- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
|Cardicor 1.25mg:||white, round film-coated tablets|
|Cardicor 2.5mg:||white, heart shaped, scored and film-coated tablets|
|Cardicor 3.75mg:||off-white, heart shaped, scored and film coated tablets|
|Cardicor 5mg:||yellowish white, heart shaped, scored and film-coated tablets|
|Cardicor 7.5mg:||pale yellow, heart shaped, scored and film-coated tablets|
|Cardicor 10mg:||pale orange-light orange, heart shaped, scored and film-coated tablets|
Titration phaseThe treatment of stable chronic heart failure with bisoprolol requires a titration phase The treatment with bisoprolol is to be started with a gradual uptitration according to the following steps:- 1.25 mg once daily for 1 week, if well tolerated increase to- 2.5 mg once daily for a further week, if well tolerated increase to- 3.75 mg once daily for a further week, if well tolerated increase to- 5 mg once daily for the 4 following weeks, if well tolerated increase to- 7.5 mg once daily for the 4 following weeks, if well tolerated increase to- 10 mg once daily for the maintenance therapy.The maximum recommended dose is 10 mg once daily.Close monitoring of vital signs (heart rate, blood pressure) and symptoms of worsening heart failure is recommended during the titration phase. Symptoms may already occur within the first day after initiating the therapy.
Treatment modificationIf 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 patients condition.Treatment of stable chronic heart failure with bisoprolol is generally a long-term treatment.
Renal or hepatic impairmentThere is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.
ElderlyNo dosage adjustment is required.
Paediatric populationThere is no paediatric experience with bisoprolol, therefore its use cannot be recommended in paediatric patients.
Method of administration:Bisoprolol tablets should be taken in the morning and can be taken with food. They should be swallowed with liquid and should not be chewed.
Combinations not recommendedCalcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block. Class I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone): Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.Centrally acting antihypertensive drugs such as clonidine and others (e.g. methyldopa, moxonodine, rilmenidine): Concomitant use of centrally acting antihypertensive drugs may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of rebound hypertension.
Combinations to be used with cautionCalcium antagonists of the dihydropyridine type such as felodipine and amlodipine: Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.Class-III antiarrhythmic drugs (e.g. amiodarone): Effect on atrio-ventricular conduction time may be potentiated.Topical 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.β-Sympathomimetic agents (e.g. isoprenaline, dobutamine): Combination with bisoprolol may reduce the effect of both agents.Sympathomimetics that activate both β- and α-adrenoceptors (e.g. noradrenaline, 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. 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 consideredMefloquine: increased risk of bradycardiaMonoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blockers but also risk for hypertensive crisis.
PregnancyBisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the fetus/newborn. In general, beta-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 beta-adrenoceptor blockers is necessary, beta1-selective adrenoceptor blockers are preferable.Bisoprolol should not be used during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary, the uteroplacental blood flow and the 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.
Breast-feedingIt is not known whether this drug is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.
|Common:||worsening of heart failure.|
|Rare:||increased triglycerides, increased liver enzymes (ALAT, ASAT).|
|Nervous system disorders:|
|Rare:||reduced tear flow (to be considered if the patient uses lenses).|
|Ear and labyrinth disorders:|
|Respiratory, thoracic and mediastinal disorders:|
|Uncommon:||bronchospasm in patients with bronchial asthma or a history of obstructive airways disease.|
|Common:||gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation.|
|Skin and subcutaneous tissue disorders:|
|Rare:||hypersensitivity reactions (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 and cramps.|
|Common:||feeling of coldness or numbness in the extremities, hypotension.|
|Reproductive system and breast disorders:|
|Uncommon:||sleep disorders, depression.|
AbsorptionBisoprolol is absorbed and has a biological availability of about 90% after oral administration.
DistributionThe distribution volume is 3.5 l/kg. The plasma protein binding of bisoprolol is about 30%.
Biotransformation and EliminationBisoprolol 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. Total clearance is approximately 15 l/h. The half-life in plasma of 10-12 hours gives a 24 hour effect after dosing once daily.
LinearityThe kinetics of bisoprolol are linear and independent of age.
Special populationSince 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. The pharmacokinetics in patients with stable chronic heart failure and with impaired liver or renal function has not been studied. 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.
Cardicor 1.25 mgTablet core: Silica, colloidal anhydrous; magnesium stearate, crospovidone, pregelatinised maize starch, maize starch, microcrystalline cellulose, calcium hydrogen phosphate, anhydrous.Film coating: Dimeticone, talc, macrogol 400, titanium dioxide (E171), hypromellose.
Cardicor 2.5 mgTablet core: Silica, colloidal anhydrous; magnesium stearate, crospovidone, microcrystalline cellulose, maize starch, calcium hydrogen phosphate, anhydrous.Film coating: Dimeticone, macrogol 400, titanium dioxide (E171), hypromellose.
Cardicor 3.75 mgTablet core: Silica, colloidal anhydrous; magnesium stearate, crospovidone, microcrystalline cellulose, maize starch, calcium hydrogen phosphate, anhydrous.Film coating: Iron oxide yellow (E172), dimeticone, macrogol 400, titanium dioxide (E171), hypromellose.
Cardicor 5 mgTablet core: Silica, colloidal anhydrous; magnesium stearate, crospovidone, microcrystalline cellulose, maize starch, calcium hydrogen phosphate, anhydrous.Film coating: Iron oxide yellow (E172), dimeticone, macrogol 400, titanium dioxide (E171), hypromellose.
Cardicor 7.5 mgTablet core: Silica, colloidal anhydrous; magnesium stearate, crospovidone, microcrystalline cellulose, maize starch, calcium hydrogen phosphate, anhydrous.Film coating: Iron oxide yellow (E172), dimeticone, macrogol 400, titanium dioxide (E171), hypromellose.
Cardicor 10 mgTablet core: Silica, colloidal anhydrous; magnesium stearate, crospovidone, microcrystalline cellulose, maize starch, calcium hydrogen phosphate, anhydrous.Film coating: Iron oxide red (E172), iron oxide yellow (E172), dimeticone, macrogol 400, titanium dioxide (E171), hypromellose.
Cardicor 1.25 mg, 2.5 mg and 3.75 mg3 years.
Cardicor 5 mg, 7.5 mg and 10 mg:5 years
Cardicor 1.25 mg, 2.5 mg and 3.75 mgDo not store above 25 °C.
Cardicor 5 mg, 7.5 mg and 10 mg:Do not store above 30 °C.
Bedfont Cross, Stanwell Road, Feltham, Middlesex, TW14 8NX, UK
+44 (0)208 818 7267
+44 (0)208 818 7200
+44 (0)208 818 7261
+44 (0)208 818 7274