AstraZeneca Pharmaceuticals (Ireland) Ltd

Tenormin 25 mg Film-coated Tablets.

Tenormin 50 mg Film-coated Tablets.

Tenormin 100 mg Film-coated Tablets.

25 mg Tablets

Each tablet contains 25 mg Atenolol.

50 mg Tablets

Each tablet contains 50 mg Atenolol.

100 mg Tablets

Each tablet contains 100 mg Atenolol.

Each 100 mg tablet contains 0.8 mg Sunset Yellow Lake (E110).

For a full list of excipients, see section 6.1.

Tenormin 25 mg Film-coated Tablets

Film-coated tablet

White, round, biconvex film-coated tablets, impressed Tenormin 25 on one face.

Tenormin 50 mg Film-coated Tablets

Film-coated tablet

White, round, biconvex film-coated tablets, impressed Tenormin 50 on one face.

Tenormin 100 mg Film-coated Tablets

Film-coated tablet

Orange, round, biconvex, film-coated tablets imprinted on one face with the name Tenormin and bisected on the reverse face. The scoreline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Control of hypertension.

Management of angina pectoris.

Control of cardiac arrhythmias.

In early intervention in the acute phase of myocardial infarction and for long-term prophylaxis after recovery from myocardial infarction.

Adults

Control of hypertension:

Most patients respond to 50 mg daily given orally as a single dose. If necessary, the dose may be increased to 100 mg daily. The effect will be fully established after one to two weeks. A further reduction in blood pressure may be achieved by combining Tenormin 25 mg with other antihypertensive agents.

Management of angina pectoris:

Most patients with angina pectoris will respond to 100 mg daily given orally as a single dose or as 50 mg given twice a day. It is unlikely that additional benefit will be gained by increasing the dose.

Control of cardiac arrhythmias:

An oral maintenance dose of Tenormin is 50–100 mg, given once daily.

Early and late intervention after myocardial infarction:

Oral treatment with Tenormin can be initiated in haemodynamically stable patients with 50 mg twice daily, and then 100 mg once daily. During the early phase of acute myocardial infarction, treatment with Tenormin should be initiated in hospital under close monitoring. If bradycardia and/or hypotension requiring treatment, or any other untoward effects occur, Tenormin should be discontinued.

Tenormin 100 mg daily is recommended for long-term prophylaxis of myocardial infarction.

Children:

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

Elderly:

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

Renal failure:

Since Tenormin is excreted via the kidneys dosage should be adjusted in cases of severe impairment of renal function.

No significant accumulation of Tenormin occurs in patients who have a creatinine clearance greater than 35 ml/min/1.73 m ² (normal range is100–150 ml/min/1.73 m ²).

For patients with a creatinine clearance of 15–35 ml/min/1.73 m ² (equivalent to serum creatinine of 300–600 micromol/litre), the dose should be 50 mg daily.

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

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

Tenormin as with other beta-blockers should not be used in patients with any of the following: known hypersensitivity to the active substance or any of the excipients; bradycardia; cardiogenic shock; hypotension; metabolic acidosis; severe peripheral arterial circulatory disturbances; second- or third-degree heart block; sick sinus syndrome; untreated phaeochromocytoma; uncontrolled heart failure.

Tenormin 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. Tenormin 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 may 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.

- May cause an increase in airways resistance in asthmatic patients. Tenormin is a beta₁-selective beta-blocker; consequently its use may be considered although utmost caution must be exercised. If increased airways resistance does occur, Tenormin should be discontinued and bronchodilator therapy (e.g. salbutamol) administered if necessary.

- Should only be given to patients with psoriasis after careful consideration, as psoriasis may be aggravated.

Since Tenormin is excreted via the kidneys, dosage should be reduced in patients with a creatinine clearance of below 35 ml/min/1.73 m².

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

Adrenergic neurone-blocking agents

Adrenergic neurone-blocking agents such as guanethidine, reserpine, diuretics and antihypertensive agents, including the vasodilator group, will have an additive effect on the hypotensive action of the drug.

Anaesthetic agents

Caution must be exercised when using anaesthetic agents with Tenormin. 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.

Antiarrhythmic agents (Class 1)

Class I anti-arrhythmic drugs (e.g. disopyramide) and amiodarone may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.

Calcium channel blockers

Combined use of beta-blockers and calcium channel blockers with negative inotropic effects, e.g. verapamil or 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.

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).

Digitalis glycosides

Digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time.

Dihydropyridines

Concomitant therapy with dihydropyridines, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.

Insulin and oral antidiabetic drugs

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).

Myocardial depressants

The beta-blocker should only be used with caution in patients who are receiving concomitant myocardial depressants such as halogenated anaesthetics, lidocaine, procainamide and beta-adrenoceptor stimulants such as noradrenaline (norepinephrine).

Prostaglandin synthetase-inhibiting drugs

Concomitant use of prostaglandin synthetase-inhibiting drugs, e.g. ibuprofen, indometacin, may decrease the hypotensive effects of beta-blockers.

Sympathomimetic agents

Concomitant use of sympathomimetic agents, e.g. adrenaline (epinephrine), may counteract the effect of beta-blockers.

Tenormin crosses the placental barrier and appears in the cord blood. No studies have been performed on the use of Tenormin in the first trimester and the possibility of foetal injury cannot be excluded. Tenormin has been used under close supervision for the treatment of hypertension in the third trimester. Administration of Tenormin to pregnant women in the management of mild to moderate hypertension has been associated with intra-uterine growth retardation. The use of Tenormin 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.

There is significant accumulation of Tenormin in breast milk.

Neonates born to mothers who are receiving Tenormin at parturition or breast-feeding may be at risk for hypoglycemia and bradycardia. Caution should be exercised when Tenormin is administered during pregnancy or to a woman who is breast-feeding.

Use is unlikely to result in any impairment of the ability of patients to drive or operate machinery. However, it should be taken into account that occasionally dizziness or fatigue may occur.

Tenormin 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 (10%), common (1–9.9%), uncommon (0.1–0.9%), rare (0.01–0.09%), very rare (<0.01%) including isolated reports, not known (cannot be estimated from the available data).

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.

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-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.

Beta-blocking agents, selective.

CO7A BO3.

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.

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.

Tenormin is effective and well tolerated in most ethnic populations although the response may be less in black patients.

Tenormin is compatible with diuretics, other antihypertensive agents and antianginal agents (see section 4.5).

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. 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 its low lipid solubility and its concentration in brain tissue is low. Plasma protein binding is low (approximately 3%).

Tenormin is effective for at least 24 hours after a single oral daily dose. This simplicity of dosing facilitates compliance by its acceptability to patients.

Atenolol is a drug on which extensive clinical experience has been obtained. Relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.

Tenormin 25 mg, 50 mg & 100 mg:

Gelatin

Glycerol

Heavy Magnesium Carbonate

Magnesium Stearate

Maize Starch

Hypromellose

Sodium Laurilsulfate

Titanium dioxide (E171)

Tenormin 100 mg also contains:

Macrogol 300

Sunset Yellow Lake (E110)

Talc

Not applicable.

5 years.

Do not store above 25°C.

Store in the original package. Keep the container in the outer carton.

Aluminium PVC/PVDC blister packs of 28 tablets.

No special requirements.

AstraZeneca UK Limited,

600 Capability Green,

Luton, LU1 3LU, UK.

Tenormin 25 mg Film-coated Tablets

14 August 1992/13 August 2007

Tenormin 50 mg Film-coated Tablets

04 February 1976/13 August 2007

Tenormin 100 mg Film-coated Tablets

17 May 1978/13 August 2007

15^th July 2008