Concor

Active material: Bisoprolol
When ATH: C07AB07
CCF: Beta₁-adrenoblokator
ICD-10 codes (testimony): I10, i20, I50.0
When CSF: 01.01.01.02
Manufacturer: MERCK KGaA (Germany)

DOSAGE FORM, STRUCTURE AND PACKAGING

Pills, Film-coated light yellow, heart-shaped, lenticular, with Valium on both sides.

Excipients: Colloidal anhydrous silica, magnesium stearate, krospovydon, microcrystalline cellulose, corn starch, calcium hydrogen phosphate, anhydrous.

The composition of the shell: dye iron oxide yellow (E172), Dimethicone 100, macrogol 400, Titanium oxide (E171), gipromelloza 2910/15.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pills, Film-coated light orange, heart-shaped, lenticular, with Valium on both sides.

Excipients: Colloidal anhydrous silica, magnesium stearate, krospovydon, microcrystalline cellulose, corn starch, calcium hydrogen phosphate, calcium hydrogen phosphate, anhydrous.

The composition of the shell: iron oxide red dye (E172), dye iron oxide yellow (E172), Dimethicone 100, macrogol 400, Titanium oxide (E171), gipromelloza 2910/15.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Selective beta₁-adrenoblokator, without its own sympathomimetic activity, It does not have the membrane-stabilizing action.

It reduces plasma renin activity, reducing myocardial oxygen demand, reduces heart rate (at rest and during exercise). It has hypotensive, antiarrhythmic and antianginal. Blocking in low doses β_1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, It has a negative chrono, dromo-, ʙatmo- and inotropic effect (oppressing conductivity and anxiety, slows AV-conduction). With increasing doses of the above therapeutic exerts beta₂-adrenoceptor blocking action.

PR at the beginning of the drug, first 24 no, increases slightly (as a result of reciprocal increase in the activity of α-adrenergic receptors), which, through 1-3 d returns to the original, and prolonged the appointment of reduced.

The hypotensive effect is associated with a decrease in cardiac output, sympathetic stimulation of peripheral vascular, decreased activity of the renin-angiotensin system (It is of great importance for patients with initial hypersecretion renin), restoration of sensitivity in response to a decrease in blood pressure and the influence of the central nervous system. When hypertension effect after 2-5 days, stable operation – through 1-2 of the month.

Antianginal effect is due to a decrease in myocardial oxygen demand as a result of deceleration in heart rate and contractility slight decline, lengthening of diastole, improving myocardial perfusion.

Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing AV-conduction (mainly in the antegrade and, less, in retrograde direction through the AV-node) and on additional routes.

When used in high therapeutic doses, Unlike non-selective beta-blockers, It has a less pronounced effect on the organs, содержащие b₂-adrenoreceptory (pancreas, skeletal muscle, smooth muscle peripheral arteries, bronchial and uterine) and carbohydrate metabolism, It does not cause a delay of sodium ions in the body.

Pharmacokinetics

Absorption

Bisoprolol almost completely (>90%) absorbed from the gastrointestinal tract. Its bioavailability is approximately 85-90% after ingestion; eating does not affect the bioavailability of. Bisoprolol shows linear kinetics, and its concentration in the blood plasma are proportional administered dose in the dose range from 5 to 20 mg. C_max plasma levels achieved after 2-3 no.

Distribution

Bisoprolol is widely distributed. V_d is 3.5 l / kg. Communication with the plasma proteins reaches approximately 35%; capture blood cells is not observed.

Metabolism

It is metabolized by oxidative pathway without subsequent conjugation; when there is a slight metabolization “first pass” through the liver (at approximately 10-15%). All metabolites have a strong polarity. The main metabolites, detectable in the plasma and urine, not exhibit pharmacological activity. Data, derived from experiments with human liver microsomes in vitro, show, that bisoprolol is metabolized, Firstly, via CYP3A4 (about 95%), a CYP2D6 plays only a minor role.

Deduction

The clearance of bisoprolol is determined by the balance between its excretion by the kidneys as unchanged substance (about 50%) and oxidation in the liver (about 50%) to metabolites, which are then excreted by the kidneys and. The total clearance of 15.6 ± 3.2 l /, and the renal clearance is 9.6 ± 1.6 l / h. T_1/2 is 10-12 no.

Testimony

- Arterial hypertension;

- CHD: prevention of angina attacks;

- Congestive heart failure.

Dosage regimen

The tablets should be taken orally, drinking a small amount of liquid in the morning before breakfast, during or after. Tablets should not be chewed or rubbed into powder.

Treatment of hypertension and angina

In all patients, the dose selected individually, especially taking into account the state of the patient's heart rate and.

Usually, starting dose is 5 mg (1 tab.) 1 time / day. If necessary, the dose can be increased to 10 mg 1 time / day.

In the treatment of hypertension and angina maximum recommended dose is 20 mg 1 time / day.

To patients with severely impaired renal function (CC<20 ml / min) and patients severe hepatic impairment The maximum daily dose is 10 mg.

Patients with impaired hepatic or renal function mild or moderate, and elderly patients correct dosing regimen, usually, not required.

Treatment of chronic heart failure

Home treatment of chronic heart failure drug Concor^® necessarily require the special titration phase and regular medical monitoring.

Prerequisites for the treatment Concor^®:

– Chronic heart failure with no signs of exacerbation in the previous 6 weeks;

– virtually unchanged basic therapy during the previous 2 of the week;

– Treatment optimal doses of ACE inhibitors (or other vasodilator in case of intolerance to ACE inhibitors), diuretics and, optional, cardiac glycosides.

Treatment of chronic heart failure Concor^® It begins in accordance with the following scheme titration. This may require individual adaptation depending on, how well patients tolerate the prescribed dose, t. it is. dose can be increased only if, if the previous dose was well tolerated.

To ensure the above mentioned titration mode in the initial stages of treatment is recommended to use the drug Concor^® Work.

The maximum recommended dose Concor^® in the treatment of chronic heart failure 10 mg 1 time / day.

Patients are advised to take the doctor picked up drug dose, If no side reactions occur.

After the start of treatment at a dose 1.25 mg (1/2 tab. drug Concor^® Work) the patient should be monitored for 4 no (control heart rate, FROM, conduction disorders, signs of worsening of heart failure).

During the titration phase or after it can be a temporary worsening of heart failure, fluid retention, bradycardia or hypotension. In this case, it is recommended to pay attention to the selection of doses of concomitant therapy base (optimize the dose of the diuretic and / or ACE inhibitor) prior to dose reduction Concor^®. Treatment Konkorom^® should be interrupted only if absolutely necessary.

After stabilizing the patient's condition should be a re-titration, or continue treatment.

In applying the drug in elderly patients dose adjustment is required.

The duration of treatment for all indications

Treatment with Concor^® usually is a long. If necessary, the treatment may be interrupted, and renewed in compliance with certain rules. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If you want to discontinuation of treatment, the dose should be reduced gradually.

Side effect

The frequency of adverse reactions, below, determined by the following gradations: Often (≥10%); often (>1%, <10%); infrequently (>0.1%, <1%); rarely (>0.01%, <0.1%); rarely (≤0.01%, including isolated reports).

Cardio-vascular system: Often – a decrease in heart rate (bradycardia, especially in patients with chronic heart failure); often – hypotension (especially in patients with chronic heart failure), manifestation of vasospasm (increased peripheral circulatory disorders, cold feeling in extremities (paresthesia); infrequently – violation of AV-conduction, orthostatic hypotension, decompensated heart failure, with the development of peripheral edema.

CNS: infrequently – dizziness, headache, asthenia, fatigue, sleep disorders, depression; rarely – hallucinations, nightmares, convulsions. Typically, these effects are mild and disappear, usually, during 1-2 weeks after initiation of treatment.

On the part of the organ of vision: rarely – blurred vision, decrease in lacrimation (to consider when wearing contact lenses); rarely – conjunctivitis.

The respiratory system: infrequently – bronchospasm in patients with asthma or obstructive airways disease; rarely – nasal allergy.

From the digestive system: often – nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa; rarely – hepatitis, increase the level of liver enzymes in the blood (IS, GOLD).

On the part of the musculoskeletal system: infrequently – muscular weakness, cramps in the calf muscles, arthralgia.

Reproductive system: rarely – potency disorders.

Laboratory findings: rarely – elevated triglycerides in the blood; in some cases – thrombocytopenia, agranulocytosis.

Allergic reactions: rarely – itching, erythema, rash.

Dermatological reactions: rarely – Sweating; rarely – alopecia. Beta-blockers may exacerbate psoriasis.

Contraindications

- Acute heart failure;

- Chronic heart failure decompensation;

- Shock, caused by impaired cardiac function (cardiogenic shock);

- Collapse;

— AV-blockade II and III degrees, without pacemaker;

- SSS;

- Sinoatrialynaya blockade;

- Vыrazhennaya bradycardia (Heart Rate<50 u. / min.);

- Marked reduction of blood pressure (systolic blood pressure <90 mmHg.);

- Severe bronchial asthma or a history of COPD;

- Late stages of peripheral circulatory disorders, Raynaud's disease;

- Pheochromocytoma (without the simultaneous use of alpha-blockers);

- Metabolic acidosis;

- Simultaneous MAO inhibitors (except the MAO-B inhibitor);

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Hypersensitivity to bisoprolol or to any of the components to other beta-blockers.

FROM caution use in patients with hepatic insufficiency, chronic renal failure, myasthenia, thyrotoxicosis, diabetes, AV-blockade I degree, Prinzmetal angina, depression (incl. history), psoriaze, in elderly patients.

Pregnancy and lactation

Use of the drug Concor^® Pregnancy may only, when the intended benefits to the mother outweighs the potential risk to the fetus.

Beta-blockers reduce blood flow to the placenta and can affect fetal development. It should closely monitor the blood flow in the placenta and the uterus, as well as to monitor the growth and development of the unborn child, in the case of dangerous manifestations in relation to pregnancy or fetal, take alternative therapeutic measures. You should carefully examine the newborn after birth. First 3 life of the day may have symptoms of lowering blood glucose and HR.

Data allocation of bisoprolol with breast milk or the safety of bisoprolol exposure to infants is not. The drug Concor^® not recommended for women during lactation.

Cautions

The patient should not abruptly discontinue and change the recommended dose without first consulting your doctor, because it can lead to temporary impairment of the heart. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation is necessary, the dose should be reduced gradually.

Monitoring of patients, taking Concor^®, It should include measurement of blood pressure and heart rate (at the beginning of treatment – daily, then 1 once every 3-4 Months), conduct an electrocardiogram, determination of blood glucose in patients with diabetes mellitus (1 once every 4-5 Months). Elderly patients is recommended to monitor renal function (1 once every 4-5 Months).

It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in HR<50 u. / min.

Before treatment is recommended study of respiratory function in patients with a history of bronchopulmonary history.

Patients, using contact lenses, should be considered, that in the context of drug treatment may decrease the production of tear fluid.

In applying the drug Concor^® in patients with pheochromocytoma has the paradoxical risk of hypertension (if not previously achieved effective alpha adrenoblockade).

When thyrotoxicosis Konkor^® may mask certain clinical signs of hyperthyroidism (eg, taxikardiju). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, as able to exacerbate symptoms.

In diabetes the use of the drug may mask tachycardia, induced hypoglycemia. Unlike some neselektivnыh beta adrenoblokatorov Concor^® virtually no increase insulin-induced hypoglycemia or delay recovery of the concentration of glucose in the blood to normal levels.

With simultaneous use of clonidine its reception can be terminated only after a few days after the lifting of Concor^®.

Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine with aggravated allergic history.

In the case of the need for a planned surgical treatment for drug should be discontinued 48 h before general anesthesia. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate I / atropine (1-2 mg).

Drugs, that drain the depot of catecholamines (in t. no. reserpine), may enhance the action of beta-blockers, so patients, taking such drug combinations, We should be under constant medical supervision in order to identify significant decrease in blood pressure or bradycardia.

Patients with diseases bronhospasticheskimi can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensives. In excess doses Concor^® there is a risk of bronchospasm.

In the case of elderly patients increasing bradycardia (Heart Rate<50 u. / min), significant decrease in blood pressure (systolic blood pressure<100 mmHg.), AV-blockade, necessary to reduce the dose or stop treatment.

It is recommended to discontinue therapy with Concor^® in the development of depression.

Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. Abolition of the drug was gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 day).

Should be lifted before the study drug content in the blood and urine catecholamines, normetanefrina, vanilinmindalnoy acid, antinuclear antibodies.

Effects on ability to drive vehicles and management mechanisms

Bisoprolol does not affect the ability to drive in the study of patients with coronary heart disease. However, due to individual responses ability to drive or operate a technically complex mechanisms may be compromised. It should pay special attention to early treatment, after a change in dose, as well as the simultaneous use of alcohol.

Overdose

Symptoms: arrhythmia, ventricular premature beats, vыrazhennaya bradycardia, AV блокада, marked reduction in blood pressure, acute heart failure, gipoglikemiâ, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: gastric lavage, appointment of adsorbing drugs, simptomaticheskaya therapy. At which developed AV-blockade should be in / enter 1-2 mg atropine, epinephrine, or install a temporary pacemaker. If ventricular arrhythmia – lidokain (Class IA drugs do not apply). In marked decrease in blood pressure, patients should be in the Trendelenburg position, if there are no signs of pulmonary edema – I / O solutions plazmozameschayuschie, at their ineffectiveness – epinephrine, Dopamine, doʙutamin (to maintain chronotropic and inotropic effects and eliminate significant decrease in blood pressure). In heart failure – cardiac glycosides, Diuretic, glucagon. In convulsions – in / diazepam. When bronchospasm – inhaled beta₂-adrenostimulyatorov.

Drug Interactions

The effectiveness and tolerability of drugs may affect the simultaneous use of other drugs. Such interaction may also occur in those cases, when two drugs are taken over a short period of time. Physician should be informed about the use of other drugs, even if the application is carried out without a prescription.

Allergens, used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients, receiving bisoprolol.

Iodine radiopaque diagnostic tools for I / O administration increases the risk of anaphylactic reactions.

Phenytoin in in / in the introduction, drugs for inhalation general anesthesia (hydrocarbon derivatives) cardiodepressive increase the severity of the action and the probability of reduction of blood pressure.

The effectiveness of insulin and of oral hypoglycemic drugs may vary during the treatment with bisoprolol (masking the symptoms of developing hypoglycemia: taxikardiju, increased blood pressure).

The clearance of lidocaine and xanthine (except difillina) It may decrease due to the possible increase of their concentration in the blood plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

NSAIDs, SCS and estrogens weaken hypotensive effect of bisoprolol (delay of sodium ions, blockade of prostaglandin synthesis by the kidneys).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening of bradycardia, AV-blockade, heart failure and congestive heart failure.

Nifedipine can lead to a significant reduction in blood pressure.

Diuretic, klonidin, simpatolitiki, hydralazine, and other antihypertensive drugs may cause an excessive decrease of blood pressure.

The action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin during treatment with bisoprolol can be extended.

Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics drugs increase CNS depression.

Not recommended simultaneous application with MAO inhibitors due to a significant increase in the hypotensive action. Break in treatment between the reception of MAO inhibitors and bisoprolol must not be less than 14 days.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders. Ergotamine increases the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in blood plasma.

Рифампицин укорачивает T_1/2 bisoprolol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 5 years.