SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
Bisoprolol 10mg tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Bisoprolol 10 mg tablet contains 8.49 mg bisoprolol equivalent to 10 mg
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
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.
Chronic stable angina pectoris
Posology and method of 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.
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.
No dosage adjustment is normally required. It is recommended to start with the lowest
Bisoprolol tablets are not recommended for use in children due to a lack of data (see
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.
Bisoprolol is contraindicated in patients with:
hypersensitivity to the active substance or to any of the excipients listed in section
acute heart failure or during episodes of heart failure decompensation requiring i.v.
AV block of second or third degree
sick sinus syndrome
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
untreated phaeochromocytoma (see 4.4).
combinations with floctafenine and sultopride (see also section 4.5)
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
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
concomitant treatment with anticholinesterastic drugs (including tacrine): atrio-
ventricular conduction time and/or bradycardia may be increased (see also
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
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
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.
Interaction with other medicinal products and other forms of interaction
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
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
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.
Fertility, pregnancy and lactation
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
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.
It is not known whether bisoprolol fumarate is excreted in human milk. Therefore
breastfeeding is not recommended during administration of Bisoprolol tablets.
Effects on ability to drive and use machines
This medicinal product could have a minor influence on the ability to drive and use
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.
The following terminologies have been used in order to classify the occurrence of
Very common (
1/100 to <1/10)
1/1,000 to <1/100)
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
Metabolism and nutrition disorders
Rare: Increased triglycerides, hypoglycaemia
Very rare: Hypoglycaemic shock
Uncommon: Sleep disorders, depression
Rare: Nightmares, hallucinations
Nervous system disorders
Common: Tiredness, exhaustion, dizziness*, headache*
Rare: Reduced tear flow (to be considered if the patient uses lenses)
Very rare: Conjunctivitis
Ear and labyrinth disorders
Rare: Hearing disorders
Uncommon: Bradycardia, AV-conduction disturbances (slowed AV-conduction or
increase of existing AV-block), worsening of pre-existing heart failure
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
Common: Gastrointestinal complaints such as nausea, vomiting, diarrhoea, abdominal
pain, and constipation
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
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.
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.
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.
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.
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.
Administer bronchodilator therapy such as isoprenaline, beta
drugs and/or aminophylline.
Administer i.v. glucose.
Limited data available suggest that bisoprolol is hardly dialysable.
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.
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.
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.
List of excipients
Colouring agent of Bisoprolol 10 mg tablets: Beige PB 27215 (lactose monohydrate
and iron oxides red and yellow (E172)
Special precautions for storage
Do not store above 30
Nature and contents of container
Bisoprolol 10 mg tablets are presented in:
Blisters comprising of PVC/PVdC/aluminium foil, contained within a printed carton
Pack sizes: 10, 20, 28, 30, 50, 56, 60 or 100 tablets.
Not all pack sizes may be marketed.
Special precautions for disposal and other handling
No special requirements for disposal.
MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading style: Actavis)
Devon EX32 8NS
MARKETING AUTHORISATION NUMBER
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
20/03/2002 / 16/11/2011
DATE OF REVISION OF THE TEXT