Bisoprolol 10mg tablets

Main information

  • Trade name:
  • Bisoprolol 10mg tablets
  • Dosage:
  • 10mg
  • Pharmaceutical form:
  • Tablet
  • Administration route:
  • Oral
  • Class:
  • No Controlled Drug Status
  • Prescription type:
  • Valid as a prescribable product
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Bisoprolol 10mg tablets
    United Kingdom
  • Language:
  • English

Therapeutic information

  • Product summary:
  • BNF: 02040000

Status

  • Source:
  • eMC
  • Authorization number:
  • PL 00142/0510
  • Last update:
  • 29-01-2019

Summary of Product characteristics: dosage, interactions, side effects

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Bisoprolol 10mg tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Bisoprolol 10 mg tablet contains 8.49 mg bisoprolol equivalent to 10 mg

bisoprolol fumarate.

Excipient with known effect

Each tablet contains 130.20 mg of lactose monohydrate per tablet

For the full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM

Tablet

Bisoprolol 10 mg tablets, are mottled beige, round and convex with the following

identification markings: BI centrally above a break-line with 10 below.

The tablet can be divided into equal doses.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic Indications

Hypertension

Chronic stable angina pectoris

4.2

Posology and method of administration

Posology

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.

Special Populations

Renal or liver impairment

Adjustment of dose in patients with mild to moderate liver- or kidney impairment is

usually not necessary. In patients with severe renal impairment (creatinine clearance

< 20 ml/min) or severe liver impairment, the dose should not exceed 10 mg once

daily. This dosage may eventually be divided into halves.

Elderly

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

possible dose.

Paediatric population

Bisoprolol tablets are not recommended for use in children due to a lack of data (see

section 5.3).

Discontinuation of treatment

Treatment should not be stopped abruptly (see section 4.4). The dosage should be

diminished slowly by a weekly halving of the dose.

Method of administration

Bisoprolol 10 mg tablets are for oral administration.

The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of

water). The tablet can be taken with or without food.

4.3

Contraindications

Bisoprolol is contraindicated in 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

AV block of second or third degree

sick sinus syndrome

sinoatrial block

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

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

severe bronchial asthma or severe chronic obstructive pulmonary disease

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

syndrome

metabolic acidosis

untreated phaeochromocytoma (see 4.4).

combinations with floctafenine and sultopride (see also section 4.5)

4.4

Special warnings and precautions for use

Bisoprolol must 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 beta-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 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, 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 pulmonary 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 beta

-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): atrio-

ventricular 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

beta-blockade reduces the risk of arrhythmia during induction and intubation.

The anaesthesiologist should be informed when the patient is receiving

bisoprolol fumarate. 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 beta-blocking agents bisoprolol fumarate 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

Prinzmetal's angina: beta-blocking agents may increase the number and duration

of anginal attacks in patients with Printzmetal's angina. The use of beta

selective adrenoceptor blocking agents is possible in cases of mild forms and

only in combination with a vasodilating agent.

peripheral arterial occlusive disease, such as Raynaud's phenomena and

intermittent claudication: intensification of complaints might happen especially

during start of therapy.

In patients with phaeochromocytoma (see section 4.3), bisoprolol fumarate must

not be administered until after alpha-receptor blockade

pre-existing or existing psoriasis, Bisoprolol tablets should only be given after a

thorough risk/ benefit assessment

The initiation of treatment with Bisoprolol tablets necessitates regular monitoring,

especially when treating elderly patients. The cessation of therapy with Bisoprolol

tablets 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.

Bisoprolol 10 mg tablets contain 130.20 mg lactose monohydrate. Patients with rare

hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-

galactose malabsorption should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction

Combinations contra-indicated

Floctafenine: beta blockers may impede the compensatory cardiovascular reactions

associated with hypotension or shock that may be induced by floctafenine.

Sultopride: bisoprolol fumarate should not be concomitantly administered with

sultopride since there is an increased risk of ventricular arrhythmia.

Combinations not recommended

Calcium antagonists of the verapamil type, bepridil type and to a lesser extent of the

diltiazem type: Negative effect on contractility and atrio-ventricular conduction.

Intravenous administration of verapamil in patients on beta-blocker treatment may

lead to profound hypotension and atrio-ventricular block.

Centrally-acting antihypertensive drugs (e.g. clonidine, methyldopa, guanfacin

moxonidine, rilmenidine): Concomitant use of centrally-acting antihypertensive drugs

may lead to reduction of heart rate and cardiac output and to vasodilatation. Abrupt

withdrawal may increase the risk of 'rebound hypertension'.

Monoamineoxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive

effect of the beta-blocker but also risk for hypertensive crisis.

Combinations to be used with caution

Class I antiarrhythmic drugs (e.g. disopyramide, quinidine): effect on atrio-ventricular

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 atrial conduction time may

be potentiated (see section 4.4).

Calcium antagonists of the dihydropyridine type: 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.

Parasympathomimetic drugs (including tacrine); atrio-ventricular conduction time

and/or bradycardia may be increased (see also section 4.4).

Other beta-blocking agents, including topical beta-blockers (e.g. eye-drops, for

glaucoma treatment) may, add to the systemic effects of bisoprolol.

Insulin and oral anti-diabetic drugs: Increase of blood sugar lowering effect. Blockade

of beta-adrenoceptor may mask symptoms of hypoglycaemia.

Digitalis glycosides: reduction in 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).

Ergotamine derivatives: exacerbation of peripheral circulatory disturbances.

Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine): combination with

bisoprolol fumarate may reduce effects of both agents.

Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g.

norepinephrine, epinephrine): 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.

Tricyclic antidepressants, barbiturates, phenothiazines as well as other

antihypertensive agents and other drugs with blood pressure lowering potential:

increased risk of hypotension.

Baclofen: increased antihypertensive activity.

Amifostine: increased hypotensive activity.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs may reduce the

hypotensive effect of bisoprolol (inhibition of vasodilative prostaglandin by NSAID

and water and sodium retention with pyrazolone NSAID),

Combinations to be considered

Mefloquine: increased risk of bradycardia.

Corticosteroids: decrease of antihypertensive effect due to water and sodium

retention.

Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive

effect of the beta-blockers but also risk of hypertensive crisis.

Rifampicin: Slight reduction of the half-life of bisoprolol possible due to the induction

of hepatic drug metabolising enzymes. Normally no dosage adjustment is necessary.

4.6

Fertility, pregnancy and lactation

Pregnancy

Bisoprolol fumarate has pharmacological effects that may cause harmful effects on

pregnancy and/or the foetus/newborn. In general, beta-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 foetus and newborn infant. If treatment with beta-

adrenoceptor blocking agents is necessary, beta1-adrenoceptor blocking agents are

preferable.

Bisoprolol fumarate should not be used during pregnancy unless clearly necessary. If

treatment with bisoprolol fumarate is considered necessary, the uteroplacental blood

flow and 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.

Breastfeeding

It is not known whether bisoprolol fumarate is excreted in human milk. Therefore

breastfeeding is not recommended during administration of Bisoprolol tablets.

4.7

Effects on ability to drive and use machines

This medicinal product could have a minor influence on the ability to drive and use

machines.

In a study with coronary heart disease patient’s 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 following terminologies have been used in order to classify the occurrence of

undesirable effects:

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)

Immune system disorders

Rare: Allergic rhinitis, the appearance of antinuclear antibodies with exceptional

clinical symptoms such as lupus syndrome, which disappear upon cessation of

treatment.

Metabolism and nutrition disorders

Rare: Increased triglycerides, hypoglycaemia

Very rare: Hypoglycaemic shock

Psychiatric disorders

Uncommon: Sleep disorders, depression

Rare: Nightmares, hallucinations

Nervous system disorders

Common: Tiredness, exhaustion, 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

Uncommon: Bradycardia, AV-conduction disturbances (slowed AV-conduction or

increase of existing AV-block), worsening of pre-existing heart failure

Vascular disorders

Common: Feeling of coldness or numbness of the extremities, hypotension,

Raynaud’s disease, increase of existing intermittent claudication

Uncommon: 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: Beta-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 and administration site conditions

Common: Fatigue*

Uncommon: Asthenia

Investigations

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

*These symptoms especially occur at the beginning of the therapy. They are generally

mild and usually disappear within 1 - 2 weeks.

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose

Symptoms

The most common signs expected with overdose of a beta-blocker are bradycardia,

hypotension, bronchospasm, acute cardiac insufficiency and hypoglycaemia. To date

a few cases of overdose (maximum: 2000 mg) 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.

Management

In general, if overdose occurs, bisoprolol treatment should be discontinued and

supportive and symptomatic treatment should be provided. Based on the expected

pharmacological actions and recommendations for other beta-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

transvenous cardiac pacemaker insertion.

Acute worsening of heart failure

Administer i.v. diuretics, inotropic agents, vasodilating agents.

Bronchospasms

Administer bronchodilator therapy such as isoprenaline, beta

-sympathomimetic

drugs and/or aminophylline.

Hypoglycaemia

Administer i.v. glucose.

Limited data available suggest that bisoprolol is hardly dialysable.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Beta blocking agents, selective, ATC code: C07AB07

Bisoprolol is a potent, highly beta

-selective-adrenoceptor blocking agent devoid of

intrinsic sympathomimetic activity. As with other beta

-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 beta-receptors reduces heart action and thus

reduces oxygen demand.

Bisoprolol possesses similar local anaesthetic properties to propranolol.

5.2

Pharmacokinetic properties

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%. 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.

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 usually not

required for patients with mild to moderate impaired liver function or renal

insufficiency. In patients with severe renal impairment (creatinine clearance < 20

ml/min) or severe liver impairment, the dose should not exceed 10 mg once daily.

This dosage may eventually be divided into halves.

The kinetics of bisoprolol fumarate 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

Non-clinical data reveal no special hazard for humans based on conventional studies

of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenicity. Like

other beta-blocking agents, bisoprolol fumarate 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

Lactose monohydrate

cellulose, microcrystalline

Magnesium stearate

Crospovidone

Colouring agent of Bisoprolol 10 mg tablets: Beige PB 27215 (lactose monohydrate

and iron oxides red and yellow (E172)

6.2

Incompatibilities

Not applicable.

6.3.

Shelf Life

3 years

6.4

Special precautions for storage

Do not store above 30

6.5

Nature and contents of container

Bisoprolol 10 mg tablets are presented in:

Blisters comprising of PVC/PVdC/aluminium foil, contained within a printed carton

box.

Pack sizes: 10, 20, 28, 30, 50, 56, 60 or 100 tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

No special requirements for disposal.

7

MARKETING AUTHORISATION HOLDER

Actavis UK Limited (Trading style: Actavis)

Whiddon Valley

Barnstaple

Devon EX32 8NS

United Kingdom

8.

MARKETING AUTHORISATION NUMBER

PL 00142/0510

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

20/03/2002 / 16/11/2011

10

DATE OF REVISION OF THE TEXT

08/04/2016