Metoprolol - instructions for use, dose, side effects, contraindications

Active substance:
Metoprolol tartrate	50.00 mg	100.00 mg
Excipients:
Lactose Monohydrate	119,60 mg	239.20 mg
Potato starch	10.88 mg	21.76 mg
Povidone (medium molecular weight polyvinylpyrrolidone	1.52 mg	3.04 mg
Magnesium stearate	2.00 mg	4.00 mg
Carboxymethyl starch sodium (primogel)	6.00 mg	12.00 mg
Talc	4.00 mg	8.00 mg
Silica colloidal dioxide (aerosil)	6.00 mg	12.00 mg

Description:

Dosage 50 mg: Tablets are white or white with a yellowish hue of color, flat-cylindrical shape, with a bevel.

Dosage of 100 mg: Tablets are white or white with a yellowish hue of color, flat-cylindrical shape, with a facet and a risk.

Pharmacotherapeutic group:beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

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 formation of cAMP (cyclo adenosine monophosphate) from ATP (adenosine triphosphate), reduces the intracellular current of Ca²⁺, has a negative chrono-, dromo-, batmo- and inotropic effect (it cuts the heart rate, inhibits conduction and excitability, reduces myocardial contractility).

The total peripheral resistance of the vessels at the beginning of beta-blockers (in the first 24 hours after oral administration) increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), which is returned to the initial one 1-3 days later, and decreases with long-term administration.

Hypotensive effect is associated with a decrease in the minute volume of circulation and the synthesis of renin, suppression of the activity of the renin-angiotensin-aldosterone system (is 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 in blood pressure ) and, as a result, a decrease in peripheral sympathetic influences. Reduces high blood pressure 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.

Antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in the heart rate (diastole 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 the tolerance of exercise. By increasing the end diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.

Antiarrhythmic effect due to the elimination of arrhythmogenic factors (tachycardia, increased sympathetic nervous system activity, increased cAMP levels, hypertension), decrease the rate of spontaneous excitation of the sinus and ectopic pacemaker and deceleration atrioventricular conduction (preferably antegrade and to a lesser extent, in the retrograde direction through the atrioventricular node ) and on additional paths.

If supraventricular tachycardia, atrial fibrillation, sinus tachycardia with functional heart disease and hyperthyroidism slows the heart rate and may even lead to the restoration of sinus rhythm.

Prevents the development of migraine.

In contrast to nonselective beta-blockers, when given in average therapeutic doses, it has a less pronounced effect on organs containing beta₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism; the severity of atherogenic action does not differ from that of propranolol.

With many years of intake reduces the concentration of cholesterol in the blood.

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

Pharmacokinetics:

Metoprolol is rapidly and almost completely absorbed (95%) in the gastrointestinal tract. The solubility in fats is moderate. It is subjected to intensive presystemic metabolism, bioavailability is 50% at the first intake and increases to 70% with repeated application. Connection with plasma proteins - 10%. TS_mOh - 1,5-2 hours after administration. During the course of treatment, bioavailability increases. Food intake increases bioavailability by 20-40%. Rapidly distributed in tissues, the placental barrier penetrates the blood-brain barrier. It penetrates into the mother's milk (the concentration is higher than in the plasma).

Metabolized in the liver, 2 metabolites have beta-adrenoblocking activity. In the metabolism of the drug takes part isoenzyme CYP2D6. T_1/2- from 3,5 to 7 hours with ingestion. About 5% of the drug is excreted unchanged by the kidneys. It is not removed during hemodialysis.

Significant accumulation of metabolites is observed in patients with creatine kinase 5 ml / min, while the beta-adrenoblocking activity of the drug does not increase.

Treatment of patients with reduced renal function does not require dose adjustment.

Disturbance of liver function slows the metabolism of the drug, and in cases of insufficient liver function, the dose of the drug should be reduced.

Indications:

- Arterial hypertension (as a monotherapy or in combination with other antihypertensive agents), including hyperkinetic type, tachycardia;

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

- heart rhythm disturbances (supraventricular tachycardia and 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 II-III degree (without artificial pacemaker

- sinoatrial blockade;

- syndrome of weakness of the sinus node;

- sinus bradycardia (heart rate less than 50 beats per minute);

- chronic heart failure in the stage of decompensation;

- angina of Prinzmetal;

- acute myocardial infarction (heart rate less than 45 beats per minute, interval P-Q more than 0.24 s, systolic blood pressure less than 100 mm Hg);

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;

- simultaneous administration of monoamine oxidase inhibitors;

- simultaneous administration of blockers of "slow" calcium channels (BCCC) such as verapamil;

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

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

- patients receiving long-term or intermittent therapy with inotropes and acting on beta-adrenergic receptors.

Carefully:

Diabetes mellitus, metabolic acidosis, renal dysfunction (creatinine clearance less than 40 ml / min), myasthenia gravis, atrioventricular block I degree, thyrotoxicosis, depression (incl.and history), psoriasis, liver dysfunction, allergic reactions in the anamnesis (possibly increased sensitivity to allergens, weighty arterial hypertension and reduced therapeutic response to epinephrine), elderly age, chronic obstructive pulmonary disease, bronchial asthma, peripheral circulation disorders, pheochromocytoma (with simultaneous use of adrenoblockers).

Pregnancy and lactation:

In pregnancy metoprolol appoint according to strict indications if the intended benefit to the mother exceeds the potential risk to the fetus (due to the possible development of fetal bradycardia, arterial hypotension, hypoglycemia). At the same time, careful monitoring is carried out, especially for fetal development. Strict monitoring of newborns is necessary within 48-72 hours after delivery.

If the drug is needed during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, during or immediately after eating, the tablets can be divided in half, but not chewed and washed down with liquid.

With arterial hypertension the initial dose is 50-100 mg in 1-2 doses (morning and evening), with insufficient therapeutic effect, the daily dose can be increased to 100-200 mg or additionally use other antihypertensive agents. The maximum daily dose is 200 mg.

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

With angina pectoris, arrhythmia, prevention of migraine attacks - 100-200 mg per day in two divided doses (morning and evening).

With functional disorders of cardiac activity, accompanied by tachycardia; hyperthyroidism - 50 mg twice a day (morning and evening).

Elderly patients it is recommended to start treatment with 50 mg / day.

Renal insufficiency does not require dose adjustment.

With hepatic insufficiency a dose adjustment may be required depending on the clinical condition.

Side effects:

From the nervous system: increased fatigue, weakness, headache, slowing of the speed of mental and motor reactions. Paresthesia in the extremities (in patients with intermittent claudication and Raynaud's syndrome), tremors, convulsions, depression, anxiety, decreased attention, drowsiness, insomnia, nightmarish dreams, confusion or short-term memory loss, hallucinations, asthenia, myasthenia gravis.

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, lowering of arterial pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness). Rarely, a decrease in myocardial contractility, the development of chronic heart failure (edema, edema of the feet and / or lower legs, shortness of breath), heart rhythm disturbances, manifestation of angiospasm (increased peripheral circulatory disturbance, coldness of the lower limbs, Raynaud's syndrome), conduction disorders myocardium, cardialgia. Very rarely - exacerbation of pre-existing violations of atrioventricular conduction.

From the digestive system: nausea, vomiting, abdominal pain, dryness of the oral mucosa, constipation or diarrhea, in some cases - impaired liver function (dark urine, icteric sclera or skin, cholestasis), changes in taste.

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

From the respiratory system: congestion of the nose, bronchospasm at the appointment in high doses (loss of selectivity and / or in predisposed patients), dyspnea.

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

Allergic reactions: urticaria, skin itching, rash.

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

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

Other: Back pain or joint pain, weight gain, loss of libido and / or potency, the sudden cessation of treatment - a syndrome of "cancellation" (increasing angina attacks, increased blood pressure).

Overdose:

Symptoms: expressed severe sinus bradycardia, dizziness, atrioventricular block (up to the full development of cross block and cardiac arrest), decreased blood pressure, fainting, arrhythmia, ventricular premature beats, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, loss of consciousness, coma, nausea , vomiting, cyanosis.The first signs of an overdose appear after 20 minutes-2 hours after taking the drug.

Treatment: gastric lavage and administration of absorbent drugs; symptomatic therapy: with a marked decrease in blood pressure - the patient should be in the Trendelenburg position; in case of excessive reduction in blood pressure, bradycardia and heart failure - intravenously, with an interval of 2-5 min, beta-adrenostimulators - until the desired effect is achieved or intravenously 0.5-2 mg of atropine. In the absence of a positive effect - dopamine, dobutamine or norepinephrine. When hypoglycemia - the introduction of 1-10 mg of glucagon, the installation of transvenous intracardiac electrostimulator. When bronchospasm should be administered intravenously stimulants beta₂adrenoreceptors. With convulsions, slow intravenous diazepam administration.

Hemodialysis is ineffective.

Interaction:

Allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving metoprolol.

Iodine-containing radiopaque drugs for intravenous administration increase the risk of developing anaphylactic reactions.

Phenytoin with intravenous administration, drugs for inhalation of general anesthesia (derivatives of hydrocarbons) increase the severity of cardio-depressive action and the likelihood of lowering blood pressure.

Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in the plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Hypotensive effect weakens non-steroidal anti-inflammatory drugs (delay Na+ and synthesis blockade Pg kidneys), glucocorticosteroids and estrogens (delay Na+).

Cardiac glycosides, methyldopa, reserpine and guanfacine, slow calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, atrioventricular blockades, cardiac arrest and heart failure. Nifedipine can lead to a significant decrease in blood pressure.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to excessive lowering of blood pressure.

Lengthens the effect of nondepolarizing muscle relaxants and anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase the inhibition of the central nervous system.

It is not recommended simultaneous use with monoamine oxidase inhibitors due to a significant increase in hypotensive effect, a break in the treatment between taking monoamine oxidase inhibitors and metoprolol should be at least 14 days.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

Special instructions:

Control of patients taking beta-blockers includes monitoring the heart rate and blood pressure (at the beginning of the treatment - every day, then once every 3-4 months), the concentration of glucose in the blood in diabetics (1 every 4-5 months ).The patient should be taught how to calculate the heart rate and instructed about the need for medical advice at a heart rate of less than 50 beats per minute.

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

In elderly patients, it is recommended that the kidney function is monitored (once every 4-5 months). It can intensify the symptoms of peripheral arterial circulation.

Cancellation of the drug is carried out gradually, reducing the dose for 10 days.

With arterial hypertension, the effect occurs after 2-5 days, a stable effect is observed after 1-2 months.

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. In "smokers" the effectiveness of beta-blockers is lower.

With combined therapy with clonidine, the latter should be discontinued a few days after metoprolol cancellation, in order to avoid hypertensive crisis. At a dose above 200 mg / day, cardioselectivity decreases.

Metoprolol may mask certain clinical manifestations of thyrotoxicosis (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 necessary, the appointment of patients with bronchial asthma as a concomitant therapy is used beta₂-adrenostimulators; at pheochromocytoma - alpha-adrenoblockers.

If it is necessary to perform a surgical procedure, it is necessary to warn the anesthesiologist about the therapy (choice of a medicament for general anesthesia with minimal negative inotropic action), the drug cancellation is not recommended.

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

Drugs that reduce catecholamine stores (for example, reserpine), can enhance the action of beta-blockers, so patients who take such combinations of drugs should be under constant observation of the doctor for the detection of excessive reduction in blood pressure or bradycardia.

In the case of the appearance in elderly patients of an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure below 100 mmHg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney disorders, it is necessary to reduce the dose or stop treatment. It is recommended to stop therapy with skin rashes and the development of depression caused by the use of beta-blockers.

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 (an increase in angina attacks, an increase in blood pressure). Special attention should be paid to stenocardia when the drug is withdrawn.

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

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

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.

Form release / dosage:Tablets, 50 mg and 100 mg.

Packaging:

10 tablets per contour cell pack.

1, 2, 3, 5 or 10 contour of cellular packages with instructions for use in a pile of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000692

Date of registration:28.09.2011 / 24.12.2014

Expiration Date:28.09.2016

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Representation: & nbspMOSCOW ENDOCRINE FACTORY FGUP MOSCOW ENDOCRINE FACTORY FGUP Russia

Information update date: & nbsp24.07.2016

Illustrated instructions

Instructions

Metoprolol (Metoprolol)