BISOPROLOL

Posology Treatment of hypertension and chronic stable angina pectoris Adults The dosage should be individually adjusted. It is recommended to start with 5 mg per day. The usual dose is 10 mg once daily with a maximum recommended dose of 20 mg per day.

Patients with renal impairment In patients with severe renal impairment (creatinine clearance < 20 ml/min) the dose should not exceed 10 mg once daily. This dosage may eventually be divided into halves. Patients with severe liver impairment No dosage adjustment is required, however careful monitoring is advised.

4). The dosage should be diminished slowly by a weekly halving of the dose. Treatment of stable chronic heart failure Adults 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.

Titration phase The treatment of stable chronic heart failure with bisoprolol requires a titration phase. 5mg once daily for the 4 following weeks, if well tolerated increase to - 10mg once daily for the maintenance therapy The maximum recommended dose is 10mg 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.

The following definitions apply to the frequency terminology used hereafter:

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) Frequency not known (cannot be estimated from available data) Psychiatric disorders: Uncommon: sleep disorders, depression.

Rare: nightmares, hallucinations.

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.

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).

Vascular disorders:

Common: feeling of coldness or numbness in the extremities, hypotension especially in patient with heart failure. Uncommon: orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders:

Uncommon: bronchospasm in patients with bronchial asthma or a history of obstructive airways disease. Rare: allergic rhinitis.

2). 2).

Precautions:

Applies only to hypertension or angina pectoris: Bisoprolol must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.

Applies only to chronic heart failure:

The initiation and cessation of treatment with bisoprolol necessitates regular monitoring. 2). 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 Applies to all indications: 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 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-blockade reduces the incidence of arrhythmias and myocardial ischemia during induction and intubation, and the post- operative period.

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