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

Excipientslactose monohydrate (sugar milk) 0.08949 g or 0.12778 g, potato starch 0.04275 g or 0.06349 g, povidone (kollidon-30 or plasdon K-29/30) 0.003 g or 0, 0048 g, silicon dioxide colloid (aerosil 300) 0.003 g or 0.0048 g, crospovidone (clolidone CL-M or polyplasdone XL-10) 0.007 g or 0.0112 g, magnesium stearate 0.002 g or 0.0032 g , stearic acid 0.002 g or 0.0032 g.

Description:Round tablets of flat-cylindrical shape, with a facet and a risk, white or white with a yellowish hue of color. Allowed a slight "marble".

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. Has an insignificant membrane-stabilizing effect and does not possess internal sympathomimetic activity. It has antihypertensive, antianginal and antiarrhythmic action.

Blocking beta 1-adrenoreceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate, reduces intracellular calcium flow, has a negative chrono-, dromo-, batmo- and inotropic effect (reduces heart rate, inhibits conduction and excitability, reduces myocardial contractility ).

The total peripheral vascular resistance 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 elimination of stimulation of beta2-adrenoreceptors), which returns to the initial one after 1-3 days, and after prolonged application is reduced.

Antihypertensive action is caused by a reflex decrease in the minute volume of blood and the synthesis of renin,inhibition of the activity of the renin-angiotensin-aldosterone system (is more important in patients with initial renin hypersecretion) 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 elevated blood pressure (BP) at rest, with physical stress and stress.

The antihypertensive 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 final diastolic pressure in the left ventricle of the heart and increasing the stretching of the muscle fibers of the ventricles can increase the demand for myocardium in oxygen, especially in patients with chronic heart failure.

Antiarrhythmic effect (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) conduction (predominantly in the 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, it slows down the heart rate (HR) or even can lead to a restoration of the rhythm.

Prevents the development of migraine.

In contrast to nonselective beta-blockers, when used in average therapeutic doses, it has a less pronounced effect on organs containing beta2-adrenoreceptors (pancreas,skeletal muscles, smooth musculature of the peripheral arteries, bronchi and uterus) and carbohydrate metabolism.

When used in large doses (more than 100 mg / day) it blocks beta1 and beta2-adrenergic receptors.

Pharmacokinetics:

Absorption in the gastrointestinal tract with ingestion is complete (95%). 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 blood plasma proteins - 10%. Time to reach the maximum concentration of metoprolol is 1.5-2 hours. During the course of treatment, bioavailability increases. Food intake increases bioavailability by 20-40%.

Rapidly distributed in tissues, penetrates the blood-brain barrier, the placental barrier. Penetrates into breast milk (concentration is higher than in blood plasma).

Metabolized in the liver, two metabolites have beta-adrenoblocking activity. The isozyme CYP2D6 is involved in the metabolism of the drug. The half-life of metoprolol is 3.5 to 7 hours with oral administration. It is not removed during hemodialysis.

A significant accumulation of metabolites is observed in patients with a creatinine clearance of 5 ml / min, while the beta-adrenergic blocking activity of the drug does not increase.

Bioavailability increases with hepatic insufficiency, while its overall clearance is reduced.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);

- 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, other components of the drug and other beta-blockers, cardiogenic shock, atrioventricular block II-III systolic sinus node syndrome, severe bradycardia (heart rate less than 50 beats / min), acute and chronic heart failure in decompensation stage, prinzmetal angina, acute myocardial infarction (heart rate less than 45 beats / min, PQ interval is more than 0, 24 s, systolic blood pressure less than 100 mm Hg), pheochromocytoma (without simultaneous use of alpha-blockers),simultaneous administration of monoamine oxidase inhibitors or simultaneous iv injection of verapamil; lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome, severe peripheral circulatory disorders, severe bronchial asthma and bronchospasm in the anamnesis; age to 18 years, lactation period.

Carefully:

Diabetes mellitus, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease, renal / hepatic insufficiency, myasthenia gravis, pheochromocytoma (with simultaneous use with alpha-adrenoblockers), thyrotoxicosis, atrioventricular blockade of the I stage, depression (including in the anamnesis) , psoriasis, peripheral circulation disorders ("intermittent" lameness, Raynaud's syndrome), a burdened allergic anamnesis, pregnancy, elderly age.

Pregnancy and lactation:

During pregnancy appoint only for severe indications if the intended benefit to the mother exceeds the potential risk to the fetus (due to the possible development of a newborn bradycardia, arterial hypotension, hypoglycemia and respiratory depression). Treatment should be interrupted for 48-72 hours before childbirth.In cases where this is not possible, it is necessary to ensure strict observation of newborns within 48-72 hours after delivery.

Because the metoprolol penetrates into breast milk, the drug should not be taken during lactation or during the treatment of the mother should stop breastfeeding.

Dosing and Administration:

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

With arterial hypertension (in monotherapy or in combination with other antihypertensive drugs), the initial dose is 50-100 mg 1-2 times a day (morning and evening); with insufficient therapeutic effect, the daily dose can be increased to 100-200 mg. The maximum daily dose is 200 mg.

With functional disorders of cardiac activity, accompanied by tachycardia: 50 mg twice a day (morning and evening). Elderly patients are advised to begin treatment with 50 mg / day.

Cardiac ischemia: myocardial infarction (secondary prevention) - 200 mg / day, divided into 2 doses (morning and evening).

Prevention of angina attacks, with heart rhythm disorders 100-200 mg 1-2 times a day (morning and evening).

With hyperthyroidism - 50 mg twice a day (morning and evening).

Preventing migraine attacks - 100-200 mg 1-2 times a day (morning and evening).

Side effects:

Frequency: very often - more than 1/10, often - more than 1/100 less than 1/10, infrequently - more than 1/1000 and less than 1/100, rarely - more than 1/10000 and less than 1/1000, very rarely, messages - not less than 1/10000.

When using the drug metoprolol sometimes possible:

From the side - cardiovascular system: often bradycardia, orthostatic hypotension (including fainting), manifestation of angiospasm (increased peripheral circulatory disturbance, coldness of the lower extremities, Raynaud's syndrome), palpitation; infrequent - temporary enhancement of symptoms of chronic heart failure, cardiogenic shock in patients with myocardial infarction, aggravation of pre-existing atrioventricular conduction disorders; rarely - conduction disorders, arrhythmia; very rarely - gangrene (in patients with impaired peripheral circulation), a marked decrease in blood pressure.

From the nervous system: very often - increased fatigue; often - dizziness, headache; rarely - increased nervous excitability,anxiety, infrequently - paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, "nightmarish" dreams; very rarely - amnesia / memory impairment, depression, hallucinations, slowing of the speed of mental and motor reactions, muscle cramps, asthenia, myasthenia gravis.

From the sense organs: rarely - visual impairment, dry and painful eyes, conjunctivitis, reduced secretion of tear fluid; 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, a violation of liver function, hepatitis.

From the skin: infrequently - hives, increased sweating; rarely - alopecia; very rarely - photosensitivity, exacerbation of psoriasis, skin itching, rash, skin hyperemia, psoriasis-like skin reactions.

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

Other: infrequent - increase in weight, body; very rarely - arthralgia, thrombocytopenia, Peyronie's disease, hypoglycemia, hyperglycemia, increased titer of antinuclear antibodies, decreased libido, potency.

Overdose:

Symptoms: severe sinus bradycardia, dizziness, atrioventricular block (up to the development of complete transverse blockade and cardiac arrest), marked decrease in arterial pressure, fainting, arrhythmia, ventricular extrasystole, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, unconsciousness, coma, nausea, vomiting, cyanosis, convulsions, hypoglycemia. The first signs of an overdose appear after 20 minutes - 2 hours after taking the drug.

Treatment: gastric lavage and intake of absorbent drugs; symptomatic therapy: with a marked reduction in blood pressure, the patient should be in the Trendelenburg position; in case of excessive reduction in blood pressure, bradycardia and heart failure - intravenously (intravenously) with an interval of 2-5 minutes, beta-adrenomimetics - 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. When hypoglycemia - the introduction of 1-10 mg of dextrose, the installation of transvenous intracardiac electrostimulator. When bronhospazme apply beta2-adrenomimetiki.With convulsions - slow IV injection of diazepam. Hemodialysis is ineffective.

Interaction:

Barbiturates increase metabolism of metoprolol due to the induction of microsomal liver enzymes.

Propaphenone raises the plasma concentration of metoprolol 2-5 times (probably due to the inhibition of the propafenone isoenzyme CYP2D6).

Simultaneous IV injection of verapamil can cause bradycardia and marked decrease in blood pressure.

Class I antiarrhythmic drugs can result in the summation of a negative inotropic effect with the development of severe hemodynamic side effects in patients with left ventricular dysfunction (this combination should be avoided in patients with sinus node weakness syndrome or AV conduction disorder).

Amiodarone - the risk of developing severe sinus bradycardia (including after a long time after the abolition of amiodarone, due to its long half-life).

Diltiazem - the risk of development of severe bradycardia (mutual enhancement of the inhibitory effect on AV conduction and sinus node function).

Antihypertensive effect weakened glucocorticosteroids and estrogens (sodium ion retention).

Beta-adrenomimetics, aminophylline, theophylline, indomethacin and other non-steroidal anti-inflammatory drugs weaken the antihypertensive effect.

Diphenhydramine reduces the clearance of metoprolol, enhancing its effect.

Epinephrine is the risk of a marked decrease in blood pressure and bradycardia.

Phenylpropanolamine in high doses is a paradoxical increase in blood pressure (up to the hypertensive crisis).

Quinidine inhibits metabolism of metoprolol in fast metabolizers, leading to a significant increase in the concentration of metoprolol in plasma and an increase in its beta-adrenergic blocking effect.

Clonidine - the risk of a marked increase in blood pressure with a sharp abolition of clonidine against a background of simultaneous reception of beta-blockers, so in the case of withdrawal of clonidine, the gradual cessation of beta-blockers should begin several days before its withdrawal.

Rifampicin - enhances the metabolism of metoprolol, reducing the concentration in the plasma (due to the induction of microsomal liver enzymes).

Cimetidine, hydralazine increase the concentration of metoprolol in the blood.

Drugs for inhalation anesthesia (halogenated hydrocarbons) increase the cardiodepressive effect of metoprolol.

Incompatible with an inhibitor of monoamine oxidase type A.

Cardiac glycosides, methyldopa, reserpine, guanfacine and clonidine increase the risk of bradycardia.

Nifedipine, in addition to increasing antihypertensive effects, can lead to the development of heart failure.

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

With the simultaneous use of metoprolol and sympatholytic drugs, nitroglycerin, barbiturates, vasodilators (alprostadil) and other antihypertensive drugs (such as prazosin), the antihypertensive effect may increase, so patients taking such drug combinations should be under constant medical supervision to detect excessive BP or bradycardia.

Changes the effectiveness of insulin and hypoglycemic agents for oral administration.Increases the risk of developing hypoglycemia, increases its severity and duration, masks its symptoms (tachycardia, sweating, increased blood pressure).

When combined with ethanol, the risk of a marked decrease in blood pressure increases and an increase in the inhibitory effect on the central nervous system is noted.

Reduces clearance of lidocaine and increases its concentration in blood plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

Lengthens the effect of antidepolarizing muscle relaxants and the anticoagulant effect of coumarin derivatives.

Aldesleykin increases arterial hypotension.

Mefloquine increases the inhibition of conduction and excitability of the heart muscle.

With the simultaneous use of norepinephrine, epinephrine, other adreno-and sympathomimetics (including in the form of eye drops or in antitussive drugs), some increase in blood pressure is possible.

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 radiocontrast drugs for IV administration increase the risk of anaphylactic reactions.

Special instructions:

Control of patients taking beta-blockers includes monitoring of heart rate and blood pressure (at the beginning of administration - every day, then once every 3-4 months), the concentration of glucose in the blood in patients with diabetes mellitus (1 every 4-5 months). 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.

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.

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 use in patients with concomitant bronchial asthma, it is necessary to additionally use beta2-adrenomimetics; at pheochromocytoma - alpha-adrenoblockers.

If surgical intervention is necessary, the surgeon / anesthesiologist should be warned about the use of metoprolol (the choice of drugs for general anesthesia with minimal negative inotropic action), the drug cancellation is not recommended.

If there is an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic BP below 100 mmHg), AV blockade, bronchospasm, ventricular arrhythmias, severe 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.

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). 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. Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

With combined therapy with clonidine, the latter should be discontinued a few days after metoprolol withdrawal in order to avoid a hypertensive crisis.

At a dose above 200 mg / day, cardioselectivity decreases.

In the case of the appearance of bronchospasm in patients, it is necessary to reduce the dose or stop treatment.

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,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 50 mg and 100 mg.

Packaging:

For 10 or 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil.

For 30 tablets in a jar of polymer materials.

Each jar or 3 or 5 contour cell packs of 10 tablets or 2 contour packs of 20 tablets together with the instructions for use are placed in a pack of cardboard for consumer containers.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000950

Date of registration:18.10.2011

Expiration Date:18.10.2016

The owner of the registration certificate:MARBIOFARM, OJSC MARBIOFARM, OJSC Russia

Manufacturer: & nbsp

MARBIOFARM, OJSC Russia

Representation: & nbspMARBIOFARM, OJSCMARBIOFARM, OJSC

Information update date: & nbsp24.07.2016

Illustrated instructions

Instructions

Metoprolol (Metoprolol)