Bisoprololhemifumaraat Genthon 10 mg, film-coated tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Bisoprolol hemifumarate
Available from:
Genthon B.V.
ATC code:
C07AB; C07AB07
INN (International Name):
Bisoprolol hemifumarate
Dosage:
10 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:
PA0740/007/002
Authorization date:
2002-11-22

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

page 1/9

issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

1.31

Package Leaflet

Package leaflet: information for the user

Bisoprolol hemifumarate Genthon 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.

What is in this leaflet:

1. What Bisoprolol hemifumarate Genthon 10 mg is and what it is used for

2. What you need to know before you take Bisoprolol hemifumarate Genthon

10 mg

3. How to take Bisoprolol hemifumarate Genthon 10 mg

4. Possible side effects

5. How to store Bisoprolol hemifumarate Genthon 10 mg

6. Contents of the pack and other information

1. What Bisoprolol hemifumarate Genthon 10 mg is and what it is used for

Bisoprolol hemifumarate Genthon 5 mg contains the active substance bisoprolol

fumarate. Bisoprolol fumarate belongs to the group of blood pressure lowering

medicines.

Bisoprolol fumarate is used for:

the treatment of high blood pressure

a certain form of chest pain (chronic stable angina pectoris) caused by the

heart muscle receiving less oxygen than required. This usually occurs under

stress.

You must talk to your doctor if you do not feel better or if you feel worse.

2. What you need to know before you take Bisoprolol hemifumarate

Genthon 10 mg

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

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issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

Do not take Bisoprolol hemifumarate Genthon 10 mg

if you are allergic to bisoprolol fumarate or any of the other ingredients of

this medicine (listed in section 6)

in case of sudden occurrence or worsening of heart failure (insufficient

pumping

power

of

the

heart)

being

treated

with

called

inotropic

medicines (medicines that may lighten the effort of the heart).

if you are in a state of shock caused by a decreased pumping function of the

heart, whereby, for instance, symptoms can occur such as very low blood

pressure, disorientation, confusion and cold clammy skin.

if you suffer from irregular heart beat as a result of a certain disturbance in

the conduction of the heart (second or third degree AV block without

pacemaker, sino-atrial block).

if you have a very slow heartbeat of less than 60 beats per minute before

the start of treatment (bradycardia).

if you have a heart rhythm disorder (sick-sinus syndrome).

if you have a very low blood pressure (systolic pressure of less then 100

mm mercury, hypotension).

if you have severe asthma or other severe lung conditions with difficulty to

breathe.

if you have a severe blood circulatory impairment of the arms or the legs,

a severe form of Raynaud’s syndrome.

if you have an impaired metabolism (metabolic acidosis), whereby acids

accumulate in the blood.

if you have an untreated tumour of the adrenal medulla, which can be

associated with a sudden strong increase in blood pressure, severe headache,

perspiration and an increased heartbeat (pheochromocytoma).

if you use a certain painkiller simultaneously (floctafenine).

if you use a certain medicine against severe psychiatric disorders, for

example psychoses, simultaneously (sultopride).

Warnings and precautions

Talk

your

doctor

pharmacist

before

taking

Bisoprolol

Bisoprolol

hemifumarate Genthon 10 mg

Take special care with Bisoprolol hemifumarate Genthon 10 mg

Check to see if any of these warnings apply to you, or have applied to you in the

past. Contact your doctor immediately:

if you have heart failure

if you use a medicine against heart rhythm disorders (anti-arrhythmics)

simultaneously (see Section 2, Other medicines and Bisoprolol hemifumarate

Genthon 10 mg).

other

blood

pressure-lowering

medicines

(centrally

acting

antihypertensives;

example,

clonidine)

simultaneously,

medicines

against

heart

rhythm

disorders

and/or

increased

blood

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

page 3/9

issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

pressure

(calcium

antagonists)

(see

Section

Other

medicines

Bisoprolol hemifumarate Genthon 10 mg).

if you suffer from breathlessness or wheezing as a result of narrowing of the

airways (bronchospasms), for example if you suffer from asthma-like or

bronchitis- like lung disorders. You can still use this medicine if you do not

have

severe

lung

disorder

(see

Section

take

Bisoprolol

hemifumarate Genthon 10 mg), but you will have to make more use of

bronchodilators.

if you use medicines with a stimulating action on a certain part of the nervous

system (parasympathicomimetics) simultaneously; for example, tacrine (anti-

Alzheimer’s).

have

diabetes

with

strong

fluctuations

blood

sugar

level.

Bisoprolol fumarate can mask the symptoms of low blood sugar. Therefore,

the sugar level in the blood must be scrupulously monitored.

if you have a disorder of the thyroid (hyperthyroidism). Bisoprolol fumarate

can mask the symptoms of high levels of thyroid hormones.

if you do not ingest sufficient nutrients, for example during fasting or if you

are on a strict diet.

if you are undergoing preventative allergy therapy (desensitisation therapy),

whereby the body is made insensitive for certain substances (allergens).

if you have a mild conduction disorder of the heart, which results in heart

rhythm disorders (first degree AV-block).

if you suffer from chest pain, which is caused by local constrictions and

spasms of the blood vessels of the heart (Prinzmetal’s angina).

have

mild

blood

circulation

disorder

of

the

arms

or

legs

(Raynaud’s syndrome, intermittent claudication).

if you are being treated for a tumour of the adrenal medulla, that is

associated with a sudden strong increase in blood pressure, severe headache,

perspiration and an increased heartbeat (pheochromocytoma).

if you have a recurring skin disorder with a scaly, dry skin rash (psoriasis)

if you go into hospital to have an operation, tell the anaesthetist or other

medical staff that you are taking Bisoprolol film-coated tablets

This medicine contains bisoprolol fumarate. This substance may result in a

positive test during drug testing.

Other medicines and Bisoprolol hemifumarate 10 mg

Tell your doctor or pharmacist if your are taking, have recently taken or might take

other medicines.Other medicines may be affected by bisoprolol fumarate. They in

turn may affect how well bisoprolol fumarate works. Bisoprolol can interact with:

medicines used for the treatment of pain and which exhibit an anti-

inflammatory or fever inhibiting effect (NSAIDS) such as floctafenine.

medicines used for the treatment of psychiatric disorders (anxiety, psychoses

or depression) such as sultopride, MAO-A inhibitors, tricyclic antidepressants,

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

page 4/9

issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

phenothiazines (also used for vomiting and nausea) and barbiturates (also used

for epilepsy).

medicines used for controlling the blood pressure or medicines used for heart

problems such as calcium antagonists, centrally acting anti-hypertensives (e.g.

clonidine, methyldopa, guanfacin, moxonidine, rilmenidine), anti arrhythmics

(e.g. disopyramide, quinidine, amiodarone), digitalis glycosides,

sympathicommimetics (e.g. isoprenaline, dobutamine, noradrenaline,

adrenaline) other beta-blockers (including eye drops which are used for the

treatment of increased eye pressure).

medicines with a stimulating action on a certain part of the nervous system

(parasympathicomimetics) which, amongst others, are used for the treatment of

Alzheimer’s disease (e.g. tacrine).

medicines used for anaesthesia during surgery.

medicines used to treat migraine (e.g ergotamine).

a certain medicine that muscle relaxant (baclofen).

a medicine that decreases the side effects of cancer treatment (amifostine).

a certain medicine for malaria prevention (mefloquine).

adrenal cortex hormones that have, amongst others, an anti-inflammatory

action (corticosteroids).

iodated contrast products, used for making certain organs and blood vessels

visible on a scan.

The combination of bisoprolol and any of the drugs listed above, may influence the

bloodpressure and/or heart function.

medicines used for the treatment of diabetes; for example, insulin and anti-

diabetic medicines in tablet form.

Bisoprolol fumarate may increase the blood sugar lowering effect and can mask the

symptoms of low blood sugar content.

Bisoprolol hemifumarate Genthon 10 mg with food, drink and alcohol

Simultaneous use of alcohol can adversely affect the ability to drive a car or to

operate machinery.

Pregnancy and breast-feeding

You are only allowed to use bisoprolol fumarate when absolutely necessary

during pregnancy. There is a risk that the development of the foetus will be

affected by the use of bisoprolol fumarate. Breast feeding is not recommended

when using bisoprolol fumarate.

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.

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

page 5/9

issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

Driving and using machines

The ability to drive and to operate machinery can be adversely affected due to the

differences in reaction time after the administration of bisoprolol fumarate. This

must be borne in mind when beginning treatment, as well as during a change of

dose and when taken in combination with alcohol.

3.

How to take Bisoprolol hemifumarate Genthon 10 mg

Always take this medicine exactly as your doctor or pharmacist has told you.

Check with your doctor or pharmacist if you are not sure.

The tablets should preferably be taken in the morning with some fluids (for

example water) without chewing. The score line is only there to help you break

the tablet if you have difficulty swallowing it whole.

The following doses generally apply:

Adults

The starting dose is as low as possible. The usual dose is 10 mg per day, with a

maximum dose of 20 mg per day.

Use in patients with reduced kidney or liver function

If you have severe renal impairment or reduced liver function, then the dose

should not be more than 10 mg per day.

Use in elderly

No dose adjustment is required.

Use in children and adolescents

There is no experience with this medicine in children and adolescents. Therefore,

the use of bisoprolol fumarate in children and adolescents is not recommended.

If you take more Bisoprolol hemifumarate Genthon 10 mg than you should

If you have taken more than prescribed, then immediately contact your doctor.

Symptoms that can occur are: decreased heart rate, low blood pressure, lung

cramps, heart disorders and low blood sugar level.

Take this information leaflet and any remaining tablets with you to show to the

doctor.

If you forget to take Bisoprolol hemifumarate Genthon 10 mg

When you have forgotten to take a dose, skip this dose and take the next tablet at

the usual time. Do not take a double dose to make up for a forgotten dose.

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

page 6/9

issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

If you stop taking Bisoprolol hemifumarate Genthon 10 mg

If your doctor decides to stop the treatment with bisoprolol fumarate, then the

dose should be gradually decreased.

Stopping suddenly with taking bisoprolol fumarate may result in an increased

blood pressure and an irregular hart beat (arrhythmia). You are therefore not

allowed to abruptly stop the use of bisoprolol fumarate, but should gradually

reduce the dose in consultation with your doctor.

If you have any further questions on the use of this medicine ask your doctor or

pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody

gets them.

Common side effects (may affect up to 1 in 10 people)

dizziness and headache (especially at the beginning of treatment, the headache

is usually mild and often disappears within 1 to 2 weeks) cold or numb

fingers and toes (Raynaud’s syndrome), deterioration of circulatory disorders

in the legs (intermittent claudication), low blood pressure (hypotension),

lowering of the blood pressure when, for instance, standing up quickly from a

sitting or lying position, sometimes with associated dizziness (orthostatic

hypotension)

gastrointestinal

complaints

such

nausea,

vomiting,

diarrhoea,

abdominal

pain

constipation

fatigue

(especially

beginning of the therapy, they are generally mild and often disappear within

1-2 weeks)

Uncommon side effects (may affect up to 1 in 100 people)

sleeping disturbances, severe depression decreased heartbeat (bradycardia),

certain

conduction

disorder

heart

(AV-conduction

disorder),

worsening of pre-existing heart failure (insufficient pumping power of the

heart)

breathlessness

wheezing

narrowing

airways

(bronchospasms)

patients

with

asthma

bronchitis

like

respiratory

disorders muscle weakness and cramps, joint disorders (arthropathy)

weakness (asthenia)

Rare side effects (may affect up to 1 in 1,000 people)

inflammatory reactions of the skin, allergic inflammation of the nasal mucous

membrane that is characterised by a blocked nose, sneezing and secretion

(rhinitis)

blood

sugar

level,

associated

with

feeling

hunger,

perspiration,

dizziness

palpitations

heart

(hypoglycaemia)

nightmares, observations of things that do not exist (hallucinations) Rare:

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

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issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

fainting reduced lachrymal fluid (important when you use contact lenses)

hearing

disorders

inflammation

nasal

mucous

membrane

characterised

blocked-up

nose,

sneezing

(allergic

rhinitis)

liver

infection associated with yellow colouring of the skin or eyes (hepatitis)

rash, itchiness, reddening of the skin (allergic reactions) potency disorders

increased liver enzymes (ALAT, ASAT), elevation of certain fats in the blood

(triglycerides)

Very rare side effects (may affect up to 1 in 10,000 people)

very low blood sugar level, which may lead to unconsciousness (hypoglycaemic

shock) inflammation of the conjunctiva (conjunctivitis) (deterioration of) a

recurring skin condition in association with a scaly, dry skin rash (psoriasis) or a

similar rash, loss of hair (alopecia)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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 hemifumarate Genthon 10 mg

Keep out of the sight and reach of children.

Do not store Bisoprolol hemifumarate Genthon 10 mg above 25°C.

Store in the original package to protect from moisture and light.

Do not use this medicine after the expiry date which is stated on the packaging

after 'EXP'. The first two digits indicate the month and the last four digits indicate

the year. The expiry date refers to the last day of that month.

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

page 8/9

issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

Do not throw away any medicines via wastewater or household waste. Ask your

pharmacist how to throw away any medicines you no longer use. These measures

will help protect the environment.

6.

Contents of the pack and other information

What Bisoprolol hemifumarate Genthon 10 mg contains

The active substance is bisoprolol fumarate. One tablet contains

10 mg bisoprolol fumarate corresponding with 8.49 mg bisoprolol.

other

ingredients

microcrystalline

cellulose,

calcium

hydrogen phosphate, pregelatinised maize starch, crospovidone,

colloidal

anhydrous

silica,

magnesium

stearate,

hypromellose,

macrogol 400, titanium dioxide (E171), iron oxide yellow (E172),

iron oxide red (E172).

What Bisoprolol hemifumarate Genthon 10 mg looks like and contents of

the pack

Bisoprolol hemifumarate Genthon 10 mg is a yellow to orange, round, film-

coated tablet with a score line on both sides and the inscription "BSL10" on one

side.

Bisoprolol hemifumarate Genthon 10 mg is available in boxes of 14, 20, 28, 30,

50, 56, 60 or 100 film-coated tablets in blisters (additionally, the blisters can be

packed in an aluminium sachet) or in boxes of 50 film-coated tablets in hospital

packaging (EAV-packaging).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Genthon BV

Microweg 22

6545 CM Nijmegen

The Netherlands

Manufacturers:

Synthon BV

Microweg 22

6545 CM Nijmegen

The Netherlands

Common Technical Document

Bisoprolol hemifumarate

10 mg tablets

SynthonBV

Module 1 - Section 3.1 SPC, Labelling

and Package Leaflet

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issue date: 22-08-2016

version:M131_03.BSL.hfu.tab10.025.01.IE.296.02 approved: MJo

Aliud Pharma GMBH & Co. KG

Gottlieb-Daimler-Str. 19

D-89150 Laichingen

Germany

Synthon Hispania S.L.

Castelló, 1

Polígono las Salinas

08830 Sant Boi de Llobregat

Spain

STADA Arzneimittel AG

Stadastraße. 2 - 18

61118 Bad Vilbel,

Germany

G.L. Pharma GmbH

Schloßplatz 1,

A-8502 Lannach

Austria

This medicinal product is authorised in the Member States of the EEA under

the following names:

The Netherlands

Bisoprololfumaraat 10 mg, filmomhulde tabletten

Austria

Rivacor 10 mg

Ireland

Bisoprolol Hemifumarate Genthon 10mg film-coated

tablets

This leaflet was last approved in August 2016

Health Products Regulatory Authority

11 November 2019

CRN009G1H

Page 1 of 8

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Bisoprololhemifumaraat Genthon 10 mg, film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10 mg bisoprolol hemifumarate, equivalent to 8.49mg of bisoprolol.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

The tablet is yellow to orange, round, biconvex, scored on both sides and embossed with BSL10 on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

- Hypertension.

- Chronic stable angina pectoris.

4.2 Posology and method of administration

Posology

Renal or hepatic impairment

In patients with severe renal impairment (creatinine clearance < 20 ml/min) and in patients with severe liver function disorders

it is recommended that a daily dose of 10 mg bisoprolol hemifumarate is not exceeded.

Elderly:

No dosage adjustment is normally required. It is recommended to start with the lowest possible dose.

Paediatric population:

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

Method of administration

Bisoprolol 10 mg tablets are for oral administration.

The dosage should be individually adjusted. It is recommended to start with the lowest possible dose. In some patients, 5 mg

per day may be adequate. The usual dose is 10 mg once daily with a maximum recommended dose of 20 mg per day.

The tablets should be taken in the morning. They should be swallowed with liquid and should not be chewed.

Discontinuation of treatment

Treatment should not be stopped abruptly (see section 4.4 Special warnings and precautions for use). The dosage should be

diminished slowly by a weekly halving of the dose.

4.3 Contraindications

· 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

Health Products Regulatory Authority

11 November 2019

CRN009G1H

Page 2 of 8

· cardiogenic shock

· AV block of second or third degree (without a pacemaker)

· sick sinus syndrome

· sinoatrial block

· bradycardia with less than 60 beats/min before start of therapy

· hypotension (systolic blood pressure less than 100 mm Hg)

· severe bronchial asthma or severe chronic obstructive pulmonary disease

· late stages of peripheral arterial occlusive disease and Raynaud's syndrome

· metabolic acidosis

· untreated phaeochromocytoma (see also section 4.4).

· combinations with floctafenine and sultopride (see also section 4.5)

4.4 Special warnings and precautions for use

Bisoprolol should be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.

Other formulations of bisoprolol containing medicinal products are used in the treatment of chronic heart failure. The use of

β-blocking agents in this indication needs a very cautious approach and should be started with a very strict titration phase. In

this phase increments are necessary all of which are not possible with the current medicinal product. This product should

therefore not be used in the treatment of chronic heart failure.

The combination with amiodarone (see also section 4.5) should be used with caution considering the risk of contractility

automatism and conduction disorders (suppression of compensatory sympathetic reactions).

Combination of bisoprolol with calcium antagonists of the verapamil and diltiazem type, with class I antiarrhytmic drugs and

with centrally-acting antihypertensive drugs is generally not recommended (see also section 4.5).

Bisoprolol must be used with caution in:

· bronchospasm (bronchial asthma, obstructive airways disease): In 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 β

-stimulants may have to be increased. It is

recommended to have a functional respiratory test done before the initiation of treatment.

· concomitant treatment with anticholinesterastic drugs (including tacrine): AV conduction time and/or bradycardia may be

increased (see also section 4.5).

· concomitant treatment with anaesthetics: Attenuation of the reflex tachycardia and increase of the risk of hypotension (see

also section 4.5). Continuation of β-blockade reduces the risk of arrhythmia during induction and intubation.In patients

undergoing general anaesthesia the anaesthetist must be aware of beta-blockade. If it is thought necessary to withdraw

beta-blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.Iodated

contrast products: Beta-blockers may impede the compensatory cardiovascular reactions associated with hypotension or shock

induced by iodated contrast products.

· diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia can be masked. Blood glucose

levels should be monitored during treatment with bisoprolol.

· thyrotoxicosis, adrenergic symptoms may be masked.

· strict fasting.

· ongoing desensitisation therapy.

· As with other β-blocking agents bisoprolol may increase both the sensitivity towards allergens and the severity of

anaphylactic reactions. Adrenaline treatment does not always give the expected therapeutic effect. Higher doses of

epinephrine (adrenaline) may be necessary.

· AV block of first degree.

· Printzmetal's angina: β-blocking agents may increase the number and duration of anginal attacks in patients with

Printzmetal's angina. The use of β-1 selective adrenoceptor blocking agents is possible in cases of mild forms and only in

combination with a vasodilating agent.

· peripheral circulatory disorders, such as Raynaud's phenomena and intermittentclaudication: intensification of complaints

might happen especially during start of therapy.

· In patients with phaeochromocytoma (see section 4.3), bisoprolol must not be administered until after α-receptor blockade

has been successfully established.

pre-existing or existing psoriasis, bisoprolol should only be given after careful balancing of benefits against risks.

Health Products Regulatory Authority

11 November 2019

CRN009G1H

Page 3 of 8

The initiation of treatment with bisoprolol necessitates regular monitoring, especially when treating elderly patients. The

cessation of therapy with bisoprolol should not be done abruptly unless clearly indicated. There is a risk of myocardial

infarction and sudden death if the treatment is suddenly discontinued in patients with ischaemic heart disease. For more

information please refer to section 4.2 Posology and method of administration.

This medicinal product contains an active substance, which results in a positive test during antidoping controls.

4.5 Interaction with other medicinal products and other forms of interactions

Combinations contra-indicated

· Floctafenine: β-blockers may impede the compensatory cardiovascular reactions associated with hypotension or shock that

may be induced by floctafenine.

· Sultopride: bisoprolol should not be concomitantly administered with sultopride since there is an increase risk of ventricular

arrhythmia.

Combinations not recommended

· Calcium antagonists of the verapamil, type and to a lesser extent of the diltiazem, type: negative influence on contractility,

atrio-ventricular conduction and blood pressure (see also section 4.4).

· Clonidine and other centrally-acting antihypertensive drugs, i.e. methyldopa, guanfacin, moxonidine, rilmenidine: Increased

risk of rebound hypertension as well as exaggerated decrease in heart rate and cardiac conduction, including worsening the

cardiac insufficiency.

· Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blockers but also risk for

hypertensive crisis.

Combinations to be used with caution

· Class I antiarrhythmic drugs (e.g. disopyramide, quinidine): effect on atrio-venticular conduction time may be potentiated and

negative inotropic effect may be increased. (Strict clinical and ECG monitoring is required).

· Class III antiarrhythmic drugs (e.g. amiodarone): effect on atrio-ventricular conduction time may be potentiated (see section

4.4).

· Calcium antagonists of the dihydropyridine type: increased risk of hypotension. In patients with latent heart failure

concomitant use of β-blocking agents can lead to heart failure.

· Anticholinesterastic drugs (including tacrine): atrio-ventricular conduction time and/or bradycardia may be increased (see

also section 4.4).

· Other β-blocking agents, including eye-drops for the treatment of glaucoma, have additive effects.

· Insulin and oral anti-diabetic drugs: intensification of blood sugar lowering effect. Blockade of β-adrenoreceptor may mask

symptoms of hypoglycaemia.

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

· Anaesthetic agents: attenuation of the reflex tachycardia and increased risk of hypotension (for further information on

anaesthesia see also section 4.4).

· NSAIDs: decrease of the antihypertensive effect (inhibition of vasodilatative prostaglandin by NSAID and water and sodium

retention with pyrazolone NSAID).

· Ergotamine derivatives: exacerbation of peripheral circulatory disturbances.

· Beta-sympathomimetic agents (eg. Isoprenaline, dobutamine): combination with bisoprolol may reduce effects of both

agents.

· Sympathomimetics that activate both β- and α-adrenoceptors (e.g. noradrenaline, adrenaline): 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.

· Tricyclic antidepressants, barbiturates, phenothiazines as well as other antihypertensive agent: increased blood pressure

lowering effect.

· Baclofene: increased antihypertensive activity.

· Amifostine: increased hypotensive activity.

· Parasympathomimetic drug: Concomitant use may increase atrioventricular conduction time and the risk of bradycardia.

· Concomitant use with antihypertensive agents as well as other drugs with blood pressure lowering potential may increase the

risk of hypotension.

Combinations to be considered

· Mefloquine: increased risk of bradycardia.

· Corticosteroids: decrease of antihypertensive effect due to water and sodium retention.

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4.6 Fertility, pregnancy and lactation

Pregnancy:

Bisoprolol causes harmful pharmacological effects pregnancy and/or on the fetus/newborn. In general, β-adrenoceptor

blocking agents reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or

early labour. Adverse reactions (e.g. hypoglycaemia, bradycardia) may occur in the fetus and newborn infant. If treatment with

β-adrenoceptor blocking agents is necessary, β1-adrenoceptor blocking agents are preferable.

Bisoprolol is not recommended during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary,

the uteroplancental blood flow and fetal growth should be monitored. In case of harmful effects on pregnancy or the fetus

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.

Breastfeeding:

It is unknown whether bisoprolol/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded.

4.7 Effects on ability to drive and use machines

In a study with coronary heart disease patients, bisoprolol did not impair driving performance. However, due to individual

variations in reactions to the medicinal product, the ability to drive a vehicle or to operate machinery may be impaired. This

should be considered particularly at start of the treatment and upon change of medication as well as in conjunction with

alcohol.

4.8 Undesirable effects

The reported undesirable effects are generally attributable to the pharmacological properties of ß-blocking agents.

The following undesirable effects have been observed during treatment with bisoprolol with the following frequencies:

Common (≥1/100, < 1/10)

Uncommon (≥1/1,000, < 1/100)

Rare (≥1/10,000, < 1/1,000)

Very rare (<1/10,000)

Immune system disorders

Rare: the appearance of antinuclear antibodies with exceptional clinical symptoms such as lupus syndrome, which disappear

upon cessation of treatment, allergic rhinitis

Metabolism and nutrition disorders

Rare: hypoglycaemia

Very Rare: hypoglycaemic shock

Psychiatric disorders

Uncommon: sleep disturbances, depression

Rare: Nightmare, hallucinations

Nervous system disorders

Common: dizziness, headache (especially at the beginning of the therapy, they are generally mild and often disappear within

1-2 weeks)

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

Uncommon: bradycardia, AV-stimulus disturbances (slowed AV-conduction or increase of existing AV-block), worsening of

pre-existing heart failure

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Vascular disorders

Common: feeling of coldness or numbness of the extremities, Raynaud’s disease, increase of existing intermittent claudication

(orthostatic) hypotension

Respiratory, thoracic and mediastinal disorders

Uncommon: bronchospasm in patients with bronchial asthma or a history of obstructive airway disease

Rare: allergic rhinitis

Gastrointestinal disorders

Common: gastrointestinal complaints such as nausea, vomiting, diarrhoea, abdominal pain and constipation

Hepatobiliary disorders

Rare: hepatitis

Skin and subcutaneous tissue disorders

Rare: hypersensitivity reactions (itching, flush, rash)

Very rare: β-blocking agents may provoke or worsen psoriasis or induce psoriasis-like rash, alopecia

Musculoskeletal and connective tissue disorders

Uncommon: muscular weakness and cramps, arthropathy

Reproductive system and breast disorders

Rare: potency disorders

General disorders

Common: fatigue (especially at the beginning of the therapy, they are generally mild and often disappear within 1-2 weeks)

Uncommon: asthenia

Investigations

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

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

The most common expected symptoms with overdosage of bisoprolol are bradycardia, hypotension, bronchospasm, acute

cardiac insufficiency, conduction disorders and hypoglycaemia. 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.

Management

In the case of overdosage, bisoprolol treatment should be stopped and supportive and symptomatic treatment should be

provided. Resorption of bisoprolol in the gastrointestinal tract must be avoided; gastric lavage, or administration of adsorbents

(i.e. activated charcoal), and a laxative agent (i.e. sodium sulphate) may be used. Respiration must be monitored and if

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necessary, artificial respiration should be initiated. Bronchospasm should be counteracted with bronchodilator therapy such as

isoprenaline or ß

-sympathomimetic drugs. Cardiovascular complications should be treated symptomatically: AV-block (second

or third degree) needs careful monitoring and be treated with isoprenaline infusion or transvenous cardiac pacemaker

insertion. Bradycardia should be treated with intravenous atropine (or M-methyl-atropine). Fall in blood pressure or shock

should be treated with plasma substituting agents and vasopressors.

Hypoglycaemia can be treated with i.v.-glucose.

Limited data suggest that bisoprolol is hardly dialysable.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group

Selective ß

-blocking agents, ATC code: C07 AB07

Mechanism of action

Bisoprolol is a potent, highly ß

-selective-adrenoceptor blocking agent devoid of intrinsic sympathomimetic activity. As with

other ß-blocking agents, the mode of action in hypertension is unclear. However, it is known that bisoprolol markedly

depresses plasma renin activity.

In patients with angina, the blockade of ß-receptors reduces heart action and thus reduces oxygen demand.

Bisoprolol possesses similar local anaesthetic properties to propanolol.

5.2 Pharmacokinetic properties

Distribution

Bisoprolol is absorbed almost completely from the gastrointestinal tract.

Distribution

Together with the very small first pass effect in the liver, this results in a high bioavailability of approximately 90%. 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.

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

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 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.

Linearity/non-linearityThe kinetics of bisoprolol are linear and independent of age.

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

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

toxicity, genotoxicity or carcinogenicity.

Like other ß-blocking agents, 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

Core

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Microcrystalline cellulose

Calcium hydrogen phosphate

Pregelatinised maize starch

Crospovidone

Colloidal anhydrous silica

Magnesium stearate

Coating

Hypromellose

Macrogol 400

Titanium dioxide (E171)

Iron oxide yellow (E172)

Iron oxide red (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

PVC/PE/PVDC/Al blister in Al sachet: 2 years

PVC/PE/PVDC/Al blister: 3 years

6.4 Special precautions for storage

PVC/PE/PVDC/AL blister and PVC/PE/PVDC/AL blister in Al sachets:

Do not store above 25 °C.

Store in the original package to protect from moisture and light.

6.5 Nature and contents of container

Carton boxes with 2, 3, 5, 6 or 10 PVC/PE/PVDC/Al blister packaging of 10 tablets or PVC/PE/PVDC/Al blister packaging in Al

sachets of 10 tablets each.

Carton boxes with 1, 2 of 4 PVC/PE/PVDC/Al blister packaging of 14 tablets or PVC/PE/PVDC/Al blister packaging in Al sachets

of 14 tablets each.

Carton boxes with 50 tablets in EAV blister packaging (PVC/PE/PVDC/Al).

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Genthon B.V.

Microweg 22

6545 CM, Nijmegen

Netherlands

8 MARKETING AUTHORISATION NUMBER

PA0740/007/002

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9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22

November 2002

Date of last renewal: 20

February 2007

10 DATE OF REVISION OF THE TEXT

October 2016

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