Eden Atenolol Tablets

Eden Atenolol 50 mg
(Atenolol Tablets BP 50mg)

For the use of a Registered Medical Practitioner or Hospital or a Laboratory only

 

COMPOSITION

Each uncoated tablet contains

Atenolol BP 50mg

 

CLINICAL PHARMACOLOGY

Pharmacological Action

Beta- adrenoceptor antagonists complete with beta-adrenergic agonists for available beta-receptor sites. Unselective beta-blockers inhibit the beta1 receptors (located chiefly in cardiac muscle) and beta2 receptors (located chiefly in the bronchial and vascular musculature) inhibiting the chronotropic, inotroptic and vasodilator responses to beta-adrenergic stimulation. Atenolol is cardioselective and preferentially inhibits beta1 adrenoceptors. Beta1 selectively 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 stabilizing effects, little direct myocardial depressant activity and little or no intrinsic sympathomimetic activity.

Clinical response to beta-blockage 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 amid reduction of reflex orthostatic tachycardia.

 

Pharmacokinetics

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 880ng/ml was reached in approximately 3 hours, declining to approximately 63 ng/ml in 24 hours.

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.

Metabolism: Metabolism of atenolol in man is minimal. In animal studies, hydroxilated 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.

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.

 

INDICATION AND USAGE

• In the management of hypertension

• In the management of angina pectoris

• In the management of cardiac dysrhythmias

• In the management of myocardial infarction: early intervention in the acute phase and long term prophylaxis after recovery from myocardia infarction.

 

CONTRAINDICATION

As with other beta-adrenoceptor blocking drugs, atenolol should not be used in the following circumstances

• Patients with second degree or third degree hearth 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 acidiosis.

• Patients with hypotension.

 

INTERACTION

• The beta-blocker should only he 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).

• Neurotic 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, dilitiazem, can lead to an exaggeration of these effects, particularly in patients with impaired ventricular function and /or sino-atrial or antrio-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 Class1 antiarrythmic agents such as disopyramide.

• Beta-blockers may have hypoglyaemic or hyperglycaemic actions and may decrease or increase the patient’s 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 drug 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.

 

WARNINGS AND PRECAUTIONS

• 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.

• In 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 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 beta1 selective beta adrenoceptor-blocking drug; consequently, its use maybe considered although utmost caution must be exercised.

• Although contraindicated in severe peripheral arterial circulatory disturbance, 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.

 

PREGNANCY

The safety of amlodipine in human pregnancy has not been established. In animal studies, re-productive toxicity was observed at high doses. Use in pregnancy is only recomnmended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus.

Breast-Feeding: It is not known whether amlodipine is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breast-feeding to the child and the benefit of amlodipine therapy to the mother.

Fertility: Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse effects were found on male fertility.

 

ADVERSE REACTION

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, diarrhea, constipation and abdominal cramping. The signs of thyrotoxicosis maybe masked by atenolol treatment.

Bronchospasm may occur in patients with bronchial asthma or history of asthmatic complaints.

An increase in ANA(antinuclear antibodies) has been observed, however, the clinical relevance of this is not clear.

 

DRUG ABUSE AND DEPENDENCE

None

 

SYMPTOMS OF OVERDOSAGE AND PARTICULAR TREATMENT

Symptoms: Signs of overdosage are bradycardia, severe hypotension, bronchospasm, hypoglycaemia, acute cardiac insufficiency and heart failure.

Treatment: General treatment should include: close supervision: treatment in an intensive care ward, if ingestion is recent, the stomach should be emptied by aspiration and 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.

From first principles, excessive bradycardia may be countered by atropine 1-2mg intravenously and/or a cardiac pacemaker, followed, if necessary, 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 prenalterol 5 mg intravenously, followed if necessary by an intravenous infusion of 5 mg/hour or 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 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.
Any risk of hypotension occurring following the use of beta-adrenoceptor agonists will be reduced by the use of the more selective agents. e.g. prenalterol and dobutamine. Bronchospasm can usually be reversed by bronchodilators.

 

DOSAGE AND ADMINISTRATION

Posology

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 100mg given orally once daily or 50mg given twice daily: It is unlikely that additional benefit will be gained by increasing the dose.

Dysrhythmias: Having controlled the dysrhythmias with intravenous atenlol a suitable maintenance dosage is 50mg – 100mg daily, given as a single dose.

Myocardial Infarction: 15 minutes after the administration of the intravenous dose an oral dose of 50mg 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 100mg orally to be given once daily for up to ten days. If bradycardia and/or hypotension require treatment, or may other untoward effects occur, atenolol should be discontinued.

 

Special Populations

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 µmol/L, the atenolol oral dose should be 50mg daily or 100mg once every two days, for patients with a serum creatinine of >600 µmol/L, the oral dose of atenolol should be 50mg on alternate days or 100mg 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.

 

Method of Administration

For oral administration.

 

THE PREPARATION FOR USE

Take the whole Tablet with a glass of water.

 

PRESENTATION: 2 x 14 Tablets packed in Alu-PVC Blister Pack.

 

STORAGE CONDITION: Store at temperature not exceeding 30oC in a dry place. Protect from light.

 

KEEP OUT OF REACH AND SIGHT OF CHILDREN

 

SHELF LIFE: 36 Months

 

Manufactured by

Scott- Edil Pharmacia Ltd.

56,EPIPP, Phase1, Jharmajri 173205,

Distt. Solan (H.P.), India.

 

Imported and distributed by

Eden U.K Pharmaceutical Ltd

J116, Daminja Avenue, Housing Estate,

Fegge, Anambram State, Nigeria.