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Compound

metoprolol succinate 23.83 mg, which corresponds to the content of metoprolol tartrate 50 mg
Excipients: hypromellose - 155.96 mg, ludipress LCE (lactose monohydrate - 94.7-98.3%, povidone - 3-4%) - 117.21 mg, colloidal silicon dioxide - 1.5 mg, magnesium stearate - 1.5 mg.

Shell composition: ready-made mixture "Opadry II" orange (polyvinyl alcohol - 6 mg, talc - 2.22 mg, macrogol - 3.03 mg, titanium dioxide - 3.36 mg, red iron oxide dye - 0.009 mg, yellow iron oxide dye - 0.378 mg, iron dye black oxide - 0.003 mg) - 15 mg.

pharmachologic effect

Cardioselective beta1-blocker. It does not have a membrane-stabilizing effect and does not have internal sympathomimetic activity. It has antihypertensive, antianginal and antiarrhythmic effects.

By blocking β1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect (reduces heart rate, inhibits conductivity and excitability, reduces myocardial contractility). OPSS at the beginning of the use of beta-blockers (in the first 24 hours after oral administration) increases (as a result of a reciprocal increase in the activity of α-adrenergic receptors and the elimination of stimulation of β2-adrenergic receptors), after 1-3 days it returns to the original level, and with long-term administration it decreases.

The antihypertensive effect is due to a decrease in minute volume of blood flow and renin synthesis, inhibition of the activity of the RAAS (more important in patients with initial hypersecretion of renin) and the central nervous system, restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure) and, ultimately, a decrease in peripheral sympathetic influences. Reduces high blood pressure at rest, during physical exertion and stress. The antihypertensive effect lasts more than 24 hours.

The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance. By increasing end-diastolic pressure in the left ventricle and increasing the stretch of ventricular muscle fibers, it can increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown of AV conduction (mainly in the antegrade and to a lesser extent in the retrograde directions through the AV -node) and along additional paths.

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and thyrotoxicosis, it reduces heart rate or can even lead to the restoration of sinus rhythm.

Prevents the development of migraine.

In contrast to non-selective beta-blockers, when prescribed in average therapeutic doses, it has a less pronounced effect on organs containing β2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism; the severity of the atherogenic effect does not differ from the effect of propranolol. When taken for many years, it reduces the concentration of cholesterol in the blood. When used in large doses (more than 100 mg/day), it has a blocking effect on both subtypes of β-adrenergic receptors.

Metoprolol retard-Akrikhin extended-release tablets 50 mg No. 30

A country

Russia
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Active substance

Metoprolol + Felodipine

Compound

Active substance: metoprolol succinate.

pharmachologic effect

Cardioselective beta1-blocker. It does not have a membrane-stabilizing effect and does not have internal sympathomimetic activity. It has antihypertensive, antianginal and antiarrhythmic effects. By blocking beta1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular flow of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect action (reduces heart rate (HR), inhibits conductivity and excitability, reduces myocardial contractility). Total peripheral vascular resistance (TPVR) at the beginning of the use of beta-blockers (in the first 24 hours after oral administration) increases (as a result of a reciprocal increase in the activity of alpha -adrenergic receptors and elimination of stimulation of beta2-adrenergic receptors), which after 1-3 days returns to the original level, and with long-term administration decreases. The antihypertensive effect is due to a decrease in the minute volume of blood flow and renin synthesis, inhibition of the activity of the renin-angiotensin-aldosterone system (of greater importance in patients with initial hypersecretion of renin) and the central nervous system, restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure (BP) and, ultimately, a decrease in peripheral sympathetic influences. Reduces high blood pressure at rest, during physical exertion and stress. The antihypertensive effect lasts more than 24 hours. The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance. By increasing the end-diastolic pressure in the left ventricle and increasing the stretching of the ventricular muscle fibers, it can increase the need for oxygen, especially in patients with chronic heart failure (CHF). The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content , arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in atrioventricular (AV) conduction (mainly in the antegrade and to a lesser extent in the retrograde directions through the AV node) and along additional pathways. With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and thyrotoxicosis, it reduces heart rate or can even lead to the restoration of sinus rhythm. Prevents the development of migraines. Unlike non-selective beta-blockers, when prescribed in average therapeutic doses, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism; the severity of the atherogenic effect does not differ from the effect of propranolol. When taken for many years, it reduces the concentration of cholesterol in the blood. When used in large doses (more than 100 mg/day), it has a blocking effect on both subtypes of beta-adrenergic receptors. Pharmacokinetics. Absorption when taken orally is complete (95%). Solubility in fats is moderate. Subjected to intensive first-pass metabolism, bioavailability is 50% upon first administration and increases to 70% upon repeated use. Communication with plasma proteins – 10%. The time to reach maximum concentration in blood plasma is 6-12 hours after taking the drug. During the course of treatment, bioavailability increases. Food intake increases bioavailability by 20-40%. It is quickly distributed in tissues, penetrates the blood-brain barrier, and the placental barrier. Penetrates into breast milk. Metabolized in the liver, 2 metabolites have beta-adrenergic blocking activity. The CYP2D6 isoenzyme takes part in the metabolism of the drug. The half-life is from 3.5 to 7 hours when taken orally. It is not removed by hemodialysis. Significant accumulation of metabolites is observed in patients with a creatinine clearance of 5 ml/min, while the beta-adrenergic blocking activity of the drug does not increase. Bioavailability increases with cirrhosis of the liver, while its overall clearance is reduced.

Indications for use

Arterial hypertension. Chronic heart failure of functional class II-IV according to the NYHA classification in the compensation stage (as part of complex therapy). Coronary heart disease: prevention of attacks of stable angina, reduction of mortality and the frequency of recurrent myocardial infarction after the acute phase of myocardial infarction. Heart rhythm disturbances, including supraventricular tachycardia, decreased frequency of ventricular contraction during atrial fibrillation and ventricular extrasystoles. Functional disorders of cardiac activity accompanied by tachycardia. Prevention of migraine attacks.

Mode of application

The drug is intended for oral administration once a day, it is recommended to take it in the morning, without chewing, with water. Metoprolol retard - Akrikhin can be taken regardless of meals. In order to prevent bradycardia, the dose is selected individually and increased gradually. For arterial hypertension and angina pectoris, the initial dose is 50 mg 1 time per day; if the therapeutic effect is insufficient, the daily dose can be increased to 100-200 mg per day. For arterial hypertension, if the drug is ineffective at a dose of 100-200 mg per day, another antihypertensive agent can be added. For chronic heart failure of functional class II according to the NYHA classification (without exacerbations in the last 6 weeks and without changes in complex therapy over the last 2 weeks), the recommended initial dose – 25 mg once a day. After two weeks, the daily dose can be increased to 50 mg, then after two weeks to 100 mg, and after another two weeks to 200 mg. For chronic heart failure of functional class III-IV according to the NYHA classification, the recommended initial dose for the first 2 weeks is 12.5 mg of the drug once a day. It is possible to use metoprolol in another dosage form, for example, 25 mg scored tablets. During the period of increasing the dose, the patient should be monitored, as in some patients the symptoms of heart failure may worsen. After 1-2 weeks, the dose can be increased to 25 mg once a day. Then after 2 weeks the dose can be increased to 50 mg once daily. For patients who tolerate the drug well, the dose can be doubled every 2 weeks until a maximum dose of 200 mg of the drug is reached once a day. Secondary prevention of myocardial infarction and cardiac arrhythmias - an initial dose of 100 mg 1 time per day. For functional disorders of cardiac activity accompanied by tachycardia - 50 mg per day, if necessary, the dose can be increased to 200 mg per day. Prevention of migraine attacks: 100-200 mg 1 time per day. Elderly patients, with renal failure or patients on hemodialysis, no dose adjustment is required. Impaired liver function affects the elimination of metoprolol, so dose adjustment may be required depending on the clinical condition.

Interaction

Drugs that reduce catecholamine reserves (for example, reserpine, MAO inhibitors), when used simultaneously with metoprolol, can enhance the hypotensive effect or cause severe bradycardia. The treatment break between taking MAO inhibitors and metoprolol should be at least 14 days. Metoprolol is a substrate of the CYP2D6 isoenzyme. Medicines that inhibit or induce the activity of the CYP2D6 isoenzyme can affect the plasma concentration of metoprolol. Inhibitors of the CYP2D6 isoenzyme: some antidepressants and antipsychotics, quinidine, terbinafine, celecoxib, propafenone, diphehydramine, hydroxychlorine, cimetidine - increase the concentration of metoprolol in the blood plasma. Isoenzyme inducers CYP2D6: barbituric acid derivatives, rifampicin - reduce the concentration of metoprolol in the blood plasma. Simultaneous use with cardiac glycosides, clonidine, blockers of “slow” calcium channels (verapamil, diltiazem), amiodarone, class I antiarrhythmic drugs, drugs for general anesthesia, methyldopa, guanfacine can lead to a decrease in blood pressure and severe bradycardia. Drugs for inhalation anesthesia (hydrocarbon derivatives) increase the risk of suppression of myocardial function and the development of arterial hypotension. Simultaneous intravenous administration of verapamil can provoke cardiac arrest. Nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-agonists weaken the antihypertensive effect effect of beta-blockers. Ergot alkaloids increase the risk of peripheral circulatory disorders. When taken together with oral hypoglycemic drugs, their effect may be reduced; with insulin - increasing the risk of developing hypoglycemia, prolonging and increasing its severity, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure). Reduces the clearance of xanthines (except diaphylline), especially in patients with initially increased clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in plasma. Strengthens and prolongs the effect of non-depolarizing muscle relaxants; prolongs the anticoagulant effect of coumarins. When taking epinephrine (adrenaline) simultaneously with beta-blockers, an increase in blood pressure and bradycardia is possible. Phenylpropanolamine (norephedrine) can increase diastolic blood pressure. Allergens used for immunotherapy, or allergen extracts for skin testing when used in combination with metoprolol, increase risk of systemic allergic reactions or anaphylaxis; iodine-containing radiocontrast agents for intravenous administration increase the risk of developing anaphylactic reactions. When used together with ethanol, the risk of a pronounced decrease in blood pressure increases.

Side effect

From the cardiovascular system: often - bradycardia, orthostatic hypotension (including fainting), coldness of the lower extremities, palpitations; infrequently - temporary increase in symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, AV block of the first degree; rarely – myocardial conduction disorders, arrhythmia; very rarely - gangrene (in patients with peripheral circulatory disorders). From the central nervous system: very often - increased fatigue, decreased speed of mental and motor reactions; often – dizziness, headache; uncommon – paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, nightmares; rarely - asthenia, tremor, increased nervous excitability, anxiety; very rarely - amnesia/memory impairment, depression, hallucinations, myasthenia gravis. From the senses: rarely - blurred vision, dryness and/or irritation of the eyes, conjunctivitis; very rarely - ringing in the ears, disturbance of taste. From the digestive system: often - nausea, abdominal pain, constipation or diarrhea; infrequently – vomiting; rarely - dryness of the oral mucosa, impaired liver function, hepatitis. From the skin: infrequently - urticaria, increased sweating; rarely - alopecia; very rarely - photosensitivity, exacerbation of psoriasis, psoriasis-like skin reactions. From the respiratory system: often - shortness of breath; uncommon – bronchospasm in patients with bronchial asthma; rarely - rhinitis. Laboratory indicators: very rarely - thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of liver enzymes, hyperbilirubinemia. From the endocrine system: often - hypoglycemia (in patients with type I diabetes mellitus), rarely - hyperglycemia (in patients with type II diabetes mellitus), hypothyroid state. Other: infrequently - weight gain; rarely – impotence/sexual dysfunction; very rarely - arthralgia, thrombocytopenia.

Contraindications

Hypersensitivity to metoprolol and other beta-blockers, cardiogenic shock, AV block II-III degree, sinoatrial block, sick sinus syndrome, severe bradycardia (heart rate less than 50 beats/min), acute heart failure or decompensated CHF, arterial hypotension (systolic blood pressure less than 100 mm Hg), acute myocardial infarction (heart rate less than 45 beats/min, PQ interval more than 0.24 s, systolic blood pressure less than 100 mm Hg), lactation period, simultaneous use of monoamine oxidase inhibitors ( MAO) or simultaneous intravenous administration of verapamil, pheochromocytoma (without simultaneous use of alpha-blockers), age under 18 years (efficacy and safety have not been established), lactase deficiency, lactose intolerance, glucose-galactose malabsorption, severe bronchial asthma, severe peripheral disorders blood circulation

Overdose

Symptoms: severe bradycardia, AV block (up to the development of complete transverse block and cardiac arrest), marked decrease in blood pressure, impaired peripheral circulation, increased symptoms of heart failure, cardiogenic shock, respiratory depression, apnea, cyanosis, fatigue, dizziness, loss of consciousness, coma, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible development of esophagospasm, hypoglycemia or hyperglycemia, hyperkalemia, transient myasthenia. The first signs of overdose appear 20 minutes-2 hours after taking the drug. Treatment: If the drug has been taken recently, gastric lavage and taking adsorbents; in case of atrioventricular conduction disturbance and/or bradycardia - intravenous administration of 1-2 mg of atropine, epinephrine (adrenaline) or placement of a temporary pacemaker; if blood pressure decreases, the patient should be in the Trendelenburg position. If there are no signs of pulmonary edema - intravenous plasma replacement solutions, if ineffective - administration of epinephrine, dopamine, dobutamine; for acute heart failure - cardiac glycosides, diuretics; for convulsions - intravenous diazepam; for bronchospasm - inhaled or parenteral beta2-adrenergic agonists.

special instructions

With caution. Diabetes mellitus, first degree atrioventricular block, Prinzmetal's angina, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease, renal and/or severe liver failure, myasthenia gravis, pheochromocytoma (while taking alpha-blockers), thyrotoxicosis, depression (in including a history), psoriasis, peripheral circulatory disorders (“intermittent” claudication, Raynaud’s syndrome), pregnancy, old age. Use during pregnancy and lactation. During pregnancy, the drug should be used only for strict indications when the expected benefit for the mother exceeds the potential risk for the fetus/child (due to the possible development of bradycardia, decreased blood pressure, hypoglycemia and respiratory paralysis in the newborn). At the same time, careful monitoring is carried out especially over the development of the fetus. Treatment is stopped 48-72 hours before birth. If this is not possible, the newborn should be under especially careful observation for 48-72 hours after birth. The use of the drug is contraindicated during lactation; if it is necessary to use the drug during lactation, breastfeeding should be stopped. Monitoring of patients taking beta-blockers , includes regular monitoring of heart rate and blood pressure. The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min. It is possible that the severity of allergic reactions may increase (against the background of a burdened allergic history) and the lack of effect from the administration of usual doses of epinephrine (adrenaline). In elderly patients, it is recommended to monitor kidney function (once every 4-5 months). May increase the symptoms of peripheral arterial circulation disorders. For angina pectoris, the selected dose of the drug should ensure the heart rate at rest within 55-60 beats/min, with exercise - no more than 110 beats/min. For “smokers”, the effectiveness of beta-blockers is lower. Metoprolol retard — Akrikhin may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated because it can intensify symptoms. In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. If necessary, beta2-adrenergic agonists are used as concomitant therapy for patients with bronchial asthma; for pheochromocytoma - alpha-adrenergic blockers. If surgical intervention is necessary, it is necessary to warn the anesthesiologist about taking the drug Metoprolol retard - Akrikhin (it is necessary to choose a general anesthesia agent with minimal negative inotropic effect), discontinuation of the drug is not recommended. Reciprocal activation of the vagus nerve can be eliminated in /in the introduction of atropine (1-2 mg). In the event of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe liver dysfunction and kidneys, it is necessary to reduce the dose or stop treatment. It is recommended to discontinue therapy if skin rashes appear and the development of depression caused by taking beta-blockers. Metoprolol may increase the symptoms of peripheral circulatory disorders. With abrupt withdrawal of clonidine, blood pressure may rise sharply while taking beta-blockers. If clonidine is discontinued, discontinuation of beta-blockers should begin several days before discontinuation of clonidine. Drugs that reduce catecholamine levels (for example, reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to identify an excessive decrease in blood pressure or bradycardia. If treatment is abruptly stopped, “withdrawal” syndrome may occur (increased angina attacks, increased blood pressure). When discontinuing the drug, special attention should be paid to patients with angina pectoris, CHF, or after a myocardial infarction. Discontinuation of the drug Metoprolol retard - Akrikhin is carried out gradually, reducing the dose over 10 days. Patients using contact lenses should take into account that during treatment with beta-blockers, a decrease in the production of tear fluid is possible. During the treatment period, care must be taken when driving vehicles and doing other activities potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Dispensing conditions in pharmacies

On prescription

Indications for use

arterial hypertension;
chronic heart failure of functional class II-IV according to the NYHA classification in the compensation stage (as part of complex therapy);
IHD: prevention of attacks of stable angina, reduction of mortality and the incidence of recurrent myocardial infarction after the acute phase of myocardial infarction;
heart rhythm disturbances, including supraventricular tachycardia, decreased ventricular contraction frequency with atrial fibrillation and ventricular extrasystoles;
functional disorders of cardiac activity accompanied by tachycardia;
prevention of migraine attacks.

Directions for use and doses

The drug Metoprolol retard-Akrikhin is taken orally 1 time/day. It is recommended to take the tablets in the morning, without chewing, with water. Metoprolol retard-Akrikhin can be taken regardless of meals.

In order to prevent bradycardia, the dose is selected individually and increased gradually.

For arterial hypertension and angina pectoris, the initial dose is 50 mg 1 time / day; if the therapeutic effect is insufficient, the daily dose can be increased to 100-200 mg / day. For arterial hypertension, if the drug is ineffective at a dose of 100-200 mg/day, another antihypertensive agent can be added.

For chronic heart failure of functional class II according to the NYHA classification (without exacerbations in the last 6 weeks and without changes in complex therapy over the last 2 weeks), the recommended initial dose is 25 mg 1 time / day. After 2 weeks, the daily dose can be increased to 50 mg, then after 2 weeks - to 100 mg, after another 2 weeks - to 200 mg.

For chronic heart failure of functional class III-IV according to the NYHA classification, the recommended initial dose is 12.5 mg 1 time / day for the first 2 weeks. It is possible to use metoprolol in another dosage form, for example, 25 mg scored tablets. During the period of increasing the dose, the patient should be monitored, because In some patients, heart failure symptoms may worsen.

After 1-2 weeks, the dose can be increased to 25 mg 1 time / day. Then after 2 weeks the dose can be increased to 50 mg 1 time / day. For patients who tolerate the drug well, the dose can be doubled every 2 weeks until a maximum dose of 200 mg is reached once a day.

For secondary prevention of myocardial infarction and cardiac arrhythmias, the initial dose is 100 mg 1 time / day.

For functional cardiac disorders accompanied by tachycardia, 50 mg/day is prescribed; if necessary, the dose can be increased to 200 mg/day.

To prevent migraine attacks, 100-200 mg is prescribed once a day.

Elderly patients, patients with renal failure or patients on hemodialysis do not require dose adjustment.

Impaired liver function affects the elimination of metoprolol, so dose adjustment may be required depending on the clinical condition.

Metoprolol retard-Akrihin

Metoprolol is a substrate of the CYP2D6 isoenzyme. Medicines that inhibit or induce the activity of the CYP2D6 isoenzyme may affect the plasma concentrations of metoprolol.

CYP2D6 isoenzyme inhibitors

: some antidepressants and antipsychotics, quinidine, terbinafine, celecoxib, propafenone, diphehydramine, hydroxychlorine, cimetidine - increase the concentration of metoprolol in the blood plasma.

Inducers of the CYP2D6 isoenzyme

: barbituric acid derivatives, rifampicin - reduce the concentration of metoprolol in the blood plasma.

The combined use of Metoprolol retard-Akrikhin with the following drugs should be avoided:

Barbituric acid derivatives:

Barbiturates (the study was conducted with pentobarbital) increase the metabolism of metoprolol due to enzyme induction.

Propaphenone

: When propafenone was prescribed to four patients treated with metoprolol, an increase in the plasma concentration of metoprolol was observed by 2-5 times, while two patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprololol via the CYP2D6 isoenzyme. Taking into account the fact that propafenone has beta-blocker properties, the co-administration of metoprolol and propafenone does not seem appropriate.

Verapamil

: The combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and beta-blockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.

The combination of Metoprolol retard-Akrikhin with the following drugs may require dose adjustment:

Amiodarone

: Concomitant use of amiodarone and metoprolol can lead to severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.

Class I antiarrhythmic drugs

: Class I antiarrhythmics and beta-blockers may result in additive negative inotropic effects, which may lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and impaired AV conduction. The interaction is described using disopyramide as an example.

Nonsteroidal anti-inflammatory drugs (NSAIDs):

NSAIDs weaken the antihypertensive effect of beta-blockers. This interaction has been documented for indomethacin. It is likely that the described interaction will not be observed with sulindac. Negative interactions have been noted in studies with diclofenac.

Diphenhydramine

: Diphenhydramine reduces the clearance of metoprolol to alpha-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.

Diltiazem

: Diltiazem and beta-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.

Epinephrine (adrenaline)

: 10 cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.

Phenylpropanolamine

: Phenylpropanolamine (norephedrine) in a single dose of 50 mg can cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers may cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported while taking phenylpropanolamine.

Quinidine

: Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and an increase in beta-blockers metabolized by the CYP2D6 isoenzyme.

Clonidine

: Hypertensive reactions during abrupt withdrawal of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, if clonidine is discontinued, discontinuation of beta-blockers should begin several days before discontinuation of clonidine.

Rifampicin

: Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.

Patients taking metoprolol and other beta blockers (eye drops) or monoamine oxidase inhibitors

(MAO) should be closely monitored.
While taking beta-blockers, inhalational anesthetics
enhance the cardiodepressive effect.
While taking beta-blockers, patients receiving oral hypoglycemic agents
may require dose adjustment of the latter.

Plasma concentrations of metoprolol may increase when taking cimetidine

or
hydralazine
.

Cardiac glycosides

when used together with beta-blockers, they can increase atrioventricular conduction time and cause bradycardia.

Ergot alkaloids

increase the risk of peripheral circulatory disorders.

When taken together with insulin

- increasing the risk of developing hypoglycemia, prolonging and increasing its severity, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).

Reduces the clearance of xanthines

(except for diaphylline), especially in patients with initially increased clearance of theophylline under the influence of smoking.
Reduces the clearance of lidocaine
, increases the concentration of lidocaine in plasma.

Strengthens and prolongs the effect of non-depolarizing muscle relaxants:

prolongs the anticoagulant effect of coumarins.

Allergens

, used for immunotherapy, or allergen extracts for skin testing, when used together with metoprolol, increase the risk of systemic allergic reactions or anaphylaxis;
iodine-containing radiocontrast agents for intravenous administration
increase the risk of developing anaphylactic reactions.

When used together with ethanol

the risk of a pronounced decrease in blood pressure increases.

Contraindications

cardiogenic shock;
AV blockade II-III degree;
sinoatrial block;
SSSU;
severe bradycardia (heart rate <50 beats/min);
acute heart failure or chronic heart failure in the stage of decompensation;
arterial hypotension (systolic blood pressure <100 mm Hg);
acute myocardial infarction (heart rate <45 beats/min, PQ interval more than 0.24 s, systolic blood pressure <100 mm Hg);
severe bronchial asthma;
severe peripheral circulatory disorders;
simultaneous use of MAO inhibitors or simultaneous intravenous administration of verapamil;
pheochromocytoma (without simultaneous use of alpha-blockers);
age under 18 years (efficacy and safety have not been established);
lactation period;
lactase deficiency, lactose intolerance, glucose/galactose malabsorption syndrome;
hypersensitivity to metoprolol and other beta-blockers.

The drug should be prescribed with caution in case of diabetes mellitus, AV blockade of the first degree, Prinzmetal's angina, metabolic acidosis, bronchial asthma, COPD, severe renal and/or liver failure, myasthenia gravis, pheochromocytoma (while taking alpha-blockers), thyrotoxicosis, depression (including a history), psoriasis, peripheral circulatory disorders (intermittent claudication, Raynaud's syndrome), pregnancy, and elderly patients.

Metoprolol-Akrikhin

Registration number: P N003213/01 Trade name of the drug: Metoprolol-Akrikhin

International nonproprietary name: metoprolol

Dosage form: tablets

Composition: One tablet contains: active substance: metoprolol tartrate in terms of 100% substance - 50 mg, excipients: lactose monohydrate, colloidal silicon dioxide, potato starch, povidone, sodium carboxymethyl starch, magnesium stearate.

Description: tablets are white with a grayish or yellowish tint, flat-cylindrical, with a chamfer.

Pharmacotherapeutic group: selective beta1-blocker ATC code: C07AB02

Pharmacological properties

Pharmacodynamics Metoprolol is a cardioselective beta-adrenergic receptor blocker that does not have intrinsic sympathomimetic activity and membrane-stabilizing properties. It has hypotensive, antianginal and antiarrhythmic effects. By blocking beta1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect (reduces the heart rate (HR), inhibits conductivity and excitability, reduces myocardial contractility). The total peripheral resistance at the beginning of the use of beta-blockers (in the first 24 hours after oral administration) increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which after 1-3 days returns to the original one, and with prolonged application - decreases.

The hypotensive effect is due to a reflex decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin-aldosterone system (of greater importance in patients with initial hypersecretion of renin) and the central nervous system, restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease blood pressure) and, ultimately, a decrease in peripheral sympathetic influences. Reduces high blood pressure (BP) at rest, during physical exertion and stress.

The hypotensive effect develops quickly (systolic blood pressure decreases after 15 minutes, maximum after 2 hours) and lasts for 6 hours, diastolic blood pressure changes more slowly: a stable decrease is observed after several weeks of regular use.

The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (lengthening diastole and improving myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in atrioventricular (AV) conduction (mainly in the antegrade and, to a lesser extent, in retrograde directions) through the AV node and along additional pathways.

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and hyperthyroidism, it reduces heart rate, or can even lead to the restoration of sinus rhythm.

Prevents the development of migraine. When used in average therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism. When used in large doses (more than 100 mg/day), it has a blocking effect on both subtypes of beta-adrenergic receptors.

Pharmacokinetics Absorption when taken orally is complete (95%). The maximum concentration in blood plasma is achieved 1-2 hours after oral administration. The half-life averages 3.5 hours (range 1 to 9 hours). Subjected to intensive first-pass metabolism, bioavailability is 50% upon first administration and increases to 70% upon repeated use. Eating increases bioavailability by 20-40%. The bioavailability of metoprolol increases in liver cirrhosis. Communication with blood plasma proteins - 10%. Penetrates through the blood-brain and placental barriers. Passes into breast milk in small quantities. Metabolized in the liver, 2 metabolites have beta-adrenergic blocking activity. The CYP2D6 isoenzyme takes part in the metabolism of the drug. About 5% is excreted unchanged by the kidneys. Treatment of patients with reduced renal function does not require dose adjustment of the drug. Impaired liver function slows down the metabolism of the drug, and in cases of insufficiency of liver function, the dose of the drug should be reduced. It is not removed by hemodialysis.

Indications for use: • arterial hypertension (as monotherapy or in combination with other antihypertensive drugs), • coronary heart disease: myocardial infarction (secondary prevention - complex therapy), prevention of angina attacks, • cardiac arrhythmias (supraventricular tachycardia, ventricular extrasystole), •hyperthyroidism (complex therapy), •prevention of migraine attacks.

Contraindications • hypersensitivity to metoprolol or other components of the drug, other beta-blockers, • cardiogenic shock, • atrioventricular block (AV) II-III degree, • sick sinus syndrome, • severe bradycardia, • chronic heart failure in the stage of decompensation, • Prinzmetal's angina, • arterial hypotension (if used for secondary prevention of myocardial infarction - systolic blood pressure less than 100 mm Hg, heart rate less than 45 beats/min), • lactation period (see “Pregnancy and lactation”), • simultaneous taking monoamine oxidase inhibitors (MAO) or simultaneous intravenous administration of verapamil (see “Interaction with other drugs”), • age under 18 years (efficacy and safety have not been established), • lactose intolerance, lactase deficiency or Glucose-galactose malabsorption.

With caution Diabetes mellitus, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease (pulmonary emphysema, chronic obstructive bronchitis), obliterating peripheral vascular diseases (“intermittent” claudication, Raynaud’s syndrome), chronic liver and/or renal failure, myasthenia gravis, pheochromocytoma ( with simultaneous use of alpha-blockers), AV blockade of the first degree, thyrotoxicosis, depression (including history), psoriasis, pregnancy, old age.

Pregnancy and lactation During pregnancy, it is prescribed taking into account the ratio of benefit to the mother and risk to the fetus (due to the development of bradycardia, arterial hypotension, hypoglycemia in the fetus). At the same time, careful monitoring is carried out, especially over the development of the fetus. It is necessary to monitor newborns for 48-72 hours after delivery. The effect of metoprolol on a newborn during breastfeeding has not been studied, therefore women taking Metoprolol-Akrikhin should stop breastfeeding.

Directions for use and dosage: The tablets are taken orally during or immediately after meals, do not chew, and are washed down with a small amount of liquid. Arterial hypertension. The initial daily dose is 50-100 mg in 1-2 doses (morning and evening). If the therapeutic effect is insufficient, the daily dose can be gradually increased to 100-200 mg and/or additional prescription of other antihypertensive drugs. The maximum daily dose is 200 mg. Angina pectoris, arrhythmias, prevention of migraine attacks. 100-200 mg per day in two doses (morning and evening).

Secondary prevention of myocardial infarction. 200 mg per day in two doses (morning and evening).

Hyperthyroidism. 50 mg 2 times a day (morning and evening).

In elderly patients, with impaired renal function, and also if hemodialysis is necessary, the dose is not changed. In case of liver dysfunction, the dose of the drug should be reduced depending on the clinical condition.

Side effects From the central nervous system: increased fatigue, weakness, headache, slowdown in the speed of mental and motor reactions. Rarely - paresthesia in the limbs (in patients with intermittent claudication and Raynaud's syndrome), depression, anxiety, decreased attention, drowsiness, insomnia, nightmares, confusion or short-term memory impairment, muscle weakness. From the senses: rarely - decreased vision, decreased secretion of tear fluid, dry and sore eyes, conjunctivitis, tinnitus.

From the cardiovascular system: sinus bradycardia, palpitations, decreased blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness). Rarely - decreased myocardial contractility, temporary worsening of symptoms of chronic heart failure (edema, swelling of the feet and/or lower legs, shortness of breath), arrhythmias, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), impaired myocardial conduction.

From the digestive system: nausea, vomiting, abdominal pain, dry mouth, diarrhea, constipation, change in taste.

From the skin: urticaria, skin itching, rash, exacerbation of psoriasis, psoriasis-like skin reactions, skin hyperemia, exanthema, photodermatosis, increased sweating, reversible alopecia.

From the respiratory system: nasal congestion, difficulty exhaling (bronchospasm when prescribed in high doses - loss of selectivity and/or in predisposed patients), shortness of breath.

From the endocrine system: hypoglycemia (in patients receiving insulin), rarely - hyperglycemia (in patients with insulin-dependent diabetes mellitus).

Laboratory indicators: rarely - thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of liver enzymes, extremely rarely - hyperbilirubinemia.

Effect on the fetus: possible intrauterine growth retardation, hypoglycemia, bradycardia.

Other: back or joint pain, like all beta-blockers, in isolated cases can cause a slight increase in body weight, decreased libido and/or potency.

Overdose Symptoms: severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked decrease in blood pressure, arrhythmia, ventricular extrasystole, bronchospasm, fainting, in case of acute overdose - cardiogenic shock, loss of consciousness, coma, atrioventricular block (up to the development of complete transverse blockade and cardiac arrest), cardialgia. The first signs of overdose appear 20 minutes -2 hours after taking the drug. Treatment: gastric lavage and taking adsorbents, symptomatic therapy: in case of a pronounced decrease in blood pressure, the patient should be in the Trendelenburg position; in case of an excessive decrease in blood pressure, bradycardia and heart failure - intravenously, at intervals of 2-5 minutes, beta - adrenergic agonists - until the desired effect is achieved or 0.5-2 mg of atropine sulfate intravenously. If there is no positive effect, dopamine, dobutamine or norepinephrine (norepinephrine). As subsequent measures, it is possible to administer 1-10 mg of glucagon and install a transvenous intracardial pacemaker. For bronchospasm, beta2-agonists should be administered intravenously. Metoprolol is poorly excreted by hemodialysis.

Interaction with other drugs • Concomitant use with monoamine oxidase inhibitors (MAOIs) is not recommended due to a significant increase in the hypotensive effect. The treatment break between taking MAO inhibitors and metoprolol should be at least 14 days. • Simultaneous intravenous administration of verapamil can provoke cardiac arrest. • Simultaneous administration of nifedipine leads to a significant decrease in blood pressure. •Inhalation anesthetics (hydrocarbon derivatives) increase the risk of suppression of myocardial function and the development of arterial hypotension. •Beta-adrenergic agonists, theophylline, cocaine, estrogens (sodium retention), indomethacin and other non-steroidal anti-inflammatory drugs (sodium retention and blocking renal prostaglandin synthesis) weaken the hypotensive effect. •There is an increased inhibitory effect on the central nervous system with ethanol, a summation of the cardiodepressive effect with anesthesia, and an increased risk of peripheral circulatory disorders with ergot alkaloids. •When taken together with hypoglycemic agents for oral administration, their effect may be reduced; with insulin, the risk of developing hypoglycemia may increase, its severity will increase and prolong, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure). • When combined with antihypertensive drugs, diuretics, nitroglycerin or blockers of “slow” calcium channels, a sharp decrease in blood pressure may develop (special caution is required when combined with prazosin), an increase in the severity of the decrease in heart rate and inhibition of atrioventricular conduction - when using metoprolol with verapamil, diltiazem, antiarrhythmic drugs (amiodarone), reserpine, methyldopa, clonidine, guanfacine, general anesthetics and cardiac glycosides. •If metoprolol and clonidine are taken simultaneously, then when metoprolol is discontinued, clonidine is discontinued after a few days (due to the risk of withdrawal syndrome). •Inducers of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of metoprolol, a decrease in its concentration in the blood plasma and a decrease in effect. Inhibitors (cimetidine, oral contraceptives, phenothiazines) - increase the concentration of metoprolol in plasma. •Allergens used for immunotherapy or allergen extracts for skin testing when used in combination with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiocontrast agents for intravenous administration increase the risk of anaphylactic reactions. •Reduces the clearance of xanthine (except for diphylline), especially with the initially increased clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in the blood plasma. •Enhances and prolongs the effect of antidepolarizing muscle relaxants, prolongs the anticoagulant effect of coumarins. •When used together with ethanol, the risk of a pronounced decrease in blood pressure increases.

Special instructions •Monitoring of patients taking beta-blockers includes regular monitoring of heart rate (HR) and blood pressure, blood glucose levels in patients with diabetes. If necessary, for patients with diabetes mellitus, the dose of insulin or hypoglycemic agents prescribed orally should be selected individually. •The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min. When taking a dose above 200 mg per day, cardioselectivity decreases. •In case of heart failure, treatment with metoprolol is started only after reaching the compensation stage. • Possible increased severity of hypersensitivity reactions (against the background of a burdened allergic history) and lack of effect from the administration of usual doses of epinephrine (adrenaline). •May increase symptoms of peripheral arterial circulatory disorders. •Discontinuation of the drug is carried out gradually, reducing the dose over 10 days. •If treatment is abruptly stopped, “withdrawal” syndrome may occur (increased attacks of angina, increased blood pressure). •When discontinuing the drug, special attention should be paid to patients with angina pectoris. •For exertional angina, the selected dose of the drug should ensure a heart rate at rest within the range of 55-60 beats/min, and during exercise - no more than 110 beats/min. •Patients who use contact lenses should take into account that during treatment with beta-blockers, the production of tear fluid may decrease. •Metoprolol may mask some clinical manifestations of hyperthyroidism (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can increase symptoms. •In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal levels. •If necessary, beta2-adrenergic agonists are used as concomitant therapy for patients with bronchial asthma; for pheochromocytoma, alpha-blockers are used. •If surgical intervention is necessary, it is necessary to warn the anesthesiologist about the therapy being performed (choosing a general anesthesia agent with minimal negative inotropic effect); discontinuation of the drug is not recommended. •Drugs that reduce catecholamine reserves (for example, reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect an excessive decrease in blood pressure and bradycardia. •In elderly patients, regular monitoring of liver function is recommended. •Adjustment of the dosage regimen is required only if an elderly patient develops increasing bradycardia (less than 50 beats/min), a pronounced decrease in blood pressure (systolic blood pressure below 100 mm Hg), atrioventricular block, bronchospasm, ventricular arrhythmias, severe dysfunction liver, sometimes it is necessary to stop treatment. •In patients with severe renal impairment, monitoring of renal function is recommended. •Special monitoring of the condition of patients with depressive disorders taking metoprolol should be carried out; in case of depression caused by taking beta-blockers, it is recommended to discontinue therapy. •Due to the lack of sufficient clinical data, the drug is not recommended for use in children.

Effect on the ability to drive vehicles and complex equipment. At the beginning of treatment with metoprolol, patients may experience dizziness and fatigue. In this case, they should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions. In the future, dose safety is determined individually.

Release form Tablets 50 mg. 10 tablets in a blister pack. 3 blister packs along with instructions for use in a cardboard pack.

Storage conditions: In a dry place, protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children.

Shelf life: 4 years. Do not use after the expiration date.

Conditions for dispensing from pharmacies By prescription.

Manufacturer/Organization accepting consumer complaints: Open Joint-Stock Company Chemical and Pharmaceutical Plant AKRIKHIN (JSC AKRIKHIN), Russia 142450, Moscow region, Noginsky district, Staraya Kupavna, st. Kirova, 29. Phone/fax: +

special instructions

Monitoring of patients taking beta-blockers includes regular monitoring of heart rate and blood pressure. The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

It is possible that the severity of allergic reactions may increase (against the background of a burdened allergic history) and there will be no effect from the administration of usual doses of epinephrine (adrenaline).

In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).

Taking the drug Metoprolol retard-Akrikhin may increase the symptoms of peripheral arterial circulation disorders.

For exertional angina, the selected dose of the drug should ensure the heart rate at rest within the range of 55-60 beats/min, and during exercise - no more than 110 beats/min.

In smoking patients, the effectiveness of beta-blockers is lower.

Metoprolol retard-Akrikhin may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.

In diabetes mellitus, taking Metoprolol retard-Akrikhin can mask tachycardia caused by hypoglycemia.

If necessary, beta2-adrenergic agonists are used as concomitant therapy for patients with bronchial asthma; for pheochromocytoma - alpha-blockers.

If it is necessary to perform surgical intervention, it is necessary to warn the anesthesiologist about taking the drug Metoprolol retard-Akrikhin (it is necessary to choose a general anesthesia agent with minimal negative inotropic effect); discontinuation of the drug is not recommended.

Reciprocal activation of the vagus nerve can be eliminated by intravenous atropine (1-2 mg).

In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or stop treatment.

It is recommended to discontinue therapy if skin rashes appear and depression develops caused by taking beta-blockers.

If clonidine is abruptly discontinued, blood pressure may rise sharply while taking beta-blockers. If clonidine is discontinued, discontinuation of beta blockers should begin several days before discontinuation of clonidine.

Drugs that reduce catecholamine levels (for example, reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect an excessive decrease in blood pressure or bradycardia.

If treatment is abruptly stopped, withdrawal syndrome may occur (increased angina attacks, increased blood pressure). When discontinuing the drug, special attention should be paid to patients with angina pectoris, chronic heart failure, and after a myocardial infarction. Discontinuation of the drug Metoprolol retard-Akrikhin is carried out gradually, reducing the dose over 10 days.

Patients who use contact lenses should take into account that during treatment with beta-blockers, there may be a decrease in the production of tear fluid.

Impact on the ability to drive vehicles and machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Metoprolol-Akrikhin tablet 50 mg x30