Metoprolol retard akrikhin instructions for use. Metoprolol akrikhin instructions for use. Side effects on the cardiovascular system

In chronic heart failure II functional class according to the NYHA classification (without exacerbations for the last 6 weeks and without changes in complex therapy for the last 2 weeks), the recommended initial dose is 25 mg once a day. After two weeks, the daily dose can be increased to 50 mg, then after two weeks to 100 mg, after another two weeks to 200 mg.

In chronic heart failure III-IV functional class 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 tablets with a risk. 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 may be increased to 25 mg once a day. Then after 2 weeks the dose can be increased to 50 mg once a day. For patients who tolerate the drug well, the dose can be doubled every 2 weeks until a maximum dose of 200 mg once daily is reached.

Secondary prevention of myocardial infarction and cardiac arrhythmias - an initial dose of 100 mg 1 time per day.

With 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 kidney failure or patients on hemodialysis, dose adjustment is not required.

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

Metoprolol retard is prescribed by medical professionals to lower blood pressure and eliminate the symptoms of coronary disease. The drug allows you to normalize the heart rate, with prolonged use for several years, reduces cholesterol levels. As a result, it is possible to stabilize blood pressure indicators, reduce the risk of developing myocardial infarction, atherosclerotic changes in blood vessels and the development of ischemia.

Release form, composition and packaging

The cardioselective beta-adrenergic blocker is available in tablet form. A unit of medication contains 25, 50 or 100 mg of metoprolol succinate. Tablets are visually distinguished by brown-yellow color and round shape.

Additionally used ingredients:

• povidone;
• milk sugar;
• hypromellose;
• colloidal dehydrogenated silica;
• magnesium stearate.

The surface of the tablets is covered with an outer film coating consisting of macrogol, talc, titanium dioxide and polyvinyl alcohol. The yellow-brown color of the tablets is due to the presence of red, black and yellow dyes based on iron oxide. Blisters contain 10 units of the drug.

pharmachologic effect

The drug allows you to stabilize the rhythm of heart contractions, has a hypotensive and antianginal effect. Pharmacological properties based on the suppression of the activity of beta-adrenergic receptors of the heart. As a result, the conduction of nerve impulses in the myocardium is inhibited, excitability and heart rate (HR) decrease.

The total peripheral resistance after a single dose increases during the first day, after which it returns to its original values ​​within 24-72 hours. With prolonged use of metoprolol, it gradually decreases.

The antianginal effect is due to a decrease in the oxygen demand of cardiomyocytes. This occurs as a result of a decrease in heart rate and the susceptibility of the myocardium to impulses of the sympathetic nervous system. There is an increase in myocardial resistance to physical exertion, the severity and frequency of angina attacks decrease.

The pressure decreases on the background of drug therapy due to a decrease in the minute volume of blood and increased production of renin. The hypotensive effect persists for 24 hours and is not weakened by stressful conditions, physical activity.

Unlike non-selective beta1-blockers, metoprolol does not have a strong effect on carbohydrate metabolism and does not suppress the action of beta2-adrenergic receptors. With regular intake for 1-5 years, a decrease in plasma cholesterol concentration can be observed.

The drug is 95% absorbed into the microvilli small intestine from where it enters the arteries. During the first passage through the liver cells, bioavailability is reduced to 50%, while metoprolol undergoes intensive transformation with the formation of 2 active metabolites. When taking a repeated dose, bioavailability rises to 70%. Metoprolol succinate reaches maximum values ​​in serum within 6-12 hours. Parallel food intake increases bioavailability by 25-40%.

There is a low degree of binding to plasma proteins - 10%. The elimination half-life lasts from 3.5 to 7 hours. The drug is excreted through the kidneys.

Indications for use Metoprolol retard

IN clinical practice the drug is used for:

• lowering high blood pressure (BP);
• stabilization of the heart rate against the background of ventricular extrasystoles, supraventricular tachycardia, atrial fibrillation;
• elimination of coronary heart disease and as a prevention of exacerbations of stable angina pectoris, reducing the likelihood of a fatal outcome or the occurrence of a re-infarction of the heart muscle;
• heart failure treatment chronic form;
• elimination of violations of the functional activity of the heart.

The medicine is used as preventive measure in the fight against migraines.

Dosing regimen of metoprolol retard

The medicine should be taken 1 time per day. It is recommended to take the tablets in the morning. To reduce the risk of bradycardia, the dosage for each patient is selected on an individual basis. With insufficient therapeutic effect, a single dose is gradually increased.

Side effect

Contraindications to the use of metoprolol retard

It is strictly forbidden to prescribe the drug to people with the following diseases:

• atrioventricular block II-III degree and sinoatrial block;
• heart rate below 50 beats per minute;
• cardiogenic shock;
• acute myocardial infarction;
• severe bronchial asthma;
• acute heart failure;
• hereditary form of hypolactasia, lactase deficiency, glucose-galactose malabsorption syndrome;
• pheochromocytoma;
• severe disorders of peripheral circulation;
• increased susceptibility to metoprolol and auxiliary components.

special instructions

Careful monitoring of blood pressure and heart rate is necessary during the period drug therapy. The patient should inform the attending physician about a decrease in heart rate below 50 beats / min or the appearance of adverse reactions from the CNS. The therapeutic effect is reduced by smoking.

In patients predisposed to the manifestation of allergies, the body may not respond to the standard dosage of epinephrine and the appearance of anaphylactic reactions. Before performing surgery, it is necessary to inform the anesthesiologist on duty about taking Metoprolol.

medicinal product able to disguise clinical picture thyrotoxicosis. Patients with this pathological process it is strictly forbidden to abruptly stop therapy, because it is possible to increase the symptomatic picture of thyrotoxicosis.

In some cases, with a sharp withdrawal of therapy, the development of a withdrawal syndrome, characterized by an increase in blood pressure, an increase in angina pectoris, is possible. Stop taking by gradually reducing the dosage within 7-10 days.

Patients who use contact lenses, it is important to consider that the production of tear fluid decreases during treatment with beta-blockers.

Use during pregnancy and lactation

The drug is taken under strict medical supervision only in cases where the benefit to the mother's body is higher than the expected appearance of abnormalities in the fetus during embryonic development. During pregnancy, careful monitoring of the embryo is necessary. Drug therapy is stopped 1-3 days before the expected onset of labor. The newborn should be under the supervision of a specialist within 24-72 hours after birth.

During therapy with metoprolol, breastfeeding should be discontinued.

Use in children

The drug is prohibited for use in children under 18 years of age.

Application for violations of kidney function

Dose adjustment is not required.

Overdose

Abuse of the drug may cause:

• severe bradycardia;
• pronounced drop in blood pressure;
• peripheral circulatory disorders;
• dyspnea;
• disorders of atrioventricular conduction;
• tremor and fine motor disorders;
• muscle cramps;
• oppression of consciousness;
• bronchospasm;
• cardiogenic shock, coma;
• blockade and cardiac arrest;
• loss of glycemic control.

The first symptoms of an overdose begin to appear 20-120 minutes after taking a high dosage. If the patient has taken the drug within the last 4 hours, it is necessary to wash the stomach cavity, induce vomiting and give an adsorbent. With severe bradycardia, intravenous administration of adrenaline or atropine at a dose of 1-2 mg is necessary. With a decrease in blood pressure, it is necessary to transfer the patient to a horizontal position and raise the legs. At acute insufficiency heart requires the use of cardiac diuretics.

drug interaction

Reserpine and monooxidase blockers, when taken concomitantly with metoprolol, can reduce the level of catecholamines, due to which an increase in the antihypertensive effect is possible. Care must be taken because this combination of medications can lead to severe bradycardia. To reduce the risk of side effect the interval between doses of drugs should be 2 weeks.

Means that inhibit the activity of the CYP2D6 isoenzyme: psychotic drugs, neuroleptics, Cimetidine, Terbinafine - increase the serum level of metoprolol in the blood. At the same time, a decrease in concentration is observed with the use of Rifampicin and barbiturates.

Drugs for inhalation anesthesia increase the likelihood of developing hypotension. They can cause inhibition of myocardial contractility.

If Verapamil is administered intravenously during drug therapy with Metoprolol retard, cardiac arrest may occur. Beta-agonists and non-steroidal anti-inflammatory drugs suppress the hypotensive effect.

Metoprolol can reduce the therapeutic effect of hypoglycemic agents, so people with diabetes should consult with their doctor about adjusting the dosage of glycemic drugs. Insulin therapy is prohibited - metoprolol increases the likelihood of developing hypoglycemia and diabetic coma.

Iodine-containing contrast media for radiography intravenous administration increase the likelihood of anaphylactic shock. During the period of therapy with Metoprolol retard, alcohol should not be taken - ethanol causes a sharp drop in blood pressure. Succinate increases the plasma concentration of Lidocaine.

Terms and conditions of storage

The medicine can be stored for 2 years at temperature regime up to +20°C. It is recommended to keep the tablets in a place isolated from the sun.

The difference between Metoprolol and Metoprolol retard

The peculiarity of Metoprolol retard-Akrikhin tablets is a prolonged action that lasts for 24 hours. In contrast, the classic Metoprolol contains a tartrate salt, which has a rapid therapeutic effect within 30 minutes for a short period.

During treatment, it is possible to change the results of tests during laboratory research(increased levels of urea, transaminases, phosphatases, LDH).

Precautionary measures

In patients with chronic heart failure, myocardial contractility may deteriorate, necessitating the use of cardiac glycosides and / or diuretics with careful monitoring of the hemodynamic status. In case of increasing bradycardia or AV blockade, it is necessary to reduce the dose or inject atropine intravenously. Against the background of diabetes mellitus and hyperfunction thyroid gland metoprolol may mask tachycardia caused by hypoglycemia or thyrotoxicosis. In patients with diabetes, dose adjustment of antidiabetic drugs and careful monitoring of glycemic levels are necessary. When performing surgery against the background of treatment, the anesthetic with the least negative inotropic effect should become the means of choice. Perhaps a more pronounced development of a hypersensitivity reaction and the absence of a therapeutic effect of conventional doses of adrenaline against the background of an aggravated allergic history. When concomitant treatment with clonidine is stopped, metoprolol is discontinued gradually, a few days before clonidine is discontinued, due to the risk of developing a severe hypertensive crisis. In patients with pheochromocytoma, the use is possible only in conjunction with alpha-adrenolytics. Reception of metoprolol is stopped 2-3 days before delivery (the risk of developing bradycardia, hypotension and hypoglycemia in the newborn), in exceptional cases, newborns after childbirth should be under medical supervision for 48-72 hours. Should refrain from using pediatric practice because the safety and efficacy of its use in children have not been determined. When canceling treatment, the dose should be reduced gradually over 10-14 days. Patients with coronary artery disease should be under close medical supervision during this period. Use with caution while driving Vehicle and people whose profession is associated with increased concentration of attention.

The use of metoprolol retard quinacrine during pregnancy and lactation

Perhaps if the expected effect of therapy outweighs the potential risk to the fetus. At the time of treatment should stop breastfeeding.

Overdose

Symptoms: arterial hypotension, acute heart failure, bradycardia, cardiac arrest, AV blockade, cardiogenic shock, bronchospasm, impaired breathing and consciousness / coma, nausea, vomiting, generalized convulsions, cyanosis (appear after 20 minutes - 2 hours after ingestion).

Treatment: gastric lavage, symptomatic therapy: the introduction of atropine sulfate (in / in quickly 0.5-2 mg) - with bradycardia and impaired AV conduction; glucagon (1-10 mg IV, then IV drip 2-2.5 mg / h) and dobutamine - in case of a decrease in myocardial contractility; adrenomimetics (norepinephrine, adrenaline, etc.) - with arterial hypotension; diazepam (in / in slowly) - to eliminate seizures; inhalation of beta-adrenergic agonists or intravenous jet administration of aminophylline for the relief of bronchospastic reactions; pacing.

Interaction

Hypotension is potentiated by sympatholytics, nifedipine, nitroglycerin, diuretics, hydralazine and other antihypertensive drugs. Antiarrhythmic and anesthetic drugs increase the risk of developing bradycardia, arrhythmias, and hypotension. Digitalis preparations potentiate the slowing of AV conduction. Simultaneous intravenous administration of verapamil and diltiazem may cause cardiac arrest. Beta-agonists, aminophylline, cocaine, estrogens, indomethacin and other NSAIDs weaken the antihypertensive effect. Enhances and prolongs the action of antidepolarizing muscle relaxants. The combination with alcohol leads to a mutual strengthening of the inhibitory effect on the central nervous system. Allergens increase the risk of severe systemic allergic reactions or anaphylaxis. Changes the effectiveness of insulin and oral antidiabetic agents and increases the risk of hypoglycemia. Oral contraceptives, cimetidine, ranitidine, phenothiazines - increase the level of metoprolol in the blood, rifampicin - reduces. Reduces the clearance of lidocaine, the effectiveness of beta2-agonists (it is necessary to increase the dose of the latter). Incompatible with MAO inhibitors type A.

Side effects Metoprolol retard akrikhin

From the nervous system and sensory organs: at least 10% - weakness; 1–9.9% - dizziness and headache; 0.1-0.9% - decreased concentration, drowsiness / insomnia, nightmares, depression, muscle cramps, paresthesia; 0.01–0.09% - nervousness, anxiety, weakening of libido, visual impairment, xerophthalmia, conjunctivitis; less than 0.01% - lethargy, fatigue, anxiety, confusion, amnesia / short-term memory loss, hallucinations, tinnitus, taste disturbance.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): 1–9.9% - bradycardia, palpitations, hypotension, cold extremities; in 0.1–0.9% - heart failure, AV blockade, edematous syndrome, chest pain; in 0.01–0.09% - a decrease in myocardial contractility, arrhythmias, less than 0.01% - gangrene (in patients with severe impairment of peripheral circulation); violation of myocardial conduction, syncope, thrombocytopenia, leukopenia, agranulocytosis.

From the digestive tract: 1-9.9% - nausea, abdominal pain, diarrhea or constipation; 0.1–0.9% - vomiting; 0.01-0.09% - dryness in the mouth, abnormal liver function; flatulence, dyspepsia, heartburn, hepatitis.

From the respiratory system: shortness of breath (1–9.9%), bronchospasm (0.1–0.9%), vasomotor rhinitis (0.01–0.09%), dyspnea.

From the side of the skin: 0.1–0.9% - rash, dystrophic changes skin; 0.01–0.09% - reversible alopecia; less than 0.01% - photosensitivity, exacerbation of psoriasis; itching, erythema, urticaria, hyperhidrosis.

Others: weight loss (0.1-0.9%), arthralgia, arthritis, myalgia, muscle weakness, Peyronie's disease.

Application restrictions

Diabetes mellitus, hypoglycemia, aggravated allergic history, metabolic acidosis, bronchial asthma, emphysema, non-allergic bronchitis, hyperthyroidism, psoriasis, pheochromocytoma, abnormal liver and / or kidney function, myasthenia gravis, depression, general anesthesia, elderly and children.

Metoprolol retard akrikhin contraindications

Hypersensitivity, AV block II and III degree, sinoatrial block, acute or chronic (in the stage of decompensation) heart failure, sick sinus syndrome, severe sinus bradycardia(heart rate less than 60 bpm), cardiogenic shock, arterial hypotension (systolic blood pressure less than 100 mm Hg), severe peripheral circulatory disorders, pregnancy, breast-feeding.

Indications for use Metoprolol retard akrikhin

Arterial hypertension of moderate and moderate severity (monotherapy or in combination with other antihypertensive drugs), ischemic heart disease, hyperkinetic cardiac syndrome, cardiac arrhythmia (sinus tachycardia, ventricular and supraventricular arrhythmia, including paroxysmal tachycardia, supraventricular tachycardia, extrasystole, atrial flutter and fibrillation, atrial tachycardia), hypertrophic cardiomyopathy, mitral valve prolapse, myocardial infarction (prevention and treatment), migraine (prevention), thyrotoxicosis (complex therapy); treatment of akathisia caused by antipsychotics.

pharmachologic effect

Pharmacological action - antianginal, hypotensive, antiarrhythmic. Blocks predominantly beta1-adrenergic receptors of the heart, does not have internal sympathomimetic and membrane stabilizing activity. It reduces cardiac output and SAD, slows down the heart rate, weakens the stimulating effect of catecholamines on the myocardium during physical exertion and mental stress, and prevents reflex orthostatic tachycardia. The antihypertensive effect is due to a decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin system and the central nervous system, restoration of baroreceptor sensitivity and, as a result, a decrease in peripheral sympathetic influences. The hypotensive effect develops rapidly (SBP decreases after 15 minutes, maximum - after 2 hours) and lasts for 6 hours; when taking metoprolol succinate - clinical effect blockade of beta1-adrenergic receptors persists for 24 hours. DBP changes more slowly: a stable decrease is observed after several weeks of regular intake. The antianginal effect is a consequence of a decrease in the frequency and strength of heart contractions, energy costs and myocardial oxygen demand. It reduces the frequency and severity of IHD attacks, the mortality rate in patients with diagnosed myocardial infarction, and increases exercise tolerance. Metoprolol succinate reduces the risk of death (including sudden death), the occurrence of re-infarction (including in patients with diabetes mellitus) and improves the quality of life of patients with acute infarction myocardium and idiopathic dilated cardiomyopathy. The antiarrhythmic effect is manifested in the elimination of arrhythmogenic sympathetic influences on the conduction system of the heart, slowing down the sinus rhythm and the rate of propagation of excitation through the AV node, inhibition of automatism and lengthening the refractory period. It has a moderate negative inotropic effect. Cardioselectivity is maintained when using daily doses not exceeding 200 mg. Due to the selective action on beta1-adrenergic receptors, the risk of bronchospasm is theoretically reduced (in patients with bronchial asthma, the vital function of the lungs decreases less), hypoglycemia and peripheral vasoconstriction.

In experiments on dogs (up to 105 mg/kg/day, for 1 year), rats (up to 800 mg/kg/day, for 2 years) and mice (up to 750 mg/kg/day, for 21 months) no signs of carcinogenicity were found, but histological changes such as hepatic cell hyperplasia and induration of lung tissue by macrophages were revealed. When administered to albino mice at doses up to 750 mg/kg/day for 21 months, it increased the incidence of benign lung adenomas in females, however, when the experiment was repeated, an increase in the incidence of any tumors was not observed. The results of the test for dominant lethal mutations in mice, the study of somatic cell chromosomes, the test for anomalies in the nuclei of somatic cells in interphase, etc., indicated the absence of mutagenic properties. In rats treated with doses 55.5 times the maximum daily human dose (450 mg), it had no effect on fertility, increased post-implantation mortality and reduced survival of newborn animals (no signs of teratogenicity).

Metoprolol tartrate is rapidly and almost completely (95%) absorbed when taken orally and undergoes intensive first pass metabolism. Bioavailability is about 50% at the first dose and increases to 70% with repeated use. About 12% binds to plasma albumin. It is rapidly distributed in tissues, penetrates the BBB (the level in the central nervous system is 78% of plasma concentration), the placental barrier, breast milk (concentrations exceed plasma levels). The volume of distribution is 5.5 l/kg. Cmax is achieved within 1-2 hours after administration, the level in the blood varies significantly. T1 / 2 - from 3 to 7 hours. Biotransformed in the liver, with the formation of two active metabolites. It is excreted mainly by the kidneys in the form of metabolites, Cl - 1 l / min. When ingested, less than 5% is excreted in the urine unchanged, with intravenous infusion - about 10%. In case of impaired renal function, bioavailability does not change, but the rate of excretion of metabolites may decrease. In patients with cirrhosis of the liver, metabolism and total clearance slow down (no dosage adjustment is required). Not removed by hemodialysis. With intravenous infusion of metoprolol tartrate for 10 minutes or more, the maximum effect develops after 20 minutes, the decrease in heart rate at doses of 5 and 10 mg is 10 and 15%, respectively. After oral administration in equal doses, Cmax of metoprolol succinate is 1/4–1/2 Cmax of metoprolol tartrate, but it persists for a longer time. Bioavailability at doses of 50-400 mg (1 time per day) is 23% less than that after taking a similar dose of tartrate. Pharmacokinetic parameters do not depend on the age of patients.

Characteristic

Metoprolol tartrate: white, practically odorless crystalline powder, highly soluble in water, methylene chloride, chloroform and alcohol, slightly soluble in acetone, insoluble in ether.

Metoprolol succinate: white crystalline powder, freely soluble in water, soluble in methanol, sparingly soluble in ethanol, slightly soluble in dichloromethane and 2-propanol, practically insoluble in ethyl acetate, acetone, diethyl ether and heptane.

Chemical name Metoprolol retard akrikhin

(±)-1--3-[(1-methylethyl)amino]-2-propanol (as tartrate or succinate)

Beta 1-blocker

Active substance

Release form, composition and packaging

Excipients: hypromellose - 155.96 mg, ludipress LCE (lactose monohydrate - 94.7-98.3%, - 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, iron dye red oxide - 0.009 mg, iron dye yellow oxide - 0.378 mg, iron dye oxide black - 0.003 mg) - 15 mg.

Long-acting film-coated tablets from light green to green, round, biconvex; on a break - white with a grayish or creamy shade of color.

Excipients: hypromellose - 161.29 mg, ludipress LCE (lactose monohydrate - 94.7-98.3%, povidone - 3-4%) - 87.42 mg, colloidal silicon dioxide - 1.5 mg, magnesium stearate - 1.5 mg.

Shell composition: ready-made mixture "Opadry II" green (polyvinyl alcohol - 6 mg, talc - 2.22 mg, macrogol - 3.03 mg, titanium dioxide - 2.925 mg, quinoline yellow dye (aluminum varnish) - 0.268 mg, iron dye black oxide - 0.015 mg, dye (aluminum varnish) - 0.542 mg) - 15 mg.

10 pieces. - cellular contour packings (3) - packs of cardboard.

Long-acting film-coated tablets yellowish-brown, round, biconvex; on a break - white with a grayish or creamy shade of color.

Excipients: hypromellose - 184.84 mg, ludipress LCE (lactose monohydrate - 94.7-98.3%, povidone - 3-4%) - 412.84 mg, colloidal silicon dioxide - 3.5 mg, magnesium stearate - 3.5 mg.

Shell composition: ready-made mixture "Opadry II" orange (polyvinyl alcohol - 14 mg, talc - 5.18 mg, macrogol - 7.07 mg, titanium dioxide - 7.84 mg, iron dye red oxide - 0.021 mg, iron dye yellow oxide - 0.882 mg, iron dye oxide black - 0.007 mg) - 35 mg.

30 pcs. - polypropylene cans (1) - packs of cardboard.
30 pcs. - plastic bottles (1) - cardboard packs.

pharmachologic effect

Cardioselective beta 1-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 in low doses β 1 -adrenergic receptors of the heart, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect (reduces heart rate, inhibits conductivity and excitability, reduces myocardial contractility) . OPSS at the beginning of use (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 β 2 -adrenergic receptors), after 1-3 days it returns to the original, and decreases with long-term administration.

The antihypertensive effect is due to a decrease in the minute volume of blood flow and renin synthesis, inhibition of the activity of the RAAS (it is more important in patients with initial renin hypersecretion) and the central nervous system, restoration of the sensitivity of baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure) and, as a result, 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 (lengthening of diastole and improvement in myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity 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 muscle fibers of the ventricles, it can increase the need for oxygen, 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 in 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 with functional heart diseases and thyrotoxicosis, it slows down the heart rate or can even lead to the restoration of sinus rhythm.

Prevents the development of migraine.

Unlike non-selective beta-blockers, when administered in medium therapeutic doses, it has a less pronounced effect on organs containing β 2 - adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism; the severity of the atherogenic action does not differ from the action of propranolol. With long-term use, it reduces the concentration of cholesterol in the blood. When used in high doses (more than 100 mg / day), it has a blocking effect on both subtypes of β-adrenergic receptors.

Pharmacokinetics

Suction

Absorption when taken orally is complete (95%). Solubility in fats is moderate. Exposed to intensive first pass metabolism, bioavailability - 50% at the first dose and increases to 70% with repeated use. The time to reach Cmax in the blood is 6-12 hours after taking the drug. During the course of treatment, bioavailability increases. Eating increases bioavailability by 20-40%.

Distribution

Plasma protein binding - 10%. It is rapidly distributed in tissues, penetrates the BBB, the placental barrier. Penetrates into breast milk.

Metabolism

Metabolized in the liver, 2 metabolites have beta-blocking activity. The CYP2D6 isoenzyme takes part in the metabolism of the drug.

breeding

T 1/2 - from 3.5 to 7 hours when taken orally. Not removed by hemodialysis.

Pharmacokinetics in special clinical situations

A significant accumulation of metabolites is observed in patients with CC 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

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

Contraindications

• cardiogenic shock;
• AV block II-III degree;
• sinoatrial blockade;
• SSSU;
• severe bradycardia (HR<50 уд./мин);
• acute heart failure or chronic heart failure in the stage of decompensation;
• arterial hypotension (systolic blood pressure<100 мм рт.ст.);
• acute myocardial infarction (HR<45 уд/мин, интервал PQ более 0.24 с, систолическое АД <100 мм рт.ст.);
• severe bronchial asthma;
• severe disorders of peripheral circulation;
• simultaneous administration of MAO inhibitors or simultaneous intravenous administration of verapamil;
• pheochromocytoma (without concomitant use of alpha-blockers);
• age up to 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.

Carefully the drug should be prescribed for diabetes mellitus, AV blockade of the 1st degree, Prinzmetal's angina, metabolic acidosis, bronchial asthma, COPD, severe renal and / or hepatic insufficiency, myasthenia gravis, pheochromocytoma (while taking alpha-blockers), thyrotoxicosis, depression (in including history), psoriasis, peripheral circulatory disorders (intermittent claudication, Raynaud's syndrome), pregnancy, as well as elderly patients.

Dosage

The drug Metoprolol retard-Akrikhin is taken orally 1 time / day. Tablets are recommended to be taken in the morning, without chewing, with water. Metoprolol retard-Akrikhin can be taken with or without food.

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

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

At chronic heart failure II functional class according to the NYHA classification(without exacerbations for the last 6 weeks and without changes in complex therapy for 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 - up to 100 mg, after another 2 weeks - up to 200 mg.

At chronic heart failure III-IV functional class according to the NYHA classification the recommended initial dose is the first 2 weeks 12.5 mg 1 time / day. It is possible to use metoprolol in another dosage form, for example, 25 mg tablets with a risk. During the period of increasing the dose, the patient should be monitored, because. in some patients, symptoms of heart failure 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. Patients who tolerate the drug well can double the dose every 2 weeks until a maximum dose of 200 mg 1 time / day is reached.

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

At functional disorders of cardiac activity, accompanied by tachycardia, appoint 50 mg / day, if necessary, the dose can be increased to 200 mg / day.

For prevention of migraine attacks appoint 100-200 mg 1 time / day.

Elderly patients, patients with renal insufficiency or patients on hemodialysis dose adjustment is not required.

Liver dysfunction affect the excretion of metoprolol, therefore, dose adjustment may be required depending on the clinical condition.

Side effects

Frequency of side effects: very often (> 1/10), often (> 1/100 and<1/10), нечасто (>1/1000 and<1/100), редко (>1/10 000 and<1/1000), очень редко (<1/10 000, включая отдельные сообщения).

From the side of the cardiovascular system: often - bradycardia, orthostatic hypotension (including with fainting), coldness of the lower extremities, palpitations; infrequently - a temporary increase in symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, AV blockade of the first degree; rarely - myocardial conduction disturbances, arrhythmia; very rarely - gangrene (in patients with peripheral circulatory disorders).

From the side of the central nervous system: very often - increased fatigue, a decrease in the speed of mental and motor reactions; often - dizziness, headache; infrequently - 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 sense organs: rarely - blurred vision, dryness and / or irritation of the eyes, conjunctivitis; very rarely - ringing in the ears, a violation of taste sensations.

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 side of the skin: infrequently - urticaria, increased sweating; rarely - alopecia; very rarely - photosensitivity, exacerbation of the course of psoriasis, psoriasis-like skin reactions.

From the respiratory system: often - shortness of breath; infrequently - bronchospasm in patients with bronchial asthma; rarely - rhinitis.

From the side of 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 1 diabetes mellitus), rarely - hyperglycemia (in patients with type 2 diabetes mellitus), hypothyroid state.

Others: infrequently - an increase in body weight; rarely - impotence / sexual dysfunction; very rarely - arthralgia, thrombocytopenia.

Overdose

Symptoms: severe bradycardia, AV blockade (up to the development of complete transverse blockade and cardiac arrest), excessive decrease in blood pressure, impaired peripheral circulation, increased symptoms of heart failure, cardiogenic shock, respiratory depression, apnea, cyanosis, increased fatigue, dizziness, loss of consciousness, coma , tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, esophagospasm may develop, hypoglycemia or hyperglycemia, hyperkalemia, transient myasthenia gravis. The first signs of an overdose appear 20 minutes to 2 hours after taking the drug.

Treatment: if the drug has been taken recently - gastric lavage and intake of adsorbents; in violation of AV conduction and / or bradycardia - in / in the introduction of 1-2 mg of atropine, epinephrine (adrenaline) or the setting of a temporary pacemaker; with a decrease in blood pressure, the patient should be transferred to the Trendelenburg position. If there are no signs of pulmonary edema - in / in, if ineffective - the introduction of epinephrine, dopamine, dobutamine; in acute heart failure - cardiac glycosides, diuretics; with convulsions - in / in diazepam; with bronchospasm - inhalation or parenteral beta 2-agonists.

drug interaction

Means that reduce catecholamine stores (eg, reserpine, MAO inhibitors), when used simultaneously with metoprolol, may increase the hypotensive effect or cause severe bradycardia. A break in treatment between taking MAO inhibitors and metoprolol should be at least 14 days.

Metoprolol is a substrate of the CYP2D6 isoenzyme. Medicinal products that inhibit or induce CYP2D6 activity may affect the plasma concentration of metoprolol.

Inhibitors of CYP2D6 (some antidepressants and neuroleptics, quinidine, terbinafine, celecoxib, propafenone, diphenhydramine, hydroxychlorine, cimetidine) increase the concentration of metoprolol in blood plasma.

CYP2D6 inducers (barbituric acid derivatives, rifampicin) reduce plasma concentrations of metoprolol.

Simultaneous administration of metoprolol with cardiac glycosides, clonidine, slow calcium channel blockers (verapamil, diltiazem), amiodarone, class I antiarrhythmic drugs, general anesthesia agents, methyldopa, guanfacine can lead to a decrease in blood pressure and severe bradycardia.

Means for inhalation anesthesia (derivatives of hydrocarbons), when used simultaneously with metoprolol, increase the risk of myocardial function inhibition and the development of arterial hypotension.

Simultaneous / in the introduction of verapamil can provoke cardiac arrest.

NSAIDs and beta-agonists weaken the antihypertensive effect of beta-blockers.

Ergot alkaloids, when used simultaneously with metoprolol, increase the risk of peripheral circulatory disorders.

When metoprolol is taken together with oral hypoglycemic drugs, their effect may be reduced; with insulin - an increased risk of developing hypoglycemia, lengthening and increasing its severity, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).

Metoprolol reduces the clearance of xanthines (except for diaphylline), especially in patients with initially increased clearance of theophylline under the influence of smoking.

Metoprolol reduces the clearance of lidocaine, increases the concentration of lidocaine in plasma.

Metoprolol enhances and prolongs the action of non-depolarizing muscle relaxants; prolongs the anticoagulant effect of coumarins.

With the simultaneous administration of epinephrine (adrenaline) with beta-blockers, an increase in blood pressure and bradycardia is possible.

Phenylpropanolamine (norephedrine), when used simultaneously with metoprolol, may increase diastolic blood pressure.

Allergens used for immunotherapy or allergen extracts for skin tests when used together with metoprolol increase the risk of systemic allergic reactions or anaphylaxis.

With the combined use of metoprolol with ethanol, the risk of a pronounced decrease in blood pressure increases.

special instructions

Control 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 should be instructed to consult a doctor if the heart rate is less than 50 bpm.

It is possible to increase the severity of allergic reactions (against the background of a burdened allergic history) and the lack of effect from the administration of conventional doses of epinephrine (adrenaline).

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

With angina pectoris, the selected dose of the drug should provide heart rate at rest in the range of 55-60 beats / min, with exercise - no more than 110 beats / min.

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

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

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

If it is necessary to prescribe to patients with bronchial asthma, beta 2-agonists are used as concomitant therapy; with pheochromocytoma - alpha-blockers.

If it is necessary to perform a surgical intervention, it is necessary to warn the anesthesiologist about taking the drug Metoprolol retard-Akrikhin (it is necessary to choose a drug for general anesthesia with a minimal negative inotropic effect), drug withdrawal 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.

With the abrupt abolition of clonidine, blood pressure may rise sharply, while taking beta-blockers. If clonidine is discontinued, discontinuation of beta-blockers should begin a few days before clonidine is discontinued.

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

With a sharp cessation of treatment, a withdrawal syndrome may occur (increased angina attacks, increased blood pressure). Particular attention when discontinuing the drug should be given to patients with angina pectoris, chronic heart failure, after myocardial infarction. Cancellation of the drug Metoprolol retard-Akrikhin is carried out gradually, reducing the dose within 10 days.

Patients using contact lenses should take into account that against the background of treatment with beta-blockers, a decrease in the production of lacrimal fluid is possible.

Influence on the ability to drive vehicles and control mechanisms

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

Pregnancy and lactation

During pregnancy, the drug Metoprolol retard-Akrikhin should be used only under strict indications, when the expected benefit to the mother outweighs the potential risk to the fetus / child (due to the possible development of bradycardia in the newborn, lowering blood pressure, hypoglycemia and respiratory paralysis). At the same time, careful monitoring is carried out especially for the development of the fetus. Treatment is stopped 48-72 hours before the onset of delivery. If this is not possible, then the newborn should be under particularly close supervision for 48-72 hours after delivery.

Use in the elderly

Elderly patients do not require dose adjustment.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored in a dry, dark place, out of the reach of children, at a temperature not exceeding 25°C. Shelf life - 2 years.