vomiting, diarrhoea, constipation and abdominal cramping.
The signs of thyrotoxicosis may be masked by atenolol treatment.
Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints.
An increase in ANA (antinuclear antibodies) has been observed, however, the clinical relevance of this is not clear.
4.9 Overdose
After investigation of an overdose or in the case of hypersensitivity the patient should be kept under close supervision and be treated in an intensive care ward. Absorption of any drug material still present in the gastrointestinal tract can be prevented by gastric lavage, administration of activated charcoal and a laxative. Administration of calcium ions, or the use of a cardiac pacemaker may also be considered. In patients intoxicated with hydrophilic beta-antagonists haemodialysis or haemoperfusion may be considered.
From first principles, excessive bradycardia may be countered by atropine 1 - 2 mg intravenously, and if necessary, this may be followed by a beta-agonist, such as isoprenaline 25 pg initially, or orciprenaline 0.5 mg given by slow intravenous injection. Care must be taken to ensure that the blood pressure does not fall too low if the dose of the beta-adrenoceptor agonist has to be increased. Glucagon has also been reported to be useful as a cardiac stimulant in a dose of 10 mg intravenously.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Beta-adrenoceptor antagonists compete with beta-adrenergic agonists for available beta receptor sites. Unselective beta-blockers inhibit both the betai receptors (located chiefly in cardiac muscle) and beta2 receptors (located chiefly in the bronchial and vascular musculature), inhibiting the chronotropic, inotropic and vasodilator responses to beta-adrenergic stimulation. Atenolol is cardioselective and preferentially inhibits beta1 adrenoceptors. Beta1 selectivity has been confirmed by the inability of Atenolol to reverse the beta2 mediated vasodilating effects of adrenaline
or isoprenaline. This contrasts with the effect of nonselective beta-blockers which completely reverse the vasodilating effects of adrenaline.
Atenolol does not have membrane stabilising effects, little direct myocardial depressant activity and little or no intrinsic sympathomimetic activity.
Clinical response to beta-blockade includes slowing of the sinus heart rate, depressed AV conduction, decreased cardiac output at rest and on exercise, reduction of systolic blood pressure on exercise, reduction of both supine and standing blood pressure, inhibition of isoprenaline-induced tachycardia and reduction of reflex orthostatic tachycardia.
5.2 Pharmacokinetic properties
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Absorption: |
Atenolol is consistently absorbed when administered orally; with approximately 50 - 60 % of the dose administered being absorbed. After an oral dose of 100 mg a mean peak serum level of 880 ng/ml was reached in approximately 3 hours, declining to approximately 63 ng/ml in 24 hours. |
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Distribution: |
Atenolol is widely distributed throughout the body, but only a small amount of the drug reaches the brain. Atenolol is not significantly bound to serum proteins. In pregnancy, atenolol readily crosses the placenta, the umbilical and maternal serum being approximately equal at birth. |
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Metabolism: |
Metabolism of atenolol in man is minimal. In animal studies, a hydroxylated compound, with minor beta-blocking activity, has been identified as a minor metabolite of Atenolol, but Atenolol does not appear to be metabolised to any significant extent in man. |
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Excretion: |
Atenolol is excreted unchanged, mainly through the kidneys. About 40 -50 % of a single oral dose is excreted in the urine of healthy subjects. The elimination half-life of Atenolol is approximately 6 - 7 hours. In renal dysfunction, the elimination of Atenolol is closely related to the glomerular filtration rate, although important accumulation probably only occurs if the glomerular filtration is less than 30 ml/min. |
Preclinical safety data
5.3
No further data is presented given the well-known pre-clinical and clinical profile of Atenolol.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablets contain:
Gelatin
Heavy Magnesium Carbonate Magnesium Stearate Microcrystalline Cellulose Maize Starch Sodium Laurilsulfate Purified Talc Purified Water
6.2 Incompatibilities
None known.
6.3 Shelf life
5 years.
6.4
Special precautions for storage
Do not store above 25 °C.
For blisters: ‘Store in the original packaging’
For bottles/containers: ‘Keep the container tightly closed’
6.5 Nature and contents of container
1. Amber glass bottles with closures of LD-polyethylene
2. PP container with desiccant
3. Al/PVC blister strips
Pack sizes 28, 100, 250 tablets.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Zanza Laboratories (Holdings) Limited
Unit 2A
Olympic Way
Sefton Business Park
LIVERPOOL
L30 1RD
8 MARKETING AUTHORISATION NUMBER(S)
PL 39874/0032
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
21 January 2004
10
DATE OF REVISION OF THE TEXT
29/12/2011