Bisoprolol Mylan 1.25 mg film-coated tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
BISOPROLOL FUMARATE
Available from:
McDermott Laboratories Ltd., T/A Gerard Laboratories
ATC code:
C07AB; C07AB07
INN (International Name):
BISOPROLOL FUMARATE
Dosage:
1.25 milligram(s)
Pharmaceutical form:
Film-coated tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Beta blocking agents, selective; bisoprolol
Authorization status:
Not marketed
Authorization number:
PA0577/153/001
Authorization date:
2011-08-19

Colours

Non-Print

Colours

Date:

Time:

Equate CMYK

with

Dimensions

Main Font

Body Text Size

Min Text Size used

Page Count

No. of colours

Description

Component Type

Affiliate Item Code

Superceded Affiliate Item Code

TrackWise PR No.

MA No.

Packing Site/Printer

Supplier Code

Sign-offs

v3/July 2017

Pharma Code

SAP No.

Vendor Job No.

Trackwise Proof No.

Client Market

Keyline/Drawing No.

Barcode Info

3D Render ID

Times New Roman

9.5 pt

9.5 pt

170 x 480 mm

Bisoprolol Fumarate 2.5 mg,5 mg,10 mg,7.5 mg,1.25 mg 28

Leaflet

1750777

1431839

1750777

Komarom

50070087

5769

372794

Ireland

Black

05 Jul 2019

11:26

PA0577/153/001-

002, 004-006

1. What Bisoprolol Mylan is and what it

is used for

This medicine contains the active substance

bisoprolol fumarate, which belongs to a family of

medicines called beta-blockers. Bisoprolol is used

in combination with other medicines to treat stable

heart failure

Heart failure occurs when the heart muscle is

too weak to pump blood around the circulation

adequately. This results in breathlessness and

swelling.

Bisoprolol slows down the heart rate and makes the

heart more efficient at pumping blood around the

body.

2. What you need to know before you

take Bisoprolol Mylan

Do not take Bisoprolol Mylan if you:

are allergic to bisoprolol or any of the other

ingredients of this medicine (listed in section 6)

have severe asthma

have a slow or irregular heart rate. Ask your

doctor if you are not sure

have very low blood pressure

have severe blood circulation problems (which

may cause your fingers and toes to tingle or turn

pale or blue)

have heart failure that suddenly becomes worse

and / or that may require hospital treatment

have excess acid in the blood, a condition known

as metabolic acidosis

have untreated phaeochromocytoma, a rare

tumour of the adrenal gland

Warnings and precautions

Talk to your doctor or pharmacist before taking this

medicine if you:

have asthma or chronic lung disease

have diabetes. Bisoprolol can hide the symptoms

of low blood sugar

are fasting from solid food

have any heart problems

have any liver or kidney problems

have any problems with the circulation in your

limbs

are taking verapamil or diltiazem, medicines used

to treat heart conditions. Concomitant use is not

recommended, see also “Other medicines and

Bisoprolol Mylan”

have (or have had) psoriasis (a recurring skin

rash)

have phaeochromocytoma (a rare tumour of the

adrenal gland). Your doctor will need to treat this

before prescribing bisoprolol for you

have a thyroid problem. The tablets can hide

symptoms of an overactive thyroid

During Treatment

Talk to your doctor or pharmacist if you:

are going to be given a general anaesthetic during

an operation – tell your doctor that you are taking

bisoprolol

are treated for hypersensitivity (allergic) reactions.

Bisoprolol may make your allergy worse or more

difficult to treat.

have chronic lung disease or less severe asthma

please inform your doctor immediately if you

start to experience new difficulties in breathing,

cough, wheezing after exercise, etc. when using

bisoprolol.

worsening of symptoms of blockage of the main

blood vessels to the legs, especially at the start of

treatment.

Children and adolescents

No information is available on the use of this

medicine in children.

Other medicines and Bisoprolol Mylan

Tell your doctor or pharmacist if you are already

taking or using any of the following as they may

interact with your medicine:

medicines for controlling the blood pressure

or medicines for heart problems (such as

amiodarone, amlodipine, clonidine, digitalis

glycosides, diltiazem, disopyramide, felodipine,

flecainide, lidocaine, methyldopa, moxonidine,

phenytoin, propafenone, quinidine, rilmenidine,

verapamil)

medicines for depression e.g. imipramine,

amitriptyline, moclobemide

medicines to treat mental illness e.g.

phenothiazines such as levomepromazine

medicines used for anaesthesia during an

operation (see also “Warnings and precautions”)

medicines used to treat epilepsy e.g. barbiturates

such as phenobarbital

certain pain killers (for instance acetyl salicylic

acid, diclofenac, indomethacin, ibuprofen,

naproxen)

medicines for asthma or medicines used for a

blocked nose

medicines used for certain eye disorders such as

glaucoma (increased pressure in the eye) or used

to widen the pupil of the eye

certain medicines to treat clinical shock (e.g.

adrenaline, dobutamine, noradrenaline)

mefloquine, a medicine for malaria

all these drugs as well as bisoprolol may influence

the blood pressure and/or heart function

Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other

medicines.

Pregnancy, breast-feeding and fertility

Bisoprolol can be harmful to the pregnancy and/or

to the child (increased possibility of premature birth,

miscarriage, retarded growth, low blood glucose

level and reduced heart rate of the child).

Therefore

do not

use this medicine during

pregnancy.

It is unknown if bisoprolol is excreted in the breast

milk. Breast-feeding during the use of this medicine

is therefore

not

recommended.

No information is available on the effects of

bisoprolol on fertility.

If you are pregnant or breast-feeding, think you may

be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this

medicine.

Driving and using machines

The use of bisoprolol may sometimes result in

dizziness or fatigue (see ‘Possible side-effects’).

If you suffer from these side effects,

do not

operate

vehicles and/or machines. These side-effects are

likely to happen at the start of treatment, or with a

change in the amount of bisoprolol you take.

Bisoprolol fumarate contains sodium

This medicine contains less than 1 mmol sodium

(23 mg) per tablet, that is to say essentially ‘sodium-

free’

5 mg, 7.5 mg and 10 mg tablets only:

Bisoprolol Mylan tablets contain sunset yellow

Sunset yellow (E110) may cause allergic reactions.

3. How to take Bisoprolol Mylan

Before you start using Bisoprolol Mylan, you should

already be taking other medicines for heart failure

including an ACE-inhibitor, a diuretic and (as an

added option) a cardiac glycoside.

Always take this medicine exactly as your doctor

has told you. Check with your doctor or pharmacist

if you are not sure.

Adults

Treatment with bisoprolol must be started at a

low dose and increased gradually. Your doctor

will decide how to increase the dose, and this will

normally be done in the following way:

1.25 mg bisoprolol once daily for one week

2.5 mg bisoprolol once daily for one week

5 mg bisoprolol once daily for four weeks

7.5 mg bisoprolol once daily for four weeks

10 mg bisoprolol once daily for maintenance (on-

going) therapy.

The maximum recommended daily dose is 10 mg

bisoprolol.

Depending on how well you tolerate the medicine,

your doctor may also decide to lengthen the time

between dose increases. If your condition gets

worse or you no longer tolerate the drug, it may be

necessary to reduce the dose again or to interrupt

treatment. In some patients a maintenance dose

lower than 10 mg bisoprolol may be sufficient.

Your doctor will tell you what to do.

Patients with liver or kidney problems

Your doctor will take extra care when adjusting the

dose of Bisoprolol Mylan.

Use in children and adolescents

The use of Bisoprolol is

not

recommended as

there is insufficient experience with the use of this

medicine in children and adolescents.

Elderly patients

In general an adjustment of the dose is not needed.

It is recommended to start with the lowest possible

dose.

If you notice that the Bisoprolol dose is too strong

or does not work well enough, please consult your

doctor or pharmacist.

Package leaflet: Information for the patient

Bisoprolol Mylan 1.25 mg, 2.5 mg, 5 mg, 7.5 mg or 10 mg

film-coated tablets

bisoprolol fumarate

Read all of this leaflet carefully before you start taking this medicine

because it contains important

information for you.

– Keep this leaflet. You may need to read it again.

– If you have any further questions, ask your doctor or pharmacist.

– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

What is in this leaflet

1. What Bisoprolol Mylan

is and what it is used for.

What you need to know before you take

Bisoprolol Mylan.

3. How to take Bisoprolol Mylan.

4. Possible side effects.

5. How to store Bisoprolol Mylan.

6. Contents of the pack and other information.

50070087

Colours

Non-Print

Colours

Date:

Time:

Equate CMYK

with

Dimensions

Main Font

Body Text Size

Min Text Size used

Page Count

No. of colours

Description

Component Type

Affiliate Item Code

Superceded Affiliate Item Code

TrackWise PR No.

MA No.

Packing Site/Printer

Supplier Code

Sign-offs

v3/July 2017

Pharma Code

SAP No.

Vendor Job No.

Trackwise Proof No.

Client Market

Keyline/Drawing No.

Barcode Info

3D Render ID

Times New Roman

9.5 pt

9.5 pt

170 x 480 mm

Bisoprolol Fumarate 2.5 mg,5 mg,10 mg,7.5 mg,1.25 mg 28

Leaflet

1750777

1431839

1750777

Komarom

50070087

5769

372794

Ireland

Black

05 Jul 2019

11:26

PA0577/153/001-

002, 004-006

Route and/or method of administration

The tablets should be taken in the morning

Swallow the tablets with a glass of water.

The tablets should not be chewed.

The 2.5 mg, 5 mg, 7.5 mg and 10 mg

tablets can be divided into equal doses. The 1.25 mg

tablets should not be broken.

If you take more Bisoprolol Mylan than you

should

If you take more Bisoprolol Mylan than you

should contact your doctor or casualty department

immediately

. Take the container and any remaining

tablets with you.

If you forget to take Bisoprolol Mylan

Do not

take a double dose to make up for the

forgotten dose. Take the next dose on time. If you

miss several doses, contact your doctor.

If you stop taking Bisoprolol Mylan

If you suddenly stop taking Bisoprolol Mylan you

are likely to suffer from side effects. Your doctor

will reduce your dose slowly over 2 weeks.

If you have any further questions on the use of this

medicine, please ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side

effects, although not everybody gets them.

The following side effects are important and will

require immediate action if you experience them.

You should stop taking Bisoprolol Mylan and see

your doctor immediately if the following symptoms

occur:

Very common side effects

(affecting more than 1 in

10 people):

slow heart beat

Common side effects

(affecting fewer than 1 in 10

people):

worsening of heart failure causing increased

breathlessness and / or retention of fluid.

Uncommon side effects

(affecting fewer than 1 in

100 people):

worsening of irregular heart beat

depression

breathing problems in patients with asthma or

chronic lung disease

Rare side effects

(affecting fewer than 1 in 1,000

people):

inflammation of the liver (hepatitis) causing

abdominal pain, loss of appetite and sometimes

jaundice with yellowing of the whites of the eyes

and skin and dark urine

If you feel dizzy or weak, or have breathing

difficulties please contact your doctor as soon as

possible.

The following side-effects have also been reported:

Common side effects

(affecting fewer than 1 in 10

people):

cold hands and/or feet

numbness of hands and/or feet

low blood pressure

feeling sick, vomiting, diarrhoea, constipation

tiredness

headache.

Uncommon side effects

(affecting fewer than 1 in

100 people):

sleep disorders

dizziness when standing up

muscle weakness, muscle cramps.

Rare side effects

(affecting fewer than 1 in

1,000 people):

changes in blood test results

reduced tear flow (can be a problem if you wear

contact lenses)

hearing disorders

blocked, runny nose

allergic reactions such as itching, redness and skin

rash

reduced sexual performance

nightmares

hallucinations (imagining things)

fainting.

Very rare side effects

(affecting fewer than 1 in

10,000 people):

inflammation of the eye (conjunctivitis)

aggravation of the skin condition psoriasis or the

appearance of a similar dry, scaly rash

hair loss.

Reporting of side effects

If you get any side effects, talk to your doctor,

pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. You can

also report side effects directly via HPRA

Pharmacovigilance, Earlsfort Terrace, IRL – Dublin

2; Tel: +353 1 6764971; Fax: +353 1 6762517;

Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

By reporting side effects you can help provide more

information on the safety of this medicine.

5. How to store Bisoprolol Mylan

Keep this medicine out of the sight and reach of

children.

Do not use this medicine after the expiry date which

is stated on the carton and the bottle or blister after

EXP. The expiry date refers to the last day of that

month.

Blister: Store below 30°C.

Bottle: This medicinal product does not require any

special storage conditions.

Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures

will help protect the environment.

6. Contents of the pack and other

information

What Bisoprolol Mylan film-coated tablets

contain:

Each film-coated tablet contains either 1.25 mg,

2.5 mg, 5 mg, 7.5 mg or 10 mg of the active

ingredient bisoprolol fumarate.

The other ingredients are: Tablet: Cellulose

microcrystalline, butylhydroxyanisole, colloidal

anhydrous silica, magnesium stearate, sodium lauril

sulfate, croscarmellose sodium, iron oxide yellow

(E172) (2.5 mg, 5 mg and 7.5mg tablets only), iron

oxide red (E172) (2.5 mg and 10 mg tablets only).

Film coat: Titanium dioxide (E171), polydextrose

(E1200), hypromellose (E464), quinoline yellow

(5 mg and 7.5 mg tablets only), macrogol, iron oxide

yellow (E172) (10 mg tablets only), indigo carmine

(E132) (5 mg tablet only), sunset yellow (E110) (5

mg, 7.5 mg and 10 mg tablets only) (see section 2

“Bisoprolol Mylan contains sunset yellow”).

What Bisoprolol Mylan looks like and contents of

the pack

Film-coated tablet

1.25 mg tablet:

White, oval, biconvex film-coated

tablets; ‘BL’ & ‘1’ engraved on one face of the

tablet; ‘M’ engraved on the other face of the tablet.

2.5 mg tablet:

White to off-white, oval, biconvex

film-coated tablets with side notches and debossed

with “BL & 2” on either side of scoreline on one

side and “M” on the other side.

5 mg tablet:

Pale yellow, oval, biconvex film-

coated tablets with side notches; ‘BL’ & ‘4’

engraved on either side of the scoreline on one face

of the tablet; ‘M’ engraved on the other face of the

tablet.

7.5 mg tablet:

Yellow, oval, biconvex film-coated

tablets with side notches; ‘BL’ & ‘5’ engraved on

either side of the scoreline on one face of the tablet;

‘M’ engraved on the other face of the tablet.

10 mg tablet:

Pale orange to light orange, oval,

biconvex film-coated tablets with side notches; ‘BL’

& ‘6’ engraved on either side of the scoreline on one

face of the tablet; ‘M’ engraved on the other face of

the tablet.

Bisoprolol Mylan Tablets are packed in blister

packs containing 10, 20, 28, 30, 50, 56, 84, 98 and

100 film-coated tablets. Bisoprolol Mylan Tablets

are packed in bottles containing 10, 28, 30, 50, 56,

84, 98, 100, 500 and 1000 film-coated tablets. Not

all pack sizes may be marketed.

Marketing Authorisation Holder:

McDermott Laboratories Ltd,

t/a Gerard Laboratories

35/36 Baldoyle Industrial Estate,

Grange Road, Dublin 13, Ireland

Manufacturer:

McDermott Laboratories Ltd,

t/a Gerard Laboratories

35/36 Baldoyle Industrial Estate,

Grange Road, Dublin 13, Ireland

Generics [UK] Ltd, Station Close,

Potters Bar, Hertfordshire, EN6 1TL,

United Kingdom

Mylan Hungary Kft., H-2900, Komárom,

Mylan útca.1, Hungary

This medicinal product is authorised in the

Member States of the EEA

under the following names:

Country

Product Name

Ireland

Bisoprolol Mylan 1.25 mg, 2.5 mg,

5 mg, 7.5 mg, 10 mg film-coated

tablets

Spain

Bisoprolol COR MYLAN 2.5 mg,

5 mg, 10 mg comprimidos recubiertos

Sweden

Bisomyl 1.25 mg, 2.5 mg, 5 mg,

10 mg filmdragerade tabletter

United

Kingdom

Bisoprolol fumarate 1.25 mg, 2.5 mg,

3.75 mg, 5 mg, 7.5 mg, 10 mg film-

coated tablets

This leaflet was last revised in 07/2019.

1750777

50070087

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 1 of 9

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Bisoprolol Mylan 1.25 mg film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 1.25 mg of bisoprolol fumarate

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet (tablet)

White, oval, biconvex film coated tablets; approximately 9 mm x 7 mm; 'BL' & '1' engraved on one face of the tablet; 'M'

engraved on the other face of the tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Treatment of stable chronic heart failure with reduced systolic ventricular function in addition to ACE inhibitors, and diuretics,

and optionally cardiac glycosides (for additional information see section 5.1).

4.2 Posology and method of administration

Posology

Adults

Treatment of stable chronic heart failure

Standard treatment of CHF consists of an ACE inhibitor (or an angiotensin receptor blocker in case of intolerance to ACE

inhibitors), a beta-blocking agent, 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.

Transient worsening of heart failure, hypotension, or bradycardia may occur during the titration period and thereafter.

Close monitoring of vital signs (heart rate, blood pressure) and symptoms of worsening heart failure is recommended during

the titration phase. Symptoms may occur within the first day after initiating the therapy.

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 2 of 9

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.

Special populations

Hepatic or renal impairment:

There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired

hepatic or renal function. Titration of the dose in these populations should therefore be made with particular caution.

Elderly

No dosage adjustment is normally required.

Paediatric population

No data are available.

Method of administration

For oral use.

Bisoprolol Mylan tablets should be taken in the morning and can be taken with food. They should be swallowed with liquid and

should not be chewed.

4.3 Contraindications

Bisoprolol is contraindicated in chronic heart failure patients with:

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

acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy

cardiogenic shock

second or third degree AV block

sick sinus syndrome

sinoatrial block

symptomatic bradycardia

symptomatic hypotension

severe bronchial asthma

severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome

untreated phaeochromocytoma (see section 4.4)

metabolic acidosis

4.4 Special warnings and precautions for use

Special warnings

The treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase (see section 4.2)

Especially in patients with ischaemic heart disease the cessation of therapy with bisoprolol must not be done abruptly unless

clearly indicated, because this may lead to transitional worsening of heart condition (see section 4.2)

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'

Precautions

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 3 of 9

The initiation and cessation of treatment with bisoprolol necessitates regular monitoring. For the posology and method of

administration please (see section 4.2).

There is no therapeutic experience of bisoprolol treatment in heart failure in patients with the following diseases and

conditions:

insulin dependent diabetes mellitus (type I)

severely impaired renal function

severely impaired hepatic function

restrictive cardiomyopathy

congenital heart disease

haemodynamically significant organic valvular disease

myocardial infarction within 3 months

Bisoprolol must be used with caution in:

bronchospasm (bronchial asthma, obstructive airways diseases)

diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia (e.g. tachycardia,

palpitations, sweating) can be masked

strict fasting

ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards

allergens and the severity of anaphylactic reactions. Epinephrine treatment may not always yield the expected

therapeutic effect.

first degree AV block

Prinzmetal's angina

peripheral arterial occlusive disease. Aggravation of symptoms may occur especially when starting therapy

general anaesthesia.

Patients with psoriasis or with a history of psoriasis should only be given beta-blockers (e.g. bisoprolol) after a careful

balancing of benefits against risks.

The symptoms of thyrotoxicosis may be masked under treatment with bisoprolol.

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

In patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischemia

during induction and intubation, and the post-operative period. It is currently recommended that maintenance of

beta-blockade be continued peri-operatively. The anaesthetist must be aware of beta-blockade because of the potential for

interactions with other drugs, resulting in bradyarrhythmias, attenuation of reflex tachycardia, and decreased reflex ability to

compensate for blood loss. If it is thought necessary to withdraw beta-blocker therapy before surgery, this should be done

gradually and completed about 48 hours before anaesthesia.

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, for details please refer to section 4.5.

Although cardioselective (beta1) beta-blockers may have less effect on lung function than non-selective beta- blockers, as with

all beta-blockers, these should be avoided in patients with 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 obstructive airways

diseases, the treatment with bisoprolol should be started at the lowest possible dose and patients should be carefully

monitored for new symptoms (e.g. dyspnoea, exercise intolerance, cough).

In bronchial asthma or other chronic obstructive pulmonary diseases, which may cause symptoms, concomitant

bronchodilating therapy is recommended. Occasionally an increase of the airway resistance may occur in patients with asthma,

therefore the dose of beta2-stimulants may have to be increased.

4.5 Interaction with other medicinal products and other forms of interactions

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 4 of 9

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 beta-blocker

treatment may lead to profound hypotension and atrioventricular block.

Centrally acting antihypertensive drugs (e.g. clonidine, methyldopa, moxonidine, rilmenidine): Concomitant use of

centrally acting antihypertensive drugs may further decrease the central sympathetic tonus (and may thus lead to a

reduction of heart rate and cardiac output, and to vasodilation). Abrupt withdrawal, particularly if prior to

beta-blocker discontinuation, may increase risk of “rebound hypertension”.

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

atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.

Combinations to be used with caution:

Calcium antagonists of the dihydropyridine type (e.g. amlodipine, felodipine): 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 beta-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: Increase of blood sugar lowering effect. Blockade of beta-adrenoreceptors may

mask symptoms of hypoglycaemia.

Anaesthetic agents: Attenuation of the reflex tachycardia and increase of the risk of hypotension (for further

information on general anaesthesia see also section 4.4).

Digitalis glycosides: Reduction of heart rate, increase of atrio-ventricular conduction time.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs may reduce the hypotensive effect of bisoprolol.

Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine): Combination with bisoprolol may reduce the effect

of both agents.

Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g. noradrenaline, adrenaline): Combination

with bisoprolol may unmask the alpha-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 beta-blockers.

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 beta-blockers but

also risk for hypertensive crisis.

4.6 Fertility, pregnancy and lactation

Pregnancy

Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the fetus/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 fetus and newborn infant. If

treatment with β-adrenoceptor blockers is necessary, β1-selective adrenoceptor blockers are preferable.

Bisoprolol is not recommended during pregnancy unless clearly necessary. If treatment is considered necessary, monitoring of

the uteroplacental blood flow and fetal growth is recommended. In case of harmful effects on pregnancy or the fetus

consideration of alternative treatment is recommended. The newborn infant must be closely monitored. Symptoms of

hypoglycaemia and bradycardia are generally to be expected within the first 3 days.

Breast-feeding

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.

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 5 of 9

4.7 Effects on ability to drive and use machines

In a study of coronary heart disease patients, bisoprolol did not impair driving performance. However, depending on the

individual patient’s response to treatment, the ability to drive a vehicle or to use machines may be impaired. This should be

considered particularly at the start of treatment and upon change of medication or in conjunction with alcohol.

4.8 Undesirable effects

The following definitions apply to the frequency terminology used hereafter:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data).

Psychiatric disorders:

Uncommon: sleep disorders, depression.

Rare: nightmares, hallucinations.

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.

Cardiac disorders:

Very common: bradycardia.

Common: worsening of pre-existing heart failure.

Uncommon: AV-conduction disturbances.

Vascular disorders:

Common: feeling of coldness or numbness in the extremities, hypotension especially in patients with heart failure.

Uncommon: orthostatic hypotension.

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.

Hepatobiliary disorders:

Rare: hepatitis.

Skin and subcutaneous tissue disorders:

Rare: hypersensitivity reactions such as itching, flush, rash.

Very rare: alopecia, beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash.

Musculoskeletal and connective tissue disorders:

Uncommon: muscular weakness, muscle cramps.

Reproductive system and breast disorders:

Rare: potency disorders.

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 6 of 9

General disorders and administration site conditions:

Common: asthenia, fatigue.

Investigations

Rare: increased triglycerides, increased liver enzymes (ALAT, ASAT).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517;

Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

Symptoms

With overdose (e.g. daily dose of 15 mg instead of 7.5 mg) third degree AV-block, bradycardia, and dizziness have been

reported. In general, the most common signs expected with overdose of a beta-blocker are bradycardia, hypotension,

bronchospasm, acute cardiac insufficiency and hypoglycaemia. There is limited experience with overdose of bisoprolol, only a

few cases of overdose (maximum: 2000 mg) with bisoprolol have been reported in patients suffering from hypertension and/or

coronary heart disease showing bradycardia and/or hypotension; all patients recovered. There is a wide inter-individual

variation in sensitivity to one single high dose of bisoprolol and patients with heart failure are probably very sensitive.

Therefore it is mandatory to initiate the treatment of these patients with a gradual uptitration according to the scheme given in

section 4.2.

Management

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 beta-blockers, the following general measures

may 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

transvenous cardiac pacemaker insertion.

Acute worsening of heart failure: Administer i.v. diuretics, inotropic agents, vasodilating agents.

Bronchospasm: Administer bronchodilator therapy such as isoprenaline, beta2-sympathomimetic drugs and/or aminophylline.

Hypoglycaemia: Administer i.v. glucose.

Limited data suggest that bisoprolol is hardly dialysable.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Beta blocking agents, selective, ATC code: C07 AB07

Mechanism of action

Bisoprolol is a potent, highly beta1-selective adrenoreceptor blocking agent lacking intrinsic sympathomimetic activity and

without relevant membrane stabilising activity. It only shows low affinity to the beta2-receptor of the smooth muscles of

bronchi and vessels as well as to the beta2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 7 of 9

not to be expected to influence the airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends

beyond the therapeutic dose range.

Pharmacodynamic effect

Bisoprolol is also used for the treatment of hypertension and angina pectoris.

In acute administration in patients with coronary heart disease without chronic heart failure bisoprolol reduces the heart rate

and stroke volume and thus the cardiac output and oxygen consumption. In chronic administration the initially elevated

peripheral resistance decreases.

Clinical efficacy

In total 2647 patients were included in the CIBIS II trial. 83% (n = 2202) 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% (relative reduction 34%). 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 admission 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%). The numbers of fatal and disabling strokes during the total study period were 20 in the bisoprolol group and 15 in the

placebo group.

The CIBIS III trial investigated 1010 patients aged ≥65 years with mild to moderate chronic heart failure (CHF; NYHA class II or

III) and left ventricular ejection fraction ≤35%, who had not been treated previously with ACE inhibitors, beta-blocking agents,

or angiotensin receptor blockers. Patients were treated with a combination of bisoprolol and enalapril for 6 to 24 months after

an initial 6 months treatment with either bisoprolol or enalapril.

There was a trend toward higher frequency of chronic heart failure worsening when bisoprolol was used as the initial 6 months

treatment. Non inferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis,

although the two strategies for initiation of CHF treatment showed a similar rate of the primary combined endpoint death and

hospitalization at study end (32.4% in the bisoprolol-first group vs. 33.1 % in the enalapril-first group, per-protocol population).

The study shows that bisoprolol can also be used in elderly chronic heart failure patients with mild to moderate disease.

5.2 Pharmacokinetic properties

Absorption

Bisoprolol is absorbed almost completely from the gastrointestinal tract. Together with the very small first pass effect in the

liver, this results in a high bioavailability of approximately 90%.

Distribution

The plasma protein binding of bisoprolol is about 30 %. The distribution volume is 3.5 l/kg. The total clearance is approximately

15 l/h.

The plasma elimination half-life (10-12 hours) provides 24 hours efficacy following a once daily dosage.

Biotransformation

50% is metabolised by the liver to inactive metabolites which are then excreted by the kidneys.

Elimination

Bisoprolol is excreted from the body by two routes. 50% is metabolised by the liver to inactive metabolites which are then

excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolised form. Since the elimination takes

place in the kidneys and the liver to the same extent a dosage adjustment is not required for patients with impaired liver

function or renal insufficiency.

Other special population

In patients with chronic heart failure (NYHA stage III) the plasma levels of bisoprolol are higher and the half-life is prolonged

compared to healthy volunteers. Maximum plasma concentration at steady state is 64±21 ng/ml at a daily dose of 10 mg and

the half-life is 17±5 hours.

5.3 Preclinical safety data

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 8 of 9

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose

toxicity, genotoxicity or carcinogenicity.

Like other beta-blockers, bisoprolol caused maternal (decreased food intake and decreased body weight) and embryo/fetal

toxicity (increased incidence of resorptions, reduced birth weight of the offspring, retarded physical development) at high

doses but was not teratogenic.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet

Cellulose microcrystalline

Butylhydroxyanisole

Colloidal anhydrous silica

Magnesium stearate

Sodium lauril sulfate

Croscarmellose sodium

Film coat

Titanium dioxide (E171)

Polydextrose FCC (E1200)

Hypromellose (E464)

Macrogol

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Blister: 2 years

Bottle: 2 years

6.4 Special precautions for storage

Blister: Store below 30°C.

Bottle: This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/Al blister packs. Blister pack comprises of clear transparent PVC film with backing of aluminium foil coated with heat seal

lacquer containing 10, 20, 28, 30, 50, 56, 84, 98 and 100 film-coated tablets.

White HDPE bottles with white opaque polypropylene cap containing 10, 28, 30, 50, 56, 84, 98, 100, 500 and 1000 film-coated

tablets.

Bottle contains a perforated HDPE canister holding silica gel and activated carbon desiccant.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

McDermott Laboratories Ltd t/a Gerard Laboratories

35/36 Baldoyle Industrial Estate

Grange Road

Health Products Regulatory Authority

17 September 2019

CRN008WVM

Page 9 of 9

Dublin 13

Ireland

8 MARKETING AUTHORISATION NUMBER

PA0577/153/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 19th August 2011

Date of Last Renewal: 10th October 2015

10 DATE OF REVISION OF THE TEXT

September 2019

Similar products

Search alerts related to this product

View documents history

Share this information