Consumer medicine information

Noumed Bisoprolol

Bisoprolol fumarate

BRAND INFORMATION

Brand name

Noumed Bisoprolol

Active ingredient

Bisoprolol fumarate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Noumed Bisoprolol.

SUMMARY CMI

Noumed Bisoprolol

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Noumed Bisoprolol?

Noumed Bisoprolol contains the active ingredient bisoprolol fumarate. Noumed Bisoprolol is used to treat heart failure. It is usually used in combination with other medicines. For more information, see Section 1. Why am I using Noumed Bisoprolol? in the full CMI.

2. What should I know before I use Noumed Bisoprolol?

Do not use if you have ever had an allergic reaction to bisoprolol fumarate or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use Noumed Bisoprolol? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Noumed Bisoprolol and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Noumed Bisoprolol?

  • The usual starting dose is 1.25 mg once daily for one week. If well tolerated, your doctor will gradually increase your dose over the next ten weeks.
  • The usual dose for maintenance therapy is 10 mg once daily.
  • More instructions can be found in Section 4. How do I use Noumed Bisoprolol? in the full CMI.

5. What should I know while using Noumed Bisoprolol?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Noumed Bisoprolol.
  • If you become pregnant while taking this medicine, tell your doctor immediately.
  • If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking NOUMED BISOPROLOL.
Things you should not do
  • Do not stop using this medicine or lower the dosage suddenly without checking with your doctor.
  • Do not take this medicine 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.
Driving or using machines
  • This medicine may cause tiredness, dizziness or light-headedness in some people, especially after the first dose. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.
  • Be careful driving or operating machinery until you know how NOUMED BISOPROLOL affects you.
Drinking alcohol
  • Be careful drinking alcohol while you are taking Noumed Bisoprolol.
  • If you drink alcohol, dizziness or light‐headedness may be worse.
Looking after your medicine
  • Keep your medicine in a cool dry place where the temperature stays below 25°C.

For more information, see Section 5. What should I know while using Noumed Bisoprolol? in the full CMI.

6. Are there any side effects?

Common side effects: tiredness or exhaustion, dizziness, headache, sleep disturbances, nightmares, nausea or vomiting, diarrhoea or constipation, coldness or numbness in the hands or feet.

Serious side effects: muscular weakness or cramps, dizziness or lightheadedness (sometimes with fainting), especially on standing up, which may be due to low blood pressure, a very slow heart beat, hallucinations, depression, skin reactions such as rash, itching, worsening of psoriasis, difficulty hearing, swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing, signs of worsening heart failure such as shortness of breath, sometimes with tiredness or weakness, swelling of the feet or legs due to fluid build up, chest tightness, wheezing, rattly breathing, yellowing of the skin or eyes, dark coloured urine, itching, generally feeling unwell, constant flu‐like symptoms such as fever, sore throat, lack of energy, irregular heart beating. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Noumed Bisoprolol

Active ingredient(s): bisoprolol fumarate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Noumed Bisoprolol. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Noumed Bisoprolol.

Where to find information in this leaflet:

1. Why am I taking Noumed Bisoprolol?
2. What should I know before I take Noumed Bisoprolol?
3. What if I am taking other medicines?
4. How do I take Noumed Bisoprolol?
5. What should I know while taking Noumed Bisoprolol?
6. Are there any side effects?
7. Product details

1. Why am I taking Noumed Bisoprolol?

Noumed Bisoprolol contains the active ingredient bisoprolol fumarate. Noumed Bisoprolol is a beta‐blocker. It works by affecting the body's response to some 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. NOUMED BISOPROLOL also slows your heart rate, which in turn increases the efficiency of your heart.

Noumed Bisoprolol is used to treat heart failure. It is usually used in combination with other medicines. NOUMED BISOPROLOL can help to reduce the number of heart failure episodes needing hospital admission and also the risk of sudden death.

Heart failure occurs when the heart muscle is weak and unable to pump enough blood to supply the body's needs. Heart failure may start off with no symptoms, but as the condition progresses patients may feel short of breath and notice swelling of the feet and ankles due to fluid build up.

2. What should I know before I take Noumed Bisoprolol?

Warnings

Do not take Noumed Bisoprolol if:

  • you are allergic to bisoprolol fumarate, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
    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
  • you have or have had any of the following medical conditions
    - cardiogenic shock, a serious heart condition causing low blood pressure
    - heart conditions where the electrical activity controlling your heart rate does not work properly, causing a very slow heart rate or uneven heart beating
    - hypotension, low blood pressure
    - severe asthma or chronic obstructive lung disease
    - late stages of peripheral arterial occlusive disease
    - Raynaud's syndrome, a condition causing numbness, tingling and color change in fingers and toes when exposed to the cold
    - untreated phaeochromocytoma, a rare tumour of the adrenal gland
    - metabolic acidosis, when there is too much acid in the blood.
  • It has passed the expiry date printed on pack, or if the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • have any other medical conditions such as:
    - asthma, difficulty breathing or other lung problems
    - Prinzmetal angina or variant angina
    - diabetes
    - any allergic conditions
    - psoriasis, a skin disease with thickened patches of red skin, often with silvery scales
    - hyperthyroidism, an over active thyroid gland
    - any blood vessel disorder causing poor circulation in the arms and legs
    - kidney problems
    - liver problems
    - phaeochromocytoma, a rare tumour of the adrenal gland.
  • take any medicines for any other condition
  • plan to have surgery

The anaesthetist must be told that you are taking NOUMED BISOPROLOL before surgery, in order to allow for your condition and medications.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. NOUMED BISOPROLOL is not recommended while you are breastfeeding.

3. What if I am taking other medicines?

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

Some medicines may interfere with Noumed Bisoprolol and affect how it works.

  • calcium antagonists, medicines used to treat high blood pressure and angina such as diltiazem, verapamil
  • clonidine, a medicine used to treat high blood pressure
  • monoamine oxidase inhibitors, medicines used to treat depression such as phenelzine, tranylcypromine
  • anti‐arrhythmic drugs used to treat irregular or abnormal heartbeat such as flecainide, amiodarone, disopyramide
  • certain medicines used to treat arthritis, pain or inflammation such as indomethacin or ibuprofen
  • other beta‐blockers, including eye drops
  • insulin and oral drugs for diabetes
  • anaesthetic agents used in surgery
  • digoxin, a medicine used to treat heart failure
  • ergot derivatives, medicines commonly used to treat migraines
  • tricyclic antidepressants
  • barbiturates, medicines used to treat epilepsy
  • phenothiazines, a type of medicine used to treat some mental conditions
  • rifampicin, a medicine use to treat tuberculosis
  • mefloquine, a medicine used to treat malaria
  • adrenaline, a medicine used to treat allergic reactions.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Noumed Bisoprolol.

4. How do I take Noumed Bisoprolol?

How much to take

  • The usual starting dose is 1.25 mg once daily for one week. If well tolerated, your doctor will gradually increase your dose over the next ten weeks. The usual dose for maintenance therapy is 10 mg once daily.
  • Follow the instructions provided and use Noumed Bisoprolol until your doctor tells you to stop.
  • Ask your doctor or pharmacist if you are unsure of the correct dose for you.
  • They will tell you exactly how much to take.
  • Follow the instructions they give you.
  • If you take the wrong dose, NOUMED BISOPROLOL may not work as well and your problem may not improve.

When to take Noumed Bisoprolol

  • Take your medicine during or immediately after food in the morning. This will lessen the chance of side effects.

How to take Noumed Bisoprolol

Swallow the tablets with a glass of water. Do not crush or chew the tablets.

If you need to break NOUMED BISOPROLOL, hold tablet with both hands and snap along break line.

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

This medicine helps to control your condition, but does not cure it. It is important to keep taking your medicine every day, usually as long term treatment. It is very important that you do not stop taking NOUMED BISOPROLOL suddenly.

If you forget to take Noumed Bisoprolol

Noumed Bisoprolol should be taken regularly at the same time each day. If you miss your dose at the usual time, take your dose as soon as you remember, and continue to take it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

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 Noumed Bisoprolol

If you think that you have taken too much Noumed Bisoprolol, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Symptoms of an overdose may include dizziness, very slow heart rate, difficulty breathing and shock.

5. What should I know while taking Noumed Bisoprolol?

Things you should do

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

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking NOUMED BISOPROLOL.

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

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

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

It may interfere with the results of some tests.

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

Your doctor may check your eyes, thyroid, lipid and blood glucose levels from time to time to make sure the medicine is working and to prevent unwanted side effects.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.

Your doctor may think it is not working effectively and change your treatment unnecessarily.

Remind any doctor, dentist or pharmacist you visit that you are using Noumed Bisoprolol.

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 continues or gets worse, talk to your doctor.

Things you should not do

  • Do not stop using this medicine suddenly.
  • Do not take NOUMED BISOPROLOL 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 dosage without checking with your doctor.
  • Stopping NOUMED BISOPROLOL suddenly may cause your condition to worsen or other heart complications may occur. NOUMED BISOPROLOL should only be reduced gradually over a period of about two weeks before stopping completely.

Diabetes

  • If you are being treated for diabetes, make sure you check your blood sugar level regularly and report any changes to your doctor.
  • NOUMED BISOPROLOL may change how well your diabetes is controlled. It may also cover up some of the symptoms of low blood sugar, called hypoglycaemia, such as fast heart beat. NOUMED BISOPROLOL may make hypoglycaemia last longer. Your dose of diabetic medicines, including insulin, may need to change.
  • Take this medicine with caution under strict fasting conditions.
  • Ask your doctor or pharmacist to answer any questions you may have.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Noumed Bisoprolol affects you.

Noumed Bisoprolol may cause dizziness in some people, especially after the first dose. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

If you drink alcohol, dizziness or light‐headedness may be worse.

Looking after your medicine

  • Keep your medicine in the original container. If you take it out of its original container it may not keep well.
  • Keep your medicine in a cool dry place where the temperature stays below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • tiredness or exhaustion
  • dizziness
  • headache
  • sleep disturbances, nightmares
  • nausea or vomiting
  • diarrhoea or constipation
  • coldness or numbness in the hands or feet
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • muscular weakness or cramps
  • dizziness or light‐headedness (sometimes with fainting), especially on standing up, which may be due to low blood pressure
  • a very slow heart beat
  • hallucinations
  • depression
  • skin reactions such as rash, itching, worsening of psoriasis
  • difficulty hearing.
  • swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing
  • signs of worsening heart failure such as shortness of breath, sometimes with tiredness or weakness, swelling of the feet or legs due to fluid build up
  • chest tightness, wheezing, rattly breathing
  • yellowing of the skin or eyes, dark coloured urine, itching, generally feeling unwell
  • constant flu‐like symptoms such as fever, sore throat, lack of energy
  • irregular heart beating.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Noumed Bisoprolol contains

Active ingredient (main ingredient)Bisoprolol fumarate
Other ingredients
(inactive ingredients)		calcium hydrogen phosphate
microcrystalline cellulose
pregelatinised maize starch
croscarmellose sodium
colloidal anhydrous silica
magnesium stearate
Opadry II OY‐L‐28900
iron oxide yellow (5 & 10 mg tablets only)
iron oxide red (10 mg tablet only)
Potential allergenslactose

Do not take this medicine if you are allergic to any of these ingredients.

What Noumed Bisoprolol looks like

NOUMED BISOPROLOL 2.5mg Film Coated Tablets: White coloured, round, snap‐tab film‐coated tablet, divisible in two parts, with a one‐sided embossment “BIS 2.5”. Each film‐coated tablet contains 2.5 mg bisoprolol fumarate.
(AUST R 285578)

NOUMED BISOPROLOL 5mg Film Coated Tablets: Yellow coloured, round, snap‐tab film‐coated tablet, divisible in four parts, with a one‐sided embossment “BIS 5”. Each film‐coated tablet contains 5 mg bisoprolol fumarate.
(AUST R 285579)

NOUMED BISOPROLOL 10mg Film Coated Tablets: Apricot coloured, round, snap‐tab film‐coated tablet, divisible in four parts, with a one‐sided embossment “BIS 10”. Each film‐coated tablet contains 10 mg bisoprolol fumarate.
(AUST R 285580)

NOUMED BISOPROLOL tablets are available in blisters

(Al/Al) of 28 tablets.

Who distributes Noumed Bisoprolol

Sponsor

Avallon Pharmaceuticals Pty Ltd
Level 5, 7 Eden Park Drive
Macquarie Park NSW 2113
Tel: 1800 930 999
www.avallon-pharma.com.au

This leaflet was prepared in August 2022.

Published by MIMS October 2022

BRAND INFORMATION

Brand name

Noumed Bisoprolol

Active ingredient

Bisoprolol fumarate

Schedule

S4

 

1 Name of Medicine

Bisoprolol fumarate.

2 Qualitative and Quantitative Composition

Each Noumed Bisoprolol film‐coated tablet contains either 2.5 mg, 5 mg or 10 mg of the active ingredient bisoprolol fumarate.

Excipients with known effect.

Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Noumed Bisoprolol 2.5 mg film coated tablets.

White coloured, round, snap‐tab film‐coated tablet, divisible in two parts, with a one‐sided embossment "BIS 2.5". Each film‐coated tablet contains 2.5 mg bisoprolol fumarate.

Noumed Bisoprolol 5 mg film coated tablets.

Yellow coloured, round, snap‐tab film‐coated tablet, divisible in four parts, with a one‐sided embossment "BIS 5". Each film‐coated tablet contains 5 mg bisoprolol fumarate.

Noumed Bisoprolol 10 mg film coated tablets.

Apricot coloured, round, snap‐tab film‐coated tablet, divisible in four parts, with a one‐sided embossment "BIS 10". Each film‐coated tablet contains 10 mg bisoprolol fumarate.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of stable chronic moderate to severe heart failure in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides.

4.2 Dose and Method of Administration

Treatment of chronic heart failure (CHF) consists of an ACE inhibitor (or an angiotensin receptor blocker in case of intolerance to ACE inhibitors), a β‐blocker, diuretics, and when appropriate cardiac glycosides.
Patients should be stable (without acute failure) when bisoprolol treatment is initiated.
It is recommended that the treating physician should be experienced in the management of chronic heart failure.

Titration phase.

The treatment of stable chronic heart failure with bisoprolol requires a titration phase. The treatment with bisoprolol is to be started with a gradual uptitration according to the following steps:
1.25 mg once daily for 1 week, if well tolerated increase to
2.5 mg once daily for a further week, if well tolerated increase to
3.75 mg once daily for a further week, if well tolerated increase to
5 mg once daily for the 4 following weeks, if well tolerated increase to
7.5 mg once daily for the 4 following weeks, if well tolerated increase to
10 mg once daily for the maintenance therapy.
The maximum recommended dose is 10 mg once daily.
Close monitoring of vital signs (heart rate, blood pressure), conduction disturbances and symptoms of worsening heart failure is recommended during the titration phase. Symptoms may already occur within the first day after initiating the therapy. Transient worsening of heart failure, hypotension, or bradycardia may occur during titration period and thereafter.

Note.

The 1.25 mg, 3.75 mg and 7.5 mg tablets are not currently registered by Avallon Pharmaceuticals Pty Ltd.

Treatment modification.

If the maximum recommended dose is not well tolerated, gradual dose reduction may be considered. In case of transient worsening of heart failure, hypotension, or bradycardia, reconsideration of the dosage of the concomitant medication is recommended. It may also be necessary to temporarily lower the dose of bisoprolol or to consider discontinuation.
The reintroduction and/or uptitration of bisoprolol should always be considered when the patient becomes stable again.
If discontinuation is considered, gradual dose decrease is recommended, since abrupt withdrawal may lead to acute deterioration of the patient's condition.
Treatment of stable chronic heart failure with bisoprolol is generally a long‐term treatment.

Administration.

Bisoprolol tablets should be taken in the morning and can be taken with food. They should be swallowed with liquid and should not be chewed.

Special population.

Renal or hepatic impairment.

There is no information regarding the pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.

Elderly.

No dosage adjustment is required.

Children.

There is no paediatric experience with bisoprolol, therefore its use cannot be recommended for children.

4.3 Contraindications

Bisoprolol is contraindicated in patients with: acute heart failure, episodes of heart failure decompensation requiring intravenous inotropic therapy, cardiogenic shock; second or third degree AV block (without a pacemaker); sick sinus syndrome or sinoatrial block; bradycardia with less than 60 beats/min before the start of therapy; hypotension (systolic blood pressure less than 100 mmHg); severe bronchial asthma or severe chronic obstructive pulmonary disease; late stages of peripheral arterial occlusive disease; Raynaud's syndrome; untreated phaeochromocytoma (see Section 4.4 Special Warnings and Precautions for Use); metabolic acidosis; hypersensitivity to bisoprolol or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Use with caution in the following circumstances.

The treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase. The initiation and cessation of treatment with bisoprolol necessitates regular monitoring.
There is no therapeutic experience of bisoprolol treatment of heart failure in patients with the following diseases and conditions: NYHA class II heart failure, insulin dependent diabetes mellitus (type 1), impaired renal function (serum creatinine ≥ 300 micromol/L), impaired liver function, patients older than 80 years, restrictive cardiomyopathy, congenital heart disease, haemodynamically significant organic valvular disease, myocardial infarction within 3 months.
Combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type, with Class I antiarrhythmic drugs and with centrally acting antihypertensive drugs is generally not recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

General anaesthesia.

Beta‐blockade reduces the incidence of arrhythmias and myocardial ischaemia during induction and intubation, and the post‐operative period. It is currently recommended that maintenance β‐blockade be continued peri‐operatively. The anaesthetist must be made aware of β‐blockade because of the potential for interactions with other drugs, resulting in severe bradyarrhythmias, attenuation of the reflex tachycardia 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, trichlorethylene) were sometimes associated with severe circulatory depression in the presence of β‐blockade. If it is thought necessary to withdraw β‐blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.

Abrupt withdrawal.

The cessation of therapy with bisoprolol should not be done abruptly unless clearly indicated. Care should be taken if β‐blockers have to be discontinued abruptly in patients, particularly in patients with coronary artery disease. Severe exacerbation of angina and precipitation of myocardial infarction and ventricular arrhythmias have occurred following abrupt discontinuation of β‐blockade in patients with ischaemic heart disease. Therefore, it is recommended that the dosage be reduced gradually over a period of about 8‐14 days during which time the patient's progress should be assessed. Bisoprolol should be temporarily reinstituted if the angina worsens markedly or if acute coronary insufficiency develops. If the drug must be withdrawn abruptly, close observation is required. In the peri‐operative period, β‐blockers should not be withdrawn unless indicated.

Cardiac failure.

There is inadequate evidence of efficacy and safety of bisoprolol treatment in heart failure in patients with NYHA class II heart failure.

Conduction disorders.

Very rarely, a pre‐existing AV conduction disorder of moderate degree may become aggravated (possibly leading to AV block). Bisoprolol should be administered with caution to patients with first degree AV block (see Section 4.3 Contraindications).

Effects on the heart rate.

If the patient develops increasing bradycardia (heart rate less than 50 to 55 beats/minute), the dosage of bisoprolol should be gradually reduced or treatment gradually withdrawn (see Section 4.3 Contraindications).

Prinzmetal angina.

There is a risk of exacerbating coronary artery spasm if patients with Prinzmetal or variant angina are treated with a β‐blocker. Cases of coronary vasospasm have been observed. If this treatment is essential, it should only be undertaken in a Coronary or Intensive Care Unit.

Peripheral circulation.

Beta‐blockade may impair the peripheral circulation and exacerbate the symptoms of peripheral vascular disease. An intensification of complaints may occur, particularly at initiation of therapy (see Section 4.3 Contraindications).

Peripheral arterial occlusive disease.

Aggravation of symptoms may occur especially when starting therapy.

Bronchial asthma and chronic obstructive lung disease.

Although cardioselective (beta1) beta‐blockers may have less effect on lung function than nonselective beta blockers, as with all beta‐blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for their use. Where such reasons exist bisoprolol may be used with caution. In patients with bronchial asthma or other chronic obstructive airway diseases, which may cause symptoms, bronchodilating therapy should be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of β2‐stimulants may have to be increased. Bisoprolol is contraindicated in patients with severe bronchial asthma or severe chronic obstructive lung disease.

Diabetes.

Bisoprolol should be used with caution in patients with diabetes mellitus, especially those who are receiving insulin or oral hypoglycaemic agents. Diabetic patients should be warned that β‐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, β‐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. Such effects on the glucose metabolism may occur with non‐selective beta‐blockers but they are less likely with a β1‐selective agent like bisoprolol. Nevertheless, diabetic patients receiving bisoprolol should be monitored to ensure that diabetes control is maintained.

Other metabolic effects.

Beta‐adrenoceptors are involved in the regulation of lipid as well as carbohydrate metabolism. Some beta‐blockers affect the lipid profile adversely although the long‐term clinical significance of this change is unknown and the effect is more apparent with non‐selective beta‐blockers while it appears to be less for drugs with β1‐adrenoceptor‐selectivity and for those with intrinsic sympathomimetic activity.

Thyrotoxicosis.

Under treatment with bisoprolol the symptoms of thyrotoxicosis may be masked.

Phaeochromocytoma.

In patients with phaeochromocytoma bisoprolol must not be administered until after alpha‐receptor blockade.

Allergic conditions.

As with other β‐blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Adrenaline (epinephrine) treatment does not always give the expected therapeutic effect.

Psoriasis.

Patients with psoriasis, or with a history of psoriasis, should only be given β‐blockers after carefully balancing the benefits against the risks.

Effects on the eye and skin.

Various rashes and conjunctival xeroses have been reported with β‐blocking agents. Cross reactions may occur between β‐blockers, therefore substitutions within the group may not necessarily preclude occurrence of symptoms.

Strict fasting.

Bisoprolol must be used with caution in patients undergoing strict fasting.

Use in hepatic impairment.

Caution is advised in patients with CHF and impaired hepatic function since there is no information regarding pharmacokinetics in these patients. Renal function should be monitored in patients with severe liver disease. Renal impairment may develop in patients with liver disease during bisoprolol treatment, leading to a need for dose reduction.

Use in renal impairment.

No dosage adjustment is required in patients with impairment of the kidney due to excretion equally by both liver and kidney. Nevertheless, caution is advised since there is no information regarding pharmacokinetics in CHF patients.

Use in the elderly.

Based on age alone no dosage adjustments are required; however, caution is advised in patients greater than 80 years old since data in this age group is limited (see Section 5.2 Pharmacokinetic Properties).

Paediatric use.

The safety and efficacy in children have not been established.
There is no paediatric experience with bisoprolol; therefore, its use cannot be recommended for children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

General.

The clearance of bisoprolol is 'balanced' between renal elimination of the unchanged drug and hepatic metabolism, renal clearance accounting for at least 50% of the dose. The remainder is subject to metabolism primarily by CYP3A4, with a minor contribution from CYP2D6. Bisoprolol plasma concentrations are expected to increase during concurrent administration of CYP3A4 inhibitors by not more than a factor of 2, and decrease during concurrent administration of CYP3A4 inducers. Due to the minor role of CYP2D6 in bisoprolol metabolism, CYP2D6 inhibitors and genetic differences in CYP2D6 activity do not significantly alter bisoprolol plasma concentrations. Bisoprolol may increase the plasma concentrations of other drugs metabolised by CYP3A4 and possibly those metabolised by CYP2D6.

Combinations not recommended.

Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type.

Negative influence on contractility and atrio‐ventricular conduction. Intravenous administration of verapamil in patients on β‐blocker treatment may lead to profound hypotension and atrioventricular block.

Class I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone).

Effect on atrio‐ventricular conduction time may be potentiated and negative inotropic effect increased.

Centrally acting antihypertensive drugs such as clonidine and others (e.g. methyldopa, moxonidine, rilmenidine).

Concomitant use of centrally acting antihypertensive drugs may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to β‐blocker discontinuation, may increase risk of "rebound hypertension".

Combinations to be used with caution.

Calcium antagonists of the dihydropyridine type such as felodipine and amlodipine.

Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.

Class‐III antiarrhythmic drugs (e.g. amiodarone).

Effect on atrio‐ventricular conduction time may be potentiated.

Topical β‐blockers (e.g. eye drops for glaucoma treatment).

May add to the systemic effects of bisoprolol.

Parasympathomimetic drugs.

Concomitant use may increase atrio‐ventricular conduction time and the risk of bradycardia.

Insulin and oral antidiabetic drugs.

Intensification of blood sugar lowering effect. Blockade of β-adrenoreceptors may mask symptoms of hypoglycaemia.

General anaesthetics.

Beta‐blockade reduces the incidence of arrhythmias and myocardial ischaemia during induction and intubation, and the post‐operative period. It is currently recommended that maintenance β‐blockade be continued peri‐operatively. The anaesthetist must be made aware of β-blockade because of the potential for interactions with other drugs, resulting in severe bradyarrhythmias, attenuation of the reflex tachycardia and hypotension, the decreased reflex ability to compensate for blood loss, hypovolaemia and regional sympathetic blockade, and the increased propensity for vagal‐induced bradycardia (see Section 4.4 Special Warnings and Precautions for Use, General anaesthesia).

Digitalis glycosides.

Reduction of heart rate, increase of atrioventricular conduction time.

Non‐steroidal anti‐inflammatory drugs (NSAIDs).

NSAIDs may reduce the hypotensive effect of bisoprolol.

β‐Sympathomimetic agents (e.g. isoprenaline, dobutamine).

Combination with bisoprolol may reduce the effect of both agents.

Sympathomimetics that activate both β‐ and α‐adrenoceptors (e.g. noradrenaline (norepinephrine), adrenaline (epinephrine)).

Combination with bisoprolol may unmask the α‐adrenoceptor‐mediated vasoconstrictor effects of these agents leading to blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with nonselective β-blockers.
Higher doses of adrenaline (epinephrine) may be necessary for treatment of allergic reactions. Concomitant use with antihypertensive agents as well as with other drugs with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.

Combinations to be considered.

Mefloquine.

Increased risk of bradycardia.

Monoamine oxidase inhibitors (except MAO‐B inhibitors).

Enhanced hypotensive effect of the β-blockers but also risk for hypertensive crisis.

Ergotamine derivatives.

Exacerbation of peripheral circulatory disturbances.

Rifampicin.

Slight reduction of the half‐life of bisoprolol is possible due to the induction of hepatic drug‐metabolising enzymes. Normally no dosage adjustment is necessary.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No effect on fertility was observed in male or female rats treated with bisoprolol at oral doses up to 150 mg/kg/day (associated with bisoprolol plasma concentrations (AUC) about 50 times those expected in humans after daily doses of 10 mg bisoprolol).
(Category C)1
1 Australian Pregnancy Category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. In general, β‐adrenoceptor blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. hypoglycaemia and bradycardia) may occur in the foetus and newborn infant. If treatment with β-adrenoceptor blockers is necessary, β1‐selective adrenoceptor blockers are preferable.
Bisoprolol should not be used during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary, the uteroplacental blood flow and the foetal growth should be monitored. In case of harmful effects on pregnancy or the foetus alternative treatment should be considered. The newborn infant must be closely monitored. Symptoms of hypoglycaemia and bradycardia are generally to be expected within the first 3 days.
Studies in rats have shown that bisoprolol and/or its metabolites cross the placenta and distribute to the foetus.
Administration of bisoprolol at oral doses of ≥ 50 mg/kg/day to pregnant rats or ≥ 12.5 mg/kg/day to pregnant rabbits caused embryofoetal toxicity, resorptions and abortions. The no‐effect dose for embryofoetal toxicity and mortality was 40 mg/kg/day (associated with plasma drug concentrations (AUC) 11 times that expected in humans after 10 mg/kg/day bisoprolol) for rats and 10 mg/kg/day for rabbits (associated with AUC lower than that expected in humans after 10 mg/kg/day doses). No evidence for teratogenic effects of bisoprolol was observed at any dose in rats or rabbits.
 Bisoprolol and/or its metabolites have been found in the milk of lactating rats.
Treatment of rats with bisoprolol at oral doses of 150 mg/kg/day from late gestation and during the lactation period was associated with decreased offspring birth weight and retarded physical development. The no‐effect dose (50 mg/kg) for these effects was associated with an AUC about 14 times greater than that expected in humans.
There are no data on the excretion of bisoprolol in human breast milk or the safety of bisoprolol exposure in infants. Therefore, breastfeeding is not recommended during administration of bisoprolol.

4.7 Effects on Ability to Drive and Use Machines

Bisoprolol may cause dizziness or fatigue (see Section 4.8 Adverse Effects (Undesirable Effects)) and, therefore, may adversely affect the patient's ability to drive or use machinery. In a study with coronary heart disease patients bisoprolol did not impair driving performance. However, due to individual variations in reactions to the drug, the ability to drive a vehicle or operate machinery may be impaired. This should be considered particularly at the start of treatment and upon change of medication, as well as in conjunction with alcohol.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

Table 1 shows incidences of adverse events reported from both the placebo and the bisoprolol cohort of the CIBIS II trial. Regardless of causal relationship all adverse events are included. Each patient is only counted once for each adverse event occurring in at least 1% of the study population.

Postmarketing data.

The following definitions apply to the frequency terminology used hereafter: very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000, including isolated reports.

Investigations.

Rare: increased triglycerides, increased liver enzymes (ALT, AST).

Cardiac disorders.

Very common: bradycardia.
Common: worsening of heart failure.
Uncommon: AV‐conduction disturbances.

Nervous system disorders.

Common: dizziness, headache.
Rare: syncope.

Eye disorders.

Rare: reduced tear flow (to be considered if the patient uses lenses).
Very rare: conjunctivitis.

Ear and labyrinth disorders.

Rare: hearing disorders.

Respiratory, thoracic and mediastinal disorders.

Uncommon: bronchospasm in patients with bronchial asthma or a history of obstructive airways disease.
Rare: allergic rhinitis.

Gastrointestinal disorders.

Common: gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation.

Skin and subcutaneous tissue disorders.

Rare: hypersensitivity reactions (itching, pruritus, flush, rash and angioedema).
Very rare: β‐blockers may provoke or worsen psoriasis or induce psoriasis‐like rash, alopecia.

Musculoskeletal and connective tissue disorders.

Uncommon: muscular weakness and cramps.

Vascular disorders.

Common: feeling of coldness or numbness in the extremities, hypotension.
Uncommon: orthostatic hypotension.
Frequency not known: syncope.

General disorders.

Common: asthenia, fatigue.

Hepatobiliary disorders.

Rare: hepatitis.

Reproductive system and breast disorders.

Rare: erectile dysfunction, potency disorders.

Psychiatric disorders.

Uncommon: sleep disorders, depression.
Rare: nightmares, hallucinations.

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.

4.9 Overdose

Symptoms.

The most common signs expected with overdosage of a β‐blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency and hypoglycaemia. There is limited experience with overdose of bisoprolol, only a few cases of overdose with bisoprolol have been reported. Bradycardia and/or hypotension were noted. All patients recovered. There is a wide interindividual variation in sensitivity to one single high dose of bisoprolol and patients with heart failure are probably very sensitive.

Treatment.

In general, if overdose occurs, discontinuation of bisoprolol treatment and supportive and symptomatic treatment is recommended.
Based on the expected pharmacologic actions and recommendations for other β‐blockers, the following general measures should be considered when clinically warranted.

Bradycardia.

Administer intravenous atropine. If the response is inadequate, isoprenaline or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary.

Hypotension.

Intravenous fluids and vasopressors should be administered. Intravenous glucagon may be useful.

AV block (second or third degree).

Patients should be carefully monitored and treated with isoprenaline infusion or temporary pacing.

Acute worsening of heart failure.

Administer intravenous diuretics, inotropic agents, vasodilating agents.

Bronchospasm.

Administer bronchodilator therapy such as isoprenaline, β2‐sympathomimetic drugs and/or aminophylline.

Hypoglycaemia.

Administer intravenous glucose.
Limited data suggest that bisoprolol is hardly dialysable.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Bisoprolol is a β1‐selective‐adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity. It only shows very low affinity to the β2‐receptor of the smooth muscles of bronchi and vessels as well as to the β2‐receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and β2‐mediated metabolic effects. Its β1‐selectivity extends beyond the therapeutic dose range. However, its beta1-selectivity is not absolute and at doses greater than the maximum recommended of 10 mg, bisoprolol may also inhibit beta2‐adrenoreceptors.
The haemodynamic effects of bisoprolol are those that can be expected from β‐adrenoceptor blockade. Besides the negative chronotropic effect resulting in a reduction in resting and exercise heart rate there is, as shown in acute studies with intravenous administration, a fall in resting and exercise cardiac output with only little change in stroke volume, and a small increase in right atrial pressure at rest or during exercise. The decrease in cardiac output correlates with the heart rate reduction, and the observed increases in total peripheral resistance and pulmonary arterial resistance after acute administration are considered to be due to reflex autonomic changes resulting from the negative chronotropic and slight negative inotropic effects.
Acute intravenous administration of 10 mg bisoprolol to hypertensive patients reduced glomerular filtration rate (GFR), renal blood flow (RBF) and plasma renin activity (PRA) whereas the renal vascular resistance was reduced after short‐term treatment (10 mg bisoprolol per os for 4 weeks) with no significant changes in RBF, GFR or PRA. Adrenaline (epinephrine) and noradrenalin (norepinephrine) levels also remained unaffected after the 4‐week treatment in hypertensive patients.
Bisoprolol shows the same pattern of cardiac electrophysiologic effects as other β‐adrenoceptor blocking agents. It acts on those parts of the conduction system that are influenced by the sympathetic nervous system. In electrophysiological studies it reduced heart rate, prolonged sinoatrial (SA) and atrioventricular (AV) nodal conduction, and prolonged the refractory periods of the SA and AV node. There was no statistically significant effect on atrial effective refractory period in patients with a history of syncope or cardiac arrhythmias. However, in patients with coronary artery disease, there was a small significant increase in right atrial effective and functional refractory periods. Right ventricular effective refractory period was temporarily prolonged during a study in patients with coronary artery disease, but the clinical relevance of the small increase is uncertain. RR and PR intervals were increased and QTc intervals reduced but all parameters remained within normal limits after bisoprolol.

Clinical trials.

In total 2,647 ambulatory patients with chronic heart failure were included in the CIBIS II trial in accordance with the following inclusion/exclusion criteria.

Inclusion criteria.

CHF of at least three months duration (stable for at least 6 weeks).

Exclusion criteria.

Resting heart rate < 60 beats/min; supine systolic BP < 100 mmHg; myocardial infarction or unstable angina within the preceding 3 months; percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within the preceding 6 months; atrioventricular block of second degree or greater without a functioning pacemaker, haemodynamically significant organic valvular disease; obstructive or restrictive cardiomyopathy.
83% (n=2202) of patients were in NYHA class III and 17% (n=445) were in NYHA class IV. They had stable symptomatic systolic heart failure (ejection fraction ≤ 35%, based on echocardiography). Total mortality was reduced from 17.3% to 11.8% (absolute reduction 5.5%; relative reduction 34% [95% confidence interval 19‐46%]).
A decrease in sudden death (3.6% vs. 6.3%, relative reduction 44%) and a reduced number of heart failure episodes requiring hospital admission (12% vs 17.6%, relative reduction 36%) was observed. Finally, a significant improvement of the functional status according to NYHA classification has been shown. During the initiation and titration of bisoprolol hospital admissions due to bradycardia (0.53%), hypotension (0.23%), and acute decompensation (4.97%) were observed, but they were not more frequent than in the placebo‐group (0%, 0.3% and 6.74%).

5.2 Pharmacokinetic Properties

Absorption.

Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract and, because of its small first pass metabolism of about 10%‐15%, has an absolute bioavailability of about 85‐90% after oral administration. The bioavailability is not affected by food. The drug shows linear kinetics and the plasma concentrations are proportional to the administered dose over the dose range 5 to 20 mg. Peak plasma concentrations occur within 2‐3 hours.

Distribution.

Bisoprolol is extensively distributed. The volume of distribution is 3.5 L/kg. Binding to plasma proteins is approximately 35%; uptake into human blood cells was not observed.

Metabolism.

In humans, only oxidative metabolic pathways have been detected with no subsequent conjugation. All metabolites, being very polar, are renally eliminated. The major metabolites in human plasma and urine were found to be without pharmacological activity. In vitro data from studies in human liver microsomes show that bisoprolol is primarily metabolized via CYP3A4 (~95%) with CYP2D6 having only a minor role. The minor contribution of CYP2D6 to the metabolism of bisoprolol observed in vitro is consistent with the in vivo data in extensive and restricted debrisoquine metabolisers, which showed no difference between the two groups of metabolisers. Bisoprolol is a racemate consisting of the R and S enantiomers. The intrinsic clearance by human recombinant CYP3A4 appears to be nonstereoselective while the metabolism by CYP2D6 is stereoselective (R/S =1.50).

Excretion.

The clearance of bisoprolol is 'balanced' between renal elimination of the unchanged drug (~50%) and hepatic metabolism (~50%) to metabolites which are also renally excreted. The total clearance of the drug is 15.6 ± 3.2 L/h with renal clearance being 9.6 ± 1.6 L/h. In a study with 14C‐labelled bisoprolol the total urinary and fecal excretion was 90 ± 2.7% and 1.4 ± 0.1% of the dose, respectively (mean ± SEM recoveries of the total dose within 168 hours). Bisoprolol has an elimination half‐life of 10‐12 hours.

Renal impairment.

Since the clearance of bisoprolol is balanced between renal and hepatic mechanisms, the accumulation of bisoprolol in patients with either complete renal or hepatic impairment should not exceed 2. In a study in patients with a mean creatinine clearance of 28 mL/min the accumulation was less than 2, and it has been shown that as the creatinine clearance falls the AUC increases as does the t½ and Cmax. According to these studies in patients with renal impairment no dosage adjustment is normally required up to the maximum dose of 10 mg bisoprolol.

Hepatic impairment.

There were no clinically relevant differences in the pharmacokinetics of bisoprolol between patients with normal or impaired hepatic function. Thus, dose reduction is not required in patients with liver disease. Renal function should be monitored in patients with severe liver disease, since renal impairment may develop and require dose reduction.

Chronic cardiac failure.

In a small substudy of the CIBIS II study in patients with CHF (NYHA III) on 10 mg bisoprolol, the steady state AUC was greater, the t½ longer (17 ± 5 hours) and the clearance lower than in healthy volunteers, the values being similar to those observed in patients with renal impairment. Bisoprolol pharmacokinetics in patients with CHF and concomitant impaired liver and/or renal function have not been studied, however dose reduction may be required in such patients.

Elderly.

Some pharmacokinetic parameters (t½, AUC, Cmax) have been found to be greater in the elderly compared to those in the young which appears to be due to a reduction in renal clearance in the elderly. However, the pharmacokinetic differences between the young and the elderly are unlikely to be clinically significant, and based on age alone no dosage adjustments are required.
Following oral administration of Noumed Bisoprolol 5 mg to healthy subjects under fasting conditions, a mean peak plasma concentration (Cmax) of bisoprolol of approximately 21.6 nanogram/mL was achieved within approximately 1.6 hours (Tmax).

5.3 Preclinical Safety Data

Genotoxicity.

No evidence for genotoxic activity was observed with bisoprolol in in vitro assays of gene mutation (reverse mutation in Salmonella typhimurium, forward mutation in Chinese hamster V79 fibroblasts) or chromosomal damage (CHO cytogenetic assay). Negative findings were also obtained with bisoprolol in in vivo assays of chromosomal damage (Chinese hamster bone marrow cytogenetic assay and the mouse micronucleus test).

Carcinogenicity.

Bisoprolol showed no evidence of carcinogenic activity when administered orally (via the diet) to mice for 20‐26 months at doses up to 250 mg/kg/day and to rats for 24 months at doses up to 125 mg/kg/day. These doses were associated with plasma drug concentrations (AUC) 38 times (mice) or 15‐18 times (rats) greater than those expected in humans after 10 mg/day of bisoprolol.

6 Pharmaceutical Particulars

6.1 List of Excipients

Calcium hydrogen phosphate, microcrystalline cellulose, pregelatinised maize starch, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, Opadry II OY‐L‐28900, iron oxide yellow (5 and 10 mg tablets only) and iron oxide red (10 mg tablet only).

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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.

6.5 Nature and Contents of Container

Noumed Bisoprolol tablets are available in blisters (Al/Al) of 28 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: (2RS)‐1‐[4‐[[2‐(1‐Methylethoxy)ethoxy]methyl]phenoxy]‐3‐[(1methylethyl)amino]propan‐2‐ol fumarate.
Empirical formula: C40H66N2O12. MW: 767.
Bisoprolol fumarate is a white crystalline substance with a melting range of 100‐104°C. It is very soluble in water and methanol, freely soluble in ethanol, glacial acetic acid and chloroform. As the substance is present in the form of a racemate, the aqueous solution does not show optical activity.

CAS number.

104344‐23‐2.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes