Atenolol Tablets 50mg
Out of date information, search another1. Trade Name of the Medicinal Product
Atenolol 50mg Tablets
2. Qualitative and Quantitative Composition
Each tablet contains 50mg of Atenolol.
Excipients with known effect:
Each Atenolol 50mg tablet contains 70mg of lactose For the full list of excipients, see section 6.1
3. Pharmaceutical Form Film-coated tablet (tablet).
White/off white round bi-convex film coated, unscored tablet, marked “A50”, approximate size 8.8mm X 3.6mm.
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.
Older people:
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 100-150 ml/min/1.73m2).
For patients with a creatinine clearance of 15-35 ml/min/1.73m2 (equivalent to serum creatinine of 300-600 gmol/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 gmol/litre), the oral dose should be one 25mg tablet daily, 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 (including sino-atrial block)
Untreated phaeochromocytoma
Severe peripheral arterial circulatory disturbances
Metabolic acidosis
Hypotension
Hypersensitivity to atenolol or any of the excipients listed in section 6.1
4.4. Special warnings and precautions for use
Heart Failure: care must be exercised in patients with heart failure because of the negative inotropic effects of atenolol. Such patients should be well controlled on digitalis before therapy commences. Close monitoring for progressive failure is essential. Similarly, care must be taken with patients with poor cardiac reserve.
Ischaemic Heart disease: atenolol 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. If necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris. Patients should be followed during withdrawal, especially those with ischaemic heart disease.
Anaesthesia: in patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischemia during induction and intubation, and the post-operative period. It is currently recommended that maintenance beta-blockade be continued peri-operatively. 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 and completed about 48 hours before anaesthesia. 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. The anaesthesist must be aware of beta-blockade because of the potential for interactions with other drugs, resulting in bradyarrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss.
Untreated Congestive Heart disease: although contraindicated in uncontrolled heart failure (see section 4.3), atenolol may be used in patients whose signs of heart failure have been controlled. Caution must be exercised in patients whose cardiac reserve is poor.
Prinzmetal's angina: beta-blockers may increase the number and duration of angina attacks in patients with Prinzmetal's angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. Non-selective beta-blockers should not be used for these patients, atenolol is a beta1-selective beta-blocker; consequently, its use may be considered although utmost caution must be exercised.
Peripheral Circulatory Disease: although contraindicated in severe peripheral arterial circulatory disturbances (Raynaud's disease or syndrome, intermittent claudication) (see section 4.3), beta-blockers should be used with great caution as aggravation of these disorders may occur.
First Degree Heart Block: due to its negative effect on conduction time, caution must be exercised if atenolol is given to such patients..
Thyrotoxicosis: atenolol as with other beta-blockers may mask the signs of thyrotoxicosis.
Bradycardia: beta-blockers 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.
Allergies: beta-blockers may cause a more severe reaction to a variety of allergens when given to patients with a history of anaphylactic reaction to such allergens as beta blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions. Such patients may be unresponsive to the usual doses of adrenaline (epinephrine) used to treat the allergic reactions.
Hypersensitivity: : atenolol may cause a hypersensitivity reaction including angioedema and urticaria.
Psoriasis: patients with anamnestically known psoriasis should take beta-blockers only after careful consideration.
Elderly: atenolol should be used with caution, starting with a lesser dose but tolerance is usually good in the elderly (see Section 4.2).
Diabetics: the symptoms of hypoglycaemia may be masked by atenolol, in particular tachycardia. Diabetic patients should be warned that this 'warning sign' may not occur.
Insulin sensitivity may be reduced in patients treated with atenolol.
Liver or Kidney Insufficiency: 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 or in patients with liver insufficiency.
Respiratory Disorders: although cardioselective (betai) 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 history of asthma, bronchospasm or 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, terbutaline 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 or pharmacist”.
Phaeochromocytoma: 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
Alcohol - concomitant use with alcohol may lead to an enhanced hypotensive effect.
Alpha blockers - some patients experience acute postural hypotension, tachycardia and palpitations when they start to take certain alpha blockers (e.g. prazosin, alfuzosin, and terazosin), this can be exacerbated if they are already taking a beta-blocker. It is recommended that they should start with a low dose of these alpha blockers, and the first dose should be taken just before they go to bed. Patients should be warned about the possibility of postural hypotension and how to manage it (lay down, raise legs and get up slowly). When adding a beta-blocker to an alpha blocker it may be advisable to decrease the dose of the alpha blocker and re-titrate as necessary.
Calcium channel blockers - concomitant therapy with dihydropyridines, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency. Combined use of beta-blockers and calcium channel blockers with negative inotropic effects, e.g. verapamil and to a lesser extent with diltiazem, can lead to an exaggeration of these effects particularly in patients with impaired ventricular function. This combination should not be used at all in patients with conduction abnormalities due to the negative influence on contractility and auriculo-ventricular conduction. 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.Cardiac glycosides - digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time.
Clonidine - 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.)
Anti-arrhythmics - caution should be exercised when prescribing a beta-adrenoceptor blocking drug with Class I anti-arrhythmic drugs (e.g. disopyramide, quinidine and amiodarone), which may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.
Concomitant use of sympathomimetic agents that activate both beta- and alpha-adrenoceptors, e.g. noradrenaline (norepinephrine) and adrenaline (epinephrine) mayunmask the alpha-adrenoceptor-mediated vasoconstrictor effects of these agents leading to blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with non selective beta-blockers.
Antidiabetics - 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 Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. ibuprofen and indometacin, may decrease the hypotensive effects of beta-blockers.
Anaesthetics - caution must be exercised when using anaesthetic agents with atenolol (see section 4.4). 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.
Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine) - combination with atenolol may reduce effects of both agents.
Concomitant use with antihypertensive agents as well as other drugs with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.
4.6. Pregnancy and lactation
Pregnancy
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 deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in foetus and neonate. Atenolol has been used under close supervision for the treatment of pregnancy-associated 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. No studies have been performed on the use of atenolol in the first trimester and the possibility of foetal injury cannot be excluded.
The possibility of foetal injury cannot be excluded and the use of atenolol in women who are, or may become, pregnant or who are breast feeding, requires that the anticipated benefits be weighed against the possible risks, particularly in the first and second trimester.
Breast-feeding
There is significant accumulation of atenolol in breast milk. Breast feeding is therefore not recommended during administration of these compounds.
Neonates in the postnatal period born to mothers who are receiving atenolol at parturition or breast-feeding may be at increased risk of cardiac and pulmonary complications, hypoglycaemia and bradycardia.
4.7. Effects on Ability to Drive and Use Machines
There are no studies on the effect of this medicine on the ability to drive. However, it should be taken into account that occasionally dizziness or fatigue may occur.
4.8. Undesirable effects
The following undesired events, listed by body system, have been reported with the following frequencies: common ((>1/100), uncommon (>1/1000 < 1/100), rare (>1/10000 < 1/1000), very rare (<1/10000) including isolated reports, unknown (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Rare: Thrombocytopenia
Endocrine disorders
Beta-blockers may mask the symptoms of thyrotoxicosis.
Metabolic and Nutrition Disorders
Beta-blockers may mask the symptoms of hypoglycaemia.
Psychiatric disorders:
Uncommon: Sleep disturbances
Rare: Mood changes, nightmares, confusion, psychoses and hallucinations. Rarely cases of insomnia have been reported.
Unknown: Depression
Nervous system disorders:
Rare: Dizziness, headache, paraesthesia
Eye disorders:
Rare: Dry eyes, impaired vision
Cardiac disorders:
Common: Bradycardia
Rare: Heart failure deterioration, a slowed AV-conduction or increase of an existing AV-block), postural hypotension which may be associated with syncope.Unknown: cardiac arrest and circulatory collapse
Vascular disorders:
Common: Cold extremities
Rare: Intermittent claudication may be increased if already present, insusceptible patients Raynaud's phenomenon.
Unknown: Cyanotic extremities
Respiratory, thoracic and mediastinal disorders:
Rare: Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints.
Gastrointestinal disorders:
Common: Nausea, diarrhoea, gastrointestinal disturbances Rare: Dry mouth Unknown: Vomiting
Hepatobiliary 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, purpura
Unknown: Hypersensitivity reactions, including angioedema, urticaria.
Musculoskeletal and connective tissue disorders:
Common: Muscle fatigue
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. In all cases, cessation of therapy should be gradual.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the internet at www.mhra.gov.uk/yellowcard.
4.9. Overdose
The most important effects are on the heart. Signs of overdosage are bradycardia, severe hypotension, bronchospasm, pulmonary oedema, syncope, cardiogenic shock and acute cardiac insufficiency. First or second degree AV block may occur and rarely arrhythmias.
After ingestion of an overdose or in the case of hypersensitypeivity, the patient should be kept under close supervision and treated in an intensive care ward.
General treatment should include: close supervision; 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.
5.1. Pharmacodynamic Properties
Pharmacotherapeutic group: Selective Beta blocking agents, ATC code: C07AB
Atenolol is a beta-adrenoceptor blocking drug which is Beta, selective (i.e. acts preferentially on Beta,-adrenergic receptors in the heart). It is without intrinsic sympathomimetic and membrane stabilising activities. Human studies indicate that it crosses the blood brain barrier only to a negligible extent. As with other beta-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. However, the response may be less in black patients.
Atenolol is effective for at least 24 hours after a single oral dose. The drug facilitates compliance by its acceptability to patients and simplicity of dosing. The narrow dose range and early patient response ensure that the effect of the drug in individual patients is quickly demonstrated. Atenolol is compatible with diuretics, other hypotensive agents and antianginals (but see section 4.5). Since it acts preferentially on beta-receptors in the heart, atenolol may, with care, be used successfully in the treatment of patients with respiratory disease, who cannot tolerate non-selective beta-blockers.
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 to standard 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 (approx. 4050%), peak plasma concentrations occur after 2-4 hours. 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 6-7 hours; this may be increased in patients with renal impairment, as the kidney is the major route of elimination. Atenolol diffuses across the placenta and is excreted in breast milk. Atenolol penetrates tissues poorly due to its low lipid solubility and its concentration in brain tissue is low. Plasma protein binding is low (about 3%).
5.3 Preclinical Safety Data
Not applicable.
6.1 List of Excipients
Lactose, microcrystalline cellulose, talc, maize starch, povidone, lactose (tablettose), sodium starch glycollate, sodium lauryl sulfate, colloidal silicon dioxide, Stearic Acid, magnesium stearate, titanium dioxide (E171), methylcellulose and PEG 6000.
6.2 Incompatibilities
None.
6.3. Shelf Life
4 years.
6.4. Special Precautions for Storage
Store in the original package in order to protect from light and moisture.
6.5. Nature and Contents of Container
Blister packaging (14 tablets/strip) in aluminium foil, subsequently packed in printed cardboard carton containing 28 tablets in each.
Polypropylene securitainer with a polythylene (LDPE) cap with a tamper evident tear-strip closure containing 100 tablets.
Not all pack sizes may be marketed
6.6. Special precautions for disposal and other handling
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Ltd
3 Howard Road
Eaton Socon
St Neots
Cambridgeshire
PE19 8ET
UK.
8 MARKETING AUTHORISATION NUMBER(S)
PL 11311/0014
9. Date of Authorisation/Renewal of Authorisation
Date of first authorisation: 08th February 1999 Date of latest renewal: 14th February 2001
10 DATE OF REVISION OF THE TEXT
22/11/2013