BISOPROLOL

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. Posology Titration phase The treatment of stable chronic heart failure with bisoprolol requires a titration phase.

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. Page 3 of 14 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. Patients with 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.

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 should not be chewed.

The following definitions apply to the frequency terminology used hereafter:

Very common (≥ 1/10) Common (≥ 1/100, < 1/10) Uncommon (≥ 1/1,000, < 1/100) Rare (≥ 1/10,000, < 1/1,000) Very rare (< 1/10,000) Frequency not known (cannot be estimated from available data) Cardiac disorders Very common: Bradycardia.

Common:

Worsening of heart failure.

Uncommon:

AV-conduction disturbances.

Investigations Rare:

Increased triglycerides, increased liver enzymes (ALAT, ASAT).

Nervous system disorders Common:

Dizziness, headache.

Rare:

Syncope Page 8 of 14 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 and cramps.

Vascular disorders Common:

Feeling of coldness or numbness in the extremities, hypotension.

Uncommon:

Orthostatic hypotension.

General disorders Common:

Asthenia, fatigue.

Hepatobiliary disorders Rare:

Hepatitis.

Reproductive system and breast disorders Rare:

Erectile dysfunction Psychiatric disorders Uncommon: Sleep disorders, depression.

Rare:

Nightmares, hallucinations. 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.

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4 Special warning and precautions for use Page 4 of 14 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 (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.

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 Page 5 of 14 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

v. 4) • Metabolic acidosis