Instructions Concor film-coated tablets 10 mg No. 50
Composition
active ingredient: bisoprolol;
1 tablet contains 5 mg or 10 mg of bisoprolol fumarate;
excipients: colloidal anhydrous silicon dioxide, magnesium stearate, crospovidone, microcrystalline cellulose, corn starch, calcium hydrogen phosphate anhydrous;
film coating for 5 mg tablets: iron oxide yellow (E 172), dimethicone 100, macrogol 400, titanium dioxide (E 171), hypromellose 2910/15;
film coating for 10 mg tablets: iron oxide yellow (E 172), iron oxide red (E 172), dimethicone 100, macrogol 400, titanium dioxide (E 171), hypromellose 2910/15.
Dosage form
Film-coated tablets.
Main physicochemical properties:
5 mg tablets: yellowish-white, heart-shaped, biconvex, film-coated tablets, scored on both sides;
10 mg tablets: light orange, heart-shaped, biconvex, film-coated tablets, scored on both sides.
Pharmacotherapeutic group
Selective beta-adrenergic blockers.
ATX code C07A B07.
Pharmacological properties
Pharmacodynamics
Bisoprolol is a highly selective ß1-adrenoblocker. It has no intrinsic sympathomimetic activity and no clinically significant membrane-stabilizing properties. The drug has a very low affinity for ß2-receptors of bronchial and vascular smooth muscle, as well as for ß2-receptors involved in metabolic regulation. Thus, bisoprolol does not affect airway resistance and ß2-mediated metabolic effects. The selectivity of bisoprolol for ß1-adrenoreceptors extends beyond the therapeutic dose range.
Bisoprolol does not have a pronounced negative inotropic effect.
The maximum effect of bisoprolol occurs 3-4 hours after oral administration. The plasma half-life is 10-12 hours, which results in 24-hour efficacy after a single dose. The maximum antihypertensive effect is achieved after 2 weeks of administration.
In intensive therapy in patients with coronary heart disease without chronic heart failure, bisoprolol reduces cardiac output and myocardial oxygen demand by reducing heart rate and stroke volume. With prolonged therapy, increased peripheral resistance decreases. The antihypertensive effect of ß-blockers is also based on the mechanism of action of reducing plasma renin activity.
Bisoprolol inhibits the response to sympathoadrenergic activity by blocking cardiac β1 receptors. This leads to a slowdown in heart rate and a decrease in myocardial contractile function, which leads to a decrease in myocardial oxygen demand. This achieves the desired effect in patients with angina pectoris and ischemic heart disease.
Pharmacokinetics
Absorption. After oral administration, more than 90% of bisoprolol is absorbed from the gastrointestinal tract. Absorption is independent of food intake. The first-pass effect is ≤ 10%. Bioavailability is about 90%. Distribution. The volume of distribution is 3.5 l/kg. Binding to plasma proteins is about 30%.
Metabolism and excretion. Bisoprolol is excreted from the body in two ways: 50% is biotransformed in the liver with the formation of inactive metabolites and excreted by the kidneys, 50% is excreted by the kidneys unchanged. The total clearance of bisoprolol is 15 l/h. Due to the long half-life (10-12 hours), the drug retains its therapeutic effect for 24 hours when used once a day.
Linearity. The pharmacokinetics of bisoprolol are linear, and their parameters do not depend on age.
Special patient groups. Since bisoprolol is excreted from the body by the kidneys and liver to an equal extent, no dosage adjustment is required in patients with impaired liver function or renal dysfunction. Pharmacokinetics in patients with stable chronic heart failure and with impaired liver or renal function have not been studied. In patients with chronic heart failure of the III functional class (according to NYHA), the level of bisoprolol in the blood plasma is higher and the half-life is longer compared to healthy volunteers. The maximum plasma concentration in the equilibrium state is 64 + 21 ng / ml with a daily dose of 10 mg and a half-life of 17 + 5 hours.
Indication
- Arterial hypertension;
- ischemic heart disease (angina);
- chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides.
Contraindication
- Acute heart failure or heart failure in a state of decompensation requiring inotropic therapy;
- cardiogenic shock;
- atrioventricular block II and III degree (except in patients with an artificial pacemaker);
- sick sinus syndrome;
- sinoatrial block;
- symptomatic bradycardia;
- symptomatic arterial hypotension;
- severe form of bronchial asthma;
- late stages of peripheral circulatory disorders or Raynaud's disease;
- untreated pheochromocytoma;
- metabolic acidosis;
- hypersensitivity to bisoprolol or other components of the drug.
Interaction with other medicinal products and other types of interactions
Combinations that are not recommended for use.
Treatment of chronic heart failure.
- Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): possible potentiation of the effect on atrioventricular conduction and increased negative inotropic effect.
All indications.
- Calcium antagonists (verapamil group, to a lesser extent diltiazem): negative effect on myocardial contractile function and atrioventricular conduction. Intravenous administration of verapamil in patients taking ß-blockers can lead to severe hypotension and atrioventricular block.
- Centrally acting antihypertensives (clonidine, methyldopa, moxonidine, rilmenidine): possible worsening of heart failure due to decreased central sympathetic tone (decreased heart rate and cardiac output, vasodilation). Abrupt withdrawal of the drug, especially if preceded by withdrawal of ß-adrenoceptor blockers, may increase the risk of rebound hypertension.
Combinations that should be used with caution.
Treatment of arterial hypertension or coronary heart disease (angina pectoris).
- Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): possible potentiation of the effect on atrioventricular conduction and increased negative inotropic effect.
All indications.
- Calcium antagonists of the dihydropyridine type (e.g. nifedipine, felodipine, amlodipine): possible increased risk of arterial hypotension. The possibility of increased negative effects on myocardial inotropic function in patients with heart failure cannot be excluded.
- Class III antiarrhythmic drugs (e.g. amiodarone): possible potentiation of the effect on atrioventricular conduction.
- Topical ß-blockers (e.g. contained in eye drops for the treatment of glaucoma): possible enhancement of the systemic effects of bisoprolol.
- Parasympathomimetics: possible increase in atrioventricular conduction time and increased risk of bradycardia.
- Insulin and oral hypoglycemic agents: potentiation of the hypoglycemic effect. Blockade of ß-adrenoceptors may mask the symptoms of hypoglycemia.
- Anesthetic agents: increased risk of myocardial depression and hypotension (see section "Special warnings and precautions for use").
- Cardiac glycosides: decrease in heart rate, increase in atrioventricular conduction time.
- Non-steroidal anti-inflammatory drugs (NSAIDs): possible weakening of the hypotensive effect of bisoprolol.
- ß-sympathomimetics (e.g. orciprenaline, isoprenaline, dobutamine): use in combination with Concor may lead to a decrease in the therapeutic effect of both agents. Higher doses of adrenaline may be required for the treatment of allergic reactions.
- Sympathomimetics that activate α- and β-adrenergic receptors (e.g. adrenaline, noradrenaline): α-adrenergic receptor-mediated vasoconstriction may occur, leading to increased blood pressure and increased intermittent claudication. This interaction is more likely with non-selective β-blockers.
When used concomitantly with antihypertensive agents and agents with hypotensive effects (e.g. tricyclic antidepressants, barbiturates, phenothiazines), the risk of arterial hypotension may increase.
Possible combinations.
- Mefloquine: possible increased risk of bradycardia.
- MAO inhibitors (except MAO inhibitors type B): increased hypotensive effect of ß-blockers, but there is a risk of developing hypertensive crisis.
Application features
Treatment of stable chronic heart failure with bisoprolol should begin with a titration phase.
In patients with coronary heart disease, treatment should not be stopped abruptly without urgent need, as this may lead to transient deterioration of the condition. Initiation and discontinuation of bisoprolol treatment requires regular monitoring.
Currently, there is insufficient therapeutic experience in the treatment of heart failure in patients with the following diseases and pathological conditions: type 1 diabetes mellitus (insulin-dependent), severe renal impairment, severe hepatic impairment, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant acquired valvular heart disease, myocardial infarction within the last 3 months.
The drug should be used with caution in patients with the following conditions:
- bronchospasm (in bronchial asthma, obstructive airway diseases);
- diabetes mellitus with significant fluctuations in blood glucose levels, while symptoms of hypoglycemia (tachycardia, palpitations, sweating) may be hidden;
- strict diet;
- desensitization therapy. Like other ß-blockers, bisoprolol may increase sensitivity to allergens and increase the severity of anaphylactic reactions. In such cases, treatment with adrenaline does not always give a positive therapeutic effect;
- atrioventricular block I degree;
- Prinzmetal's angina;
- obliterating diseases of peripheral arteries (at the beginning of therapy, complaints may increase);
In patients undergoing general anesthesia, the use of ß-blockers reduces the incidence of arrhythmias and myocardial ischemia during induction of anesthesia, intubation, and the postoperative period. It is recommended to continue the use of ß-blockers during the perioperative period. It is imperative to warn the anesthesiologist about the use of ß-adrenoceptor blockers, as the doctor must take into account the potential interaction with other drugs, which can lead to bradyarrhythmia, reflex tachycardia, and a decrease in the ability of the reflex mechanism to compensate for blood loss. In the case of discontinuation of bisoprolol before surgery, the dose should be gradually reduced and the drug should be discontinued 48 hours before general anesthesia.
Combinations of bisoprolol with calcium antagonists of the verapamil or diltiazem group, with class I antiarrhythmic drugs and with centrally acting antihypertensive agents are not recommended (see section "Interaction with other medicinal products and other types of interactions").
Although cardioselective ß-blockers (ß1) have less effect on lung function than non-selective ß-blockers, their use, like all ß-blockers, should be avoided in obstructive airway diseases unless there are compelling reasons for therapy. If necessary, Concor should be used with caution. In patients with obstructive airway diseases, treatment with bisoprolol should be initiated at the lowest possible dose and patients should be monitored for the development of new symptoms (such as dyspnea, exercise intolerance, cough).
In bronchial asthma or other chronic obstructive pulmonary diseases that may cause symptoms, concomitant therapy with bronchodilators is indicated. In some cases, patients with bronchial asthma may require higher doses of ß2-sympathomimetics due to increased airway resistance while taking the drug.
Patients with psoriasis (including those with a history of psoriasis) are prescribed ß-blockers (e.g. bisoprolol) after careful benefit/risk assessment.
Patients with pheochromocytoma are prescribed Concor only after the appointment of α-adrenergic blockers. Symptoms of thyrotoxicosis may be masked by taking the drug. When using Concor, a positive result may be observed during doping control.
Use during pregnancy or breastfeeding
Pregnancy. Bisoprolol has pharmacological properties that may cause harmful effects on the course of pregnancy and/or the development of the fetus/newborn. As a rule, ß-blockers reduce placental blood flow, which can cause intrauterine growth retardation, intrauterine death, spontaneous abortion or premature birth. Adverse effects in the fetus and newborn (e.g. hypoglycemia, bradycardia) may develop. If treatment with ß-blockers is necessary, it is preferable that it be a ß1-selective adrenoblocker.
During pregnancy, the drug should be used only if the expected benefit to the mother outweighs the potential risk to the fetus. It is necessary to monitor uteroplacental blood flow and fetal growth. In case of harmful effects on the course of pregnancy or the fetus, alternative treatment should be considered.
After delivery, the newborn should be closely monitored. Symptoms of hypoglycemia and bradycardia can be expected during the first 3 days.
Breastfeeding. There is no data on the excretion of bisoprolol into breast milk, therefore it is not recommended to use Concor during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
In studies involving patients with coronary heart disease, the drug did not affect the ability to drive a car. However, in individual cases, the drug may affect the ability to drive or operate complex mechanisms. Special attention should be paid at the beginning of treatment, when changing the dose of the drug or when interacting with alcohol.
Method of administration and doses
Concor should be taken without chewing, in the morning on an empty stomach, during or after breakfast, with a small amount of liquid.
Arterial hypertension; ischemic heart disease (angina pectoris).
Treatment should be started gradually with low doses and then increased. The recommended dose is 5 mg (1 tablet of Concor 5 mg) per day. In mild hypertension (diastolic blood pressure up to 105 mm Hg), a dose of 2.5 mg is suitable.
If necessary, the daily dose may be increased to 10 mg (1 tablet of Concor 10 mg) per day. Further dose increases are justified only in exceptional cases. The maximum recommended dose is 20 mg per day.
Dose adjustments are determined by the physician individually depending on pulse rate and therapeutic benefit.
Chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides.
Concor is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.
Therapy should be carried out by a doctor with experience in the treatment of chronic heart failure.
Treatment of stable chronic heart failure with Concor is initiated according to the titration schedule below and may be adjusted depending on individual body responses.
– 1.25 mg* bisoprolol fumarate once daily for 1 week, if well tolerated, increase to
– 2.5 mg* bisoprolol fumarate once daily for the next 1 week, if well tolerated, increase to
– 3.75 mg* bisoprolol fumarate once daily for the next 1 week, if well tolerated, increase to
– 5 mg bisoprolol fumarate once daily for the next 4 weeks, if well tolerated, increase to
– 7.5 mg bisoprolol fumarate once daily for the next 4 weeks, if well tolerated, increase to
– 10 mg of bisoprolol fumarate once daily as maintenance therapy.
* At the beginning of chronic heart failure therapy, it is recommended to use Concor Cor, film-coated tablets, 2.5 mg.
The maximum recommended dose of bisoprolol fumarate is 10 mg once daily.
During the titration phase, the following vital signs (blood pressure, heart rate) and symptoms of heart failure progression should be monitored. Symptoms may develop from the first day after starting treatment.
Treatment modification.
If the maximum recommended dose is not tolerated, a gradual dose reduction may be considered. If during or after the titration phase there is a gradual worsening of heart failure, hypotension or bradycardia, dose adjustment is recommended, which may require a temporary reduction in the bisoprolol dose or possibly discontinuation of treatment. After the patient's condition has stabilized, the possibility of reinitiating bisoprolol treatment should always be considered.
Treatment with the drug should not be stopped suddenly, especially in patients with ischemic heart disease, as this may lead to a deterioration in the patient's condition. If necessary, treatment with the drug is recommended to be discontinued slowly, gradually reducing the dose (for example, reducing the dose by half every week).
Treatment of stable chronic heart failure is usually long-term.
The course of treatment with Concor is long and depends on the nature and severity of the disease.
Patients with hepatic and/or renal insufficiency.
Arterial hypertension; ischemic heart disease. For patients with mild to moderate hepatic or renal impairment, dose adjustment is usually not required. For patients with severe renal impairment (creatinine clearance less than 20 ml/min) and patients with severe hepatic impairment, the dose should not exceed a daily dose of 10 mg Concor. There are limited data on the use of bisoprolol in patients on dialysis. There is no need to change the dosage regimen.
Chronic heart failure. There are no data on the pharmacokinetics of bisoprolol in patients with chronic heart failure concomitant with impaired liver or kidney function, therefore, increasing the dose should be done with caution.
Elderly patients do not require dose adjustment.
Children
There is no clinical data on the efficacy and safety of the drug for the treatment of children, therefore the drug should not be used in this category of patients.
Overdose
Symptoms.
In case of overdose (for example, using a daily dose of 15 mg instead of 7.5 mg), cases of third-degree atrioventricular block, bradycardia and dizziness have been reported. The most common signs of overdose are:
ß-blockers are bradycardia, hypotension, acute heart failure, hypoglycemia and bronchospasm. Currently, several cases of overdose in patients with arterial hypertension and / or ischemic heart disease are known (maximum dose - 2000 mg bisoprolol). Bradycardia and / or hypotension were noted. All patients recovered. There is a wide variability in individual sensitivity to a single high dose of bisoprolol, patients with heart failure may be more sensitive to the drug. Therefore, treatment should be started with a gradual increase in dosage (see section "Method of administration and dosage").
Treatment.
In case of overdose, treatment with the drug is discontinued and supportive and symptomatic therapy is carried out. There is limited evidence that bisoprolol is difficult to dialyze. In case of suspected overdose, the following general measures should be considered, in accordance with the expected pharmacological action and based on recommendations for other ß-blockers.
For bradycardia: intravenous atropine. If there is no response, isoprenaline or another drug with a positive chronotropic effect is administered with caution. In exceptional cases, transvenous administration of an artificial pacemaker may be necessary.
For hypotension: intravenous fluids and vasoconstrictors. Intravenous glucagon may be useful.
In case of exacerbation of chronic heart failure: intravenous administration of diuretics, inotropic drugs, vasodilators.
For bronchospasm: bronchodilators (e.g. isoprenaline), ß2-adrenomimetics and/or aminophylline.
For hypoglycemia: intravenous glucose administration.
Adverse reactions
Adverse effects are classified according to the frequency of occurrence into the following categories:
very common (> 1/10), common (> 1/100 and < 1/10), uncommon (> 1/1000 and < 1/100), rare (> 1/10000 and < 1/1000), very rare (< 1/10000), unknown (frequency not determined from the data).
From the heart.
Very common: bradycardia (in patients with chronic heart failure).
Common: signs of worsening heart failure (in patients with chronic heart failure).
Uncommon: atrioventricular conduction disturbances, bradycardia (in patients with arterial hypertension or ischemic heart disease), signs of worsening heart failure (in patients with arterial hypertension or ischemic heart disease).
From the nervous system.
Common: dizziness*, headache*.
Rare: syncope.
From the organs of vision.
Rare: decreased tear production (should be taken into account when wearing contact lenses).
Very rare: conjunctivitis.
From the side of the hearing organs.
Rare: hearing impairment.
On the part of the respiratory system.
Uncommon: bronchospasm in patients with a history of bronchial asthma or obstructive airways disease.
Rare: allergic rhinitis.
From the digestive tract.
Common: nausea, vomiting, diarrhea, constipation.
Skin and connective tissue disorders.
Rare: hypersensitivity reactions including itching, redness, rash.
Very rare: alopecia. Treatment with ß-blockers may cause worsening of psoriasis in the form of psoriatic rash.
On the part of the musculoskeletal system.
Uncommon: muscle weakness, cramps.
From the liver.
Rare: hepatitis.
From the vascular system.
Common: feeling of coldness or numbness in the extremities, hypotension (in patients with chronic heart failure).
Uncommon: orthostatic hypotension (in patients with chronic heart failure), hypotension (in patients with hypertension or coronary heart disease).
From the reproductive system.
Rare: impotence.
Mental disorders.
Uncommon: depression, sleep disorders.
Rare: nightmares, hallucinations.
Laboratory indicators.
Rare: increased blood triglyceride levels, increased activity of liver enzymes in blood plasma (AST, ALT).
General disorders.
Common: asthenia (in patients with chronic heart failure), fatigue*.
Uncommon: asthenia (in patients with arterial hypertension or ischemic heart disease).
* Applies only to patients with arterial hypertension or coronary heart disease. These symptoms usually occur at the beginning of therapy, are mild and disappear within the first 1-2 weeks.
In case of side effects or adverse reactions, you should immediately inform your doctor.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children!
Packaging
30 tablets in a blister; 1 blister in a cardboard box.
25 tablets in a blister; 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Merck KGaA, Germany.
Location of the manufacturer and its business address
Frankfurter Strasse 250, 64293 Darmstadt, Germany/Frankfurter Strasse 250, 64293 Darmstadt, Germany.
