Bisostad 5

Rx

Indications

• Treatment of high blood pressure (hypertension).
• Treatment of coronary heart disease (angina pectoris).
• Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides.

Dosage

• Treatment of hypertension or angina pectoris
  In all cases the dose regimen is adjusted individually by your doctor, in particular according to the pulse rate and therapeutic success. The usual initial dose is 5 mg bisoprolol (1 tablet of Bisostad 5) once daily. In milder forms of hypertension (diastolic blood pressure up to 105 mmHg) therapy with 2.5 mg once daily may be adequate. If necessary, the dose may be increased to 10 mg bisoprolol (2 tablets of Bisostad 5) once daily. The maximum recommended dose is 20 mg bisoprolol once daily.
• Treatment of stable chronic heart failure (CHF)
  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. The initiation of treatment of stable chronic heart failure with Bisostad 5 necessitates a special titration phase and requires regular monitoring by the doctor.
  Preconditions for treatment with bisoprolol is stable chronic heart failure without acute failure.
  It is recommended that the treating physician be experienced in the management of chronic heart failure.
  The treatment of stable chronic heart failure with bisoprolol is initiated according to the following titration scheme, individual adaptation may be necessary depending on how well the patient tolerates each dose, i.e. the dose is to be increased only, if the previous dose is well tolerated.
  1^st week: 1.25 mg bisoprolol once daily (Bisostad 5 is not suitable for initial treatment of stable chronic heart failure. Lower strengths are available for this purpose). If well tolerated increase to
  2^nd week: 2.5 mg bisoprolol (½ tablet Bisostad 5) once daily, if well tolerated increase to
  3^rd week: 3.75 mg bisoprolol once daily (Bisostad 5 is not suitable for initial treatment of stable chronic heart failure. Lower strengths are available for this purpose). If well tolerated increase to
  4^th – 7^th week: 5 mg bisoprolol (1 tablet Bisostad 5) once daily, if well tolerated increase to
  8^th – 11^th week: 7.5 mg bisoprolol (1 ½ tablets Bisostad 5) once daily, if well tolerated increase to.
  12^th week and beyond: 10 mg bisoprolol (2 tablets Bisostad 5) once daily as maintenance treatment.
  The maximum recommended dose is 10 mg bisoprolol once daily. Patients should be titrated to and maintained at this dose unless prevented by adverse effects. Close monitoring of vital signs (blood pressure, heart rate) and symptoms of worsening heart failure is recommended during the titration phase.
  Treatment modification
  If during the titration phase or thereafter, transient worsening of heart failure, hypotension or bradycardia occurs, reconsideration of the dosage of 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.
  Duration of treatment for all indications
  Treatment with Bisostad 5 is generally a long-term therapy. The treatment may be interrupted if necessary and reintroduced as appropriate.
  Do not stop treatment abruptly or change the recommended dose without talking to your doctor first since this might lead to a transitory worsening of heart condition. Treatment must not be discontinued suddenly. If discontinuation is necessary, the dose is gradually decreased.
  Special population
  Renal or hepatic impairment:
  – Treatment of hypertension or angina pectoris: In patients with liver or kidney function disorders of mild to moderate severity no dosage adjustment is normally required. In patients with severe renal impairment (creatinine clearance < 20 ml/min) and in patients with severe hepatic impairment a daily dose of 10 mg bisoprolol must not be exceeded.
  – Treatment of stable chronic heart failure: There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and concomitant hepatic or renal impairment. Titration of the dose in these populations must therefore be made with particular caution.
  Elderly: No dosage adjustment is required.
  Children: There is insufficient experience with bisoprolol in children, therefore the use of Bisostad 5 cannot be recommended for children.

Usage

Orally administered. The tablets should be taken in the morning with or without food. They should be swallowed with liquid and should not be chewed.

• Hypersensitivity to bisoprolol or to any of the ingredients.
• Acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy.
• Cardiogenic shock.
• AV block of second or third degree.
• Sick sinus syndrome.
• Sinoatrial block.
• Symptomatic bradycardia.
• Symptomatic hypotension.
• Severe bronchial asthma or severe chronic obstructive pulmonary disease.
• Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome.
• Untreated phaeochromocytoma.
• Metabolic acidosis.

Very common

• Bradycardia in patients with chronic heart failure.

Common

• Dizziness, headache, fatigue. These symptoms especially occur at the beginning of the therapy in patients with hypertension or angina pectoris. They are generally mild and usually disappear within 1 – 2 weeks.
• Worsening of pre-existing heart failure in patients with chronic heart failure.
• Feeling of coldness or numbness in the extremities, hypotension (especially in patients with heart failure).
• Gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation.
• Asthenia (patients with chronic heart failure).

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 treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase.
The initiation and cessation of treatment of stable chronic heart failure 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 liver function.
+ Restrictive cardiomyopathy.
+ Congenital heart disease.
+ Haemodynamically significant organic valvular disease.
+ Myocardial infarction within 3 months.

Applies to all indications
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.
There is a risk of myocardial infarction and sudden death if the treatment is suddenly discontinued in patients with coronary heart disease.
Bisoprolol must be used with caution in:
– Bronchospasm (bronchial asthma, chronic obstructive pulmonary disease (COPD)): 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. Where such reasons exist, this medicinal product may be used with caution. In patients with obstructive airways diseases, the treatment with bisoprolol should be started at the lowest possible dose and patients should be carefully monitored for new symptoms (e.g. dyspnoea, exercise intolerance, cough). In bronchial asthma or other chronic obstructive lung diseases, which may cause symptoms, bronchodilating therapy should be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of beta2-stimulants may have to be increased.
– Diabetes mellitus with large fluctuations in blood glucose values: Symptoms of hypoglycaemia (e.g. tachycardia, palpitations or sweating) 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.
– AV block of first degree.
– 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 ischaemia during induction and intubation, and the post-operative period. It is currently recommended that maintenance of beta-blockade should be continued peri-operatively. The anaestheist must be aware of beta-blockade because of the potential for interactions with other medicinal products, 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-blocking agent therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.
– Patients with psoriasis or a history of psoriasis should only be given beta-blocking agents (e.g. bisoprolol) after carefully balancing the benefits against the risks.
– In patients with phaeochromocytoma bisoprolol must not be administered until after alpha-receptor blockade.
– Under treatment with bisoprolol the symptoms of a thyrotoxicosis may be masked.
– Combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type, with Class I antiarrhythmic medicinal products and with centrally acting antihypertensive medicinal products is generally not recommended.

Bisoprolol is not recommended during pregnancy unless clearly necessary.

It is not known whether this drug is excreted in human milk. Therefore, breast-feeding is not recommended during administration of bisoprolol.

In a study with coronary heart disease patients bisoprolol did not impair driving performance. Depending on the individual patient’s response the ability to drive a vehicle or to use machines may be impaired. This needs to be considered particularly at start of treatment, upon change of medication, or in conjunction with alcohol.