Concor

Concor

bisoprolol

Manufacturer:

Merck

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Bisoprolol fumarate.
Description
Excipients/Inactive Ingredients: Tablet Core: Anhydrous colloidal silica, magnesium stearate, crospovidone, microcrystalline cellulose, maize starch, anhydrous calcium hydrogen phosphate.
Film-Coating: Dimethicone, macrogol 400, titanium dioxide and hypromellose, yellow iron oxide (Concor 5 and Concor 10), and red iron oxide (Concor 10 only).
Action
Pharmacology: Pharmacodynamics: Bisoprolol, the active ingredient of Concor, is a β1-selective adrenoceptor-blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity. It only shows very 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.
Pharmacokinetics: Absorption: Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract (GIT) and because of its small first-pass metabolism of approximately 10%, has a bioavailability of approximately 90% after oral administration. The bioavailability is not affected by food intake. Bisoprolol shows linear kinetics and the plasma concentrations are proportional to the administered dose over the dose range 5-20 mg. Peak plasma concentrations occur within 2 to 3 hours.
Distribution: Bisoprolol is extensively distributed. The volume of distribution is 3.5 L/kg. Binding to plasma proteins is approximately 30%.
Metabolism: Bisoprolol is metabolised via oxidative pathways with no subsequent conjugation. All metabolites, being very polar, are renally eliminated. The major metabolites in human plasma and urine were found to be without pharmacological activity. In vitro data from studies in human liver microsomes show that bisoprolol is primarily metabolised via CYP3A4 (approximately 95%) with CYP2D6 having only a minor role.
Elimination: The clearance of bisoprolol is "balanced" between renal elimination of the unchanged molecule (approximately 50%) and hepatic metabolism (approximately 50%) to metabolites which are also renally excreted. The total clearance of bisoprolol is approximately 15 L/hr. Bisoprolol has an elimination half-life of 10 to 12 hours.
Indications/Uses
Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to angiotensin-converting enzyme (ACE) inhibitors and diuretics, and optionally, cardiac glycosides.
Concor 5 and 10 mg: High blood pressure (hypertension). Coronary heart disease [(CHD); angina pectoris].
Dosage/Direction for Use
Stable Chronic Heart Failure: Standard treatment of chronic heart failure consists of an ACE-inhibitor (or an angiotensin receptor blocker in case of intolerance to ACE-inhibitors), a β-blocker, diuretics, and when appropriate, cardiac glycosides. The initiation of treatment of stable chronic heart failure with Concor necessitates a special titration phase.
Precondition 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 ie, the dose is to be increased only if the previous dose is well tolerated.
1st Week: Bisoprolol fumarate 1.25 mg once daily.*
2nd Week: Bisoprolol fumarate 2.5 mg once daily.
3rd Week: Bisoprolol fumarate 3.75 mg once daily.*
4th-7th Week: Bisoprolol fumarate 5 mg once daily.*
8th-11th Week: Bisoprolol fumarate 7.5 mg once daily.*
≥12th Week: Bisoprolol fumarate 10 mg once daily as maintenance treatment.*
Maximum Recommended Dose: Bisoprolol fumarate 10 mg once daily.
*Concor 2.5 mg is suitable for initial treatment of stable chronic heart failure. Higher strengths are available for maintenance treatment.
Close monitoring of vital signs (eg, blood pressure, heart rate) and symptoms of worsening heart failure is recommended during the titration phase. Symptoms may already occur within the 1st day after initiating therapy.
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: Treatment with Concor 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 the advise of the physician since this might lead to a transitory worsening of heart condition. Especially in patients with ischaemic heart disease, treatment must not be discontinued suddenly. If discontinuation is necessary, the daily dose is gradually decreased.
Concor 5/Concor 10: Hypertension or Angina Pectoris: In all cases the dose regimen is adjusted individually by the physician, in particular according to the pulse rate and therapeutic success.
Usual Initial Dose: Bisoprolol fumarate 5 mg once daily. If necessary, the dose may be increased to bisoprolol fumarate 10 mg once daily.
Maximum Recommended Dose: Bisoprolol fumarate 20 mg once daily.
Concor must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.
Special Populations: Renal or Hepatic Impairment: In patients with mild to moderate liver or kidney function disorders, no dosage adjustment is normally required in the treatment of hypertension or angina pectoris. In patients with severe renal impairment [creatinine clearance (CrCl) <20 mL/min)] and in patients with severe hepatic impairment, the patient must not exceed a daily dose of bisoprolol fumarate 10 mg.
There is no information regarding the 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 no paediatric experience with bisoprolol; therefore, its use cannot be recommended for children.
Administration: Concor tablets are taken in the morning with or without food. Concor is swallowed whole with some liquid and not be chewed.
Overdosage
Symptoms: The most frequent signs of Concor overdosage include slow heart rate (bradycardia), marked drop in blood pressure, acute heart failure, hypoglycaemia and bronchospasm.
Treatment: In the case of suspected Concor overdosage, inform the physician immediately. The effect of overdosage may vary from one person to the next and patients with heart failure are probably very sensitive.
Depending on the degree of overdosage, the physician can then decide which measures to take.
In general, if overdosage occurs, bisoprolol treatment is stopped and supportive and symptomatic treatment is provided. Limited data suggest that bisoprolol is hardly dialysable.
Contraindications
Hypersensitivity to bisoprolol or to any of the excipients of Concor (see Description).
Acute heart failure or during episodes of heart failure decompensation requiring IV therapy with substances increasing the contractility of the heart; shock induced by disorders of cardiac function (cardiogenic shock); severe disturbances of atrioventricular conduction (2nd or 3rd degree AV block) without a pacemaker; sick sinus syndrome, sinoatrial block; slowed heart rate, causing symptoms (symptomatic bradycardia); decreased blood pressure, causing symptoms (symptomatic hypotension); severe bronchial asthma or severe chronic obstructive pulmonary disease; severe forms of peripheral arterial occlusive disease or Raynaud's syndrome; untreated tumours of the adrenal gland (phaeochromocytoma); metabolic acidosis.
Special Precautions
Diabetes Mellitus with Extremely Fluctuating Blood Glucose Levels: Symptoms of markedly reduced blood glucose (hypoglycaemia) eg, tachycardia, palpitations or sweating can be masked; strict fasting; ongoing desensitisation therapy; mild disturbances of atrioventricular conduction (1st degree AV block); disturbed blood flow in the coronary vessels due to vasospasms (Prinzmetal's angina); peripheral arterial occlusive disease (aggravation of symptoms may occur especially when starting therapy); patients with psoriasis or with a personal history of psoriasis.
Respiratory System: In bronchial asthma or other symptomatic chronic obstructive pulmonary diseases, concomitant bronchodilator therapy is indicated. An increase in airway resistance may occasionally occur in patients with asthma, requiring a higher dose of β2-sympathomimetics.
Allergic Reactions: β-blockers, including Concor, may increase the sensitivity to allergens and the severity of anaphylactic reactions because the adrenergic counterregulation under β-blockade may be alleviated. Treatment with adrenaline may not always yield the expected therapeutic effect.
General Anaesthesia: In patients undergoing general anaesthesia, the anaesthetist must be aware of β-blockade. If it is thought necessary to withdraw Concor before surgery, this should be done gradually and completed about 48 hrs prior to anaesthesia.
Phaeochromocytoma: In patients with a tumour of the adrenal gland (phaeochromocytoma), Concor may only be administered after previous α-receptor blockade.
Thyrotoxicosis: Under treatment with Concor, the symptoms of a thyroid hyperfunction (thyrotoxicosis) may be masked.
Special Populations: So far, no sufficient therapeutic experience is available for Concor in patients with heart failure and concomitant insulin-dependent type I diabetes mellitus, severely impaired kidney function, severely impaired hepatic function, restrictive cardiomyopathy, congenital heart diseases or haemodynamically relevant organic valvular heart disease. No sufficient therapeutic experience is available either in patients with heart failure and myocardial infarction within the last 3 months.
Effects on the Ability to Drive or Operate Machinery: In a study with patients suffering from coronary heart disease, bisoprolol did not affect the driving performance of the patients. However, depending on the individual patient's response to treatment, an effect on the ability to drive a vehicle or to use machines may be impaired. This needs to be considered particularly at the start of treatment, upon change of medication or in conjunction with alcohol.
Use in pregnancy & lactation: During pregnancy, Concor is only recommended following careful assessment of benefit-to-risk ratio by the physician.
In general, β-blockers reduce placental blood flow and may affect the development of the unborn child. Placental and uterine blood flow as well as the growth of the unborn child must be monitored, and in case of harmful effects on pregnancy or the foetus, alternative therapeutic measures considered.
The newborn infant must be monitored closely after delivery. Symptoms of reduced blood glucose and slowed pulse rate generally may occur within the first 3 days of life.
There are no data on the excretion of bisoprolol in human breast milk or the safety of bisoprolol exposure in infants. Therefore, administration of Concor is not recommended during breastfeeding.
Use in children: There is insufficient experience with bisoprolol in children; therefore, the use of Concor cannot be recommended for children.
Use In Pregnancy & Lactation
During pregnancy, Concor is only recommended following careful assessment of benefit-to-risk ratio by the physician.
In general, β-blockers reduce placental blood flow and may affect the development of the unborn child. Placental and uterine blood flow as well as the growth of the unborn child must be monitored, and in case of harmful effects on pregnancy or the foetus, alternative therapeutic measures considered.
The newborn infant must be monitored closely after delivery. Symptoms of reduced blood glucose and slowed pulse rate generally may occur within the first 3 days of life.
There are no data on the excretion of bisoprolol in human breast milk or the safety of bisoprolol exposure in infants. Therefore, administration of Concor is not recommended during breastfeeding.
Adverse Reactions
The adverse effects described as follows are sorted according to system organ classes. Frequencies are classified as follows: Very common (>1/10); common (<1/10); uncommon (<1/100); rare (<1/1000); very rare (<1/10,000).
Investigations: Rare: Increased triglycerides, increased liver enzymes (ALAT, ASAT).
Cardiac Disorders: Very Common: Bradycardia (in patients with chronic heart failure). Common: Worsening of preexisting heart failure (in patients with chronic heart failure). Uncommon: AV-conduction disturbances, bradycardia (in patients with hypertension or angina pectoris); worsening of preexisting heart failure (in patients with hypertension or angina pectoris).
Nervous System Disorders: Common: Dizziness*, headache*.
Eye Disorders: Rare: Reduced tear flow (to be considered if the patient uses contact 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 eg, nausea, vomiting, diarrhoea, constipation.
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: Muscle weakness, muscle cramps.
Vascular Disorders: Common: Feeling of coldness or numbness in the extremities, hypotension especially in patients with heart failure.
General Disorders: Common: Asthenia (in patients with chronic heart failure), fatigue*. Uncommon: Asthenia (in patients with hypertension or angina pectoris).
Hepatobilary Disorders: Rare: Hepatitis.
Reproductive System and Breast Disorders: Rare: Potency disorders.
Psychiatric Disorders: Uncommon: Depression, sleep disorders. Rare: Nightmares, hallucinations.
Applies only to patients with hypertension or angina pectoris: *These symptoms especially occur at the beginning of the therapy. They are generally mild and usually disappear within 1-2 weeks.
Inform the physician if any of the side effects listed previously is noticed, or any other unwanted or unexpected effects. To prevent serious reactions, consult a physician immediately if a side effect is severe, occurred suddenly or gets worse rapidly.
Drug Interactions
The effect and tolerability of medicines can be influenced by simultaneous intake of other medication. Such interactions can also occur if a short time has elapsed since the use of the other medication. Inform the physician if any other medicine is being taken.
Combinations Not Recommended: Treatment of Stable Chronic Heart Failure: Class-I antiarrhythmic medicines (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) may increase the depressant effect of Concor on atrioventricular impulse conduction and the contractility of the heart.
All Indications: Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type may lead to reduced contractility of the heart muscle and delayed atrioventricular impulse conduction when used concomitantly with Concor. Especially IV administration of verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block.
Centrally-acting blood pressure-lowering medicines (eg, clonidine, methyldopa, moxonodine, rilmenidine) may lead to a reduction of heart rate and cardiac output, as well as to vasodilation due to a decrease in the central sympathetic tonus. Abrupt withdrawal, particularly if prior to β-blocker discontinuation, may increase risk of "rebound hypertension".
Combinations to be Used with Caution: Treatment of Hypertension or Coronary Heart Disease (Angina Pectoris): Class-I antiarrhythmic medicines (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) may increase the depressant effect of Concor on atrioventricular impulse conduction and the contractility of the heart.
All Indications: Calcium antagonists of the dihydropyridine type (eg, nifedipine felodipine, amlodipine) may increase the risk of hypotension when used concomitantly with Concor. An increased risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
Class-III antiarrhythmic medicines (eg, amiodarone) may increase the inhibitory effect of Concor on atrioventricular impulse conduction.
Topical β-blockers (eg, eye drops for glaucoma treatment) may add to the systemic effects of Concor.
Parasympathomimetic medicines may increase the inhibitory effect on atrioventricular impulse conduction and the risk of bradycardia when used concomitantly with Concor.
The blood sugar-lowering effect of insulin or oral antidiabetic medicines may be increased. Warning signs of reduced blood glucose (hypoglycemia), especially accelerated heart rate (tachycardia) may be masked or suppressed. Such interactions are considered to be more likely with nonselective β-blockers.
Anaesthetic agents may increase the risk of cardiodepressive actions of Concor, leading to hypotension (see Precautions: General Anesthesia).
Cardiac glycosides (digitalis) may lead to an increase in impulse conduction time and thus, reduction in heart rate when used concomitantly with Concor.
Nonsteroidal anti-inflammatory medicines may reduce the blood pressure-lowering effect of Concor.
Beta-Sympathomimetics (eg, isoprenaline, dobutamine) used in combination with Concor may lead to a reduced effect of both agents.
A combination of Concor with sympathomimetics that activate both β- and α-adrenoceptors (eg, noradrenaline, adrenaline) may intensify the α-adrenoceptor-mediated vasoconstrictor effects of these agents leading to blood pressure increase. Such interactions are considered to be more likely with nonselective β-blockers.
Antihypertensive agents as well as other medicines with blood pressure-lowering potential (eg, tricyclic antidepressants, barbiturates, phenothiazines) may increase the blood pressure-lowering effect of Concor.
Combinations to be Considered: Mefloquine may increase the risk of decelerating the heart rate (bradycardia), if used in combination with Concor.
Monoamine oxidase (MAO) inhibitors (except MAO-B inhibitors) may enhance the hypotensive effect of the β-blockers. Concomitant use may also be a risk for hypertensive crisis.
Storage
Do not store above 30°C.

MIMS Class
ATC Classification
C07AB07 - bisoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
Presentation/Packing
FC tab 2.5 mg (white, heart-shaped, biconvex, scored on both sides) x 10 x 10's. 5 mg (yellowish white, heart shaped, biconvex, scored on both sides) x 10 x 10's. 10 mg (pale orange to light orange, heart shaped, biconvex, scored on both sides) x 10 x 10's.
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