Concor AM tabs 5mg + 5mg #30

Instruction for Concor AM

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Concor AM is a combined drug with antihypertensive and antianginal action.

Release form and composition

The drug is produced in the form of tablets: almost white or white, on one side with a line, on the other - with MS engraving, odorless (10 pcs. In a blister, in a cardboard box 3 blisters and instructions for use of Concor AM), the form depends from the dosage (bisoprolol + amlodipine):
    Concor AM 5 mg + 5 mg - oblong, slightly biconvex;
    Concor AM 5 mg + 10 mg - round flat, with a chamfer;
    Concor AM 10 mg + 5 mg - oval, slightly biconvex;
    Concor AM 10 mg + 10 mg - round, slightly biconvex.
1 tablet contains:
    active ingredients: bisoprolol fumarate - 5/5/10/10 mg + amlodipine - 5/10/5/10 mg (in the form of amlodipine besylate in the amount of 6.95 / 13.9 / 6.95 / 13.9 mg), respectively ;
    additional substances: magnesium stearate, microcrystalline cellulose, colloidal anhydrous silicon dioxide, sodium carboxymethyl starch (type A).

Pharmacodynamics

Concor AM is a combined antihypertensive drug that exhibits pronounced antihypertensive and antianginal properties as a result of the complementary action of two active components: amlodipine, a slow calcium channel blocker (BMCC), and bisoprolol, a selective β1-adrenergic blocker.

Amlodipine

Amlodipine - being BMCC, it blocks calcium channels and reduces the transmembrane transit of calcium ions into cells, mostly into smooth muscle cells inside the vascular wall than into muscle cells of the heart (cardiomyocytes). The antihypertensive activity of amlodipine is caused by a direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance.
The mechanism of the antianginal effect of this drug is not fully understood, it is assumed that it is due to the following two effects:
    expansion of peripheral arterioles reduces total peripheral vascular resistance (OPSR), i.e., reduces afterload; due to the fact that amlodipine does not lead to the development of reflex tachycardia, the consumption of oxygen and energy by the myocardium decreases;
    expansion of large coronary arteries and arterioles improves oxygen supply to both normal and ischemic areas of the myocardium; these effects contribute to the improvement of oxygen supply to the heart muscle even with the development of spasm of the coronary arteries (unstable angina pectoris or Prinzmetal angina pectoris).
With arterial hypertension, taking Concor AM once a day provides a clinically significant decrease in blood pressure in the patient's lying and standing position during the entire 24-hour period between amlodipine doses. As a result of the slow development of the antihypertensive effect of the active component, it does not cause acute arterial hypotension.
In the presence of angina pectoris, the use of the drug once a day helps to increase the total time of physical activity, the period before the onset of an angina attack, as well as the time until a pronounced decrease in the ST interval. The tool provides a decrease in the frequency of angina attacks and the need for sublingual nitroglycerin intake.
The negative effect of amlodipine on the metabolism of blood plasma lipids, as well as its relationship with other metabolic disorders have not been identified.

Bisoprolol

Bisoprolol is a selective β1-adrenergic blocker that does not demonstrate its own sympathomimetic activity and does not exhibit a membrane stabilizing effect. It differs only in a small affinity for β2-adrenergic receptors located in the smooth muscles of the bronchi and blood vessels, as well as for β2-adrenergic receptors involved in the regulation of metabolism. Thus, in general, bisoprolol does not affect airway resistance and metabolic processes with which β2-adrenergic receptors are associated.
The selective effect of bisoprolol on β1-adrenergic receptors is also noted outside the therapeutic range. It does not show a pronounced negative inotropic effect.
After oral administration, the maximum effect of Concor AM is observed after 3-4 hours. When bisoprolol is used once a day, its therapeutic effect lasts for 24 hours, which is due to a 10-12-hour period of elimination (T1 / 2) from blood plasma. The maximum antihypertensive effect is usually noted 14 days after the start of the course. The drug also reduces the activity of the sympathoadrenal system (SAS) by blocking β1-adrenergic receptors of the heart.
With a single oral administration against the background of coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol reduces the heart rate (HR) and stroke volume of the heart, as a result of which it reduces the ejection fraction of the heart and myocardial oxygen demand. With long-term treatment, the initially increased TPR decreases. The weakening of renin activity in blood plasma is one of the components of the hypotensive action of β-blockers.

Pharmacokinetics

Amlodipine

After oral administration, amlodipine is well absorbed. The maximum concentration of the agent (Cmax) in the blood plasma is reached after 6-12 hours. Taking Concor AM at the same time with food does not affect its absorption. Its absolute bioavailability can be 64–80%, the apparent volume of distribution (Vd) is 21 l / kg. Equilibrium concentration (Css) in blood plasma is observed 7-8 days after the start of the course and is 5-15 ng / ml. According to in vitro studies, it was found that circulating amlodipine binds approximately 93–98% to plasma proteins.
About 90% of an oral dose of amlodipine is extensively metabolized in the liver to inactive pyridine derivatives. On average, 10% of the dose is excreted unchanged in the urine, approximately 60% of the formed inactive metabolites are excreted by the kidneys, and 20–25% through the intestines. The decrease in the level of concentration of the substance in the blood plasma has a two-phase nature. The final T1 / 2 is approximately 35-50 hours, which makes it possible to take the drug once a day. The total clearance is 7 ml / min / kg (25 l / h in patients weighing 60 kg), in elderly patients - 19 l / h.

Bisoprolol

Bisoprolol is almost completely (over 90%) absorbed from the digestive tract. As a result of a slight metabolic transformation during the first passage through the liver (about 10%), the bioavailability of Concor AM after oral use is approximately 90%, food intake does not affect this indicator. The substance is characterized by linear kinetics, and its plasma concentration levels are proportional to the administered dose (in the dose range of 5–20 mg). In blood plasma, Cmax is reached after 2-3 hours.
Bisoprolol has a rather wide distribution, Vd is 3.5 l / kg, it binds to blood plasma proteins up to about 30%.
The drug is metabolized by the oxidative pathway without further conjugation. All the resulting metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites detected in blood plasma and urine have no pharmacological activity. The data obtained during in vitro experiments with human liver microsomes indicate that the metabolic transformation of bisoprolol is carried out mainly with the help of the CYP3A4 isoenzyme (about 95%), and only to a small extent with the participation of the CYP2D6 isoenzyme.
The clearance of bisoprolol is determined by the balance between renal excretion unchanged (approximately 50%) and metabolism in the liver (approximately 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l / h, T1 / 2 is 10-12 hours.

Indications for use

Concor AM is recommended for use for the treatment of arterial hypertension when replacing treatment with monocomponent drugs amlodipine and bisoprolol in unchanged doses.

Contraindications

For amlodipine:
    unstable angina (except for Prinzmetal's angina);
    acute myocardial infarction (during the first 28 days);
    obstruction of the left ventricular outlet (including clinically significant aortic stenosis).
For bisoprolol:
    acute heart failure or CHF in the stage of decompensation, requiring the implementation of inotropic support;
    atrioventricular (AV) block II – III degree, in the absence of a pacemaker;
    sinoatrial blockade;
    sick sinus syndrome (SSS);
    severe bradycardia with a heart rate below 60 beats / min;
    Raynaud's syndrome or severe peripheral arterial circulation disorders;
    severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD);
    metabolic acidosis;
    pheochromocytoma (without combined use with α-blockers).
For a combination of amlodipine + bisoprolol:
    age under 18;
    shock (including cardiogenic);
    severe arterial hypotension (systolic blood pressure below 100 mm Hg);
    hypersensitivity to the active ingredients of the agent (including other derivatives of dihydropyridine) and / or to any of the additional substances.
With extreme caution, it is necessary to use Concor AM in the following conditions / diseases:
    CHF, including non-ischemic etiology of III-IV functional class according to NYHA classification (New York Association of Cardiology);
    Prinzmetal's angina;
    AV block I degree;
    mild / moderate degree of peripheral arterial circulation disorders;
    arterial hypotension;
    acute myocardial infarction (after the first 28 days);
    hypertrophic obstructive cardiomyopathy;
    aortic / mitral stenosis;
    bronchial asthma and COPD;
    hepatic and / or renal failure;
    concomitant desensitizing therapy (since bisoprolol can lead to increased sensitivity to allergens and increased anaphylactic reactions);
    pheochromocytoma (when combined with α-blockers);
    diabetes mellitus, characterized by significant fluctuations in blood glucose levels;
    general anesthesia;
    hyperthyroidism (bisoprolol can mask the symptoms of the disease);
    type 1 diabetes mellitus;
    psoriasis (including history);
    elderly age;
    fasting (strict diet).

Concor AM, instructions for use: method and dosage

Concor AM is taken orally once a day in the morning. Food intake does not diminish the effect of Concor AM.
The tablet is recommended to be swallowed whole without chewing, but if there are difficulties with swallowing, it can be broken. It must be remembered that the risk serves only to facilitate the breaking of the tablet, and not to divide the latter into two equal doses!
The daily dose of the drug is 1 tablet of a certain dosage. The attending physician individually for each patient conducts the selection and titration of the dose in the process of using monocomponent preparations, including the active substances contained in the Concor AM.
Drug therapy is usually long-term.

Side effects

Adverse reactions recorded when using amlodipine:
    immune system: extremely rare - allergic reactions;
    hematopoietic organs and lymphatic system: extremely rarely - thrombocytopenia, leukopenia;
    nervous system: often - dizziness, drowsiness, headache (mainly at the beginning of the course); infrequently - tremor, paresthesia, hypesthesia, dysgeusia, fainting; extremely rare - peripheral neuropathy, muscle hypertension;
    organ of hearing and labyrinthine disorders: infrequently - tinnitus;
    organ of vision: infrequently - visual impairment (including diplopia);
    mental disorders: infrequently - mood changes (including anxiety), insomnia, depression; rarely - confusion of consciousness;
    cardiovascular system: often - flushing of the face, palpitations; infrequently - a pronounced decrease in blood pressure; extremely rare - vasculitis, ventricular tachycardia, bradycardia, atrial fibrillation, myocardial infarction;
    metabolism and nutrition: extremely rare - hyperglycemia;
    liver and biliary tract: extremely rarely - jaundice and hepatitis (mainly with cholestasis);
    digestive system: often - abdominal pain, nausea; infrequently - dyspepsia, changes in bowel movements (including constipation / diarrhea), dryness of the oral mucosa; extremely rare - gingival hyperplasia, gastritis, pancreatitis;
    skin and subcutaneous tissues: infrequently - increased sweating, discoloration of the skin, rash, itching, exanthema, purpura, alopecia; extremely rarely - photosensitivity, exfoliative dermatitis, exudative erythema multiforme, Stevens-Johnson syndrome;
    allergic reactions: extremely rarely - urticaria, angioedema, Quincke's edema;
    respiratory system: infrequently - rhinitis, shortness of breath; extremely rare - cough;
    genitals and mammary gland: infrequently - gynecomastia, impotence;
    urinary system: infrequently - pollakiuria, nocturia, painful urge to urinate;
    musculoskeletal system: often - ankle swelling; infrequently - back pain, myalgia, arthralgia, muscle cramps;
    laboratory and instrumental data: infrequently - increase / decrease in body weight; extremely rarely - increased activity of liver enzymes, mainly with cholestasis;
    general disorders: often - increased fatigue, peripheral edema; infrequently - asthenia, pain (including in the chest), general malaise.
Adverse reactions recorded when using bisoprolol:
    nervous system: often - dizziness *, headache *; infrequently - insomnia; rarely - fainting;
    mental disorders: infrequently - depression; rarely - nightmares, hallucinations;
    liver and biliary tract: rarely - hepatitis;
    digestive system: often - constipation, diarrhea, nausea, vomiting;
    metabolism: rarely - an increase in the concentration of triglycerides;
    organ of vision: rarely - a decrease in lacrimation (must be taken into account when using contact lenses); extremely rare - conjunctivitis;
    respiratory system: infrequently - bronchospasm (with indications of a history of bronchial asthma or airway obstruction); rarely - allergic rhinitis;
    organ of hearing and labyrinthine disorders: rarely - hearing impairment;
    musculoskeletal system: infrequently - muscle cramps, muscle weakness;
    cardiovascular system: often - a feeling of numbness / coldness in the extremities, a marked decrease in blood pressure; infrequently - a violation of AV conduction, aggravation of the severity of symptoms of CHF, bradycardia, orthostatic hypotension;
    genitals and mammary gland: rarely - impotence;
    skin and subcutaneous fatty tissue: rarely - hypersensitivity reactions (rash, pruritus, skin flushing); extremely rare - alopecia; β-blockers may increase the risk of a psoriasis-like rash or exacerbation of psoriasis symptoms;
    laboratory and instrumental data: rarely - increased activity of hepatic transaminases in the blood [aspartate aminotransferase (ACT) and alanine aminotransferase (ALT)];
    general disorders: often - increased fatigue *; infrequently - exhaustion *.
* As a rule, these symptoms occur at the beginning of therapy, are mild and disappear within 7-14 days after the start of the course.

Overdose

Amlodipine

Symptoms of an overdose of amlodipine can be a significant decrease in blood pressure with the possible development of severe peripheral vasodilation and the occurrence of reflex tachycardia (the risk of severe and persistent arterial hypotension with the risk of shock and death is aggravated).
With these symptoms, gastric lavage, activated carbon intake, measures aimed at maintaining the function of the cardiovascular system are prescribed. They monitor the performance of the heart and lungs, control the volume of circulating blood (BCC) and urine output. The lower extremities of the patient are given an elevated position, intensive symptomatic therapy is carried out. In order to restore vascular tone, vasoconstrictors are prescribed (in the absence of contraindications); to remove the effects of calcium channel blockade, calcium gluconate is administered intravenously (iv). Hemodialysis is ineffective.

Bisoprolol

Symptoms of an overdose of bisoprolol can be bronchospasm, a marked decrease in blood pressure, severe bradycardia, AV blockade, acute heart failure, hypoglycemia. Among individual patients, the sensitivity to a single dose of a large dose of bisoprolol varies significantly, and patients with CHF are likely to have high sensitivity.
If an overdose is suspected, it is required to stop taking Concor AM and carry out supportive symptomatic treatment. If the development of severe bradycardia is observed, intravenous atropine is injected; if the effect is insufficient, careful administration of funds with a positive chronotropic effect may be prescribed. In some cases, it is possible to temporarily install a pacemaker.
With a pronounced decrease in blood pressure, plasma-substituting solutions and vasopressor drugs are injected intravenously. IV glucagon may also be given. With the development of AV blockade (II – III degree), constant monitoring of the condition and the introduction of β-adrenomimetics (including epinephrine), as well as infusion of isoprenaline, are required; if necessary, install a pacemaker.
In case of exacerbation of CHF, diuretics, drugs with a positive inotropic effect and vasodilators are administered intravenously.
For bronchospasm, bronchodilators are prescribed, including β2 -adrenomimetics and / or aminophylline; for hypoglycemia, dextrose (glucose) is administered intravenously.
During dialysis, bisoprolol is almost not excreted.

Special instructions

In the presence of stage III – IV heart failure according to the NYHA classification, amlodipine can provoke the development of pulmonary edema, this complication is not associated with an increase in symptoms of the course of CHF.
Reception of Concor AM should not be interrupted suddenly, especially in patients with coronary artery disease, as this can cause a temporary worsening of cardiac pathology. If it is necessary to stop taking the drug, the dose must be reduced gradually.
In patients with pheochromocytoma, it is recommended to prescribe bisoprolol only after blockade of α-adrenergic receptors.
Before performing general anesthesia, the anesthesiologist should be informed about the treatment with β-blockers. When it is necessary to stop taking the latter before surgery, the cancellation should be done gradually and completed approximately 48 hours before anesthesia.
Patients with bronchial asthma or COPD should use bronchodilating agents simultaneously with Concor AM. In bronchial asthma, an increase in airway resistance is possible, and therefore a higher dose of β2 -adrenomimetics may be required.

Influence on the ability to drive vehicles and complex mechanisms

During therapy with Concor AM, care must be taken when driving vehicles and controlling technically complex and potentially dangerous mechanisms.

Application during pregnancy and lactation

In experimental studies, the embryotoxic and fetotoxic effects of amlodipine were not identified, but its use during pregnancy is allowed only when the expected benefit to the mother significantly outweighs the possible risk to the fetus.
There are no data to support the excretion of amlodipine in breast milk. Since it has been established that other BMCCs, which are dihydropyridine derivatives, are excreted in breast milk, if it is necessary to treat with amlodipine during lactation, it is necessary to resolve the issue of stopping breastfeeding.
Due to the fact that β-blockers reduce blood flow in the placenta and can have a negative effect on the development of the fetus, the use of bisoprolol during pregnancy is possible only when the intended benefits of treatment with the drug for the mother are significantly higher than the potential risk to fetal health. If it is necessary to take bisoprolol by pregnant women, it is required to monitor the blood flow in the placenta and uterus and monitor the development and growth of the unborn child, and in the event of adverse reactions in relation to pregnancy and / or the fetus, resort to alternative methods of therapy. The newborn should be carefully examined after childbirth, because during the first three days of life, he may develop symptoms of bradycardia and hypoglycemia.
It is not known whether bisoprolol is excreted in breast milk, therefore, if taking Concor AM is necessary during lactation, breastfeeding should be discontinued.

Childhood use

Concor AM is contraindicated for persons under 18 years of age due to the lack of data confirming its efficacy and safety in patients of this age category.

With impaired renal function

In patients with severe renal impairment (with creatinine clearance (CC) below 20 ml / min), the maximum daily dose of bisoprolol should be 10 mg. In the presence of impaired renal function of mild or moderate severity, as a rule, there is no need to adjust the dosage regimen.
Since amlodipine is not excreted by dialysis, patients on dialysis need to use Concor AM with extreme caution.

For violations of liver function

In patients with functional disorders of the liver, the excretion of amlodipine may be slowed down, therefore, drug therapy should be carried out with caution. In the presence of severe liver dysfunctions, the maximum dose of bisoprolol should not exceed 10 mg per day.

Use in the elderly

Elderly patients Concor AM is prescribed in usual doses, caution is required only when increasing the dose during titration.

Drug interactions

Interaction reactions that are possible with the combination of amlodipine with other medicinal substances / agents:
    thiazide diuretics, β-blockers, sublingual nitroglycerin preparations, nonsteroidal anti-inflammatory drugs (NSAIDs), long-acting nitrates, antibiotics and hypoglycemic agents for oral administration: there was no development of undesirable effects in these interactions;
    antifungal drugs of the azole group (itraconazole, fluconazole), protease inhibitors (saquinavir, indinavir, ritonavir), macrolides (clarithromycin, erythromycin), diltiazem, verapamil and other moderate and strong inhibitors of CYP3A4: possibly an increase in plasma plasma concentrations up to amlodinavir especially these effects can be expressed in elderly patients, which may require dose adjustment);
    St. John's wort, rifampicin and other inducers of CYP3A4: a decrease in plasma concentrations of amlodipine is possible (this combination requires caution);
    simvastatin: there may be an increase in the concentration of this agent in the blood plasma; when combined with amlodipine, the daily dose of simvastatin should not exceed 20 mg;
    other antihypertensive drugs: it is possible to enhance their antihypertensive action;
    digoxin, atorvastatin, ethanol (drinks containing alcohol), cyclosporin, warfarin: no effect of amlodipine on the pharmacokinetic parameters of these drugs was observed;
    tacrolimus: an increase in its level in the blood is possible (monitoring of the plasma concentration of tacrolimus is recommended);
    cimetidine, aluminum / magnesium (as part of antacids), sildenafil, grapefruit juice: no effect on the pharmacokinetics of amlodipine was noted.
It is not recommended to combine bisoprolol with the following substances / agents:
    methyldopa, clonidine, rilmenidine, moxonidine (antihypertensive drugs of central action): the threat of a decrease in heart rate and a decrease in cardiac output increases, as a result of a decrease in central sympathetic tone, the risk of vasodilation also increases; abrupt withdrawal, especially before the withdrawal of β-blockers, may increase the risk of rebound arterial hypertension;
    verapamil, diltiazem: the risk of a decrease in myocardial contractility, a pronounced decrease in blood pressure and a violation of AV conduction is aggravated.
Interaction reactions possible with the combination of bisoprolol with the following drugs / agents, requiring caution:
    nifedipine and other BMCC, dihydropyridine derivatives: the risk of arterial hypotension may increase; in the presence of CHF, there is a threat of further deterioration of the contractile function of the heart;
    parasympathomimetics: it is possible to increase violations of AV conduction and aggravate the risk of developing bradycardia;
    disopyramide, phenytoin, quinidine, lidocaine, propafenone, flecainide (class I antiarrhythmics): AV conductivity and myocardial contractility may decrease;
    amiodarone and other class III antiarrhythmics: possible aggravation of AV conduction disturbances;
    eye drops for the treatment of glaucoma (β-blockers for local use): there may be an increase in the systemic side effects of bisoprolol (decrease in heart rate, decrease in blood pressure);
    insulin or antidiabetic oral agents: their hypoglycemic effect may be increased; signs of hypoglycemia (tachycardia) may be masked; (these interactions are most likely when using non-selective β-blockers);
    cardiac glycosides: there may be an increase in the time of the impulse and the development of bradycardia;
    means for general anesthesia: it is possible to weaken reflex tachycardia and aggravate the risk of arterial hypotension;
    NSAIDs: there may be a weakening of the antihypertensive effect of bisoprolol;
    dobutamine, isoprenaline (β-adrenergic agonists): there is a risk of reducing the effect of these drugs and bisoprolol;
    antihypertensive drugs; barbiturates, tricyclic antidepressants, phenothiazines and other drugs with potential antihypertensive activity: an increase in the antihypertensive effect of bisoprolol is possible;
    epinephrine, norepinephrine and other adrenomimetics that affect β- and α-adrenergic receptors: the vasoconstrictor effect of these drugs, which occurs with the participation of α-adrenergic receptors, may increase, which leads to the threat of an increase in blood pressure;
    monoamine oxidase (MAO) inhibitors, except for MAO-B inhibitors: the likelihood of an increase in the antihypertensive effect of β-blockers increases, a hypertensive crisis may develop;
    ergotamine derivatives: the risk of peripheral circulatory disorders increases;
    mefloquine: the risk of developing bradycardia increases;
    rifampicin: the T1 / 2 of bisoprolol is slightly shortened (dose changes are usually not required).

Terms and conditions of storage

Store out of the reach of children at a temperature not exceeding 30 ° C.
Shelf life is 3 years.

Reviews about Concor AM

Patients note the effectiveness of the double-acting drug in the treatment of arterial hypertension, leaving mostly positive reviews about Concor AM. The drug reliably lowers blood pressure and keeps it within the normal range throughout the day after administration, helps to stabilize the heart rate, demonstrates a gradual hypotensive effect (within 30-40 minutes), without leading to a sharp decrease in pressure.
Many patients consider the disadvantage of Concor AM a large number of side effects that occur during therapy. Some complain about the high cost of the antihypertensive drug.

Terms of sell

You can buy Concor AM witout a prescription.