Concor AM, pills 10mg+10mg 30pcs

Composition

1 tablet of the drug contains:

Active ingredient:

10 mg bisoprolol and 10 mg amlodipine (as 13.9 mg amlodipine bezylate) fumarate

excipients:

microcrystalline cellulose 261.1 mg,

sodium carboxymethyl starch (type A) 10 mg,

magnesium stearate 3.0 mg,

colloidal anhydrous silicon dioxide 2 mg

Pharmacological action

Pharmacodynamics

Concor AM has pronounced antihypertensive and antianginal effects due to the complementary action of two active ingredients: BMCC-amlodipine and a selective beta-1-adrenoblocker-bisoprolol.

Mechanism of action of amlodipine:

Amlodipine blocks calcium channels, reduces the transmembrane transfer of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

The antihypertensive effect of amlodipine is due to the direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance.

The mechanism of antianginal action is not fully understood, it may be associated with the following two effects: :

• Dilation of the peripheral arterioles reduces total peripheral resistance, i. e. afterload. Since amlodipine does not cause reflex tachycardia, the energy and oxygen consumption of the myocardium is reduced.
• Dilation of large coronary arteries and coronary arterioles improves oxygen supply to both normal and ischemic areas of the myocardium. These effects improve the oxygen supply to the myocardium, even in cases of coronary artery spasm (Prinzmetal angina or unstable angina).

In patients with arterial hypertension, taking the drug once a day causes a clinically significant decrease in blood pressure in the “lying” and “standing” positions throughout the entire 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute arterial hypotension.

In patients with angina pectoris, taking the drug once a day increases the total time to perform physical activity, the time to develop an angina attack, as well as the time to significantly reduce the ST interval, and also reduces the frequency of angina attacks and the need for sublingual nitroglycerin intake.

There was no negative effect of amlodipine on the metabolism of plasma lipids, blood glucose, and serum uric acid.

Mechanism of action of bisoprolol: Bisoprolol is a selective beta-1-adrenoblocker, without its own sympathomimetic activity, and does not have a membrane-stabilizing effect.

It has only a slight affinity for beta-2 – adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for beta-2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect the resistance of the respiratory tract and metabolic processes in which beta-2-adrenergic receptors are involved.

The selective effect of the drug on beta-1-adrenergic receptors remains beyond the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect. The maximum effect of the drug is achieved 3-4 hours after ingestion. Even when bisoprolol is prescribed once a day, its therapeutic effect persists for 24 hours due to a 10-12-hour half-life from blood plasma. As a rule, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment.

Bisoprolol reduces the activity of the sympathoadrenal system (SAS) by blocking the beta-1-adrenergic receptors of the heart.

When taken once orally in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol reduces the heart rate (HR), reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, the initially increased total peripheral vascular resistance (OPSS) decreases. A decrease in the activity of renin in blood plasma is considered as one of the components of the antihypertensive effect of beta-blockers.

Pharmacokinetics

Amlodipine:

Suction: Amlodipine is well absorbed after oral use. The maximum concentration in the blood plasma is noted after 6-12 hours. Taking the drug with food does not affect its absorption. Absolute bioavailability is 64-80%. Distribution: The apparent volume of distribution is 21 l / kg. Steady-state plasma concentrations (5-15 ng/ml) are reached 7-8 days after starting the drug. In vitro studies have shown that circulating amlodipine is approximately 93-98% bound to plasma proteins.

Metabolism and elimination: Amlodipine undergoes intensive metabolism in the liver. Approximately 90% of the dose taken is converted to inactive pyridine derivatives. Approximately 10% of the dose taken is excreted unchanged in the urine. Approximately 60% of the inactive metabolites are excreted by the kidneys and 20-25% by the intestines. The decrease in blood plasma concentration is biphasic. The final half-life is approximately 35-50 hours, which allows the drug to be administered once a day. Total clearance is 7 ml / min / kg (25 l / h in a patient weighing 60 kg). In elderly patients, it is 19 l/h. No significant changes in the pharmacokinetics of amlodipine were observed in elderly patients and patients with renal insufficiency. Due to reduced clearance, patients with hepatic insufficiency should be given lower initial doses.

Bisoprolol: Suction. Bisoprolol is almost completely absorbed (more than 90%) from the gastrointestinal tract. Its bioavailability due to insignificant metabolism “at the first pass” through the liver (at about 10%) is about 90% after oral use. Food intake does not affect bioavailability. Bisoprolol shows linear kinetics, and its plasma concentrations are proportional to the dose taken in the range from 5 to 20 mg. The maximum concentration in the blood plasma is reached in 2-3 hours.

Distribution. Bisoprolol is distributed fairly widely. The volume of distribution is 3.5 l / kg. Binding to plasma proteins reaches approximately 30%. Metabolism. It is metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and excreted by the kidneys. The main metabolites found in blood plasma and urine do not show pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is primarily metabolized by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role. Output. The clearance of bisoprolol is determined by the balance between renal excretion unchanged (about 50%) and liver metabolism (about 50%) to metabolites that are also excreted by the kidneys. The total clearance is 15 l / h. The elimination half-life is 10-12 hours.

Indications

Arterial hypertension: replacement of monocomponent therapy with amlodipine and bisoprolol in the same doses.

Use during pregnancy and lactation

On amlodipine: In experimental studies, the fetotoxic and embryotoxic effects of the drug have not been established, but use during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus. There are no data indicating the excretion of amlodipine in breast milk. However, other BMCC derivatives of dihydropyridine are known to be excreted in breast milk. Therefore, if it is necessary to prescribe amlodipine during lactation, the issue of stopping breastfeeding should be resolved.

On bisoprolol: The use of bisoprolol during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. Beta-blockers reduce blood flow in the placenta and can affect fetal development. Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child, and in case of adverse events in relation to pregnancy and/or the fetus, alternative therapies should be taken. The newborn should be carefully examined after delivery. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur. There are no data on the excretion of bisoprolol in breast milk. Therefore, its use is not recommended for women during breast-feeding. If taking bisoprolol during lactation is necessary, breast-feeding should be discontinued.

Contraindications

On amlodipine:

• unstable angina (excluding Prinzmetal angina);
• acute myocardial infarction (within the first 28 days);
• clinically significant aortic stenosis.

On bisoprolol:

• congestive heart failure or chronic heart failure (CHF) in the stage of decompensation, requiring inotropic therapy;
• atrioventricular (AV) blockade II and III degree, without pacemaker;
• the syndrome of weakness of the sinus node (SSSU);
• sinoatrial block;
• bradycardia (heart rate less than 60 beats/min );
• severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD), and
• expressed by human peripheral blood circulation or Raynaud’s syndrome;
• pheochromocytoma (without the simultaneous use of alpha-blockers);
• metabolic acidosis;

For the combination of amlodipine / bisoprolol:

• hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol and/or any of the excipients;
• severe arterial hypotension (systolic blood pressure less than 100 mm Hg);
• shock (including cardiogenic);
• children under 18 years of age (efficacy and safety have not been established)

With caution, CHF (including non-ischemic etiology of NYHA functional class III-IV), liver failure, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in blood glucose concentration, AV block I degree, Prinzmetal angina pectoris, occlusive diseases of the peripheral arteries, psoriasis (including in the anamnesis), fasting (strict diet), pheochromocytoma (with simultaneous use of alpha-adrenoblockers), bronchial asthma and COPD, simultaneous desensitizing therapy, general anesthesia, the elderly, hypotension, type 1 diabetes mellitus, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days).

Side effects

Undesirable side effects observed when using the active ingredients separately are presented according to the following frequency grouping criteria:

According to amlodipine: Blood and lymphatic system disorders: very rare: leukopenia, thrombocytopenia.

Immune system disorders: very rare: allergic reactions.

Metabolic and nutritional disorders: very rare: hyperglycemia.

Mental disorders: infrequently: insomnia, mood swings (including anxiety), depression; rarely: confusion.

Nervous system disorders: often: headache, dizziness, drowsiness (especially at the beginning of treatment); Infrequently: syncope, hypesthesia, paresthesia, dysgeusia, tremor; very rarely: muscle hypertension, peripheral neuropathy.

Visual disturbances: Infrequently: visual disturbances (including diplopia).

Hearing disorders and labyrinth disorders: infrequently: tinnitus.

Gastrointestinal disorders: often: nausea, abdominal pain; infrequently: vomiting, changes in bowel movements (including constipation or diarrhea), dyspepsia, dryness of the oral mucosa; very rarely – gastritis, gum hyperplasia, pancreatitis.

Liver and biliary tract disorders: very rare: hepatitis*, jaundice*.

Cardiac disorders: common: palpitation; very rare: myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation).

Vascular disorders: often: “hot flashes” of blood to the face, infrequently: marked decrease in blood pressure; very rarely: vasculitis.

Respiratory, thoracic and mediastinal disorders: Infrequently: shortness of breath, rhinitis; very rarely: cough.

Renal and urinary tract disorders: infrequently: pollakiuria, painful urination, nocturia.

Genital and breast disorders: infrequently: impotence, gynecomastia.

General disorders and disorders at the injection site: often: peripheral edema, increased fatigue; infrequently: chest pain, asthenia, pain, general malaise.

Musculoskeletal and connective tissue disorders: common: ankle swelling; uncommon: arthralgia, myalgia, muscle cramps, back pain.

Skin and subcutaneous disorders: infrequently: alopecia, purpura, discoloration of the skin, increased sweating, pruritus, rash, exanthema; very rarely: angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema, photosensitivity.

Laboratory and instrumental data: infrequently: weight gain, weight loss; very rarely: increased activity of “liver” enzymes*.

  * In most cases with cholestasis

On bisoprolol:

Metabolic and nutritional disorders: rare: increased triglyceride concentrations.

Mental disorders: infrequently: depression; rarely: hallucinations, nightmares.

Nervous system disorders: common: headache**, dizziness**; uncommon: insomnia; rare: fainting.

Visual disturbances: rare: reduced lacrimation (should be considered when wearing contact lenses); very rare: conjunctivitis.

Hearing disorders and labyrinth disorders: rare: hearing disorders.

Cardiac disorders: infrequently: violation of AV conduction, bradycardia, worsening of symptoms of CHF.

Vascular disorders: often: a feeling of cold or numbness in the extremities, a marked decrease in blood pressure; infrequently: orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: Infrequently: bronchospasm in patients with a history of bronchial asthma or airway obstruction; rarely: allergic rhinitis.

Gastrointestinal disorders: common: nausea, vomiting, diarrhea, constipation.

Liver and biliary tract disorders: rare: hepatitis.

Skin and subcutaneous disorders: rare: hypersensitivity reactions, such as pruritus, rash, hyperemia of the skin; very rare: alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

Musculoskeletal and connective tissue disorders: Infrequently: muscle weakness, muscle cramps.

Genital and breast disorders: rare: impotence.

General disorders and disorders at the injection site: often: increased fatigue**; infrequently: exhaustion**.

Laboratory and instrumental data: rarely: increased activity of “hepatic” transaminases in the blood

(aspartate aminotransferase (ACT), alanine aminotransferase (ALT)).

* * These symptoms are particularly common at the beginning of treatment. Usually, these symptoms are mild and usually disappear within 1-2 weeks after the start of treatment.

Interaction

On amlodipine:Concomitant use of amlodipine with thiazide diuretics, beta-blockers, long-acting nitrates, sublingual nitroglycerin preparations, nonsteroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral use is considered safe.

CYP3A4 inhibitors: Amlodipine should be used with caution at the same time as CYP3A4 inhibitors. Although no adverse events related to this interaction have been reported.

CYP3A4 inducers: Concomitant use with CYP3A4 inducers (including rifampicin, St. John’s wort) may lead to a decrease in the concentration of amlodipine in blood plasma. Caution should be exercised when using amlodipine concomitantly with CYP3A4 inducers. Grapefruit juice, cimetidine, aluminum / magnesium (as part of antacids) and sildenafil do not affect the pharmacokinetics of amlodipine.

Amlodipine may enhance the antihypertensive effect of other antihypertensive agents. Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, ethanol (alcoholic beverages), warfarin or cyclosporine. Amlodipine has no effect on laboratory parameters.

On bisoprolol:Non-recommended combinations of slow calcium channel blockers (BMCC) such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility, a pronounced decrease in blood pressure and impaired AV conduction. In particular, intravenous use of verapamil to patients taking beta-blockers may lead to severe hypotension and AV block.

Antihypertensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) when used simultaneously with bisoprolol can lead to a decrease in heart rate and cardiac output, as well as to vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before beta-blockers are discontinued, may increase the risk of developing “rebound” hypertension.

Combinations requiring caution of DMCC dihydropyridine derivatives (e. g., nifedipine) when used concomitantly with bisoprolol may increase the risk of hypotension. In patients with CHF, the risk of subsequent deterioration of the contractile function of the heart cannot be excluded.

Class I antiarrhythmic agents (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used concomitantly with bisoprolol may reduce AV conduction and myocardial contractility. Class III antiarrhythmic agents (such as amiodarone) may increase the violation of AV conduction. Parasympathomimetics, when used concomitantly with bisoprolol, may increase the violation of AV conduction and increase the risk of bradycardia.

The action of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia – particularly tachycardia-may be masked. Such interactions are more likely to occur with non-selective beta-blockers.

General anaesthetic agents may reduce reflex tachycardia and increase the risk of hypotension (see section “Special instructions”).

Cardiac glycosides, when used concomitantly with bisoprolol, can lead to an increase in pulse conduction time and to the development of bradycardia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of bisoprolol.

Concomitant use of bisoprolol with beta-adrenomimetics (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics that affect beta-and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) can increase the vasoconstrictor effects of these drugs that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely to occur with non-selective beta-blockers.

Antihypertensive agents, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may increase the antihypertensive effect of bisoprolol.

Combinations to be considered Mefloquine co-administered with bisoprolol may increase the risk of developing bradycardia. MAO inhibitors (with the exception of MAO B inhibitors) may enhance the antihypertensive effect of beta-blockers. Simultaneous use can also lead to the development of a hypertensive crisis.

Rifampicin slightly shortens the half-life (T1/2) of bisoprolol. As a rule, no dose adjustment is required. Ergotamine derivatives, when used concomitantly with bisoprolol, increase the risk of developing peripheral circulatory disorders.

How to take, course of use and dosage

Concor AM tablets for oral use. Tablets should be taken in the morning, regardless of food intake, without chewing. The recommended daily dose is 1 tablet per day of a certain dosage.

Selection and titration of the dose individually for each patient is carried out by the doctor during the appointment of monocomponent preparations containing active ingredients that are part of the Concor AM preparation. Duration of treatment

Treatment with Concor AM is usually a long-term therapy.

Impaired liver functionin patients with impaired liver function, the elimination of amlodipine may be slowed. A specific dosage regimen for this group of patients is not defined, but the drug in this case should be prescribed with caution. For patients with severe hepatic impairment, the maximum daily dose of bisoprolol is 10 mg.

Renal impairment Patients with mild or moderate renal impairment usually do not need to adjust the dosage regimen. Amlodipine is not eliminated by dialysis. Patients undergoing dialysis should be prescribed amlodipine with extreme

caution. For patients with severe renal impairment (creatinine clearance less than 20 ml/min), the maximum daily dose of bisoprolol is 10 mg.

Elderly patients: Elderly patients may be prescribed regular doses of the drug. Caution is only required when increasing the dose.

DetyPreparat is not recommended for use in children under 18 years of age due to the lack of data on efficacy and safety. Treatment should not be stopped abruptly, as this may lead to a temporary deterioration of the clinical condition. Especially treatment should not be abruptly discontinued in patients with CHD. A gradual dose reduction is recommended.

Overdose

On amlodipine:Symptoms: a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent hypotension, including shock and death). Treatment: gastric lavage, use of activated charcoal, maintenance of the cardiovascular system, monitoring of heart and lung function, elevated position of the extremities, monitoring of the volume of circulating blood and diuresis. Intensive symptomatic therapy. To restore vascular tone – the use of vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade – intravenous use of calcium gluconate. Hemodialysis is not effective.

According to Bisoprolol symptoms: AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol varies greatly among individual patients, and it is likely that patients with CHF are highly sensitive.

Treatment: if an overdose occurs, first of all, it is necessary to stop taking the drug and start supportive symptomatic therapy. For severe bradycardia: intravenous use of atropine. If the effect is insufficient, you can use caution to introduce a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily install an artificial pacemaker. With a marked decrease in blood pressure: intravenous use of plasma-substituting solutions and vasopressors. Intravenous use of glucagon may also be indicated. With AV block: patients should be constantly monitored and

treated with beta-adrenomimetics, such as epinephrine. If necessary, an artificial pacemaker can be installed. In case of exacerbation of CHF: intravenous use of diuretics, drugs with a positive inotropic effect, as well as vasodilators. In case of bronchospasm: use of bronchodilators, including beta-2-adrenomimetics and / or aminophylline. Hypoglycemia: intravenous use of dextrose (glucose). Bisoprolol practically does not respond to dialysis.

Special instructions

On amlodipine:Patients with heart failure should take amlodipine with caution. In patients with NYHA stage III-IV heart failure, amlodipine increases the risk of pulmonary edema, which is not associated with worsening of the symptoms of CHF.

On bisoprolol:Discontinuation of bisoprolol treatment should not be sudden, especially in patients with CHD, unless there are clear indications for discontinuation of the drug. Sudden withdrawal of bisoprolol can lead to a temporary deterioration of cardiac pathology. Bisoprolol should be used with extreme caution in patients with arterial hypertension or angina, in combination with heart failure.

As with other beta-blockers, bisoprolol can cause increased sensitivity to allergens and increased anaphylactic reactions, so caution should be exercised when simultaneously conducting desensitizing therapy. The use of epinephrine may not always give the expected therapeutic effect.

When using bisoprolol, the symptoms of hyperthyroidism may be masked.

In patients with pheochromocytoma, bisoprolol should be administered only after alpha-adrenergic blockade.

Before performing general anesthesia, the anesthesiologist should be informed about the patient’s use of beta-blockers. If it is necessary to cancel the beta-blocker before surgery, this should be done gradually, and completed approximately 48 hours before anesthesia.

In patients with bronchial asthma or COPD, concomitant use of bronchodilators is indicated. Patients with asthma may have increased airway resistance, which requires a higher dose of beta-2-adrenomimetics.

Influence on the ability to drive vehicles and mechanisms

During treatment with the drug, care should be taken when driving vehicles and working with technically complex mechanisms.

Form of production

Tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Amlodipine, Bisoprolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets