| Composition |
Each film-coated tablet of BIZOCAND 2.5 contains: 2.5 mg bisoprolol fumarate.
Each film-coated tablet of BIZOCAND 5 contains: 5 mg bisoprolol fumarate.
Each film-coated tablet of BIZOCAND 10 contains: 10 mg bisoprolol fumarate. |
| Properties |
Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilizing activity.
It only shows low affinity to the beta2-receptor of the smooth muscles of bronchi and vessels as well as to the beta2- receptors concerned with metabolic regulation.
Therefore, bisoprolol is generally not to be expected to influence the airway resistance and beta2-mediated metabolic effects.
Its beta1-selectivity extends beyond the therapeutic dose range. |
| Therapeutic indications |
| Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides. |
| Side effect |
The following definitions apply to the frequency terminology used hereafter:
Cardiac disorders: bradycardia. Uncommon: AV-conduction disturbances.
Rare: increased triglycerides, increased liver enzymes (ALAT, ASAT).
Nervous system disorders: dizziness, headache. |
| Contraindication |
Bisoprolol is contraindicated in chronic heart failure patients with:
• Acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy.
• Cardiogenic shock.
• Second or third degree AV block.
• Sick sinus syndrome.
• Sinoatrial block.
• Symptomatic bradycardia.
• Symptomatic hypotension.
• Severe bronchial asthma or severe chronic obstructive pulmonary disease.
• Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome.
• Untreated phaeochromocytoma.
• Metabolic acidosis.
• Hypersensitivity to bisoprolol or to any of the excipients. |
| Warnings and precautions |
The treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase.
Especially in patients with ischaemic heart disease the cessation of therapy with bisoprolol must not be done abruptly unless clearly indicated, because this may lead to transitional worsening of heart condition.
The initiation and cessation of treatment with bisoprolol necessitates regular monitoring.
There is no therapeutic experience of bisoprolol treatment of heart failure in patients with the following diseases and conditions:
• Insulin dependent diabetes mellitus (type I).
• Severely impaired renal function.
• Severely impaired hepatic function.
• Restrictive cardiomyopathy.
• Congenital heart disease.
• Haemodynamically significant organic valvular disease.
• Myocardial infarction within 3 months.
Bisoprolol must be used with caution in:
• Bronchospasm.
• Diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia can be masked.
• Strict fasting.
• Ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens.
• First degree AV block.
• Prinzmetal’s angina.
• Peripheral arterial occlusive disease. Aggravation of symptoms may occur especially when starting therapy. |
| Pregnancy and lactation |
PREGNANCy AND LACTATION:
Bisoprolol 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.
BREAST-FEEDING:
It is not known whether this drug is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol. |
| Drug interactions |
DRUG INTERACTIONS:
Combinations not recommended Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative influence on contractility andatrio-ventricular conduction.
Class I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone): Effect on atrioventricular conduction time may be potentiated and negative inotropic effect increased.
COMBINATIONS TO BE USED WITH CAUTION:
Calcium 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.
Class-III antiarrhythmic drugs (e.g. amiodarone): Effect on atrioventricular conduction time may be potentiated.
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.
Digitalis glycosides: Reduction of heart rate, increase of atrio-ventricular conduction time. |
| Dosage and Method of administration |
Standard treatment of CHF consists of an ACE inhibitor (or an angiotensin receptor blocker in case of intolerance to ACE inhibitors), a beta-blocker, diuretics, and when appropriate cardiac glycosides.
Patients should be stable (without acute failure) when bisoprolol treatment is initiated.
It is recommended that the treating physician should be experienced in the management of chronic heart failure.
Posology:
Titration phase:
The treatment of stable chronic heart failure with bisoprolol requires a titration phase
The treatment with bisoprolol is to be started with a gradual uptitration according to the following steps:
- 1.25 mg once daily for 1 week, if well tolerated increase to
- 2.5 mg once daily for a further week, if well tolerated increase to
- 3.75 mg once daily for a further week, if well tolerated increase to
- 5 mg once daily for the 4 following weeks, if well tolerated increase to
- 7.5 mg once daily for the 4 following weeks, if well tolerated increase to
- 10 mg once daily for the maintenance therapy.
The maximum recommended dose is 10 mg once daily.
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 modification:
If the maximum recommended dose is not well tolerated, gradual dose reduction may be considered.
In case of transient worsening of heart failure, hypotension, or bradycardia reconsideration of the dosage of the concomitant medication is recommended. It may also be necessary to temporarily lower the doseor 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 impairment:
There 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.
Elderly:
No dosage adjustment is required.
Paediatric population:
There 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 shouldnot be chewed. |
| Overdose |
With overdose (e.g. daily dose of 15 mg instead of 7.5 mg) third degree AV-block, bradycardia, and dizziness have been reported. In general the most common signs expected with overdosage of a beta-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency
and hypoglycaemia.
If overdose occurs, bisoprolol treatment should be stopped and supportive and symptomatic treatment should be provided. |
| Package |
| 20 F.C tablets in carton box with leaflet. |
| Storage |
| Store below 25°C. Keep Away From Children. |
