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

Excipientslactose monohydrate 45.0 mg, microcrystalline cellulose 15.5 mg, corn starch 3.0 mg, sodium carboxymethyl starch 4.0 mg, povidone-K25 4.0 mg, silicon dioxide colloid 1 , 5 mg, magnesium stearate 2.0 mg.

One 50 mg tablet contains:

active substance: metoprolol tartrate - 50.0 mg;

Excipients: lactose monohydrate (sugar milk) - 90.0 mg, microcrystalline cellulose - 31.0 mg, corn starch - 6.0 mg, sodium carboxymethyl starch 8.0 mg, povidone-K25 - 8.0 mg, silicon dioxide colloidal -3 , 0 mg, magnesium stearate 4.0 mg.

Description:

Tablets are white or white with a grayish tint of color, slight marbling is allowed, a flat-cylindrical shape, with a facet on both sides and a risk on one side.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

Cardioselective beta-1 blocker. Does not have a membrane-stabilizing action and does not possess internal sympathomimetic activity. Has antihypertensive, antianginal and antiarrhythmic action.

Blocking low-dose beta-adrenoreceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect (reduces the frequency of cardiac contractions (heart rate), inhibits conduction and excitability, reduces myocardial contractility).

Total peripheral vascular resistance (SVR) early use of beta-blockers (the first 24 h after ingestion) increases (as a result of reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of beta₂- adrenoreceptors), which after 1-3 days returns to the original, and with a long appointment decreases.

The hypotensive effect is due to the reflex decrease in the minute volume of blood and the synthesis of renin, inhibition of the activity of the renin-angiotensin-aldosterone system (RAAS) (more important in patients with initial renin hypersecretion) and the central nervous system (CNS), restoring the sensitivity of the aortic arch baroreceptors increase their activity in response to lowering blood pressure (BP)) and, as a result, a decrease in peripheral sympathetic influences. Reduces elevated 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.

The antianginal effect is determined by the decrease in myocardial oxygen demand as a result of a decrease in heart rate (diastolic elongation and improvement of myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to sympatheticinnervation. 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, it can increase the need for oxygen, especially in patients with chronic heart failure (CHF).

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

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and thyrotoxicosis, the heart rate decreases or even lead to a restoration of the 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 period on the average is 3.5 hours (ranging from 1 hour to 9 hours). It is subjected to intensive presystemic metabolism, bioavailability is 50% at the first ingestion and increases to 70% with repeated application. Eating increases bioavailability by 20-40%. Bioavailability of metoprolol increases with cirrhosis of the liver. Connection with blood plasma proteins - 10%. Penetrates through the blood-brain and placental barrier. Excreted in 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. Around 5% the drug 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 (in monotherapy or in combination with other antihypertensive agents);

- functional disorders of cardiac activity accompanied by tachycardia;

- 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;

- AV blockade II-III degree (without artificial pacemaker);

- sinoatrial blockade;

- syndrome of weakness of the sinus node;

- severe bradycardia;

- chronic heart failure in the stage of decompensation;

- angina of Prinzmetal;

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

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

- lactation period (see section "Application during pregnancy and lactation");

- simultaneous intravenous administration of blockers of "slow" calcium channels (BCCC) such as verapamil (see section "Interaction with other drugs");

- 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:FROMdiabetes mellitus, metabolic acidosis, renal dysfunction (creatinine clearance less than 40 ml / min), myasthenia gravis, AV blockade of I degree, thyrotoxicosis, depression (including history), psoriasis, impaired liver function, allergic reactions in the anamnesis (possibly increased sensitivity to allergens, weighty arterial hypertension and decreased therapeutic response to epinephrine), elderly age, chronic obstructive pulmonary disease, bronchial asthma, peripheral circulation disorders, pheochromocytoma (with simultaneous use of alpha-blockers).

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 taken metoprolol is necessary during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Tablets are taken orally at the same time as eating or immediately after eating, the tablets can be divided in half (but not chewed) and poured with 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 appointment of 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).

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

Functional disorders of cardiac activity, accompanied by tachycardia 100 mg per day in two divided doses (morning and evening).

With hyperthyroidism 150-200 mg per day in 3-4 divided doses.

In elderly patients, with violations of kidney function (CC less than 40 ml / min), and also if the hemodialysis is necessary, the dose is not changed.

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

Side effects:

From the central 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), depression, anxiety, decreased concentration, drowsiness, insomnia, nightmares, confusion or short-term memory impairment, myasthenia gravis, hallucinations, asthenia.

From the sense organs: decreased vision, reduced secretion of tear fluid, dry and painful eyes, conjunctivitis, ringing in the ears.

From the side of the cardiovascular system: sinus bradycardia, palpitations, marked decrease in blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness).Decreased contractility of the myocardium, temporary worsening of symptoms of chronic heart failure (edema of the feet and / or lower legs, shortness of breath), arrhythmias, manifestation of angiospasm (increased peripheral circulatory disturbance, cooling of the lower limbs, Raynaud's syndrome), cardialgia; aggravation of pre-existing violations AV conductivity.

From the digestive system: nausea, vomiting, abdominal pain, dryness of the oral mucosa, diarrhea, constipation, taste change, hepatitis.

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

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

From the respiratory system: rhinitis, bronchospasm, shortness of breath with physical effort.

Other: pain in the back or joints, arthralgia, like all beta-adrenoblockers in a few cases can cause a slight increase in body weight, a decrease in libido and / or potency.

Overdose:

Symptoms: pronounced sinus bradycardia, dizziness, AV blockade (up to the development of complete transverse blockade and cardiac arrest), marked decrease in blood pressure, syncope, arrhythmia, ventricular extrasystole, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, unconsciousness, coma, nausea, vomiting, cyanosis. The first signs of an overdose occur after 20 minutes - 2 hours after taking the drug.

Treatment: gastric lavage, intake of adsorptive drugs; symptomatic therapy: with a pronounced decrease in blood pressure - the patient should be in the Trendelenburg position. In case of excessive decrease in blood pressure, bradycardia and heart failure - in / with, with an interval of 2-5 minutes beta-adrenomimetic - to achieve the desired effect or iv in 0.5 - 2 mg of atropine. 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 an artificial pacemaker. When bronchospasm should be introduced in / in beta₂-adrenomimetics. With convulsions - slow IV injection of diazepam.

Hemodialysis is ineffective.

Interaction:

It is not recommended simultaneous use with monoamine oxidase (MAO) inhibitors due to a significant increase in hypotensive effect. 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 (halogenated hydrocarbons) increase the risk of oppression of myocardial function and development of arterial hypotension. There is a summation of the cardiodepressive effect (an increase in the severity of heart rate reduction and inhibition of AV conduction) with the use of metoprolol with funds for general anesthesia.

Beta₂-adrenomimetics, theophylline, cocaine, estrogens (sodium ion retention), indomethacin and other non-steroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys) weaken the hypotensive effect.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), sedatives and hypnotics increase the CNS depression.

Increased inhibitory effect on the central nervous system - with ethanol; increased risk of violations of peripheral circulation - with ergot alkaloids.

When combined with hypoglycemic agents for oral administration, a decrease in their effect is possible; with insulin - increased risk of hypoglycemia, increased its severity and lengthening, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).

When combined with antihypertensive drugs, diuretics, nitroglycerin, or blockers of "slow" calcium channels, a sharp decrease in blood pressure can develop. Particular caution is necessary when combined with prazosin; Increased severity of heart rate reduction and depression AV conduction - with the use of metoprolol with verapamil, diltiazem, antiarrhythmics (amiodarone), reserpine, methyldopa, clonidine, guanfacin 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"). Inductors of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of metoprolol, a decrease in the concentration of metoprolol in the blood plasma and a decrease in the effect. Inhibitors of microsomal liver enzymes (cimetidine, oral contraceptives, phenothiazines) - increase the concentration of metoprolol in the blood 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 agents for intravenous administration increase the risk of anaphylactic reactions.

Reduces the clearance of xanthines (except diprofilina), especially with the initially elevated clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in the blood plasma.

Strengthens and prolongs the action of nondepolarizing muscle relaxants; prolongs the anticoagulant effect of coumarin derivatives.

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

Means that reduce catecholamine stocks (for example, reserpine), can enhance the action of beta-blockers, so patients,taking such combinations of medicines, should be under the constant supervision of the doctor for the detection of excessive decrease in blood pressure or bradycardia.

Special instructions:

Control of patients taking beta-blockers includes regular monitoring of heart rate and blood pressure, blood glucose concentration 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. It is possible to increase the severity of allergic reactions (against the background of a burdened allergic medical history) and the lack of the effect of the administration of usual doses of epinephrine (adrenaline).

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 angina pectoris, the selected dose of the drug should provide a heart rate at rest within 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 100 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.

In contrast to non-selective beta-blockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of glucose concentration in the blood to a normal value.

If it is necessary to appoint patients with bronchial asthma as a concomitant therapy, use a betaa₂-adrenomimetics; at pheochromocytoma - alpha-adrenoblockers.

If surgery is necessary, an anesthesiologist should be warned about taking metoprolol (choice of a general anesthetic medicine with minimal negative inotropic effect), drug cancellation is not recommended.

Reciprocal activation n.vagus (vagus nerve) can be eliminated in / in the administration of atropine (1-2 mg).

In the case of an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure below 100 mmHg) AV blockade, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function, 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.

With a sharp cessation of treatment, there may be a "cancellation" syndrome (increased angina attacks, increased 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, 25 mg and 50 mg.

Packaging:

10, 25, 30, 50 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, 100 or 150 tablets in cans of polyethylene terephthalate for medicines or polypropylene for drugs sealed with high-pressure polyethylene caps with the first opening control or polypropylene lids with a "push-turn" system, or low-pressure polyethylene lids with control of the first opening.

One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package.

Storage conditions:

Store in a 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006698/10

Date of registration:15.07.2010 / 02.02.2018

Expiration Date:Unlimited

The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp10.05.2018

Illustrated instructions

Instructions

Metoprolol (Metoprolol)