Concor

Concor

bisoprolol

Manufacturer:

PT. Merck Tbk
The information highlighted (if any) are the most recent updates for this brand.
Full Prescribing Info
Contents
Bisoprolol hemifumarate.
Action
Pharmacology: Mode of Action: Bisoprolol is a highly β1-selective adrenoceptor-blocking agent, lacking intrinsic stimulating and relevant membrane stabilizing activity. It only shows low affinity to the β2-receptor of the smooth muscles of bronchi and vessels as well as to the β2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and β2-mediated metabolic effects. Its β1-selectivity extends beyond the therapeutic dose range.
In acute administration in patients with coronary heart disease without chronic heart failure, bisoprolol reduces the heart rate and stroke volume, and thus the cardiac output and oxygen consumption. In chronic administration, the initially elevated peripheral resistance decreases.
Efficacy: In total, 2647 patients with chronic heart failure were included in the Cardiac Insufficiency Bisoprolol Study (CIBIS) II trial. 83% (n=2202) were in New York Heart Association (NYHA) class III and 17% (n=445) were in NYHA class IV. They had stable symptomatic systolic heart failure (ejection fraction ≤35%, based on echocardiography). Total mortality was reduced from 17.3% to 11.8%  (relative reduction 34%).
A decrease in sudden death (3.6% vs 6.3%, relative reduction 44 %) and a reduced number of heart failure episodes requiring hospital admission (12% vs 17.6%, relative reduction 36%) was observed. Finally, a significant improvement of the functional status according to NYHA classification has been shown. During the initiation and titration of bisoprolol, hospital admission due to bradycardia (0.53%), hypotension (0.23%) and acute decompensation (4.97%) were observed, but they were not more frequent than in the placebo group (0%, 0.3% and 6.74%). The numbers of fatal and disabling stroke during the total study period were 20 in the bisoprolol group and 15 in the placebo group.
Bisoprolol is also used for the treatment of hypertension and angina.
Pharmacokinetics: Bisoprolol is absorbed and has a biological availability of about 90% after oral administration. The plasma protein-binding of bisoprolol is about 30%. The distribution volume is 3.5 L/kg. Total clearance is approximately 15 L/hr. The plasma half-life of 10-12 hrs gives a 24-hr effect after once-daily dosing.
Bisoprolol is excreted from the body by 2 routes. 50% is metabolized by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolized form. Since the elimination takes place in the kidneys and the liver to the same extent, a dosage adjustment is not required for patients with impaired liver function or renal insufficiency. The pharmacokinetics in patients with stable chronic heart failure and with impaired liver or renal function has not been studied.
The kinetics of bisoprolol are linear and independent of age.
In patients with chronic heart failure (NYHA stage III), the plasma levels of bisoprolol are higher and the half-life is prolonged compared to healthy volunteers. Maximum plasma concentration at steady state is 64±2 ng/mL at a daily dose of 10 mg and the shelf-life is 17±5 hrs.
Indications/Uses
Treatment of stable chronic moderate to severe heart failure with reduced systolic ventricular function (ejection fraction ≤35%, based on echocardiography) in addition to angiotensin-converting enzyme (ACE) inhibitors and diuretics, and optionally cardiac glycosides.
5 mg FC Tablet: Treatment of hypertension and coronary heart disease (angina pectoris).
Dosage/Direction for Use
Treatment of Hypertension or Angina Pectoris: 1 tab (Concor 5 mg) daily in the morning before or after breakfast. In milder forms of disease, Concor 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 6 weeks and a mainly unchanged basic therapy during the past 2 weeks. They should be treated at optimal dose with an ACE inhibitor (or other vasodilator in case of intolerance to ACE inhibitor) and a diuretic, and optionally cardiac glycosides, prior to the administration of bisoprolol.
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 has to be initiated with a titration phase as follows: The treatment with bisoprolol is to be started with a gradual up-titration according to the following steps: 1.25 mg once daily for 1 week. If well tolerated, increase to 2.5 mg up to 3.75 mg for a further week. If well tolerated, increase to 5 mg up to 7.5 mg once daily for the following weeks. If well tolerated, increase to 10 mg once daily for the maintenance therapy.
After initiation of treatment with 1.25 mg, the patients should be observed over a period of approximately 4 hrs (especially as regards to blood pressure, heart rate, conduction disturbances, signs of worsening 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 heart failure or intolerance, it is recommended first to reduce the dose of bisoprolol, or to stop immediately if necessary (in case of severe hypotension, worsening heart failure with acute pulmonary edema, cardiogenic shock, symptomatic bradycardia or atrioventrivular block).
Duration of Therapy For All Indications: Treatment of stable chronic heart failure with bisoprolol is generally a long-term treatment. The treatment with bisoprolol 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.
Special Populations: 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 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, therefore its use cannot be recommended for children.
Administration: Bisoprolol tablets should be taken in the morning and can be taken with food. The tablets should be swallowed with liquid and should not be chewed.
Overdosage
Symptoms: The most common signs 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 1 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 up-titration according to the scheme given (see Dosage & Administration).
Treatment: In general, if overdosage occurs, 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 IV 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: IV fluids and vasopressors should be administered. IV glucagon may be useful.
Atrioventricular Block (2nd- or 3rd-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 eg, isoprenaline, β2-sympathomimetic drugs and/or aminophylline.
Hypoglycaemia: Administer IV glucose.
Limited data suggest that bisoprolol is hardly dialyzable.
Contraindications
Hypersensitivity to bisoprolol or to any of the excipients of Concor. Acute heart failure or during episodes of heart failure decompensation requiring IV inotropic therapy; cardiogenic shock; 2nd- or 3rd-degree atrioventricular block (without a pacemaker); sick-sinus syndrome; sinoatrial block; symptomatic bradycardia (<60 beats/min before the start of therapy); symptomatic hypotension (systolic blood pressure <100 mmHg); severe bronchial asthma or severe chronic obstructive pulmonary disease (COPD); late stages of peripheral arterial occlusive disease and Raynaud's syndrome; untreated phaeochromocytoma; metabolic acidosis.
Warnings
Treatment of Stable Chronic Heart Failure: Treatment of stable chronic heart failure with bisoprolol has been initiated with a special titration phase (see Dosage & Administration).
Treatment of All Indications: Especially in patients with ischemic 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 (see Dosage & Administration).
Special Precautions
Treatment of Hypertension or Angina Pectoris: Bisoprolol must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.
Treatment of Stable Chronic Heart Failure: There is no therapeutic experience of bisoprolol treatment in heart failure in patients with the following diseases and conditions: New York Heart Association (NYHA) class II heart failure; insulin dependent diabetes mellitus (type I); impaired renal function (serum creatinine ≥300 micromol/L); impaired liver function; patients >80 years; restrictive cardiomyopathy; congenital heart disease; haemodynamically significant organic valvular disease; myocardial infarction within 3 months.
Treatment of All Indications: Bisoprolol must be used with caution in bronchospasm (brochial asthma, obstructive airways diseases); diabetes mellitus with large fluctuations in blood glucose values (symptoms of hypoglycaemia can be masked); strict fasting; ongoing desensitization therapy; atrioventricular block of 1st degree; prinzmetal's angina; peripheral arterial occlusive disease (intensification of complaints might happen especially during the start of therapy).
In patients undergoing general anaesthesia, the anaesthetist must be aware of β-blockade. If it is thought necessary to withdraw β-blocker therapy before surgery. This should be done gradually and completed about 48 hrs before anaesthesia.
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-blockers, 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 (eg, 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, symptoms of thyrotoxicosis may be masked.
The initiation of treatment with bisoprolol necessitates regular monitoring.
The cessation of therapy with bisoprolol should not be done abruptly unless clearly indicated.
Effects on the Ability to Drive or Operate Machinery: In study with coronary heart disease patients, bisoprolol did not impair driving performance. However, due to individual variations in reactions to bisoprolol, 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.
Use in pregnancy & lactation: 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 labor. Adverse effects (eg, hypoglycaemia and bradycardia) may occur in the fetus and newborn infant. If treatment with β-adrenoceptor blockers is necessary, β1-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 hypoglycaemia and bradycardia are generally to be expected within the first 3 days.
It is not known whether bisoprolol is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.
Use In Pregnancy & Lactation
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 labor. Adverse effects (eg, hypoglycaemia and bradycardia) may occur in the fetus and newborn infant. If treatment with β-adrenoceptor blockers is necessary, β1-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 hypoglycaemia and bradycardia are generally to be expected within the first 3 days.
It is not known whether bisoprolol is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.
Side Effects
Side effects as follows are described using the following frequencies: Very common (≥10%); common (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and <0.1%) and very rare (<0.01%) including isolated reports.
Metabolism and Nutritional Disorders: Rare: Increased triglycerides.
Psychiatric Disorders: Uncommon: Depression. Rare: Nightmares, hallucinations.
Nervous System Disorders: Common: Dizziness*, headache*. Uncommon: Sleep disturbances.
Eye Disorders: Rare: Reduced tear flow (to be considered if the patient uses contact lenses). Very Rare: Conjunctivitis.
Ear and Labyrinth Disorders: Rare: Hearing disturbances.
Cardiac Disorders: Very Common: Bradycardia (in patients with chronic heart failure). Uncommon: Atrioventricular-conduction disturbances, worsening of preexisting heart failure; bradycardia (in patients with hypertension or angina pectoris).
Vascular Disorders: Common: Feeling of coldness or numbness on the extremities, hypertension especially in patients with heart failure.
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 eg, nausea, vomiting, diarrhea, constipation.
Hepatobiliary Disorders: Rare: Increased liver enzymes (ALAT, ASAT), hepatitis.
Skin and Subcutaneous Tissue Disorders: Rare: Hypersensitivity reactions eg, itching, flush, rash. Very Rare: Alopecia, β-blockers may provoke or worsen psoriasis or induce psoriasis-like rash.
Musculoskeletal and Connective Tissue Disorders: Uncommon: Muscular weakness and cramps.
Reproductive System and Breast Disorders: Rare: Potency disorders.
General Disorders: Common: Tiredness, fatigue.
These symptoms especially occur at the beginning of the therapy. They are generally mild and usually disappears within 1-2 weeks.
Drug Interactions
Combinations Not Recommended: Treatment of Stable Chronic Heart Failure: Class I Antiarrhythmic Drugs (eg, 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 Antagonist of the Verapamil Type and to a Lesser Extent of the Diltiazem Type: Negative influence on contractility, atrioventrivular conduction and blood pressure. IV administration of verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block.
Centrally-Acting Antihypertensive Drugs eg, Clonidine and Other (eg, Methyldopa, Monoxonide, Rilmenidine): Concomitant use of centrally-acting antihypertensive drug may lead to reduction of heart rate and cardiac output to vasodilatation. Abrupt withdrawal may increase rebound hypertension.
Combinations to be Used with Caution: Treatment of Hypertension or Angina Pectoris: Class I Antiarrhythmic Drugs (eg, 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 (eg, 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 (eg, 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 (see Precautions for further information on general anaesthesia).
Digitalis Glycosides: Reduction of heart rate, increase of atrioventricular conduction time.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Decreased hypotensive effect.
Beta-Sympathomimetic Agents (eg, Isoprenaline, Dobutamine): Combination with bisoprolol may reduce the effect of both agents.
Sympathomimetic that Activates both β- and α-Adrenoreceptors (eg, 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 Antidepressant, Barbiturates, Phenothiazines as well as Other Antihypertensive Agents: Increase blood pressure-lowering effect.
Combinations to be Considered: Mefloquine: Increased risk of bradycardia.
Monoamine Oxidase Inhibitors (except Monoamine Oxidase-B Inhibitors): Enhanced hypotensive effect of β-blockers but also risk of hypertensive crisis.
Ergotamine Derivatives: Exacerbation of peripheral circulatory disturbances.
Rifampicin: Slight reduction of the half-life of bisoprolol possibly due to the induction of hepatic drug-metabolizing enzymes. Normally, no dosage adjustment is necessary.
Storage
Store below 30°C.
MIMS Class
Beta-Blockers
ATC Classification
C07AB07 - bisoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
Presentation/Packing
FC tab 1.25 mg x 50's. 2.5 mg x 100's. 5 mg x 100's. 10 mg x 3 x 10's
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