Metoprolol retard-Akrikhin
INSTRUCTIONS for the use of the medicinal product for medical use
Metoprolol retard – Akrikhin
Registration number: LP-00570
Trade name of the drug: Metoprolol retard - Akrikhin
International nonproprietary name: metoprolol
Dosage form: extended-release, film-coated tablets
Compound:
One tablet contains: active substance: metoprolol succinate in terms of 100% substance 23.83 mg, 47.66 mg and 95.32 mg, which is equivalent to 25 mg, 50 mg and 100 mg of metoprolol tartrate, respectively, excipients: hypromellose 155, 96 mg, 161.92 mg or 184.84 mg, ludipress LCE [lactose monohydrate 94.7-98.3%, povidone 3-4%] 117.21 mg, 87.42 mg or 412.84 mg, silicon dioxide colloidal 1.5 mg, 1.5 mg or 3.5 mg, magnesium stearate 1.5 mg, 1.5 mg or 3.5 mg, respectively.
Coating composition: For tablets with dosages of 25 mg and 100 mg - ready-made mixture "Opadry II" of orange color (polyvinyl alcohol 6 mg or 14 mg, talc 2.22 mg or 5.18 mg, macrogol 3.03 mg or 7.07 mg, titanium dioxide 3.36 mg or 7.84 mg, red iron oxide dye 0.009 mg or 0.021 mg, yellow iron oxide dye 0.378 mg or 0.882 mg, black iron oxide dye 0.003 mg or 0.007 mg) 15 mg or 35 mg, respectively . For tablets with a dosage of 50 mg - a ready-made mixture of Opadry II, green (polyvinyl alcohol 6 mg, talc 2.22 mg, macrogol 3.03 mg, titanium dioxide 2.925 mg, quinoline yellow dye (aluminum varnish) 0.268 mg, iron dye black oxide 0.015 mg, indigo carmine dye (aluminum varnish) 0.542 mg) 15 mg.
Description: Film-coated tablets, round, biconvex. Tablets with dosages of 25 mg and 100 mg are yellowish-brown. Tablets with a dosage of 50 mg are light green to green in color. At the break, the tablet is white with a grayish or creamy tint.
Pharmacotherapeutic group: selective beta1-blocker. ATX code: С07АВ02
Pharmacological properties
Pharmacodynamics
Cardioselective beta1-blocker. It does not have a 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 in low doses, it reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect (reduces heart rate (HR) ), inhibits conductivity and excitability, reduces myocardial contractility).
Total peripheral vascular resistance (TPVR) at the beginning of the use of beta-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 its original level after 1-3 days. and with long-term administration it decreases.
The antihypertensive effect is due to a decrease in minute volume of blood flow 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 a decrease blood pressure (BP) and ultimately a decrease in peripheral sympathetic influences. Reduces elevated blood pressure at rest, during physical stress and stress. The antihypertensive effect lasts more than 24 hours.
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 end-diastolic pressure in the left ventricle and increasing the stretch of ventricular muscle fibers, it can increase oxygen demand, especially in patients with chronic heart failure (CHF).
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.
With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and thyrotoxicosis, it reduces heart rate or can even lead to the restoration of sinus rhythm.
Prevents the development of migraine.
In contrast to non-selective beta-blockers, when prescribed 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, the severity of the atherogenic effect does not differ from the action of propranolol. When taken for many years, it reduces the concentration of cholesterol in the blood. When used in large doses (more than 100 mg/day), it has a blocking effect on both subtypes of beta-adrenergic receptors.
Pharmacokinetics Absorption 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 plasma proteins – 10%. The time to reach maximum concentration in blood plasma is 6-12 hours after taking the drug. 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. Passes into breast milk.
Metabolized in the liver, 2 metabolites have beta-adrenergic blocking activity. The CYP2D6 isoenzyme takes part in the metabolism of the drug. The half-life is 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 cirrhosis, while its overall clearance is reduced.
Indications for use Arterial hypertension.
Chronic heart failure of functional class II-IV according to the NYHA classification in the compensation stage (as part of complex therapy).
Coronary heart disease: prevention of attacks of stable angina, reduction in mortality and the incidence of recurrent myocardial infarction after the acute phase of myocardial infarction.
Heart rhythm disturbances, including supraventricular tachycardia, decreased ventricular contraction frequency with atrial fibrillation and ventricular extrasystoles.
Functional cardiac disorders accompanied by tachycardia.
Prevention of migraine attacks.
Contraindications Hypersensitivity to metoprolol and other beta-blockers, cardiogenic shock, AV block II-III degree, sinoatrial block, sick sinus syndrome, severe bradycardia (heart rate less than 50 beats/min), acute heart failure or decompensated CHF, arterial hypotension (systolic blood pressure less than 100 mm Hg), 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), lactation period, simultaneous use of monoamine oxidase inhibitors (MAO) or simultaneous intravenous administration of verapamil, pheochromocytoma (without simultaneous use of alpha-blockers), age under 18 years (efficacy and safety have not been established), lactase deficiency, lactose intolerance, glucose-galactose malabsorption, severe bronchial asthma, severe disorders peripheral circulation.
With caution Diabetes mellitus, first degree atrioventricular block, Prinzmetal's angina, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease, renal and/or severe liver failure, myasthenia gravis, pheochromocytoma (while taking alpha-blockers), thyrotoxicosis, depression (including .h. in the anamnesis), psoriasis, peripheral circulatory disorders (“intermittent” claudication, Raynaud’s syndrome), pregnancy, old age.
Use during pregnancy and lactation During pregnancy, the drug Metoprolol retard - Akrikhin should be used only according to strict indications, when the expected benefit to the mother outweighs the potential risk to the fetus/child (due to the possible development of bradycardia in the newborn, decreased blood pressure, hypoglycemia and respiratory paralysis). At the same time, careful monitoring is carried out especially over the development of the fetus. Treatment is stopped 48-72 hours before birth. If this is not possible, the newborn should be monitored especially closely for 48-72 hours after birth.
The use of the drug Metoprolol retard - Akrikhin is contraindicated during lactation; if it is necessary to use the drug during lactation, breastfeeding must be stopped.
Method of administration and dosage Metoprolol retard - Akrikhin is intended for oral administration once a day, it is recommended to take it in the morning, without chewing, with water. Metoprolol retard - Akrikhin can be taken regardless of meals. In order to prevent bradycardia, the dose is selected individually and increased gradually.
For arterial hypertension and angina pectoris, the initial dose is 50 mg 1 time per day; if the therapeutic effect is insufficient, the daily dose can be increased to 100-200 mg per day. For arterial hypertension, if the drug is ineffective at a dose of 100-200 mg per day, another antihypertensive agent can be added.
For chronic heart failure of functional class II according to the NYHA classification (without exacerbations in the last 6 weeks and without changes in complex therapy over the last 2 weeks), the recommended initial dose is 25 mg once a day. After two weeks, the daily dose can be increased to 50 mg, then after two weeks to 100 mg, and after another two weeks to 200 mg.
For chronic heart failure of functional class III-IV according to the NYHA classification, the recommended initial dose for the first 2 weeks is 12.5 mg of the drug once a day. It is possible to use metoprolol in another dosage form, for example, 25 mg scored tablets. During the dosage increase period, the patient should be monitored as symptoms of heart failure may worsen in some patients.
After 1-2 weeks, the dose can be increased to 25 mg once daily. Then after 2 weeks the dose can be increased to 50 mg once daily. For patients who tolerate the drug well, the dose can be doubled every 2 weeks until a maximum dose of 200 mg of the drug is reached once daily.
Secondary prevention of myocardial infarction and cardiac arrhythmias - initial dose of 100 mg 1 time per day.
For functional disorders of cardiac activity accompanied by tachycardia - 50 mg per day, if necessary, the dose can be increased to 200 mg per day.
Prevention of migraine attacks: 100-200 mg 1 time per day.
Elderly patients, those with renal failure, or patients on hemodialysis do not require dose adjustment.
Impaired liver function affects the elimination of metoprolol, so dose adjustment may be required depending on the clinical condition.
Side effect Frequency of side effects: very often - more than 1/10, often - more than 1/100 and 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 - less than 1/10000, including individual messages.
From the cardiovascular system: often - bradycardia, orthostatic hypotension (including fainting), coldness of the lower extremities, palpitations, infrequently - temporary increase in symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, AV block of the first degree , rarely - myocardial conduction disorders, arrhythmia, very rarely - gangrene (in patients with peripheral circulatory disorders).
From the central nervous system: very often - increased fatigue, decreased speed of mental and motor reactions, often - dizziness, headache, infrequently - paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, nightmares, rarely - asthenia , tremor, increased nervous excitability, anxiety, very rarely - amnesia/memory impairment, depression, hallucinations, myasthenia gravis.
From the senses: rarely - blurred vision, dryness and/or irritation of the eyes, conjunctivitis, very rarely - ringing in the ears, impaired sense of taste.
From the digestive system: often - nausea, abdominal pain, constipation or diarrhea, infrequently - vomiting, rarely - dry oral mucosa, impaired liver function, hepatitis.
From the skin: infrequently - urticaria, increased sweating, rarely - alopecia, very rarely - photosensitivity, exacerbation of psoriasis, psoriasis-like skin reactions.
From the respiratory system: often - shortness of breath, infrequently - bronchospasm in patients with bronchial asthma, rarely - rhinitis.
Laboratory indicators: very rarely - thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of liver enzymes, hyperbilirubinemia.
From the endocrine system: often - hypoglycemia (in patients with type I diabetes mellitus), rarely - hyperglycemia (in patients with type II diabetes mellitus), hypothyroid state.
Other: uncommon – weight gain, rare – impotence/sexual dysfunction, very rare – arthralgia, thrombocytopenia.
Overdose Symptoms: severe bradycardia, AV block (up to the development of complete transverse block and cardiac arrest), marked decrease in blood pressure, impaired peripheral circulation, increased symptoms of heart failure, cardiogenic shock, respiratory depression, apnea, cyanosis, increased fatigue, dizziness, loss of consciousness , coma, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible development of esophagospasm, hypoglycemia or hyperglycemia, hyperkalemia, transient myasthenia. The first signs of overdose appear 20 minutes to 2 hours after taking the drug.
Treatment: If the drug has been taken recently - gastric lavage and taking adsorbents; if atrioventricular conduction is impaired and/or bradycardia - intravenous administration of 1-2 mg of atropine, epinephrine (adrenaline) or placement of a temporary pacemaker; if blood pressure decreases - the patient should be kept in the Trendelenburg position. If there are no signs of pulmonary edema - intravenous plasma replacement solutions, if ineffective - administration of epinephrine, dopamine, dobutamine, for acute heart failure - cardiac glycosides, diuretics, for convulsions - intravenous diazepam, for bronchospasm - inhaled or parenteral beta2-adrenergic agonists.
Interaction with other drugs Drugs that reduce catecholamine reserves (for example, reserpine, MAO inhibitors), when used simultaneously with metoprolol, can enhance the hypotensive effect or cause severe bradycardia. The treatment break between taking MAO inhibitors and metoprolol should be at least 14 days.
Metoprolol is a substrate of the CYP2D6 isoenzyme. Medicines that inhibit or induce the activity of the CYP2D6 isoenzyme may affect the plasma concentrations of metoprolol.
Inhibitors of the CYP2D6 isoenzyme: some antidepressants and antipsychotics, quinidine, terbinafine, celecoxib, propafenone, difehydramine, hydroxychlorine, cimetidine - increase the concentration of metoprolol in the blood plasma.
Inducers of the CYP2D6 isoenzyme: barbituric acid derivatives, rifampicin - reduce the concentration of metoprolol in the blood plasma.
Concomitant use with cardiac glycosides, clonidine, blockers of “slow” calcium channels (verapamil, diltiazem), amiodarone, class I antiarrhythmic drugs, drugs for general anesthesia, methyldopa, guanfacine can lead to a decrease in blood pressure and severe bradycardia.
Inhalation anesthetics (hydrocarbon derivatives) increase the risk of suppression of myocardial function and the development of arterial hypotension.
Simultaneous intravenous administration of verapamil can provoke cardiac arrest.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-agonists weaken the antihypertensive effect of beta-blockers.
Ergot alkaloids increase the risk of peripheral circulatory disorders.
When taken together with oral hypoglycemic drugs, their effect may be reduced; when taken with insulin, the risk of developing hypoglycemia may increase, prolongation and intensification of its severity, masking of some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).
Reduces the clearance of xanthines (except diaphylline), especially in patients with initially increased clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in plasma.
Strengthens and prolongs the effect of non-depolarizing muscle relaxants, prolongs the anticoagulant effect of coumarins.
When taking epinephrine (adrenaline) simultaneously with beta-blockers, an increase in blood pressure and bradycardia is possible.
Phenylpropanolamine (norephedrine) may increase diastolic blood pressure.
Allergens used for immunotherapy or allergen extracts for skin testing when used in combination with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiocontrast agents for intravenous administration increase the risk of anaphylactic reactions.
When used together with ethanol, the risk of a pronounced decrease in blood pressure increases.
special instructions
Monitoring of patients taking beta-blockers includes regular monitoring of heart rate and blood pressure. 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 retard - Akrikhin may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.
In diabetes mellitus, it can mask tachycardia caused by hypoglycemia.
If necessary, beta2-adrenergic agonists are used as concomitant therapy for patients with bronchial asthma; for pheochromocytoma, alpha-blockers are used.
If it is necessary to perform surgical intervention, it is necessary to warn the anesthesiologist about taking the drug Metoprolol retard - Akrikhin (it is necessary to choose a general anesthesia agent with minimal negative inotropic effect); discontinuation of the drug is not recommended.
Reciprocal activation of the vagus nerve can be eliminated by intravenous atropine (1-2 mg).
In the event of increasing bradycardia (less than 50 beats/min), 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.
Metoprolol may increase symptoms of peripheral circulatory disorders.
If clonidine is abruptly discontinued, blood pressure may rise sharply while taking beta-blockers. If clonidine is discontinued, discontinuation of beta blockers should begin several days before discontinuation of clonidine.
Drugs that reduce catecholamine levels (for example, reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect an excessive decrease in blood pressure or bradycardia.
If treatment is abruptly stopped, withdrawal syndrome may occur (increased angina attacks, increased blood pressure). When discontinuing the drug, special attention should be paid to patients with angina pectoris, CHF, or after a myocardial infarction. Discontinuation of the drug Metoprolol retard - Akrikhin is carried out gradually, reducing the dose over 10 days.
Patients who use contact lenses should take into account that during treatment with beta-blockers, the production of tear fluid may decrease.
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: Long-acting, film-coated tablets, 25 mg, 50 mg and 100 mg. 10 tablets with dosages of 25 mg and 50 mg in a blister pack. 30 tablets with dosages of 100 mg in a polypropylene (polyethylene) jar or plastic bottle. Each jar or bottle, or 3 blisters along with instructions for use in a cardboard pack.
Storage conditions: In a dry place, protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children.
Best before date
2 years. Do not use after the expiration date.
Conditions for dispensing from pharmacies By prescription.
Manufacturer/Organization accepting consumer complaints
"Open Joint Stock Company "Chemical and Pharmaceutical Plant "AKRIKHIN" (JSC "AKRIKHIN"), Russia
142450, Moscow region, Noginsky district, Staraya Kupavna, st. Kirova, 29.
Phone fax.
Metoprolol retard-Akrikhin, prolong tablets. covered. captivity. about. 50 mg, 30 pcs.
Monitoring of patients taking beta-blockers includes regular monitoring of heart rate and blood pressure. 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).
Taking the drug Metoprolol retard-Akrikhin may increase the 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 smoking patients, the effectiveness of beta-blockers is lower.
Metoprolol retard-Akrikhin may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.
In diabetes mellitus, taking Metoprolol retard-Akrikhin can mask tachycardia caused by hypoglycemia.
If necessary, beta2-adrenergic agonists are used as concomitant therapy for patients with bronchial asthma; for pheochromocytoma - alpha-blockers.
If it is necessary to perform surgical intervention, it is necessary to warn the anesthesiologist about taking the drug Metoprolol retard-Akrikhin (it is necessary to choose a general anesthesia agent with minimal negative inotropic effect); discontinuation of the drug is not recommended.
Reciprocal activation of the vagus nerve can be eliminated by intravenous atropine (1-2 mg).
In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or stop treatment.
It is recommended to discontinue therapy if skin rashes appear and depression develops caused by taking beta-blockers.
If clonidine is abruptly discontinued, blood pressure may rise sharply while taking beta-blockers. If clonidine is discontinued, discontinuation of beta blockers should begin several days before discontinuation of clonidine.
Drugs that reduce catecholamine levels (for example, reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect an excessive decrease in blood pressure or bradycardia.
If treatment is abruptly stopped, withdrawal syndrome may occur (increased angina attacks, increased blood pressure). When discontinuing the drug, special attention should be paid to patients with angina pectoris, chronic heart failure, and after a myocardial infarction. Discontinuation of the drug Metoprolol retard-Akrikhin is carried out gradually, reducing the dose over 10 days.
Patients who use contact lenses should take into account that during treatment with beta-blockers, there may be a decrease in the production of tear fluid.
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.
Metoprolol
When used simultaneously with antihypertensive drugs, diuretics, antiarrhythmic drugs, nitrates, there is a risk of developing severe arterial hypotension, bradycardia, and AV block.
When used simultaneously with barbiturates, the metabolism of metoprolol is accelerated, which leads to a decrease in its effectiveness.
When used simultaneously with hypoglycemic agents, the effect of hypoglycemic agents may be enhanced.
When used simultaneously with NSAIDs, the hypotensive effect of metoprolol may be reduced.
When used simultaneously with opioid analgesics, the cardiodepressive effect is mutually enhanced.
When used simultaneously with peripheral muscle relaxants, neuromuscular blockade may be enhanced.
When used simultaneously with drugs for inhalation anesthesia, the risk of suppression of myocardial function and the development of arterial hypotension increases.
When used simultaneously with oral contraceptives, hydralazine, ranitidine, cimetidine, the concentration of metoprolol in the blood plasma increases.
When used simultaneously with amiodarone, arterial hypotension, bradycardia, ventricular fibrillation, and asystole are possible.
When used simultaneously with verapamil, the plasma Cmax and AUC of metoprolol increases. The minute and stroke volume of the heart, pulse rate, and arterial hypotension decrease. Possible development of heart failure, dyspnea and sinus node block.
With intravenous administration of verapamil while taking metoprolol, there is a risk of cardiac arrest.
With simultaneous use, bradycardia caused by digitalis glycosides may increase.
When used simultaneously with dextropropoxyphene, the bioavailability of metoprolol increases.
When used concomitantly with diazepam, a decrease in clearance and an increase in the AUC of diazepam is possible, which can lead to an increase in its effects and a decrease in the speed of psychomotor reactions.
When used simultaneously with diltiazem, the concentration of metoprolol in the blood plasma increases due to inhibition of its metabolism under the influence of diltiazem. The effect on cardiac activity is additively inhibited due to the slowing of impulse transmission through the AV node caused by diltiazem. There is a risk of developing severe bradycardia, a significant decrease in stroke and minute volume.
When used simultaneously with lidocaine, the elimination of lidocaine may be impaired.
When used simultaneously with mibefradil in patients with low activity of the CYP2D6 isoenzyme, it is possible to increase the concentration of metoprolol in the blood plasma and increase the risk of developing toxic effects.
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.
When used simultaneously with propafenone, the concentration of metoprolol in the blood plasma increases and a toxic effect develops. It is believed that propafenone inhibits the metabolism of metoprolol in the liver, reducing its clearance and increasing serum concentrations.
When used simultaneously with reserpine, guanfacine, methyldopa, clonidine, severe bradycardia may develop.
When used simultaneously with rifampicin, the concentration of metoprolol in the blood plasma decreases.
Metoprolol may cause a slight decrease in the clearance of theophylline in patients who smoke.
Fluoxetine inhibits the CYP2D6 isoenzyme, which leads to inhibition of metoprolol metabolism and its accumulation, which can enhance the cardiodepressive effect and cause bradycardia. A case of the development of lethargy is described.
Fluoxetine and mainly its metabolites are characterized by a long T1/2, so the likelihood of drug interactions remains even several days after fluoxetine is discontinued.
There are reports of a decrease in the clearance of metoprolol from the body when used simultaneously with ciprofloxacin.
When used simultaneously with ergotamine, peripheral circulatory disorders may increase.
When used simultaneously with estrogens, the antihypertensive effect of metoprolol is reduced.
With simultaneous use, metoprolol increases the concentration of ethanol in the blood and prolongs its elimination.
