COMPOSITIONS :
| Bisoprolol Fumarate Film coated tablet 2.5 mg, each film coated tablet contains : Bisoprolol fumarate 2,5 mg. |
DESCRIPTIONS :
Bisoprolol Fumarate containing Bisoprolol fumarate is available in 2.5 mg and 5 mg film coated tablet.
INDICATIONS :
Bisoprolol Fumarate Film coated tablet 2.5 mg and 5 mg : Treatment of stable chronic moderate to severe heart failure with reduced systolic ventricular function (ejection fraction ≤ 35%, based on echocardiography) in addition to ACE inhibitors and diuretics and optionally cardiac glycosides.
Bisoprolol Fumarate Film coated tablet 5 mg : Bisoprolol is already used for the treatment of hypertension and coronary heart disease (angina pectoris).
DOSAGE AND ADMINISTRATIONS :
- Treatment of hypertension or angina pectoris : 1 tablet Bisoprolol Fumarate 5 mg daily in the morning before or after breakfast. In milder form of diseases Bisoprolol Fumarate 5 mg daily may be sufficient, most patients will be controlled by 10 mg daily, only in few cases a dosage of 20 mg daily is required.
- Treatment of stable chronic heart failure : The patients should have stable chronic heart failure without acute failure during the past six weeks and a mainly unchanged basic therapy during the past two weeks. They should be treated at optimal dose with an optimal dose with an ACE inhibitor (or other vasodilator in case of intolerance to ACE inhibitors) and a diuretic and optionally cardiac glycosides, prior to the administration of Bisoprolol fumarate.
- It is recommended that the treating physician should be experienced in the management of chronic heart failure.
- Warning : The treatment of stable chronic heart failure with Bisoprolol fumarate has to be initiated with a titration phase as given in the description below.
The treatment with Bisoprolol fumarate is to be started with a gradual uptitration according to the following steps :
- 1.25 mg once daily for 1 week, if well tolerated increase to
- 2.5 mg once daily for a further week, if well tolerated increase to
- 3.75 mg once daily for a further week, if well tolerated increase to
- 5 mg once daily for the 4 following weeks, if well tolerated increase to
- 7.5 mg once daily for the 4 following weeks, if well tolerated increase to
- 10 mg once daily for the maintenance therapy.
- After initiation of the treatment with 1.25 mg, the patients should be observed over a period of approximately 4 hours (especially as regards blood pressure, heart rate, conduction disturbances, signs of worsening of heart failure).
- The maximum recommended dose is 10 mg once daily.
- Occurrence of adverse events may prevent all patients being treated with the maximum recommended dose. If necessary, the dose reached can also be decreased step by step. The treatment may be interrupted if necessary and reintroduced as appropriate. During the titration phase, in case of worsening of the heart failure or intolerance, it is recommended first to reduce the dose of Bisoprolol fumarate, or to stop immediately if necessary (in case of severe hypotension, worsening of heart failure with acute pulmonary oedema, cardiogenic shock, symptomatic bradycardia or AV block).
- Duration of therapy for all indications :
- Treatment of stable chronic heart failure with Bisoprolol fumarate is generally a long-term treatment
- The treatment with Bisoprolol fumarate is not recommended to be stopped abruptly since this might lead to a transitory worsening of heart failure. If discontinuation is necessary, the dose should be gradually decreased divided into halves weekly.
- Bisoprolol fumarate tablets should be taken in the morning and can be taken with food. They should be swallowed with liquid and should not be chewed.
- Renal or liver impairment :
- Treatment of hypertension or angina pectoris : For patients with final stage of renal impairment or severe disturbances in liver function the maximum dosage is 10 mg daily.
- Treatment of stable chronic heart failure : There is no information regarding pharmacokinetics of Bisoprolol fumarate in patients with chronic heart failure and with impaired liver or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.
- Elderly : No dosage adjustment is required.
- Children : There is no pediatric experience with Bisoprolol fumarate, therefore its use cannot be recommended for children.
OVERDOSAGE :
The most common sign expected with overdosage of a β-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency and hypoglycaemia. To date a few cases of overdose (maximum : 2000 mg) with Bisoprolol have been reported in patients suffering from hypertension and/or coronary heart disease showing bradycardia and/or hypotension; all patients recovered. There is a wide interindividual variation in sensitivity to one single high dose of Bisoprolol and patients with heart failure are probably very sensitive. Therefore it is mandatory to initiate the treatment of these patients with a gradual uptitration according to the scheme given in dosage and administration.
In general, if overdose occur, Bisoprolol treatment should be stopped and supportive and symptomatic treatment should be provided. Limited data suggest that Bisoprolol is hardly dialysable. Based on the expected pharmacologic actions and recommendations for other β-blockers, the following general measures should be considered when clinically warranted.
Bradycardia : Administer intravenous Atropine. If response is inadequate, Isoprenaline or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary.
Hypotension : Intravenous fluids and vasopressor should be administered. Intravenous glucagon may be useful.
AV block (second or third degree) : Patients should be carefully monitored and treated with Isoprenaline infusion or transvenous cardiac pacemaker insertion.
Acute worsening of heart failure : Administer IV diuretics, inotropic agents, vasodilating agents.
Bronchospasm : Administer bronchodilator therapy such as Isoprenaline, β2-sympathomimetic drugs and/or Aminophylline.
Hypoglycaemia : Administer IV glucose.
Limited data suggest that Bisoprolol is hardly dialyzable.
CONTRAINDICATIONS :
Bisoprolol is contraindicated in patients with :
- Acute heart failure or during episodes of heart failure decompensation requiring IV inotropic therapy.
- Cardiogenic shock.
- AV block of second or third degree (without a pacemaker).
- Sick sinus syndrome.
- Sinoatrial block.
- Bradycardia with less than 60 beats/minute before the start of therapy.
- Hypotension (systolic blood pressure less than 100 mmHg).
- Severe bronchial asthma or severe chronic obstructive pulmonary disease.
- Late stages of peripheral arterial occlusive disease and Raynaud’s syndrome.
- Untreated phaeochromocytoma.
- Metabolic acidosis.
- Hypersensitivity to Bisoprolol.
WARNINGS AND PRECAUTIONS :
- Bisoprolol must be used with caution in :
- Bronchospasm (bronchial asthma, obstructive airways diseases).
- Concomitant treatment with inhalation anesthetics.
- Diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycemia can be masked.
- Strict fasting.
- Ongoing desensitization therapy.
- AV block of first degree.
- Prinzmetal’s angina.
- Peripheral arterial occlusive disease (intensification of complaints might happen especially during the start of therapy).
- There is no therapeutic experience of Bisoprolol treatment in heart failure in patients with the following diseases and conditions :
- NYHA class II heart failure.
- Insulin dependent diabetes mellitus (type I).
- Impaired renal function (serum creatinine ≥ 300 micromol/l).
- Impaired liver function.
- Patients older than 80 years.
- Restrictive cardiomyopathy.
- Congenital heart disease.
- Haemodynamically significant organic valvular disease.
- Myocardial infarction within 3 months.
- Treatment of hypertension or angina pectoris : Bisoprolol must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.
- In patients undergoing general anaesthesia the anaesthetist must be aware of betablockade. If it is thought necessary to withdraw β-blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.
- 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.
- 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 β2-stimulants may have to be increased.
- As with other β-blocker, Bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Adrenaline treatment does not always give the expected therapeutic effect.
- Patients with psoriasis or with a history of psoriasis should only be given β-blockers (e.g. Bisoprolol) after carefully balancing the benefits against the risks.
- In patients with phaeochromocytoma Bisoprolol must not be administered until after α-receptor blockade.
- Under treatment with Bisoprolol the symptoms of a thyreotoxicosis may be masked.
- The initiation of treatment with Bisoprolol necessitates regular monitoring. For the posology and method of administration please refer to dosage and administration.
- The cessation of therapy with Bisoprolol should not be done abruptly unless clearly indicated.
- Use during pregnancy and lactation :
Pregnancy
Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the fetus/newborn. In general, β-adrenoceptor blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. hypoglycaemia and bradycardia) may occur in the fetus and newborn infant. If treatment with β-adrenoceptor blockers is necessary β-selective adrenoceptor blockers are preferable.
Bisoprolol should not be used during pregnancy unless clearly necessary. If treatment with Bisoprolol is considered necessary, the uteroplacental blood flow and the fetal growth should be monitored. In case of harmful effects on pregnancy or the fetus alternative treatment should be considered. The newborn infant must be closely monitored. Symptoms of hypoglycemia and bradycardia are generally to be expected within the first 3 days.
Lactation
It is not known whether this drug is excreted in human milk. Therefore, breastfeeding is not recommended during administration of Bisoprolol.
- Effects on ability to drive and use machines :
In study with coronary heart disease patients Bisoprolol did not impair driving perfomance. However, due to individual variations in reactions to the drug, the ability to drive a vehicle or to operate machinery may be impaired. This should be considered particularly at start of treatment and upon change of medication as well as in conjunction with alcohol.
DRUG INTERACTIONS :
- Combination not recommended :
Treatment of stable chronic heart failure :
Class I antiarrhythmic drugs (e.g. Disopyramide, Quinidine, Lidocaine, Phenytoin, Flecainide, Propafenone) : Effect on atrial conduction time may be potentiated and negative inotropic effect may be increased.
Treatment of all indications :
- Calcium antagonists of the Verapamil type and to a lesser extent of the Diltiazem type : Negative influence on contractility and atrio-ventricular conduction and blood pressure. Intravenous administration of Verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block.
- Centrally-acting antihypertensive drugs such as Clonidine and other (e.g. Methyldopa, Moxonidine, Rilmenidine) : Concomitant use of centrally acting antihypertensive drug may lead to reduction of heart rate and cardiac output and to vasodilatation. Abrupt withdrawal may increase of rebound hypertension.
- Combination to be used with caution :
Treatment of hypertension or angina pectoris :
Class I antiarrhythmic drugs (e.g. Disopyramide, Quinidine) : Effect on atrial conduction time may be potentiated and negative inotropic effect may be increased.
Treatment of all indications :
- Calcium antagonists of the Dihydropyridine type (e.g. Felodipine and Amlodipine) : Concomitant use may increase the risk of hypotension and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
- Class III antiarrhythmic drugs (e.g. Amiodarone) : Effect on atrial conduction time may be potentiated.
- Parasympathomimetic drugs (including Tacrine) : Atrioventricular conduction time may be increased.
- Other β-blockers, including eye drops, have additive effects.
- Insulin and oral antidiabetic drugs : Intensification of blood sugar lowering effect. Blockade of β-adrenoreceptors may mask symptoms of hypoglycaemia.
- Anaesthetic agents : Attenuation of the reflex tachycardia and increase of the risk of hypotension.
- Digitalis glycosides : Reduction of heart rate, increase of atrioventricular conduction time.
- Non-steroidal anti-inflammatory drugs (NSAIDs) : Decreased hypotensive effect.
- β-sympatomimetic agents (e.g. Isoprenaline, Dobutamine) : Combination with Bisoprolol may reduce the effect of both agents.
- Sympathomimetics that activate both β- and α-adrenoceptors (e.g. Noradrenaline, Adrenaline): Combination with Bisoprolol may lead to blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with nonselective β-blockers.
- Tricyclic antidepressants, Barbiturate, Phenothiazines as well as other antihypertensive agents.: Increase blood pressure lowering effect.
- Combination to be considered :
- Mefloquine : Increased risk of bradycardia.
- Monoamine oxidase inhibitors (except MAO-B inhibitors) : Enhanced hypotensive effect of the β-blockers agents but also risk for hypertensive crisis.
- Ergotamine derivatives : Exacerbation of peripheral circulatory disturbances.
- Rifampicin : Slight reduction of the half-life of Bisoprolol possible due to the induction of hepatic drug metabolising enzymes. Normally no dosage adjustment is necessary.
ADVERSE REACTIONS :
Very common
- Cardiac disorder : Bradycardia (in patients with chronic heart failure).
Common
- Vascular disorders : Feeling of coldness or numbness in the extremities, hypotension especially in patients with heart failure.
- CNS : Tiredness*, exhaustion*, dizziness*, headache*.
- Gastrointestinal : Nausea, vomiting, diarrhea, constipation.
Uncommon
- Musculoskeletal and connective tissue disorders : Muscular weakness and cramps.
- Cardiac disorders : AV-conduction disturbances, worsening of pre-existing heart failure, bradycardia (in patients with hypertension or angina pectoris).
- CNS : Sleep disturbances.
- Psychiatric disorder : Depression.
- Respiratory, thoracic and mediastinal disorder : Bronchospasm in patients with bronchial asthma or a history of obstructive airways disease.
Rare
- CNS : Nightmare, hallucination.
- Skin and subcutaneous tissue disorders : Hypersensitivity reactions (itching, flush, rash).
- Hepatobiliary disorders : Increased liver enzymes (ALAT, ASAT), hepatitis.
- Metabolism : Increased triglycerides.
- Reproductive system and breast disorders : Potency disorders.
- Ear-nose-throat : Hearing impairment, allergic rhinitis.
- Eyes : Reduced tear flow (to be considered if the patient use lenses).
- Respiratory, thoracic and mediastinal disorder : Allergic rhinitis.
Single cases
- Eyes : Conjunctivitis.
- Skin : β-blockers may provoke or worsen psoriasis or induce psoriasis-like rash, alopecia.
* These symptoms especially occur at the beginning of the therapy. They are generally mild and often disappear within 1 – 2 weeks.
PRESENTATIONS :
Bisoprolol Fumarate Film coated tablet 2.5 mg Box, 3 blisters @ 10 film coated caplets
Reg. No. GKL1702354517B1
STORAGE :
STORE BELOW 30ºC
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
