Metoprolol-Akrihin - instructions for use, doses, side effects, contraindications

Metoprolol refers to cardioselective beta-adrenergic receptor blockers that do not possess internal sympathomimetic activity and membrane-stabilizing properties.Has antihypertensive, antianginal and antiarrhythmic action. Blocking in low doses of beta₁-adrenoreceptors of the heart, reduces the catecholamine-stimulated cAMP formation from ATP, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic action (tends heart rate (heart rate), inhibits conduction and excitability, reduces myocardial contractility).

The total peripheral resistance at the beginning of beta-blockers (in the first 24 hours after ingestion) increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂- adrenoreceptors), which after 1-3 days returns to the original, and with prolonged use - decreases.

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

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

The antianginal effect is determined by the decrease in myocardial oxygen demand as a result of the decrease in heart rate (diastolic elongation 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.

Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular (AV) conductivity (mainly in antegrade and, to a lesser extent, in retrograde directions) through AV node and by additional paths.

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and hyperthyroidism, the heart rate decreases, or 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 exerts a less pronounced effect on organs containing beta₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism.

When used in large doses (more than 100 mg / day) has a blocking effect on both subtypes of beta adrenoreceptors.

Pharmacokinetics:

Absorption when taken orally is complete (95%). The maximum concentration in the blood plasma is achieved 1-2 hours after ingestion. The half-life is 3.5 hours on average (within 1 to 9 hours). It is subjected to intensive presystemic metabolism, bioavailability is 50% at the first intake and increases to 70% with repeated application. Food intake increases bioavailability by 20-40%. Bioavailability of metoprolol increases with cirrhosis of the liver. Connection with blood plasma proteins - 10%. Penetrates through blood-brain and placental barriers.It penetrates into breast milk in small amounts. Metabolized in the liver, 2 metabolites have beta-adrenoblocking activity. In the metabolism of the drug takes part isoenzyme CYP2D6. About 5% is excreted unchanged by the kidneys.

Treatment of patients with decreased renal function does not require correction of the dose of the drug.

Impaired liver function slows 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 (as a monotherapy or in combination with other antihypertensive agents);

- ischemic heart disease: myocardial infarction (secondary prevention - complex therapy), prevention of angina attacks;

- heart rhythm disturbances (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 blockade (AV) II-III degree;

- sinoatrial (SA) blockade;

- syndrome of weakness of the sinus node;

- severe bradycardia;

- chronic heart failure in the stage of decompensation;

- angina of Prinzmetal;

- 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 period");

- simultaneous administration of monoamine oxidase inhibitors (MAO) or simultaneous intravenous administration of verapamil (see "Interaction with other drugs");

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

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

Diabetes mellitus, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease (emphysema, chronic obstructive bronchitis), obliterating peripheral vascular diseases ("intermittent" lameness, Raynaud's syndrome), chronic hepatic and / or renal insufficiency, myasthenia gravis, pheochromocytoma application of alpha-blockers), AV blockade of I degree, thyrotoxicosis, depression (incl.and in the anamnesis), psoriasis, pregnancy, elderly age.

Pregnancy and lactation:

During pregnancy prescribe taking into account the ratio of benefit to the mother and the risk to the fetus (due to the development of fetal bradycardia, arterial hypotension, hypoglycemia). At the same time, careful monitoring is carried out, especially for fetal development. It is necessary to observe the newborns within 48-72 hours after delivery.

Influence of metoprolol on a newborn when breastfeeding not studied, therefore, women who take Metoprolol-Akrihin, you should stop breastfeeding.

Dosing and Administration:

Tablets are taken orally during or immediately after ingestion, do not chew, drink with a small amount of liquid.

Arterial hypertension

The initial daily dose is 50-100 mg in 1-2 doses (morning and evening). With insufficient therapeutic effect, the daily dose can be gradually increased to 100-200 mg and / or additional prescription 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 divided doses (morning and evening).

Secondary prevention of myocardial infarction

200 mg per day in two divided doses (morning and evening).

Hyperthyroidism

50 mg twice a day (morning and evening).

In elderly patients, with violations of kidney function, and if the need for hemodialysis does not change the dose.

With violations of liver function the dose of the drug should be reduced depending on the clinical condition.

Side effects:

From the central nervous systemRarely - paresthesia in the extremities (in patients with "intermittent" lameness and Raynaud's syndrome), depression, anxiety, decreased attention, drowsiness, insomnia, "nightmarish" dreams, confusion or short-term memory impairment, muscle weakness.

From the sense organs: rarely - reduced vision, reduced secretion of tear fluid, dry and sore eyes, conjunctivitis, tinnitus.

From the side of the cardiovascular system: sinus bradycardia, palpitation, lowering of arterial pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness).Rarely, decreased myocardial contractility, temporary worsening of symptoms of chronic heart failure (swelling, edema of the feet and / or lower legs, shortness of breath), arrhythmias, manifestation of angiospasm (increased peripheral circulatory disturbance, coldness of the lower limbs, Raynaud's syndrome), impaired myocardial conductivity.

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

From the skin: urticaria, skin itch, 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 in high doses - loss of selectivity and / or in predisposed patients), dyspnea.

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 "hepatic" enzymes; extremely rarely - hyperbilirubinemia.

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

Other: pain in the back or joints, as with all beta-blockers in rare cases may cause a slight increase in body mass, decreased libido and / or potency.

Overdose:

Symptoms: Expressed severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked reduction in blood pressure, arrhythmia, ventricular premature beats, bronchospasm, fainting, in acute overdose - cardiogenic shock, loss of consciousness, coma, atrioventricular block (up to the full development of cross blockades and cardiac arrest).

The first signs of an overdose occur after 20 minutes - 2 hours after taking the drug.

Treatment: gastric lavage and intake of absorbents; symptomatic therapy: with a marked decrease in blood pressure - the patient should be in the Trendelenburg position; in the event of excessive reduction in blood pressure, bradycardia and heart failure - in / at intervals of 2-5 minutes, 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, the installation of a transvenous intracardiac electrostimulator.

When bronchospasm should be introduced in / in beta₂-adrenomimetics.

Metoprolol is poorly excreted by hemodialysis.

Interaction:

Do not use concurrently with monoamine oxidase inhibitors (MAO) due to a significant increase in antihypertensive effects. A break in treatment between taking MAO inhibitors and metoprolol should be at least 14 days. Simultaneous iv injection of verapamil may provoke cardiac arrest. Simultaneous administration of nifedipine leads to a significant reduction in blood pressure.

Means for inhalation anesthesia (hydrocarbon derivatives) increase the risk of oppression of myocardial function and development of arterial hypotension.

Beta-adrenomimetics, theophylline, cocaine, estrogens (sodium retention), indomethacin and other non-steroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys) weaken the hypotensive effect.

There is an increase in the inhibitory effect on the central nervous system - with ethanol; the sum of the cardiodepressive effect - with anesthesia; increased risk of violations of peripheral circulation - with ergot alkaloids.

When sharing with hypoglycemic agents for oral administration possibly reducing their effect; with insulin - Increased risk of developing hypoglycemia, increasing its severity and lengthening, masking some of the symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).

When combined with antihypertensive agents, diuretics, nitroglycerin or blockers of "slow" calcium channels a sharp drop in blood pressure may develop (special caution is necessary when combined with prazosin); increase in the severity of heart rate reduction and inhibition of atrioventricular conduction - with metoprolol with verapamil, diltiazem, antiarrhythmics (amiodarone), reserpine, methyldopa, clonidine, guanfacin, general anesthetics and cardiac glycosides.

If metoprolol and clonidine take simultaneously, then with the cancellation of metoprolol clonidine cancellation after a few days (due to the risk of the syndrome of "withdrawal").

Inducers of microsomal liver enzymes (rifampicin, barbiturates) lead to an increase in metabolism of metoprolol, a decrease in its concentration in the 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 extracts of allergens for skin tests when combined with metoprolol, increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiopaque substances for intravenous administration increase the risk of anaphylactic reactions.

Reduces ground clearance xanthine (except for diphylline), especially with the initially elevated clearance of theophylline under the influence of smoking.

Reduces ground clearance lidocaine, increases the concentration of lidocaine in the blood plasma.

Enhances and prolongs the action antidepolarizing muscle relaxants; prolongs the anticoagulant effect coumarins.

When combined with ethanol the risk of a marked decrease in blood pressure increases.

Special instructions:

Control of patients taking beta-blockers includes regular monitoring of heart rate (heart rate) and blood pressure, blood glucose in patients with diabetes mellitus. If necessary, for patients with diabetes mellitus, the dose of insulin or hypoglycemic drugs administered orally should be selected individually.

It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at a heart rate of less than 50 beats per minute. When taking a dose above 200 mg per day, cardioselectivity decreases.

With heart failure, metoprolol treatment begins only after the compensation stage has been reached.

It is possible to increase the severity of reactions of hypersensitivity (against a background of a burdened allergic anamnesis) and the absence of the effect of the administration of usual doses of epinephrine (epinephrine).

It can intensify the symptoms of peripheral arterial circulation.

Cancellation of the drug is carried out gradually, reducing the dose for 10 days. With a sharp cessation of treatment, there may be a "cancellation" syndrome (increased angina attacks, increased blood pressure).

Particular attention should be paid to patients with angina when removing the drug.

With angina pectoris, 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 using contact lenses should take into account that, against the background of beta-blocker therapy, tear production can be reduced.

Metoprolol may mask certain clinical manifestations of hyperthyroidism (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. Unlike nonselective beta-blockers, it does not actually increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

If it is necessary to prescribe to patients with bronchial asthma, as a concomitant therapy, beta₂-adrenomimetics; at pheochromocytoma - alpha-adrenoblockers.

If it is necessary to carry out a surgical procedure, an anesthesiologist should be warned about the therapy(choice of means for general anesthesia with minimal negative inotropic action), drug discontinuation is not recommended.

Drugs that reduce catecholamine stocks (for example, reserpine), can enhance the action of beta-blockers, so patients taking such combinations of drugs should be under constant observation of the doctor for the detection of excessive lowering of blood pressure and bradycardia.

In elderly patients, it is recommended to regularly monitor liver function. Correction of the dosing regimen is required only in the case of an elderly patient with an increasing bradycardia (less than 50 beats per minute), a marked decrease in blood pressure (systolic blood pressure below 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, , sometimes it is necessary to stop treatment.

Patients with severe renal failure are advised to monitor kidney function.

Special monitoring should be carried out on the condition of patients with depressive disorders receiving metoprolol; In the case of development of depression caused by the use of 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.

Effect on the ability to drive transp. cf. and fur:

At the beginning of metoprolol treatment, patients may experience dizziness, fatigue. In this case, they should refrain from driving vehicles and practicing potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. In the future, the definition of dose safety is carried out individually.

Form release / dosage:

Tablets, 50 mg.

Packaging:

For 10 tablets in a planar cell package.

3 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

AT dry, protected from light, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N003213 / 01

Date of registration:16.03.2009 / 04.05.2017

Expiration Date:Unlimited

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp10.05.2018

Illustrated instructions

Instructions

Metoprolol-Acrychin (Metoprolol-Akrichin)