BISOPROLOL FUMARATE

Posology 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. Transient worsening of heart failure, hypotension, or bradycardia may occur during the titration period and thereafter. 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 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 patient’s condition.

Treatment of stable chronic heart failure with bisoprolol is generally a long- term treatment Special population Renal or hepatic impairment In patients with severe renal impairment (creatinine clearance <20 ml/min) and in patients with severe hepatic function disorders it is recommended that a daily dose of 10 mg bisoprolol fumarate is not exceeded Elderly No dosage adjustment is normally required, but 5 mg per day may be adequate in some patients; as for other adults, dosage may have to be reduced in cases of severe renal or hepatic dysfunction.

Paediatric population Bisoprolol fumarate is not recommended for use in children due to a lack of experience in children. Method of administration Oral use. Bisoprolol tablets should be taken in the morning and can be taken with food.

The following definitions apply to the frequency terminology used hereafter:

Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Investigations:

Rare: increased triglycerides, increased liver enzymes (ALAT, ASAT) Cardiac disorders: Very common: bradycardia (in patients with chronic heart failure) Common: worsening of pre-existing heart failure (in patients with chronic heart failure) Uncommon: AV-conduction disturbances; worsening of pre-existing heart failure (in patients with hypertension or angina pectoris); bradycardia (in patients with hypertension or angina pectoris) Nervous system disorders: Common: 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 Respiratory, thoracic and mediastinal disorders: Uncommon: bronchospasm in patients with bronchial asthma or a history of obstructive airways disease Rare: allergic rhinitis Gastrointestinal disorders: Common: gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation Skin and subcutaneous tissue disorders: Rare: hypersensitivity reactions (such as itching, flush, rash and angioedema) Very rare: alopecia, beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash Musculoskeletal and connective tissue disorders: Uncommon: muscular weakness muscle cramps Vascular disorders: Common: feeling of coldness or numbness in the extremities, hypotension especially in patients with heart failure Uncommon: orthostatic hypotension General disorders: Common: asthenia (patients with chronic heart failure), fatigue* Uncommon: asthenia (in patients with hypertension or angina pectoris) Hepatobiliary disorders: Rare: hepatitis Reproductive system and breast disorders: Rare: potency disorders Psychiatric disorders: Uncommon: sleep disorders, depression Rare: nightmares, hallucinations applies only to hypertension or angina pectoris: *These symptoms especially occur at the beginning of the therapy.

2). 2). The initiation and cessation of treatment of stable chronic heart failure with bisoprolol necessitates regular monitoring. There is no therapeutic experience of bisoprolol treatment in 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 (bronchial asthma, obstructive airways diseases) − 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. Epinephrine treatment may not always yield the expected therapeutic effect, − first degree AV block − Prinzmetal's angina − peripheral arterial occlusive disease.

Aggravation of symptoms may occur especially when starting therapy. − general anaesthesia. In patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischemia during induction and intubation, and the post-operative period.

It is currently recommended that maintenance beta-blockade be continued peri-operatively. The anaesthetist must be aware of beta-blockade because of the potential for interactions with other drugs, resulting in bradyarrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss.

If it is thought necessary to withdraw beta-blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia. g. bisoprolol) after carefully balancing the benefits against the risks. The symptoms of thyrotoxicosis may be masked under treatment with bisoprolol.

4) − metabolic acidosis