Gerard Laboratories

Ateni 50 mg Film-Coated Tablets

Ateni 100 mg Film-Coated Tablets

Each tablet contains either 50mg Atenolol or 100mg Atenolol

For a full list of excipients, see section 6.1.

Film-coated Tablet.

50 mg Tablet:

White film-coated, biconvex tablet, approximately 8 mm in diameter, marked 'AT 50' on one side and 'G' on the reverse.

100 mg Tablet:

White film-coated, biconvex tablet, approximately 10 mm in diameter, marked 'AT 100' on one side and 'G' on the reverse.

Atenolol is a beta-adrenoceptor blocking drug indicated for:

Adults

Hypertension: Initially 50 mg daily, either alone or in combination with a diuretic. The full effect of this dose will usually be seen within 1-2 weeks. If an optimal response is not achieved the dosage may be increased to 100 mg daily. Doses higher than 100 mg daily are unlikely to produce any further benefit.

Angina pectoris: 100 mg once daily or 50 mg twice daily.

Cardiac arrhythmias: 50-100mg daily after having controlled the arrhythmias with intravenous atenolol.

Myocardial infarction:

- Early intervention in the acute phase: 50mg orally 15 minutes after intravenous atenolol provided no untoward effects occur from the intravenous dose, followed by a further 50mg orally 12 hours after intravenous atenolol and then 12 hour later, 100mg orally daily.

- Late intervention after myocardial infarction: for patients who present some days after suffering an acute myocardial infarction an oral dose of 100mg daily is recommended for long term prophylaxis of myocardial infarction.

Discontinue atenolol if bradycardia and/or hypotension requiring treatment or any other untoward effects occur.

Children:

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

Elderly

The elderly may require reduced dosage, particularly when renal function is impaired.

Renal Impairment

Atenolol is excreted via the kidneys and dosage should be adjusted as follows:

Creatine Clearance

Patients on dialysis should be given 50mg orally after each dialysis with close monitoring as marked falls in blood pressure may occur.

Atenolol is contra-indicated for patients with:

• hypersensitivity to the active substance or any of the excipients

• in patients with second or third degree heart block

• in patients with cardiogenic shock

• uncontrolled heart failure

• sick sinus syndrome (unless a pacemaker is in situ)

• hypotension

• untreated phaeochromocytoma

• severe peripheral circulatory disturbances

• bradycardia (<45-50bpm)

• after prolonged fasting

• in metabolic acidosis (eg in some diabetics)

Special care should be taken with patients whose cardiac reserve is poor. Beta-adrenoceptor blockers should be avoided in overt heart failure. However, they may be used in patients whose signs of failure have been controlled.

One of the pharmacological actions of atenolol is to reduce heart rate. In the rare instances when symptoms may be attributable to the slow heart rate, the dose may be reduced.

Due to its negative effect on conduction time, caution must be exercised if given to patients with first degree heart block.

Atenolol modifies the tachycardia of hypoglycaemia.

In patients with phaeochromocytoma, a beta-blocker should only be given with an alpha-blocker.

While cardioselective beta-blockers such as atenolol may have less effect on pulmonary function than non-selective ones, they should be avoided in patients with reversible obstructive airways disease, bronchospasm or a history of asthma unless absolutely necessary. When administration is required, the use of a beta2-bronchodilator such as terbutaline may be advisable in some cases.

Ateni 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.

Beta-blockers should be used with great caution in patients with peripheral circulatory disorders (Raynaud's disease/syndrome, intermittent claudication) as they may aggravate these disorders.

Atenolol may increase the number and duration of angina attacks in patients with Prinzmetal's angina. Caution must be exercised when considering using atenolol with a Prinzmetal's angina patient.

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 35ml/min/1.73m² (normal range is 100-150 ml/min/1.73 m²). For patients with a creatinine clearance of 15-35 ml/min/1.73 m² (equivalent to serum creatinine of 300-600mcmol/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 <15 ml/min/1.73 m² (equivalent to serum creatinine of>600mcmol/litre) the oral dose should be 25mg daily or 50mg on alternate days and the intravenous dose should be 10mg once every four days.

Atenolol may cause a more serious 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 used to treat the allergic reactions.

Patients with known psoriasis should take beta-blockers only after careful consideration.

The patient information leaflet for this product states 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”.

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.

If a beta-blocker is withdrawn before surgery therapy, it should be discontinued for at least 24 hours.

Atenolol may mask the signs of thyrotoxicosis.

In hypertensive patients, there is evidence that beta-blockers, including atenolol, may affect glucose metabolism and may be associated with the development of diabetes.

Adrenergic neurone-blocking agents

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

Anaesthetic agents

Caution must be exercised when using anaesthetic agents with Ateni. 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)

Caution must be exercised when prescribing a beta-blocker with Class 1 antiarrhythmic agents such as disopyramide.

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.

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.

Barbituric acid derivatives

Concomitant use of derivatives of barbituric acid should be avoided.

Cimetidine

Co-administration of beta-blockers with cimetidine can increase the effect of beta-blockers.

The safety of atenolol in pregnancy has not been established and its use should be avoided unless the potential benefits are likely to outweigh the possible risk to the foetus.

Atenolol crosses the placental barrier and appears in cord blood. There have been isolated reports of intra-uterine growth retardation in association with the use of beta-blockers. Beta-blockers may cause neonatal hypoglycaemia and bradycardia.

Beta-blocking drugs reduce placental perfusion which may result in intra-uterine foetal death, immature and premature deliveries.

Atenolol is excreted in breast milk with accumulation occurring at concentrations significantly greater than corresponding plasma levels. Nursing infants must be closely monitored for bradycardia and other signs and symptoms of beta-blockade if the mother is receiving atenolol, although breast feeding is not recommended.

Although symptoms such as dizziness and fatigue have occasionally been reported in association with the use of beta-blockers, the ability to drive and use machines is usually unaffected by atenolol therapy.

Ateni tablets are well tolerated. In clinical studies, the undesired effects 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.

Cardiac disorders:

Vascular disorders:

Nervous system disorders:

Psychiatric disorders:

Gastrointestinal disorders:

Investigations:

Hepato-biliary disorders:

Blood and lymphatic system disorders:

Skin and subcutaneous tissue disorders:

Eye disorders:

Reproductive system and breast disorders:

Respiratory, thoracic and mediastinal disorders:

General disorders and administration site conditions:

In hypertensive patients, there is evidence that beta-blockers, including atenolol, may affect glucose metabolism and may be associated with the development of diabetes.

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.

Treatment:

If required, gastric emptying and charcoal. Important note! Atropine should be given before gastric emptying (due to the risk of stimulation of the vagus). Intubation and treatment with respirator should be considered. Adequate fluid substitution, infusion of glucose and ECG-supervision should be considered. Eventually the dose of atropine may need to be repeated to prevent vagal symptoms.

If circulatory failure occurs haemodynamics should be monitored and guided by this intravenous dobutamine and if necessary noradrenaline (initial 0.05µg/kg/minute, if necessary increase by 0.05µg/kg every 10 minutes). 10mg glucagons to adults (50-150 µg/kg to children) intravenously every 2 minutes if necessary followed by with an infusion of phosphodiesterase inhibitors (for example amrinone) could also be used if resistant myocardial depression develops. Infusion of sodium (-chloride or –bicarbonate) at widened QRS complex and arrhythmia. If necessary a pacemaker may be used. If circulatory collapse occurs, resuscitative action for several hours is justified. If bronchospasm occurs, terbutaline (via injection or inhalation) may be given. Symptomatic therapy. Haemodialysis could be used with severe poisoning, especially in patients with impaired renal function.

Pharmacotherapeutic group: beta-blocking agents, selective; ATC Code: C07A B03.

Atenolol is a beta-adrenoreceptor blocking agent which has preferential effect on the beta1-receptors chiefly located in the heart (cardioselective). This selectivity diminishes with increased dosage. Atenolol does not possess intrinsic sympathomimetic activity or membrane stabilising activity. By blocking beta-receptor sites, atenolol decreases heart rate and cardiac output, reduces systolic and diastolic blood pressure at rest and on exercise and reduces reflex orthostatic tachycardia.

Atenolol is incompletely absorbed (40-50%) after oral administration with peak plasma concentrations occurring within 2-4 hours. It exhibits low (6-16%) plasma protein binding. The half life of atenolol is 6-7 hours though this may increase to 16-27 hours or more in patients with renal impairment. Atenolol is primarily eliminated unchanged ( 85%) via the kidneys with minimal hepatic metabolism.

There are no additional data of relevance to the prescriber.

Core

Calcium Hydrogen Phosphate (Anhydrous)

Heavy Magnesium Carbonate

Sodium Starch Glycolate Type A

Maize Starch

Colloidal Anhydrous Silica

Magnesium Stearate

Film Coat

Opadry White Y-1-7000, consisting of the following:

Hypromellose

Titanium dioxide (E171)

Macrogol 400

Not applicable.

50mg Tablets:

2 years (Polypropylene pots with polyethylene child resistant cap).

2 years (PVdC/Aluminium foil blister packs).

100mg Talets:

2 years (Polypropylene pots with polyethylene child resistant cap).

2 years (PVdC/Aluminium foil blister packs).

Do not store above 25°C. Store in original package.

(i) Polypropylene pots with polyethylene child resistant cap - Pack sizes 28, 100, 250, 500 and 1000

(ii) PVdC/aluminium foil blister packs - Pack sizes 7, 10, 14, 15 and 28.

Not all pack sizes may be marketed.

No special requirements.

Generics [UK] Limited

Station Close

Potters Bar

Hertfordshire

EN6 1TL

United Kingdom

PA 405/19/1-2

Date of first authorisation: 9^th April 1987

Date of last renewal: 9^th April 2007

April 2010