BISOPROLOL FUMARATE

Posology Treatment of hypertension and chronic stable angina pectoris Adults The dosage should be individually adjusted. It is recommended to start with 5mg (10ml) per day. The usual dose is 10mg (20ml) once daily with a maximum recommended dose of 20mg (40ml) per day.

Patients with renal or hepatic impairment In patients with severe renal impairment (creatinine clearance < 20 ml/min) and in patients with severe hepatic function disorders the dose should not exceed 10mg (20ml) once daily. This dosage may eventually be divided into halves.

Elderly No dosage adjustment is normally required. It is recommended to start with the lowest possible dose. Paediatric population There is no experience with bisoprolol in children, therefore its use cannot be recommended for children.

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-blocking agent, 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. Titration phase The treatment of stable chronic heart failure with bisoprolol requires a titration phase.

5mg (15ml) once daily for the 4 following weeks, if well tolerated increase to • 10mg (20ml) once daily for the maintenance therapy. The maximum recommended dose is 10mg (20ml) 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 patients condition.

Treatment of stable chronic heart failure with bisoprolol is generally a long-term treatment.

Special populations Hepatic or renal impairment:

There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function. Titration of the dose in these populations should therefore be made with particular caution.

Elderly No dosage adjustment is normally required. Paediatric population There is no paediatric experience with bisoprolol in children, therefore its use cannot be recommended for children. Method of administration For oral administration only.

Bisoprolol fumarate oral solution 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 (≥ 1/1,000 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) Cardiac disorders: Very common: bradycardia (in patients with chronic heart failure).

Common: worsening of heart failure (in patients with chronic heart failure).

Uncommon:

AV-conduction disturbances (in patients with hypertension or angina pectoris); bradycardia (in patients with hypertension or angina pectoris).

Investigations:

Rare: increased triglycerides, increased liver enzymes (ALAT, ASAT).

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 and constipation.

Skin and subcutaneous tissue disorders:

Rare: hypersensitivity reactions (pruritus, 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 and cramps.

Vascular disorders:

Common: feeling of coldness or numbness in the extremities, hypotension. Uncommon: orthostatic hypotension.

General disorders:

Common: asthenia, (in 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: erectile dysfunction.

Psychiatric disorders:

Uncommon: sleep disorder, depression. Rare: nightmare, hallucination. Applies only to hypertension or angina pectoris: *These symptoms especially occur at the beginning of the therapy. They are generally mild and often disappear within 1 to 2 weeks.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

Beta-blockers could further increase the risk of severe hypoglycaemia when used concurrently with sulfonylureas. 5). • 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. g. bisoprolol) after a careful balancing of benefits against risks. The symptoms of thyrotoxicosis may be masked under treatment with bisoprolol.

In patients with phaeochromocytoma bisoprolol must not be administered until after alpha-receptor blockade. 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. Combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type, with Class I antiarrhythmic drugs and with centrally acting antihypertensive drugs is generally not recommended, for details please refer to section

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