Metoprolol 50 mg
Metoprolol
Registration number: LP-000950
Trade name of the drug: Metoprolol
International nonproprietary name: metoprolol
Dosage form: tablets
Composition per tablet: metoprolol tartrate 0.05 g or 0.1 g (calculated as 100% substance).
Excipients: lactose monohydrate (milk sugar) - 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, colloidal silicon dioxide (Aerosil 300) - 0.003 g or
0.0048 g, crospovidone (kollidon CL-M or polyplasdon 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 a flat-cylindrical shape with a chamfer and a score, white or white with a yellowish tint. Slight marbling is allowed.
Pharmacotherapeutic group: selective beta1-blocker
ATX code: [С07АВ02]
Pharmacological properties
Pharmacodynamics Cardioselective beta1-blocker. It has a slight membrane-stabilizing effect and does not have internal sympathomimetic activity. It has antihypertensive, antianginal and antiarrhythmic effects.
By blocking beta1-adrenergic receptors of the heart, it reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate, reduces the intracellular calcium current, has a negative chrono-, dromo-, batmo- and inotropic effect (reduces heart rate, inhibits conductivity and excitability, reduces myocardial contractility ).
The total peripheral vascular resistance at the beginning of the use of beta-adrenergic blockers (in the first 24 hours after oral administration) increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which returns to the original level after 1-3 days, and with long-term use it decreases.
The antihypertensive effect is due to a reflex decrease in minute blood volume and renin synthesis, inhibition of the activity of the renin-angiotensin-aldosterone system (of greater importance in patients with initial hypersecretion of renin) and the central nervous system, restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to decrease in blood pressure) and ultimately a decrease in peripheral sympathetic influences. Reduces high blood pressure (BP) at rest, during physical exertion and stress. The antihypertensive effect develops quickly (systolic blood pressure decreases after 15 minutes, maximum after 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 the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance. By increasing the end-diastolic pressure in the left ventricle of the heart and increasing the stretching of the muscle fibers of the ventricles, it can increase the myocardial oxygen demand, especially in patients with chronic heart failure. 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 paths.
In case of supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and thyrotoxicosis, it reduces the heart rate (HR) or can even lead to rhythm restoration.
Prevents the development of migraine.
In contrast to non-selective beta-blockers, when used in average therapeutic doses, it has a less pronounced effect on organs containing beta2-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 blocks beta1 and beta2 adrenergic receptors.
Pharmacokinetics Absorption in the gastrointestinal tract when taken orally is complete (95%). Solubility in fats is moderate. Subjected to intensive first-pass metabolism, bioavailability is 50% upon first administration and increases to 70% upon repeated use. Communication with blood plasma proteins - 10%. The time to reach the maximum concentration of metoprolol is 1.5-2 hours. During the course of treatment, bioavailability increases. Eating increases bioavailability by 20 - 40%.
It is quickly distributed in tissues, penetrates the blood-brain barrier, and the placental barrier. Penetrates into breast milk (concentration higher than in blood plasma).
Metabolized in the liver, two metabolites have beta-blocking activity. The CYP2D6 isoenzyme takes part in the metabolism of the drug. The half-life of metoprolol ranges from 3.5 to 7 hours when taken orally. It is not removed by hemodialysis.
A significant accumulation of metabolites is observed in patients with a creatinine clearance of 5 ml/min, while the beta-blocking activity of the drug does not increase.
Bioavailability increases in liver failure, while its overall clearance is reduced.
Indications for use
Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs); functional disorders of cardiac activity accompanied by tachycardia; coronary 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, grade II-III atrioventricular block, sinoatrial block, sick sinus syndrome, severe bradycardia (heart rate less than 50 beats/min), acute and chronic heart failure in stages of decompensation, Prinzmetal's angina, acute myocardial infarction (heart rate less than 45 beats/min, PQ interval more than 0.24 s, systolic blood pressure less than 100 mm Hg), pheochromocytoma (without simultaneous use of alpha-blockers), concomitant use of monoamine oxidase inhibitors or simultaneous intravenous administration of verapamil; lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome, severe peripheral circulatory disorders, severe forms of bronchial asthma and a history of bronchospasm; age up to 18 years, lactation period.
Directions for use and doses
Orally, during or immediately after a meal, the tablets can be divided in half (but not chewed) and washed down with liquid. For 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); if the therapeutic effect is insufficient, the daily dose can be increased to 100-200 mg. The maximum daily dose is 200 mg.
For functional disorders of cardiac activity accompanied by tachycardia - 50 mg 2 times a day (morning and evening). Elderly patients are recommended to start treatment with 50 mg/day.
Coronary heart disease: myocardial infarction (secondary prevention) - 200 mg/day, divided into 2 doses (morning and evening).
Prevention of angina attacks, in case of heart rhythm disturbances - 100-200 mg 1-2 times a day (morning and evening).
For hyperthyroidism - 50 mg 2 times a day (morning and evening).
Prevention of migraine attacks - 100-200 mg 1-2 times a day (morning and evening).
Carefully
Diabetes mellitus, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease, renal/liver failure, myasthenia gravis, pheochromocytoma (with simultaneous use with alpha-blockers), thyrotoxicosis, stage I atrioventricular block, depression (including in history) , psoriasis, peripheral circulatory disorders (“intermittent” claudication, Raynaud’s syndrome), aggravated allergic history, pregnancy, old age.
Overdose
Symptoms: severe sinus bradycardia, dizziness, atrioventricular block (up to the development of complete transverse block and cardiac arrest), marked decrease in blood pressure, fainting, arrhythmia, ventricular extrasystole, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, loss of consciousness, coma, nausea, vomiting, cyanosis, convulsions, hypoglycemia. The first signs of overdose appear 20 minutes - 2 hours after taking the drug. Treatment: gastric lavage and taking absorbent medications; 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 - intravenously (i.v.), with an interval of 2-5 minutes, beta-agonists - until the desired effect is achieved or i.v. 0.5-2 mg of atropine. If there is no positive effect, dopamine, dobutamine or norepinephrine. For hypoglycemia - administration of 1-10 mg of dextrose solution, installation of a transvenous intracardial pacemaker. For bronchospasm, beta2-adrenergic agonists are used. For convulsions - slow intravenous administration of diazepam. Hemodialysis is ineffective.
special instructions
Monitoring of patients taking beta-blockers includes monitoring heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), blood glucose concentration in patients with diabetes (once every 4-5 months). The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.
It is possible that the severity of allergic reactions may increase (against the background of a burdened allergic history) and there will be no effect from the administration of usual doses of epinephrine (adrenaline). In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).
May increase symptoms of peripheral arterial circulation disorders. For exertional angina, the selected dose of the drug should ensure the heart rate at rest within the range of 55-60 beats/min, and during exercise - no more than 110 beats/min. In smokers, the effectiveness of beta-blockers is lower.
Metoprolol may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, as it can intensify symptoms.
In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal values.
If necessary, use in patients with concomitant bronchial asthma requires additional use of beta2-adrenergic agonists; for pheochromocytoma - alpha-blockers.
If surgical intervention is necessary, it is necessary to warn the surgeon/anesthesiologist about taking metoprolol (the choice of drugs for general anesthesia with minimal negative inotropic effect); discontinuation of the drug is not recommended. In the event of increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function, it is necessary to reduce the dose or discontinue treatment. It is recommended to discontinue therapy if skin rashes appear and depression develops caused by taking beta-blockers. The drug is discontinued gradually, reducing the dose over 10 days. If treatment is abruptly stopped, nightmare dream syndrome may occur; very rarely - amnesia/memory impairment, depression, hallucinations, slowing of the speed of mental and motor reactions, muscle cramps, asthenia, myasthenia gravis. . From the senses: rarely - blurred vision, dry and sore eyes, conjunctivitis, decreased secretion of tear fluid; very rarely - ringing in the ears, disturbance of taste. . From the digestive system: often - nausea, abdominal pain, constipation or diarrhea; infrequently - vomiting; rarely - dryness of the oral mucosa, impaired liver function, hepatitis.
From the skin: infrequently - urticaria, 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; uncommon – bronchospasm in patients with bronchial asthma; rarely – rhinitis.
Other: infrequently - weight gain; very rarely - arthralgia, thrombocytopenia; Peyronie's disease, hypoglycemia, hyperglycemia, increased titer of antinuclear antibodies, decreased libido, potency.
Interaction with other drugs
Barbiturates increase the metabolism of metoprolol due to the induction of microsomal liver enzymes.
Propafenone increases the plasma concentration of metoprolol by 2-5 times (probably due to inhibition of the CYP2D6 isoenzyme by propafenone). Simultaneous intravenous administration of verapamil can cause bradycardia and a marked decrease in blood pressure.
Class I antiarrhythmic drugs can lead to additive negative inotropic effects with the development of severe hemodynamic side effects in patients with impaired left ventricular function (this combination should be avoided in patients with sick sinus syndrome or impaired AV conduction).
Amiodarone is a risk of developing severe sinus bradycardia (including long after discontinuation of amiodarone, due to its long half-life).
Diltiazem is a risk of developing severe bradycardia (mutually enhancing the inhibitory effect on AV conduction and sinus node function). The antihypertensive effect is weakened by glucocorticosteroids and estrogens (sodium ion retention).
Beta-adrenergic agonists, aminophylline, theophylline, indomethacin and other non-steroidal anti-inflammatory drugs weaken the antihypertensive effect.
Diphenhydramine reduces the clearance of metoprolol, enhancing its effect. Epinephrine - the risk of developing a pronounced decrease in blood pressure and bradycardia. Phenylpropanolamine in high doses causes a paradoxical increase in blood pressure (up to a hypertensive crisis).
Quinidine inhibits the metabolism of metoprolol in rapid metabolizers, leading to a significant increase in plasma concentrations of metoprolol and an increase in its beta-blocking effect.
Clonidine - there is a risk of a pronounced increase in blood pressure when clonidine is abruptly discontinued while taking beta-blockers simultaneously, therefore, if clonidine is discontinued, gradual cessation of beta-blockers should be started several days before its discontinuation.
Rifampicin - enhances the metabolism of metoprolol, reducing plasma concentrations (due to the induction of microsomal liver enzymes). Cimetidine and hydralazine increase the concentration of metoprolol in the blood. Medicines for inhalation anesthesia (halogenated hydrocarbons) enhance the cardiodepressive effect of metoprolol. Incompatible with monoamine oxidase type A inhibitor.
Cardiac glycosides, methyldopa, reserpine, guanfacine and clonidine increase the risk of bradycardia.
Nifedipine, in addition to enhancing the antihypertensive effect, can lead to the development
heart failure.
Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics increase depression of the central nervous system.
With the simultaneous use of metoprolol and sympatholytics, nitroglycerin, barbiturates, vasodilators (alprostadil) and other antihypertensive drugs (for example, prazosin), the antihypertensive effect may be enhanced, therefore patients taking such combinations of drugs should be under constant medical supervision to detect an excessive decrease in blood pressure or bradycardia.
Changes the effectiveness of insulin and oral hypoglycemic agents. Increases the risk of developing hypoglycemia, enhances its severity and duration, masks its symptoms (tachycardia, sweating, increased blood pressure).
When used together with ethanol, the risk of a pronounced decrease in blood pressure increases and an increased inhibitory effect on the central nervous system is noted.
Reduces the clearance of lidocaine and increases its concentration in the blood plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.
Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.
Prolongs the effect of antidepolarizing muscle relaxants and the anticoagulant effect of coumarin derivatives.
Aldesleukin increases arterial hypotension.
Mefloquine increases inhibition of conduction and excitability of the heart muscle.
When used simultaneously with norepinephrine, epinephrine, other adrenergic and sympathomimetics (including in the form of eye drops or as part of antitussives), a slight increase in blood pressure is possible.
Allergens used for immunotherapy or allergen extracts for skin testing 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 anaphylactic reactions.
Use during pregnancy and breastfeeding
During pregnancy, it is prescribed only according to strict indications if the expected benefit to the mother outweighs the potential risk to the fetus (due to the possible development of bradycardia, arterial hypotension, hypoglycemia and respiratory depression in the newborn). Treatment must be interrupted 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict monitoring of newborns for 48 to 72 hours after delivery.
Since metoprolol passes into breast milk, the drug should not be taken during breastfeeding or the mother should stop breastfeeding during treatment.
Impact on the ability to drive vehicles and machinery
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.
Release form
Tablets of 50 mg and 100 mg.
10 or 20 tablets in a blister pack made of polyvinyl chloride film and aluminum foil.
30 tablets per jar made of polymer materials.
Each jar or 3 or 5 blister packs of 10 tablets or 2 blister packs of 20 tablets, together with instructions for use, are placed in a cardboard pack for consumer packaging.
Storage conditions:
In a dry place, protected from light, at a temperature not exceeding 25ºС.
Best before date:
2 years. Do not use after the expiration date.
Units:
pack
Metoprolol, 1 mg/ml, solution for intravenous administration, 5 ml, 5 pcs.
Co-administration of Metoprolol with the following drugs should be avoided:
Barbituric acid derivatives: barbiturates (study conducted with phenobarbital) slightly increase the metabolism of metoprolol due to enzyme induction.
Propafenone: it is possible to increase the plasma concentration of metoprolol by 2-5 times and develop side effects characteristic of metoprolol. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprolol via the cytochrome P4502D6 system. Taking into account the fact that propafenone has the properties of a beta-blocker, the joint administration of metoprolol and propafenone does not seem appropriate.
Verapamil: The combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and β-blockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.
The combination of Metoprolol with the following drugs may require dose adjustment:
Class I Antiarrhythmics: Class I antiarrhythmics and β-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and atrioventricular conduction disorder. The interaction is described using disopyramide as an example.
Amiodarone: Concomitant use of amiodarone and metoprolol may result in severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.
Diltiazem: Diltiazem and β-blockers mutually enhance the inhibitory effect on atrioventricular conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs reduce the antihypertensive effect of beta-blockers. This interaction is best documented for indomethacin and celecoxib. There is no reported interaction observed for sulindac. In studies with diclofenac, the described reaction was not observed.
Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.
Epinephrine (adrenaline): Severe hypertension and bradycardia may develop in patients taking non-selective beta-blockers (including pindolol and proprapolol) and receiving epinephrine (adrenaline). It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.
Phenylpropanolamine: Phenylpropanolamine (norephedrine) in a single dose of 50 mg may cause an increase in diastolic blood pressure. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers may cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. It is possible to develop a hypertensive crisis while taking phenylpropanolamine.
Quinidine: Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden, approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased β-blockade. It is believed that a similar interaction is typical for other β-blockers in the metabolism of which cytochrome P4502D6 is involved.
Clonidine: Hypertensive reactions during abrupt withdrawal of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, if clonidine is discontinued, discontinuation of β-blockers should begin several days before discontinuation of clonidine.
Rifampicin: Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.
Cimetidine, hydralazine, selective serotonin reuptake inhibitors (including paroxetine, fluoxetine, sertraline) increase the concentration of metoprolol in the blood plasma.
Medicines for inhalation anesthesia enhance the cardiodepressive effect of metoprolol.
Patients concomitantly taking metoprolol and other β-blockers (eye drops) or monoamine oxidase inhibitors (MAOIs) should be closely monitored.
While taking β-blockers, inhalational anesthetics enhance the cardiodepressive effect.
While taking β-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.
Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving metoprolol.
Iodine-containing radiocontrast agents for intravenous administration increase the risk of anaphylactic reactions.
