BISOPROLOL FUMARATE ZENTIVA

Treatment of stable chronic heart failure Standard treatment of chronic heart failure 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 heart failure) when bisoprolol treatment is initiated. Recommendation: the treating physician should be experienced in the management of chronic heart failure. Transient worsening of heart failure, hypotension, or bradycardia may occur during the titration period and thereafter.

Posology Titration phase The treatment of stable chronic heart failure with bisoprolol requires gradual dose titration. 25 mg once daily for 1 week. 5 mg once daily for 1 further week. 75 mg once daily for 1 further week. If this dose is well tolerated, increase to • 5 mg once daily for the following 4 weeks.

5 mg once daily for the following 4 weeks. If this dose is well tolerated, increase to • 10 mg once daily for the maintenance therapy. The maximum recommended dose is 10 mg. 5 mg is not registered in your country, the dosages can be achieved by other bisoprolol products that are available.

Close monitoring of vital signs (heart rate, blood pressure) and symptoms of worsening heart failure is recommended during the titration phase. Symptoms may occur on 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 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 of treatment is considered, gradual dose decrease is recommended, since abrupt withdrawal may lead to acute deterioration of the patient’s condition.

Treatment of stable chronic heart failure with bisoprolol is generally a long-term treatment. Renal or hepatic impairment There is no information available regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function.

Tabulated list of adverse reactions The following terminologies have been used in order to classify the occurrence of adverse reactions: 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).

MedDRA System Organ Class Frequency Adverse reaction Uncommon Sleep disorders, depressionPsychiatric disorders Rare Nightmare, hallucinations Common Dizziness*, headache*Nervous system disorders Rare Syncope Rare Reduced tear flow (to be considered if the patient uses lenses) Eye disorders Very rare Conjunctivitis Ear and labyrinth disorders Rare Hearing disorders Very common Bradycardia (in patients with chronic heart failure) Cardiac disorders Common Worsening of heart failure (in patients with chronic heart failure) Uncommon AV-conduction disorder, worsening of pre-existing heart failure (in patients with hypertension or angina pectoris), bradycardia (in patients with hypertension or angina pectoris) Common Feeling of coldness or numbness in the extremities, hypotension Vascular disorders Uncommon Orthostatic hypotension Uncommon Bronchospasm in patients with bronchial asthma or a history of obstructive airways disease Respiratory, thoracic and mediastinal disorders Rare Allergic rhinitis Gastrointestinal disorders Common Gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation Hepatobiliary disorders Rare Hepatitis Rare Hypersensitivity reactions (pruritus, flush, rash and angioedema) Skin and subcutaneous tissue disorders Very rare Alopecia, beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash Musculoskeletal and connective tissue disorders Uncommon Muscle weakness, muscle cramps Reproductive system and breast disorders Rare Erectile dysfunction Common Asthenia (in patients with chronic heart failure), fatigue* General disorders Uncommon Asthenia (in patients with hypertension or angina pectoris) Investigations Rare Increased triglycerides, increased liver enzymes (ALAT, ASAT) Applies only to hypertension or angina pectoris: *These symptoms especially occur at the beginning of the therapy.

Applies to all indications Bisoprolol should be used with caution in patients with hypertension or angina pectoris and accompanying heart failure. The initiation and cessation of treatment with bisoprolol necessitates regular monitoring.

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 the heart condition. Bisoprolol must be used with caution in: • 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 and the severity of anaphylactic reactions. Adrenalin treatment does not always yield the expected therapeutic effect. • first degree AV block; • Prinzmetal’s angina: cases of coronary vasospasm have been observed.

Despite its high beta1-selectivity, angina attacks cannot be completely excluded when bisoprolol is administered to patients with Prinzmetal’s angina; • peripheral arterial occlusive disease. Aggravation of symptoms may occur especially when starting therapy.

General anaesthesia In patients undergoing general anaesthesia, beta-blockers reduce the incidence of arrhythmias and myocardial ischaemia during induction and intubation, and during the post-operative period. It is currently recommended that maintenance beta-blocker therapy be continued peri-operatively.

The anaesthetist must be aware of the beta- blocker therapy because of the potential for interactions with other pharmaceuticals, resulting in bradyarrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss.

If discontinuation of the beta-blocker therapy prior to surgery is necessary, the dose should be reduced gradually and the reduction should be complete approx. 48 hours before anaesthesia. Although cardioselective (beta1) beta-blockers may have less effect on lung function than non-selective beta-blockers, as with all beta-blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for their use.

4); • metabolic acidosis.