Consumer medicine information

Noten

Atenolol

BRAND INFORMATION

Brand name

Noten

Active ingredient

Atenolol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Noten.

What is in this leaflet

This leaflet answers some common questions about NOTEN. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking NOTEN against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What NOTEN is used for

NOTEN belongs to a group of medicines called beta-blockers.

It works by affecting the body's response to certain nerve impulses, especially in the heart. As a result, it decreases the heart's need for blood and oxygen and therefore reduces the amount of work the heart has to do. It widens the blood vessels in the body, causing blood pressure to fall. It also helps the heart to beat more regularly.

NOTEN is used to:

  • lower high blood pressure, which is called hypertension
  • prevent angina
  • treat an irregular heart beat or rhythm, called arrhythmias
  • treat heart attacks, or reduce the risk of heart complications following a heart attack

NOTEN may be either used alone or in combination with other medicines to treat your condition.

Hypertension
Everyone has blood pressure. This pressure helps to push blood all around your body. Your blood pressure changes during the day, depending on how busy you are or how you are feeling.

You have hypertension when your blood pressure stays higher than is needed, even when you are calm and relaxed.

Regular blood pressure checks are the only way of knowing that you have hypertension. There are usually no symptoms of hypertension and you may feel fine. If high blood pressure is not treated, serious health problems such as stroke, heart disease and kidney failure may occur.

NOTEN helps to lower your blood pressure.

Angina
Angina is a pain or uncomfortable feeling in the chest, often spreading to the arms or neck and sometimes to the shoulders and back. This may be caused by not enough blood and oxygen reaching your heart. The pain of angina is often brought on by exercise or stress, but it can also occur at rest.

NOTEN is used to prevent angina. It is not used to relieve a sudden attack of angina.

Irregular heart beat (arrhythmia)
An irregular heartbeat, also known as an arrhythmia, means that there is a disturbance of the heart's normal rhythm or beat. Arrhythmias may be caused by many factors, including some heart diseases, an overactive thyroid gland or chemical imbalances.

NOTEN helps restore your heart's normal rhythm.

Reducing heart complications after heart attack
After a heart attack, you may have complications such as an irregular heart beat or an increased chance of having another heart attack.

NOTEN helps to prevent these complications from occurring.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

NOTEN is not recommended for use in children, as there have been no studies of its effects in children.

There is no evidence that NOTEN is addictive.

This medicine is available only with a doctor's prescription.

Before you take NOTEN

When you must not take it

Do not take NOTEN if you have an allergy to:

  • any medicine containing atenolol
  • any of the ingredients listed at the end of this leaflet
  • any other beta-blocker medicines

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take NOTEN if you have:

  • asthma, wheezing, difficulty breathing, bronchitis or other lung problems; or have had them in the past
  • a history of allergic problems, including hay fever
  • a very slow heartbeat, less than 45 to 50 beats per minute
  • a severe blood vessel disorder causing poor circulation in the arms and legs
  • certain other heart conditions, such as heart failure
  • phaeochromocytoma (a rare tumour of the adrenal gland) that is not being treated with other medicines
  • low blood pressure, also called hypotension
  • too much acid in your blood (metabolic acidosis)
  • you are receiving certain anaesthetics for medical or dental procedures
  • you are receiving emergency treatment for shock or very low blood pressure

Do not take this medicine if you are pregnant or intend to become pregnant.

Do not take this medicine if you are breast feeding or intend to breast feed. Your doctor will discuss the possible risks and benefits of taking NOTEN during pregnancy and whilst breast feeding.

The active ingredient in NOTEN passes into breast milk and there is a possibility that your baby may be affected.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines (including eye drops), foods, preservatives, dyes or insect stings. NOTEN may make allergies worse or make them harder to treat.

Tell your doctor if you have or have had any of the following medical conditions:

  • heart problems
  • diabetes
  • an overactive thyroid gland, called hyperthyroidism
  • kidney problems
  • any blood vessel disorders causing poor blood circulation in the arms and legs

If you have not told your doctor about any of the above, tell them before you start taking NOTEN.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and NOTEN may interfere with each other. These include:

  • other beta-blocker medicines
  • medicines used to treat high blood pressure, angina or an irregular heart beat, such as verapamil or clonidine
  • medicines used to treat other heart problems
  • insulin and other medicines used to treat diabetes
  • medicines used to treat arthritis, pain or inflammation such as indometacin or ibuprofen
  • medicines commonly used during surgery or in emergency situations such as adrenaline (epinephrine), noradrenaline (norepinephrine) and certain anaesthetics

These medicines may be affected by NOTEN or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take NOTEN

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to take

Hypertension
The usual dose is from 50 mg (1 tablet) up to 200 mg (4 tablets) daily.

If your dose is 100 mg or less, you may take it once a day.

If you need to take more than 100 mg (2 tablets), take half of your dose in the morning and the other half at night.

Angina or arrhythmia (irregular heart beat)
The usual dose is from 50 mg daily (1 tablet) as a single dose up to 100 mg (2 tablets) either as a single dose or a divided dose given as 1 tablet in the morning and 1 tablet at night.

Heart attack
The usual dose is 50 mg (1 tablet) daily.

Certain people such as the elderly or those with kidney problems may require a lower dose.

How to take it

Swallow the tablets whole with a glass of water.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

It does not matter if you take NOTEN before or after food.

How long to take it

Continue taking your medicine for as long as your doctor tells you to.

This medicine helps to treat your condition but it does not cure it. It is important to keep taking your medicine even if you feel well.

Your doctor may want to gradually reduce the amount of NOTEN you are taking. This should take place over a period of approximately two weeks before stopping it completely.

Do not stop taking this medicine suddenly as this may worsen your condition.

If you forget to take it

If it is less than six hours from when you missed your dose, take it as soon as you remember, and then go back to taking your tablets at the same time you would normally

If it is more than six hours since your last dose, skip the dose you missed and take your next dose when you would normally.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much NOTEN. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much NOTEN, you may feel faint, dizzy or lightheaded, wheeze or have difficulty breathing. You may also have a very slow heartbeat.

While you are taking NOTEN

Things you must do

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking NOTEN.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you have an allergic reaction to any foods, medicines or insect stings, tell your doctor immediately. NOTEN can cause allergic reactions to be worse and harder to treat.

If you are going to have surgery, tell your surgeon or dentist that you are taking this medicine. It may affect other the medicines used during surgery.

If you have diabetes, check your blood sugar level regularly and report any changes to your doctor. NOTEN may affect your diabetes. It may hide the symptoms of low blood sugar levels, such as a fast heartbeat. It may also take longer for your low blood sugar to get back to normal even if you follow the usual treatment for diabetes. Your doctor may need to change your dose of diabetic medicines, including insulin.

If you have angina and continue to have angina attacks or have more of them while you are taking this medicine, tell your doctor. NOTEN is used to help prevent angina, so your angina attacks should become less severe and occur less often.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure.

If this problem gets worse or continues, talk to your doctor.

Make sure you drink enough water in hot weather and during exercise while you are taking NOTEN, especially if you sweat a lot. If you do not drink enough water you may feel faint, lightheaded or sick. The recommended healthy minimum water intake is 6 to 8 glasses a day.

If you have to have any medical tests, tell your doctor that you are taking this medicine.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

Do not take NOTEN to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dose without checking with your doctor. If you stop taking it suddenly, your condition may worsen or other heart complications may occur.

Do not take any new medicines with NOTEN unless your doctor has told you to.

Things to be careful of

Be careful driving or operating machinery until you know how NOTEN affects you. NOTEN may cause dizziness, tiredness, light headedness or faintness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Be careful not to over exercise when you first start taking NOTEN. This medicine helps to prevent angina resulting from physical activity and exercise. Talk to your doctor about how much exercise you can do.

Dress warmly during cold weather, especially if you will be outside for a long time (for example, when playing or watching sports in winter). NOTEN, like other beta-blocker medicines, may make you more sensitive to cold temperatures, especially if you have blood circulation problems. Beta-blockers tend to decrease blood circulation to the skin, fingers and toes.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking NOTEN.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

If you get any side effects, do not stop taking NOTEN without first talking to your doctor.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • stomach upsets such as diarrhoea, constipation, abdominal pain or heartburn (indigestion)
  • dry mouth, change in taste sensation
  • dizziness, headache or buzzing or ringing in the ears
  • slow or irregular heart beat
  • dry eyes, problems with vision
  • runny or blocked nose
  • difficulty sleeping, nightmares, vivid dreams
  • skin reactions (e.g. rash, itching, worsening of psoriasis
  • increased hair loss
  • tingling, 'pins and needles' or walking unsteadily
  • sexual problems

These side effects are usually mild.

Tell your doctor as soon as possible if you notice any of the following:

  • confusion or disorientation
  • depression or mood changes or a worsening of these
  • unusual thoughts, hallucinations (seeing, feeling or hearing things that are not there)
  • light headedness or fainting, which may be due to low blood pressure
  • yellowing of the skin and/or eyes (jaundice)

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • wheezing, chest tightness or difficulty breathing
  • unusual bruising or bleeding
  • fast, slow or irregular heart beat
  • swelling of the face, lips, tongue or other parts of the body

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using NOTEN

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store NOTEN or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

NOTEN is a white, oblong tablet marked with AT/50 and a Greek alpha symbol.

Each pack contains 30 tablets.

Ingredients

NOTEN contains 50 mg of atenolol as the active ingredient.

The tablets also contain:

  • lactose monohydrate
  • maize starch
  • povidone
  • microcrystalline cellulose
  • colloidal anhydrous silica
  • hydrogenated vegetable oil
  • crospovidone
  • sodium starch glycollate
  • purified talc
  • magnesium stearate.

The tablets are gluten free.

Manufacturer

Alphapharm Pty Limited
Level 1, 30 The Bond
30 - 34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

This leaflet was prepared in September 2019.

Australian registration numbers:

AUST R 46250 (blister pack)

noten_cmi\Sep19/00

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Noten

Active ingredient

Atenolol

Schedule

S4

 

1 Name of Medicine

Atenolol.

6.7 Physicochemical Properties

Chemical name: 2-[4-[(2RS)-2- hydroxy-3- [(1-methylethyl) amino] propoxy] phenyl] acetamide.
Molecular formula: C14H22N2O3.
Molecular weight: 266.3 g/mol.

Chemical structure.


CAS number.

29122-68-7.

2 Qualitative and Quantitative Composition

Each tablet contains 50 mg of atenolol as the active ingredient.
The tablets contain lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dosage form: uncoated tablet.
The tablets are white, oblong, normal convex, marked AT/50 on one side, α on reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Atenolol is a beta-adrenoreceptor antagonist which acts preferentially on beta-receptors in the heart. Selectivity decreases with increasing dose. It has little intrinsic sympathomimetic activity and no membrane stabilising activity.
It is structurally related to propranolol and differing from it by substitution on the aromatic ring. It is sparingly soluble in water, soluble in absolute ethanol, practically insoluble in ether.
Atenolol is a racemic mixture and its activity resides in the S(-) enantiomer. It reduces raised blood pressure by an unknown mechanism, and also inhibits exercise-induced tachycardia and decreases plasma renin concentration. It causes slight airways obstruction but less than that seen with nonselective beta-blockers. The inhibition of exercise-induced tachycardia is correlated with blood levels but there is no correlation between plasma concentrations and antihypertensive effect. Atenolol is effective and well tolerated in most ethnic populations although the response may be less in Afro-Caribbean black patients.
The possible mechanism of the anti-anginal activity of atenolol appears to be due to a reduction in left ventricular work and oxygen utilisation resulting (mainly) from the decrease in heart rate and contractility.
The antiarrhythmic effect of atenolol is apparently due to its antisympathetic effect. There is no evidence that membrane stabilising activity or intrinsic sympathomimetic activity are necessary for antiarrhythmic efficacy. By its antisympathetic effect, atenolol depresses sinus node function, atrioventricular node function and prolongs atrial refractory periods. It has no direct effect on electrophysiological properties of the His-Purkinje system.
Because of their negative inotropic effects, beta-adrenoreceptor blocking agents should be avoided in uncontrolled heart failure.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Although absorption of atenolol is variable and incomplete (40 to 60%), the virtual lack of hepatic metabolism results in relatively consistent systemic bioavailability compared to other beta-blockers. Peak blood levels occur 2 to 4 hours after administration of a single 100 mg oral dose and vary between 0.4 and 0.9 microgram/mL. Blood levels are consistent and the levels after chronic oral administration are in good agreement with those predicted from single dose results.

Distribution.

Atenolol is distributed throughout the body tissues.

Metabolism.

Less than 10% of a dose of atenolol is metabolised, the minor urinary metabolite identified being a hydroxylated derivative.
Plasma half-life, measured by blood level decay or urinary build up, varies from 7 to 9 hours.
In patients with impaired renal function, there is a progressive prolongation of the half-life.
In patients with normal renal function, the therapeutic effect, that is control of raised blood pressure, lasts for at least 24 hours following a 50 mg oral dose.

Excretion.

The main route of elimination is renal excretion.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Atenolol is indicated in the management of the following.
1. All grades of hypertension, including hypertension of renal origin.
2. Frequent disabling angina without evidence of cardiac failure.
3. Cardiac arrhythmias (acute treatment of supraventricular and ventricular arrhythmias including those associated with acute myocardial infarction).
4. Myocardial infarction - late intervention (beta-blocker class effect greater than 12 hours after onset of chest pain).

4.3 Contraindications

1. Bronchospasm. Beta-adrenergic blockade of the smooth muscle of bronchi and bronchioles may result in an increased airways resistance. These drugs also reduce the effectiveness of asthma treatment. This may be dangerous in susceptible patients.
Therefore, beta-blockers are contraindicated in any patient with a history of airways obstruction or a tendency to bronchospasm. Use of cardioselective beta-blockers can also result in severe bronchospasm. If such therapy must be used, great caution should be exercised. Alternative therapy should be considered.
2. Congestive heart failure.
3. Allergic disorders (including allergic rhinitis) which may suggest a predisposition to bronchospasm.
4. Right ventricular failure secondary to pulmonary hypertension.
5. Significant right ventricular hypertrophy.
6. Sick sinus syndrome.
7. Sinus bradycardia (less than 45 to 50 beats/minute).
8. Second- and third-degree A-V block.
9. Shock (including cardiogenic and hypovolaemic shock).
10. Hypersensitivity to the drug.
11. Anaesthesia with agents that produce myocardial depression (e.g. ether, chloroform, cyclopropane).
12. Metabolic acidosis.
13. Hypotension.
14. Severe peripheral arterial circulatory disturbances.
15. Untreated phaeochromocytoma.
16. Pregnancy and lactation (see Section 4.6 Fertility, Pregnancy and Lactation).

4.4 Special Warnings and Precautions for Use

Cardiac failure.

Beta-blockade depresses myocardial contractility and may precipitate cardiac failure in some patients with a history of cardiac failure, chronic myocardial insufficiency or unsuspected cardiomyopathy as may occur in chronic alcoholism. In patients without a history of cardiac failure, continuing depression of the myocardium may lead to cardiac failure. If signs of cardiac failure present, the patients should be fully digitalised and/or given an ACE inhibitor or vasodilators, with or without a diuretic, and carefully monitored. If cardiac failure persists, atenolol should be withdrawn (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal of therapy).

Note.

Although congestive heart failure has been considered to be a contraindication to the use of beta-blockers, there is a growing literature on the experimental use of beta-adrenergic blocking drugs in heart failure. As further trials are needed to identify which patients are most likely to respond to which drugs, beta-blockers should not normally be prescribed for heart failure outside of specialist centres.

Abrupt withdrawal of therapy.

Care should be taken if beta-blockers have to be discontinued abruptly in patients with coronary artery disease. Severe exacerbation of angina and precipitation of myocardial infarction and ventricular arrhythmias have occurred following abrupt discontinuation of beta-blockade in patients with ischaemic heart disease. Therefore, it is recommended that the dosage be reduced gradually over a period of about 8 to 14 days during which time the patient's progress should be reassessed. The drug may be reinstituted temporarily if the angina worsens. If the drug must be withdrawn abruptly, close observation is required. In the peri-operative period, beta-blockers should not be withdrawn, unless indicated.

History of anaphylactic reaction.

While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge. Such patients may be unresponsive to the usual doses of adrenaline (epinephrine) used to treat the allergic reactions.

First degree heart block.

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

Peripheral circulation.

Beta-blockade may impair the peripheral circulation and exacerbate the symptoms of peripheral vascular disease.

Prinzmetal angina.

There is a risk of exacerbating coronary artery spasm if patients with Prinzmetal or variant angina are treated with a beta-blocker.
If this treatment is essential, it should only be undertaken in a Coronary or Intensive Care Unit.

Bradycardia.

If a treated patient develops symptoms which may be attributable to a slow heart rate, the dose may be reduced.

Use in acute myocardial infarction.

In addition to the contraindications listed (see Section 4.3 Contraindications), patients with the following conditions are not suitable for treatment with Noten:
(a) Systolic blood pressure less than 120 mmHg (systolic blood pressure less than 120 mmHg in combination with a heart rate greater than 90 beats/min has a particularly poor prognosis).
(b) First degree A-V block. There is an increased incidence of cardiogenic shock (and need for inotropes), complete heart block and cardiovascular death in these patients, following atenolol.
Patients with atrial fibrillation following myocardial infarction, who were treated with atenolol, also had increased cardiovascular mortality compared with those not treated with atenolol. It is suggested that such patients be digitalised before Noten therapy is commenced.

Euthyroid hyperthyroxinaemia.

The effects of beta-blockers on thyroid hormone metabolism may result in elevations of serum free thyroxine (T4) levels. In the absence of any signs or symptoms of hyperthyroidism, additional investigation is necessary before a diagnosis of thyrotoxicosis can be made.

Anaesthesia and the peri-operative period.

Beta-blockade may have beneficial effects in decreasing the incidence of arrhythmias and myocardial ischaemia during anaesthesia and the post-operative period. It is currently recommended that maintenance of beta-blockade be continued peri-operatively. The anaesthetist must be made aware of beta-blockade because of the potential for interactions with other drugs, resulting in severe bradyarrhythmias and hypotension, the decreased reflex ability to compensate for blood loss, hypovolaemia and regional sympathetic blockade, and the increased propensity for vagal-induced bradycardia. Incidents of protracted severe hypotension or difficulty restoring normal cardiac rhythm during anaesthesia have been reported. Modern inhalational anaesthetic agents are generally well tolerated, although older agents (ether, cyclopropane, methoxyflurane, trichloroethylene) were sometimes associated with severe circulatory depression in the presence of beta-blockade.

Diabetes.

Beta-blockers affect glucose metabolism and may mask some important premonitory signs of acute hypoglycaemia, such as tachycardia.
In patients with insulin or non-insulin dependent diabetes, especially labile diabetes, or with a history of spontaneous hypoglycaemia, beta-blockade may result in the loss of diabetic control and delayed recovery from hypoglycaemia. The dose of insulin or oral hypoglycaemic agent may need adjustment.

Other metabolic effects.

Beta-adrenoreceptors are involved in the regulation of lipid as well as carbohydrate metabolism. Some drugs affect the lipid profile adversely, although the long-term clinical significance of this change is unknown and the effect appears to be less for drugs with intrinsic sympathomimetic activity.

Phaeochromocytoma.

In patients with this condition, an alpha-blocking drug (e.g. phentolamine/phenoxybenzamine) should be administered before the beta-blocker to avoid exacerbation of hypertension.

Eye and skin reactions.

Various skin rashes and conjunctival xerosis have been reported with beta-blockers. Cross-reactions may occur between beta-blockers, therefore substitutions within the group may not necessarily preclude occurrence of symptoms.
During the long-term treatment with the beta-blocking drug, practolol, a specific rash bearing a superficial resemblance to psoriasis was occasionally described. In a number of patients affected, this rash was accompanied by adverse effects on the eye (xerophthalmia and/or keratoconjunctivitis) of varying severity. This condition is called the oculomucocutaneous syndrome or practolol syndrome. In a few patients, these eye changes occurred independently of a skin rash. On rare occasions, serous otitis media, sclerosing peritonitis, pericarditis and pleurisy have been reported. Although the practolol syndrome has not been observed in patients taking other beta-blockers, the possibility of such side effects occurring should be borne in mind.
More recently, an association between Peyronie's disease (a fibrosing induration of the penis) and various beta-blockers has been suggested but is not proven.

Allergic conditions.

These may be exaggerated by beta-blockade (e.g. allergic rhinitis during the pollen season and allergic reactions to bee and wasp stings). Beta-blockers should be avoided if there is a risk of bronchospasm.

Hyperthyroidism.

Because beta-blockers may mask the clinical signs of developing or continuing hyperthyroidism, resulting in symptomatic improvement without any change in thyroid hormone status, special care should be exercised in those patients who are hyperthyroid and are also receiving beta-blockers.

Use in hepatic impairment.

No data available.

Use in renal impairment.

In patients with severe renal disease, haemodynamic changes following beta-blockade may impair renal function further. Beta-blockers which are excreted mainly by the kidney may require dose adjustment in patients with renal failure.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant therapy with calcium antagonists.

The concomitant use of beta-blockers and calcium antagonists with myocardial depressant and sinus node activity (e.g. verapamil and, to a lesser extent, diltiazem) may cause hypotension, bradycardia and asystole, particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities. Extreme caution is required if these drugs have to be used together.
The dihydropyridine calcium antagonists (e.g. nifedipine) have a weaker myocardial depressant effect and can be administered cautiously with beta-blockers. If excessive hypotension develops, the calcium antagonist should be stopped or the dosage reduced.

Antiarrhythmic drugs.

Care should be taken when prescribing beta-blockers with antiarrhythmic drugs. Class I antiarrhythmic drugs (e.g. disopyramide) and the Class III agent amiodarone may have a potentiating effect on atrial conduction time and induce negative inotropic effect, this is seen less frequently with quinidine; Class IB agents, tocainide, mexiletine and lidocaine (lignocaine); Class IC agents, flecainide and propafenone (not available in Australia); and the Class IV antiarrhythmic agents.

Use of catecholamine depleting agents.

Concomitant use of drugs such as reserpine and guanethidine requires careful monitoring since the added effect of beta-blockade may produce an excessive reduction of the resting sympathetic nervous tone.

Clonidine.

Concurrent use of beta-blockers and clonidine should be avoided because of the risk of adverse interaction and severe withdrawal symptoms. If administered concomitantly, the clonidine should not be discontinued until several days after the withdrawal of the beta-blocker.

Insulin and oral hypoglycaemics.

See Section 4.4 Special Warnings and Precautions for Use, Diabetes.

Anaesthetics.

Anaesthetics, such as methoxyflurane, are contraindicated with Noten (see Section 4.4 Special Warnings and Precautions for Use, Anaesthesia and the peri-operative period).

Digitalis/digitalis glycosides.

Digitalis/digitalis glycosides and beta-blockers are commonly used together, although there have been reports of excessive bradycardia when beta-blockers are used to treat digitalis intoxication.

Sympathomimetic agents.

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

Prostaglandin synthetase inhibitors.

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

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Beta-adrenergic blocking agents may cause pharmacological effects such as bradycardia in the foetus and newborn infant. During the final part of pregnancy and parturition, these drugs should therefore only be given after weighing the needs of the mother against the risk to the foetus.
Atenolol crosses the placental barrier in pregnant women, and under steady-state conditions, maternal and foetal blood levels of atenolol are approximately equal.
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 for longer periods 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.
Atenolol has been shown to produce a dose-related increase in embryo/fetal resorptions in rats at doses equal to or greater than 50 mg/kg. Although similar effects were not seen in rabbits, the compound was not evaluated in rabbits at doses above 25 mg/kg.
There is significant accumulation of atenolol in breast milk. Caution should be exercised when atenolol is administered to nursing women and the infant should be regularly assessed for signs of beta-blockade.

4.8 Adverse Effects (Undesirable Effects)

Adverse effects reported in clinical trials of atenolol are mainly attributable to pharmacological actions. The adverse effects listed below have been observed in patients in clinical trials who have received dosages of about 100 mg per day. It is not possible to give percentage incidences for each reaction, but if all mild and transient reactions are included as well as more serious ones, up to 10% of patients may experience some form of adverse effects.

More common adverse effects.

Gastrointestinal.

Gastrointestinal disturbances including indigestion, dry mouth, constipation.

Nervous system.

Fatigue, dizziness.

Respiratory.

Wheezing, bronchospasm (see Section 4.3 Contraindications).

Less common adverse effects.

Biochemical abnormalities.

Increases in SGOT, blood urea and serum creatinine have been reported.

Cardiovascular.

Bradycardia, left ventricular insufficiency, postural hypotension which may be associated with syncope, intermittent claudication may occur if already present, Raynaud's phenomenon, cold extremities, deterioration in heart failure, heart block.

Dermatological.

Rash, alopecia, psoriasiform skin rashes, exacerbation of psoriasis.

Gastrointestinal.

Diarrhoea.

Hepatic.

Elevations of transaminase levels have been seen infrequently, rare cases of hepatic toxicity including intrahepatic cholestasis have been reported.

Genitourinary.

Impotence.

Musculoskeletal.

Ataxia.

Nervous system.

Vivid dreams, nightmares, paraesthesia, tinnitus, vertigo, malaise, headache, insomnia, mood changes, confusion.

Ocular.

Dry eyes, visual disturbances.

Psychiatric.

Hallucinations, depression, psychoses.

Respiratory.

Asthma, dyspnoea, nasal congestion.

Haemopoietic.

Thrombocytopenia, purpura. An increase in ANA (antinuclear antibodies) has been observed, however the clinical relevance of this is not clear.

Serious or life-threatening adverse effects.

Myocardial insufficiency may require treatment with digitalis and diuretics. Bradycardia may respond to atropine. Bronchospasm may be reversed with a beta2-stimulant. Hypotension, if severe, may require use of a vasopressor.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Adults.

Hypertension.

Therapy should be initiated with 50 mg atenolol daily. This may be increased each week in daily doses of 50 mg up to a maximum of 200 mg. Where patients are controlled on daily doses of 50 to 100 mg, this may be given once daily. Doses above 100 mg daily should be given on a divided basis. Where necessary, a further reduction in blood pressure may be achieved by combining atenolol with other antihypertensive agents.
Patients can be transferred to atenolol from other antihypertensive treatments with the exception of clonidine (see Section 4.4 Special Warnings and Precautions for Use).

Angina pectoris.

Therapy should be initiated with 50 mg of atenolol daily. This may be increased if required to 100 mg daily given as a single or divided dose. It is unlikely that additional benefit will be gained by increasing the dose.

Cardiac dysrhythmias.

Having controlled the dysrhythmias with other intravenous agents, Noten given orally at a dosage of 50 to 100 mg daily will help maintain control.

Acute myocardial infarction - late intervention (> 12 hours from onset of chest pain).

Atenolol has been shown to reduce infarct size, reduce the incidence of ventricular dysrhythmias, reduce the need for opiate analgesics and reduce mortality in the first 7 post-infarction days, most of the benefit being in the first 48 hours. Data from other beta-blocker trials suggest that there is a significant reduction in mortality and a reduced incidence of non-fatal reinfarction if the beta blocker is continued for 1 to 3 years.
Maintenance oral therapy of 50 mg daily of Noten is recommended for 1 to 3 years following myocardial infarction, beginning early after intervention with other agents, or immediately in those patients who present more than 12 hours after suffering an acute myocardial infarction.

Impaired renal function.

Since Noten is excreted via the kidneys, dosage should be adjusted in cases of severe impairment of renal function. No significant accumulation of Noten occurs at a creatinine clearance greater than 35 mL/min/1.73 m2 (normal range is 100 to 150 mL/min/1.73 m2). For patients with a creatinine clearance of 15 to 35 mL/min/1.73 m2 (equivalent to serum creatinine of 300 to 600 micromol/L) the dose should be 50 mg daily or 100 mg on alternate days. For patients with a creatinine clearance less than 15 mL/min/1.73 m2 (equivalent to serum creatinine of greater than 600 micromol/L) the dose should be 50 mg on alternate days or 100 mg every fourth day.
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.

Children.

There is no experience with atenolol in children.

Elderly.

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

4.7 Effects on Ability to Drive and Use Machines

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.

4.9 Overdose

There have been no reports of overdosage to date with atenolol, but in overdosage with other beta-blockers, severe bradycardia and hypotension are commonly found. Acute heart failure and bronchospasm may also occur.

Treatment.

Severe bradycardia.

Atropine 1 to 2 mg intravenously may be used to induce vagal blockade. If bradycardia persists, an inotrope, such as intravenous isoprenaline (25 microgram initially) may be given. In refractory cases, the use of a cardiac pacemaker may be considered.

Hypotension.

Severe hypotension should respond to a sympathomimetic amine such as noradrenaline (norepinephrine). In refractory cases, the use of glucagon hydrochloride should be considered.

Bronchospasm.

Therapy with a beta2-stimulant such as salbutamol or terbutaline or therapy with aminophylline may be considered.

Acute cardiac failure.

Conventional therapy with digitalis, diuretics and oxygen should be instituted immediately. In refractory cases, the use of intravenous isoprenaline, followed if necessary, by glucagon hydrochloride or intravenous aminophylline should be considered.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets contain the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, purified talc, maize starch, crospovidone, sodium starch glycollate, povidone, magnesium stearate, vegetable hydrogenated oil and colloidal anhydrous silica.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light and moisture.

6.5 Nature and Contents of Container

Container type: PVC/PVDC/Aluminium blister packs or HDPE bottles or polypropylene pails (bulk dispensing use only).
Pack sizes: 7, 10 or 30 tablets (blister packs); 10 or 30 tablets (bottles); 11,940 or 59,700 tablets (pails).
Some strengths, pack sizes and/or pack types may not be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

Summary Table of Changes