Atenolol Tablets Bp 50mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Atenolol Tablets BP 50 mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Atenolol 50 mg per tablet.
For excipients, see 6.1
3 PHARMACEUTICAL FORM
Tablet.
Atenolol Tablets BP 50 mg are presented as orange film coated, biconvex tablets engraved with company logo on one face and A431 on the other face.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
a. Management of hypertension.
b. Management of angina pectoris.
c. Management of cardiac arrhythmias.
d. Myocardial infarction - early intervention in the acute phase.
4.2 Posology and method of administration
ADULTS
Hypertension
Usual Dose: 100 mg daily as a single dose.
Some patients may respond to 50 mg as a single daily dose.
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
100 mg once daily or 50 mg twice daily
Additional benefit is unlikely to be gained by increasing the dose.
Arrhythmias
Having controlled the arrhythmia with intravenous “atenolol” maintenance oral dose:50 - 100 mg daily as a single dose.
Myocardial infarction
Patients presenting within 12 hours of the onset of chest pains and suitable for beta-adrenoceptor blockade therapy.
Injection
Atenolol 5-10 mg administered by slow intravenous injection (1 mg/minute).
Oral dose
If no adverse effects occur following the intravenous dose, then 15 minutes later 50 mg is administered orally followed by a further 50 mg, 12 hours after the intravenous dose. Then 12 hours later 100 mg is orally given, once daily.
If bradycardia and/or hypotension requiring treatment, or any other side-effects occur, atenolol therapy should be discontinued.
Elderly Patients
Dosage requirements may be reduced especially in those with impaired renal function.
Children
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 micromol/litre) the oral dose should be 50 mg daily or 100 mg once every two days; and 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 micromol/litre), the oral dose should be 50 mg on alternate days or 100 mg once every four days; and 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.
Route of administration
Oral.
4.3 Contraindications
Atenolol, as with other beta-blockers, should not be used in patients with any of the following:
Hypersensitivity to atenolol or any of the excipients Hypotension
Severe peripheral circulatory disturbances Untreated phaeochromocytoma Metabolic acidosis Uncontrolled cardiac failure Cardiogenic shock
Heart block - 2nd or 3rd degree atrioventricular (AV) block Sinus bradycardia (heart rate less than 45 beats per minute) Sick sinus syndrome (including sino-atrial block)
4.4 Special warnings and precautions for use
Respiratory Disorders: Beta-blockers including those considered to be cardioselective but not totally cardiospecific should not be given to patients with a history of asthma, bronchospasm or reversible obstructive airways disease. However, in patients where there is no alternative to the use of a beta-blocker, then a cardioselective one can be given with extreme caution and under specialist supervision.
Occasionally, some increase in airways resistance may occur in asthmatic patients and this may usually be reversed by commonly used dosage of bronchodilators such as salbutamol, terbutaline or isoprenaline.
Patient information leaflets and labels will carry the following warnings: Patient Information Leaflet: Do not take this medicine if you have wheezing or asthma. Talk to your doctor or pharmacist first.
Labels: Do not take this medicine if you have wheezing or asthma.
Prinzmetal's angina: The number and duration of angina attacks may increase when beta-1 selective blockers such as atenolol are given to 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, and beta-1 selective blockers use in these patients must therefore be treated with extreme care.
Untreated Congestive Heart disease: Beta-blockers should not be used in such patients. The condition should first be stabilised.
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 whose cardiac reserve is poor. Myocardial contractility must be maintained and signs of failure controlled with digitalis and diuretics.
Bradycardia: Beta-blockers may induce bradycardia. If the pulse rate decreases to less than 50-55 beats per minute when the patient is at rest, the dose should be reduced.
Elderly: These patients should be treated with caution, starting with a lower dose. The elderly may be less sensitive to some of the effects of beta-blockers. Reduced metabolic and excretion capabilities in many elderly patients may lead to increased myocardial depression necessitating reduced dosage, however tolerance is usually good in the elderly.
Impaired ventricular function: Beta-adrenoceptor blocking drugs should be used with caution in combination with verapamil in patients with impaired ventricular function (see also Section 4.5 Interactions with other medicinal products and other forms of interactions). The combination should not be given to patients with conduction abnormalities. Neither drug should be administered intravenously within 48 hours of discontinuing the other.
First Degree Heart Block: Due to its negative effect on conduction time, beta blockers should only be given with caution to such patients.
Ischaemic Heart disease: Atenolol therapy should not be discontinued abruptly in patients with coronary artery disease, especially in patients with ischaemic heart disease, as there is a risk of exacerbation of angina, myocardial infarction, hypertension and arrhythmias. The dosage should be gradually reduced over 1-2 weeks, if necessary at the same time starting replacement therapy, to prevent exacerbation of angina pectoris.
Anaesthesia: In patients undergoing general anaesthesia, beta-blockade reduces 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. 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. If it is thought necessary to withdraw beta-blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.
Diabetics: Care should be taken in diabetic patients and their blood glucose monitored regularly as atenolol may mask the symptoms of hypoglycaemia, 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.
Myasthenia gravis: Atenolol should also be administered with care if given to patients with myasthenia gravis.
Liver or Kidney Insufficiency: Caution should also be exercised in patients with hepatic and renal function impairment. Liver function is reported to deteriorate in portal hypertension. Hepatic and renal functions should be monitored in order to adjust dosage requirement, especially in the elderly, and a reduced dose of atenolol be given at the start of treatment. 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.
Depression: Mental depression may be exacerbated.
Psoriasis: patients with anamnestically known psoriasis should take beta-blockers only after careful consideration.
Peripheral Circulatory Disease: In patients with peripheral circulatory disorders (Raynaud’s disease or syndrome, intermittent claudication), beta-blockers should be used with great caution as aggravation of these disorders may occur.
Allergies: Beta-blockers should be used with caution in patients with a history of hypersensitivity as they may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions. Beta-blockers may also reduce a response to adrenaline (epinephrine) that is administered in cases of allergic emergency.
Hypersensitivity: May cause a hypersensitivity reaction including angioedema and urticaria.
Thyrotoxicosis: Atenolol as with other beta-blockers may mask the signs of thyrotoxicosis.
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
Verapamil: severe hypotension and heart failure are associated with concurrent use of atenolol and verapamil. (Refer to Section 4.4 for details of warnings and precautions for use.)
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.
Anaesthetics: concurrent use of atenolol with anaesthetics, such as hydrocarbon inhalation, especially halothane, may increase the risk of reflex tachycardia, myocardial depression and hypotension because beta blockade reduces the ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli. Concomitant use is therefore best avoided. The anaesthesiologist should be informed when the patient is receiving a betablocking agent such as atenolol and choice of anaesthetic should be an agent with as little negative inotropic activity as possible, (refer to Section 4.4 for details of warnings and precautions for use, which includes information relating to preparation for surgery.)
Antidiabetics: beta-blockers may intensify the blood sugar lowering effect of antidiabetics. Concurrent use of atenolol with insulin and oral antidiabetic drugs may increase the risk of hypoglycaemia (tachycardia). Beta-blockers may mask certain symptoms of developing hypoglycaemia. (Refer to Section 4.4)
NSAIDs: concurrent administration of NSAID agents such as indometacin and ibuprofen with atenolol may reduce the antihypertensive effect possibly due to inhibition of renal prostaglandin synthesis and sodium and fluid retention caused by non-steroidal anti-inflammatory agents.
Oestrogen: concurrent use of oestrogen with atenolol may decrease the antihypertensive effect because oestrogen induced fluid retention may lead to increased blood pressure.
Xanthines: concurrent use of xanthines especially aminophylline or theophylline with atenolol may result in mutual inhibition of the therapeutic effects, in addition theophylline clearance may be decreased especially in patients with increased theophylline clearance induced by smoking.
Concurrent administration therefore, requires careful monitoring.
Phenothiazines: concomitant administration of atenolol with phenothiazines may result in an increased plasma concentration of each medication.
Non-depolarising neuromuscular blocking agents: concurrent use of gallamine or metocurine or pancuronium or tubocurarine with atenolol may potentiate and prolong the action of non-depolarising neuromuscular blocking agents.
Calcium-channel blocking agents: concurrent use of calcium-channel blocking agents, such as diltiazem, or clonidine or diazoxide or reserpine or hypotension-producing medications with atenolol may potentiate the antihypertensive effects. Beta-adrenoceptor blocking drugs should be used with caution in combination with verapamil and to a lesser extent diltiazem in patients with impaired ventricular function, and not at all in patients with conduction abnormalities due to the negative influence on contractility and auriculo-ventricular conduction. May result in severe hypotension, bradycardia and cardiac failure. Refer below for details of transferring patients from clonidine to atenolol. The risk of hypotension may be increased with concomitant use of nifedipine and possibly other dihydropyridines. In patients with latent cardiac insufficiency, treatment with beta-blocker agents may lead to cardiac failure.
Clonidine: caution should be exercised when transferring patients from clonidine to beta-adrenoceptor blocking drugs. If beta-adrenoceptor blocking drugs and clonidine are given concurrently, clonidine should not be discontinued until several days after the withdrawal of the beta-adrenoceptor blocking drug.
Anti-arrhythmic agents: concurrent use of atenolol with class 1 antiarrhythmic agents such as disopyramide, quinidine or amiodarone increases myocardial depression and may have a potentiating effect on atrial-conduction time and induce negative inotropic effect and should therefore be used with caution.
Antihypertensive and/or diuretic combinations: although some antihypertensive and/or diuretic combinations are frequently employed for therapeutic advantage, when any hypotension producing medication is used concurrently, dosage adjustment may be necessary.
Cardiac glycosides: concurrent use of digitalis glycosides may increase auriculo-ventricular conduction time.
Antihypertensive agents as well as other drugs with blood pressure lowering potential: concomitant administration with antihypertensive agents as well as other drugs with blood pressure lowering potential e.g.tri cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), barbiturates, phenothiazines and thymoxamine may increase the blood pressure lowering effect.
Concurrent use of MAOIs (except MAO-B inhibitors) should be avoided.
The antibacterial agent, linezolid, a reversible non-selective MAOI, should be avoided in cases of uncontrolled hypertension unless close observation and blood pressure monitoring is possible.
Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g. noradrenaline (norepinephrine), adrenaline (epinephrine): combination with atenolol may unmask 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.
Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine): combination with atenolol may reduce effects of both agents.
Ergotamine or ergometrine: concomitant use of ergotamine or ergometrine with atenolol leads to an increase in peripheral vasodilation.
4.6 Fertility, pregnancy and lactation
Adequate and well controlled studies in humans have not been carried out. Studies in rodents and rabbits at dosages many times the maximum human dose have shown embryotoxicity and foetal resorption.
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 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.
Atenolol crosses the placental barrier and appears in cord blood.
Beta-blockers have been associated with a decrease in placental perfusion which may result in intra uterine deaths, immature and premature deliveries. Neonatal bradycardia, hypoglycaemia and respiratory depression have rarely been associated, with both cardioselective and non cardioselective beta-blocker therapy of the mother during pregnancy. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period.
There is an approximate three-fold accumulation of atenolol in breast milk. Breast feeding is therefore not recommended during administration of these compounds.
Although the risk is small, breast-fed infants should be monitored for signs of beta-blockade, especially bradycardia.
The possibility of foetal injury cannot be excluded and use of atenolol in women who are or may become pregnant or who are breast feeding, requires that anticipated benefits be weighed against possible risks, particularly in the first and second trimester. The risks of taking atenolol during pregnancy is greater in patients with severe hypertension.
4.7 Effects on ability to drive and use machines
The effect of atenolol is unlikely to result in any impairment of ability of patients to drive or operate machinery. However, when driving vehicles or operating machines, 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 during treatment with atenolol and other beta blockers with the following frequencies: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare (<1/10000) including isolated reports, unknown (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Rare: Thrombocytopenia
Psychiatric disorders:
Uncommon: Sleep disturbances
Rare: Mood changes, nightmares, confusion, psychoses and hallucinations. Rarely cases of insomnia have been reported.
Unknown: Mental depression
Nervous system disorders:
Common: Seizures
Rare: Dizziness, headache, paraesthesia Eye disorders:
Rare: Dry eyes, visual disturbances, impaired vision
Cardiac disorders:
Common: Bradycardia
Rare: A slowed AV-conduction or increase of an existing AV-block, heart failure deterioration, precipitation of heart block, chest pain Unknown: Heart failure (cardiac arrest) and circulatory collapse
Vascular disorders:
Common: Cold extremities, hypotension, peripheral cyanosis
Rare: Postural hypotension which may be associated with syncope, intermittent
claudication may be increased if already present, in susceptible patients Raynaud's
phenomenon.
Frequency unknown: Peripheral vasoconstriction.
Respiratory, thoracic and mediastinal disorders:
Common: Dyspnoea
Rare: Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints.
Gastrointestinal disorders:
Common: Gastrointestinal disturbances: nausea, vomiting, diarrhoea, constipation.
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, purpura
Not known: Hypersensitivity reactions, including angioedema and urticaria
Musculoskeletal and connective tissue disorder:
Common: Muscle fatigue.
Frequency unknown: Swelling of ankles or lower limbs
Reproductive system and breast disorders:
Rare: Impotence, decrease in libido
General disorders and administration site conditions:
Common: Fatigue
Investigations:
Common: Irregular heart beat
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 Yellow Card Scheme 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, hypoglycaemia, acute cardiac insufficiency, pulmonary oedema, syncope, cardiogenic shock and heart failure. First or second degree AV block may occur and rarely arrhythmias.
General treatment after ingestion of an overdose or in the case of hypersensitivity should include close supervision and 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 1-2 mg 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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group : Beta blocking agents, plain, selective - atenolol ATC Code : C07A B03
Atenolol is a beta-adrenoceptor blocking drug which is beta 1- selective (i.e. acts preferentially on beta 1-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, it’s 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.
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 - 50%) with peak plasma concentrations occurring 2-4 hours after dosing. 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 it’s low lipid solubility and it’s concentration in brain tissue is low. Plasma protein binding is low (approximately 3%).
Preclinical safety data
5.3
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Calcium hydrogen phosphate Povidone
Pregelatinised Maize starch Microcrystalline cellulose Croscarmellose Sodium Magnesium stearate
Film coating materials:
Orange colour dispersion containing:
- Hypromellose
- Sunset yellow aluminium lake (E110)
- Quinoline yellow aluminium lake (E104)
- Titanium dioxide (E171)
Hypromellose
6.2 Incompatibilities
None.
6.3 Shelf life
Blister packs: 36 months as packaged for sale
Tablet containers: 36 months as packaged for sale. After first opening: 3 months.
Special precautions for storage
6.4
Blister packs: Do not store above 25°C. Store in the original package in order to protect the tablets from moisture.
Tablet containers: Do not store above 25°C. Keep the container tightly closed in order to protect the tablets from moisture.
6.5 Nature and contents of container
Blister packs of PVC/PVDC film/aluminium foil (10 or 14 tablets/strip). The blister strips are subsequently packed in printed boxboard cartons in a pack size of 28, 30, 56 and 84 tablets.
Polypropylene tablet containers with LDPE/HDPE caps in a pack size of 1000 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special instructions for use/handling.
7 MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
Units 3 & 4, Quidhampton Business Units
Polhampton Lane
Overton
Hants RG25 3ED United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20416/0025
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
19 December 2003
10
DATE OF REVISION OF THE TEXT
08/01/2014