This information is intended for use by health professionals

1. Name of the medicinal product

ATENOLOL TABLETS BP 100mg

2. Qualitative and quantitative composition

Each tablet contains 100mg Atenolol PhEur.

3. Pharmaceutical form

Film-coated tablets

White, circular, biconvex film-coated tablets impressed “A” on one side and “J” on the other side of a score line on one face, plain on the reverse.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4. Clinical particulars
4.1 Therapeutic indications

Atenolol tablets are indicated in the treatment of:

• Management of hypertension.

• Management of angina pectoris.

• Management of cardiac arrhythmias.

• Management of myocardial infarction. Early intervention in the acute phase.

4.2 Posology and method of administration

Posology

The dose must always be adjusted to individual requirements of the patients, with the lowest possible starting dosage. The following are guidelines:

Adults

Hypertension

One tablet daily. Most patients respond to 100mg daily given orally as a single dose. Some patients, however, will respond to 50mg 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 tablets 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.

Cardiac arrhythmias

A suitable initial dose of atenolol is 2.5mg (5ml) injected intravenously over a 2.5 minute period (i.e. 1mg/minute). This may be repeated at 5 minute intervals, until a response is observed up to a maximum dosage of 10mg. If atenolol is given by infusion, 0.15mg/kg bodyweight may be administered over a 20 minute period. If required, the injection or infusion may be repeated every 12 hours. Having controlled the arrhythmias with intravenous atenolol, a suitable oral maintenance dosage is 50–100mg daily, given as a single dose.

Myocardial infarction

For patients suitable for treatment with intravenous beta-blockade and presenting within 12 hours of the onset of chest pain, atenolol 5–10mg should be given by slow intravenous injection (1mg/minute) followed by atenolol 50mg orally about 15 minutes later, provided no untoward effects have occurred 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, once daily. If bradycardia and/or hypotension requiring treatment, or any other untoward effects occur, atenolol should be discontinued.

Elderly

Dosage requirements may be reduced, especially in patients with impaired renal function.

Paediatric population

There is no paediatric experience with Atenolol tablets and for this reason it is not recommended for use in children.

Renal impairment

Since Atenolol tablets are excreted via the kidneys, the dosage should be adjusted in cases of severe impairment of renal function.

No significant accumulation of atenolol occurs in patients who have a creatinine clearance greater than 35ml/min/1.73m2 (normal range is 100–150ml/min/1.73 m2).

For patients with a creatinine clearance of 15–35 ml/min/1.73 m2 (equivalent to serum creatinine of 300–600 micromol/litre), the oral dose should be 50mg daily and the intravenous dose should be 10mg once every two days.

For patients with a creatinine clearance of less than 15ml/min/1.73m2 (equivalent to serum creatinine of greater than 600 micromol/litre), the oral dose should be 25mg daily or 50mg on alternate days and the intravenous dose should be 10mg once every four days.

Patients on haemodialysis should be given 50mg orally after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

Method of administration

For administration by the oral route.

4.3 Contraindications

This medicine, as with other beta-blockers, should not be used in patients with any of the following:

• hypersensitivity to the active substance, or to any of the excipients listed in section 6.1

• cardiogenic shock

• uncontrolled heart failure

• sick sinus syndrome

• second-or third-degree heart block

• untreated phaeochromocytoma

• metabolic acidosis

• bradycardia (<45 bpm)

• hypotension

• severe peripheral arterial circulatory disturbances.

4.4 Special warnings and precautions for use

This medicine, 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 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 severe 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 creatinine 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.

As with other beta-blockers, in patients with a phaeochromocytoma, an alpha-blocker should be given concomitantly.

Patient information leaflets and labels will carry the following warnings:

Patient Information Leaflet: If you have ever had asthma or wheezing, do not take this medicine without first checking with your doctor.

Labels: Do not take this medicine if you have a history of wheezing or asthma.

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 Pregnancy and lactation

Caution should be exercised when atenolol is administered during pregnancy or to a woman who is breast-feeding.

Pregnancy

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 that 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.

Breast-feeding

There is significant accumulation of atenolol in breast milk.

Neonates born to mothers who are receiving atenolol at parturition or breast-feeding may be at risk of hypoglycaemia and bradycardia.

4.7 Effects on ability to drive and use machines

Atenolol has no or negligible influence on the ability to drive and use machines. However, 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 with the following frequencies: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) including isolated reports, not known (cannot be estimated from the available data).

System Organ Class

Frequency

Undesirable Effect

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

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

Not known

Hypersensitivity reactions, including angioedema and urticaria

Musculoskeletal and connective tissue disorders

Not known

Lupus-like syndrome

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.

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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

The symptoms of overdosage may include bradycardia, hypotension, acute cardiac insufficiency and bronchospasm.

General treatment should include: close supervision; treatment in an intensive care ward; 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. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Beta-blocking agents, plain, selective, ATC code: CO7A B03.

Mechanism of action

Atenolol is a beta-blocker which is beta1-selective, (i.e. acts preferentially on beta1-adrenergic receptors in the heart). Selectivity decreases with increasing dose.

Atenolol is without intrinsic sympathomimetic and membrane-stabilising activities and as with other beta-blockers, has negative inotropic effects (and is therefore contraindicated in uncontrolled heart failure).

As with other beta-blockers, the mode of action of atenolol 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.

Clinical efficacy and safety

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 although 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 (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 of opiate analgesics. Early mortality is decreased. Atenolol is an additional treatment to standard coronary care.

5.2 Pharmacokinetic properties

Absorption

Absorption of atenolol following oral dosing is consistent but incomplete (approximately 40–50%) with peak plasma concentrations occurring 2–4 hours after dosing. The atenolol blood levels are consistent and subject to little variability. There is no significant hepatic metabolism of atenolol and more than 90% of that absorbed reaches the systemic circulation unaltered.

Distribution

Atenolol penetrates tissues poorly due to its low lipid solubility and its concentration in brain tissue is low. Plasma protein binding is low (approximately 3%).

Elimination

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.

5.3 Preclinical safety data

Atenolol is a drug on which extensive clinical experience has been obtained. Relevant information for the prescriber is provided elsewhere in the Prescribing Information.

6. Pharmaceutical particulars
6.1 List of excipients

Also contains:

Tablet core:

Silica colloidal anhydrous

Magnesium stearate

Maize starch

Crospovidone

Sodium lauryl sulfate

Hydrogenated vegetable oil

Calcium hydrogen phosphate dihydrate (E341)

Cellulose microcrystalline (E460)

Tablet coat:

Propylene glycol

Titanium dioxide (E171)

Hypromellose 5cP (E464)

Purified talc (E553)

6.2 Incompatibilities

None known.

6.3 Shelf life

Shelf-life

Three years from the date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special precautions for storage

Blister packs

Do not store above 25°C

Store in the original package

Keep container in the outer carton

Polypropylene containers, polyethylene containers and amber glass bottles

Do not store above 25°C

Store in the original container

Keep the container tightly closed

6.5 Nature and contents of container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250 µm white rigid PVC. (ii) Surface printed 20 µm hard temper aluminium

foil with 5-6g/M2 PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 30s, 50s, 100s, 250s, 500s.

Product may also be supplied in bulk packs for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers. Maximum size of bulk packs: 50,000.

6.6 Special precautions for disposal and other handling

Not applicable.

7. Marketing authorisation holder

Accord-UK Ltd

(Trading style: Accord)

Whiddon Valley

Barnstaple

Devon

EX32 8NS

8. Marketing authorisation number(s)

PL 0142/0260

9. Date of first authorisation/renewal of the authorisation

28.4.89

Renewed: 16.3.95

10. Date of revision of the text

08.04.2020