Metoprolol retard-Acrichin pills 25mg, 30pcs

Composition

Tablets of prolonged action, covered with a film-coated yellowish-brown color, round, biconvex; at the break-white with a grayish or creamy tint of color. 1 tab. metoprolol succinate 23.83 mg, which corresponds to the content of metoprolol tartrate 25 mg

Auxiliary substances:

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 mix “Opadray II” orange color (polyvinyl alcohol-6 mg, talc-2.22 mg, macrogol-3.03 mg, titanium dioxide-3.36 mg, iron oxide red dye-0.009 mg, iron oxide yellow dye-0.378 mg, iron oxide black dye-0.003 mg) – 15 mg

Pharmacological action

Metoprolol is a cardioselective beta-adrenergic blockers that do not have internal sympathomimetic activity and membrane-stabilizing properties. It has antihypertensive, antianginal and antiarrhythmic effects. Blocking the beta-1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular flow of calcium ions, has a negative chrono -, dromo -, batmo-and inotropic effect (reduces heart rate (HR), inhibits conduction and excitability, reduces myocardial contractility).

Total peripheral resistance at the beginning of the use of beta-blockers (in the first 24 hours after ingestion) -increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and elimination of stimulation of beta-2 – adrenergic receptors), which returns to its original value after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is due to a reflex decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin-apidosterone system (which is more important in patients with initial hypersecretion of renin) and the central nervous system, restoration of sensitivity of the aortic arch baroreceptors (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 (BP) at rest, during physical exertion and stress.

The hypotensive effect develops quickly (systolic blood pressure decreases in 15 minutes, maximum – in 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 (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to 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 the 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 the heart rate, or even can lead to the restoration of sinus rhythm.

Prevents the development of migraines. When used in medium therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on the organs containing beta-2-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

Oral absorption is complete (95%). The maximum concentration in blood plasma is reached 1-2 hours after ingestion. The average elimination half-life is 3.5 hours (ranging from 1 to 9 hours). Undergoes intensive presystemic metabolism, bioavailability is 50% at the first dose and increases to 70% with repeated use. Food intake increases bioavailability by 20-40%.

The bioavailability of metoprolol increases in cirrhosis of the liver. Binding to plasma proteins is 10%. Penetrates through the blood-brain and placental barriers. Penetrates into breast milk in small amounts. It is metabolized in the liver,2 metabolites have beta-adrenoblocking activity. The isoenzyme CYP2D6 is involved 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. Impaired liver function slows down the metabolism of the drug, and in cases of insufficient liver function, the dose of the drug should be reduced. It is not removed during hemodialysis.

Indications

— arterial hypertension;

— chronic heart failure II-IV functional class NYHA classification in the stage of compensation (in the complex therapy);

— ischemic heart disease: prevention of attacks of stable angina, decrease mortality and the frequency of repeated myocardial infarction after the acute phase of myocardial infarction;

of arrhythmias, including supraventricular tachycardia, a decrease in the frequency of ventricular contraction in atrial fibrillation and ventricular extrasystoles;

functional cardiac abnormalities, accompanied by tachycardia;

— prevention of migraine attacks.

Contraindications

— cardiogenic shock;

— AV-block 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. St. )

— acute myocardial infarction (heart rate <45 beats/min, the interval PQ more 0.24 C, systolic blood pressure <100 mm Hg. St. )

— severe asthma;

severe peripheral circulatory disorders;

— simultaneous reception of MAO inhibitors or concurrent I/vedeniapina;

— pheochromocytoma (without the simultaneous use of alpha-blockers);

— age under 18 years (effectiveness and safety not established);

— lactation period;

— lactase deficiency, lactose intolerance, malabsorption syndrome glucose/galactose;

— hypersensitivity to metoprolol and other beta-blockers.

With caution should be prescribed with diabetes, AV blockade of I degree, prinzmetals angina, metabolic acidosis, asthma, COPD, renal and/or hepatic failure, severe, infants, pheochromocytoma (while taking alpha-blockers), hyperthyroidism, depression (including in history), psoriasis, disorders of peripheral blood circulation (intermittent claudication, Raynaud’s syndrome), pregnancy, and elderly patients.

Side effects

From the central nervous system:  increased fatigue, weakness, headache, slowing down the speed of mental and motor reactions. Rarely – paresthesia in the extremities (in patients with “intermittent” claudication and Raynaud’s syndrome), depression, anxiety, decreased attention, drowsiness, insomnia, “nightmarish” dreams, confusion or short-term memory impairment, muscle weakness.

From the side of the senses:  rarely-decreased vision, decreased secretion of tear fluid, dry and painful 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 aggravation of symptoms of chronic heart failure (edema, swelling of the feet and / or lower legs, shortness of breath), arrhythmias, angiospasm (increased peripheral circulatory disorders, cold of the lower extremities, Raynaud’s syndrome), impaired myocardial conduction.

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

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

Respiratory system disorders:  nasal congestion, difficulty exhaling (bronchospasm when administered 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 parameters:  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 services:  pain in the back or joints, like all beta-blockers, in isolated cases can cause a slight increase in body weight, a decrease in libido and / or potency.

Interaction

• Concomitant use with monoamine oxidase (MAO) inhibitors is not recommended due to a significant increase in the hypotensive effect. The treatment interval between taking MAO inhibitors and metoprolol should be at least 14 days.
• Simultaneous intravenous use of verapamil may cause cardiac arrest.
• Concomitant use of nifedipine leads to a significant reduction in blood pressure.
• Inhaled anaesthetic agents (hydrocarbon derivatives) increase the risk of myocardial function depression and hypotension.
• Beta-adrenomimetics, theophylline, cocaine, estrogens (sodium retention), Indometacin, and other nonsteroidal anti-inflammatory drugs (sodium retention and blocking prostaglandin synthesis by the kidneys) weaken the hypotensive effect.
• There is an increase in the depressive effect on the central nervous system – with ethanol; summation of the cardiodepressive effect – with anesthesia; an increase in the risk of peripheral circulatory disorders – with ergot alkaloids.
• When taken together with hypoglycemic agents for oral use, their effect may decrease; with insulin – an increased risk of hypoglycemia, its increased severity and lengthening, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).
• When combined with antihypertensive agents, diuretics, nitroglycerin or slow calcium channel blockers, a sharp decrease in blood pressure may develop (special caution is necessary when combined with prazosin); an increase in the severity of a decrease in heart rate and suppression of atrioventricular conduction – when using metoprolol with verapamil, diltiazem, antiarrhythmic agents (amiodarone), reserpine, methyldopa, clonidine, guanfacine, general anaesthetic agents and cardiac glycosides.
• If metoprolol and clonidine are taken simultaneously, then when metoprolol is discontinued, clonidine is canceled after a few days (due to the risk of “withdrawal”syndrome).
• Inducers of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of metoprolol, to a decrease in its concentration in blood plasma and a decrease in the effect. Inhibitors (cimetidine, oral contraceptives, phenothiazines) – increase the concentration of metoprolol in plasma.
• Allergens used for immunotherapy or allergen extracts for skin tests when combined with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiopaque substances for intravenous use increase the risk of anaphylactic reactions.
• Reduces the clearance of xanthine (except diphylline), especially with initially increased clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in blood plasma.
• Enhances and prolongs the action of antidepolarizing muscle relaxants; prolongs the anticoagulant effect of coumarins.
• When combined with ethanol, the risk of a pronounced decrease in blood pressure increases.

How to take, course of use and dosage

Tablets are taken orally during or immediately after a meal, do not chew, drink a small amount of liquid. Arterial hypertension. The initial daily dose is 50-100 mg in 1-2 divided doses (morning and evening). If the therapeutic effect is insufficient, the daily dose can be gradually increased to 100-200 mg and / or additional use of other antihypertensive agents. 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 divided doses (morning and evening).

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

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

Overdose

Symptoms:

severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked decrease in blood pressure, arrhythmia, ventricular extrasystole, bronchospasm, syncope, acute overdose – cardiogenic shock, loss of consciousness, coma, atrioventricular block (up to the development of complete transverse block and cardiac arrest), cardialgia. The first signs of overdose appear 20 minutes -2 hours after taking the drug.

Treatment:

gastric lavage and the appointment of absorbent material; symptomatic treatment: when pronounced reduction of blood pressure, the patient should be in the Trendelenburg position; in case of excessive reduction in blood pressure, bradycardia and heart failure in/in, at intervals of 2-5 min, beta-agonists – to achieve the desired effect or/0.5-2 mg atropine sulfate. In the absence of a positive effect – dopamine, dobutamine or norepinephrine (norepinephrine). As a follow-up, it is possible to administer 1-10 mg of glucagon, install a transvenous intracardial pacemaker. In case of bronchospasm, intravenous beta-2-adrenomimetics should be administered. Metoprolol is poorly excreted by hemodialysis.

Special instructions

• Monitoring of patients taking beta-blockers includes regular monitoring of heart rate (HR) and blood pressure, blood glucose in patients with diabetes mellitus. If necessary, for patients with diabetes mellitus, the dose of insulin or hypoglycemic agents prescribed by mouth should be selected individually.
• 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. When taking a dose higher than 200 mg per day, cardioselectivity decreases.
• In heart failure, treatment with metoprolol begins only after reaching the compensation stage.
• It is possible to increase the severity of hypersensitivity reactions (against the background of a burdened allergic history) and the lack of effect from the introduction of conventional doses of epinephrine (epinephrine).
• It may increase the symptoms of peripheral arterial circulation disorders.
• Discontinuation of the drug is carried out gradually, reducing the dose over 10 days.
• If treatment is abruptly discontinued, a “withdrawal” syndrome may occur (increased angina attacks, increased blood pressure).
• Special attention should be paid to patients with angina pectoris when discontinuing the drug.
• In case of stress angina, the selected dose of the drug should provide a heart rate at rest in the range of 55-60 beats / min, with a load-no more than 110 beats / min.
• Patients who use contact lenses should take into account that against the background of treatment with beta-blockers, tear fluid production may decrease.
• Metoprolol may mask some clinical manifestations of hyperthyroidism (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.
• In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal levels.
• If necessary, prescribe to patients with bronchial asthma, beta-2 – adrenomimetics are used as concomitant therapy; with pheochromocytoma, alpha-blockers are used.
• If surgical intervention is necessary, it is necessary to warn the anesthesiologist about the therapy being performed (the choice of a general anesthesia agent with minimal negative inotropic effect), and discontinuation of the drug is not recommended.
• Drugs that reduce the supply of catecholamines (for example, reserpine) can increase the effect of beta-blockers, so patients taking such combinations of drugs should be constantly monitored by a doctor for excessive lowering of blood pressure and bradycardia.
• In elderly patients, regular monitoring of liver function is recommended.
• Correction 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 liver function disorders, and sometimes it is necessary to stop treatment.
• Monitoring of renal function is recommended for patients with severe renal insufficiency.
• Special monitoring should be carried out for patients with depressive disorders taking metoprolol; in case of depression caused by taking beta-blockers, it is recommended to stop therapy.
• Due to the lack of sufficient clinical data, the drug is not recommended for use in children.

Impact 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 dangerous activities that require increased concentration of attention and speed of psychomotor reactions. In the future, the dose safety is determined individually.

Active ingredient

Metoprolol

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets