Recommendations for the use of egilok. Correct dosages of the antihypertensive drug Egilok

Registration number: P No. 015639/01 03/17/2009

Trade name: Egilok ®

International generic name: metoprolol

PHARMACOLOGICAL PROPERTIES

Mechanism of action:

Metoprolol suppresses the effects increased activity sympathetic system on the heart, and also causes a rapid decrease in frequency heart rate, contractility, cardiac output And blood pressure.

At arterial hypertension metoprolol reduces blood pressure in patients in the standing and lying position. The long-term antihypertensive effect of the drug is associated with a gradual decrease in total peripheral vascular resistance. In arterial hypertension, long-term use of the drug leads to a statistically significant decrease in the mass of the left ventricle and an improvement in its diastolic function. In men with mild or moderate degree hypertension, metoprolol reduces mortality from cardiovascular causes(first of all, sudden death, fatal and non-fatal heart attack and stroke).

Like other beta-blockers, metoprolol reduces myocardial oxygen demand by reducing systemic blood pressure, heart rate and myocardial contractility. A decrease in heart rate and a corresponding prolongation of diastole when taking metoprolol ensures improved blood supply and oxygen uptake by the myocardium with impaired blood flow. Therefore, for angina pectoris, the drug reduces the number, duration and severity of attacks, as well as asymptomatic manifestations of ischemia, and improves the patient’s physical performance. In myocardial infarction, metoprolol reduces the mortality rate by reducing the risk of sudden death. This effect is primarily associated with the prevention of episodes of ventricular fibrillation. A reduction in mortality can also be observed with the use of metoprolol in both the early and late phases of myocardial infarction, as well as in patients group high risk and sick diabetes mellitus. Use of the drug after myocardial infarction reduces the likelihood of non-fatal recurrent infarction. In chronic heart failure against the background of idiopathic hypertrophic obstructive cardiomyopathy, metoprolol tartrate, taken starting from low doses (2x5 mg/day) with a gradual increase in dose, significantly improves heart function, quality of life and physical endurance of the patient.

In case of supraventricular tachycardia, atrial fibrillation and ventricular extrasystoles, metoprolol reduces the frequency of ventricular contractions and the number of ventricular extrasystoles.

At therapeutic doses, the peripheral vasoconstrictor and bronchoconstrictor effects of metoprolol are less pronounced than the same effects of non-selective beta-blockers.

Compared with non-selective beta-blockers, metoprolol has less effect on insulin production and carbohydrate metabolism. It does not increase the duration of hypoglycemic attacks.

Metoprolol causes slight increase triglyceride concentrations and a slight decrease in free fatty acids in blood serum. There is a significant decrease in total serum cholesterol concentrations after several years of taking metoprolol.

Metoprolol is rapidly and completely absorbed into gastrointestinal tract. The drug is characterized by linear pharmacokinetics in the therapeutic dose range. Maximum concentration in blood plasma is achieved 1.5-2 hours after oral administration. After absorption, metoprolol undergoes significant first-pass metabolism through the liver. The bioavailability of metoprolol is approximately 50% with a single dose and approximately 70% with regular use.

Taking with food can increase the bioavailability of metoprolol by 30-40%. Metoprolol is slightly (~ 5-10%) bound to plasma proteins. The volume of distribution is 5.6 l/kg.

Metoprolol is metabolized in the liver by cytochrome P-450 isoenzymes. Metabolites do not have pharmacological activity.

Half-life (t 1/2) on average 3.5 hours (from 1 to 9 hours). The total clearance is approximately 1 l/min.

Approximately 95% of the administered dose is excreted by the kidneys, 5% as unchanged metoprolol. In some cases this value can reach 30%.

There were no significant changes in the pharmacokinetics of metoprolol in elderly patients.

Impaired renal function does not affect the systemic bioavailability or excretion of metoprolol. However, in these cases there is a decrease in the excretion of metabolites. In severe renal failure (rate glomerular filtration less than 5 ml/min) there is a significant accumulation of metabolites. However, this accumulation of metabolites does not increase the degree of beta-adrenergic blockade.

Impaired liver function has little effect on the pharmacokinetics of metoprolol. However, in severe liver cirrhosis and after a portacaval shunt, bioavailability may increase and overall body clearance may decrease. After portacaval shunt, the total clearance of the drug from the body is approximately 0.3 L/min, and the area under the concentration-time curve increases approximately 6 times compared with that in healthy volunteers.

Arterial hypertension (in monotherapy or (if necessary) in combination with other antihypertensive drugs); functional disorders 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.

Hypersensitivity to metoprolol or any other component of the drug, as well as other beta-blockers; atrioventricular block (AV) II or III degree; sinoatrial block; sinus bradycardia(heart rate less than 50/min), weakness syndrome sinus node; cardiogenic shock; severe peripheral circulatory disorders; heart failure in the stage of decompensation, age under 18 years (due to the lack of sufficient clinical data), simultaneous intravenous administration of verapamil, severe bronchial asthma and pheochromocytoma without simultaneous use of alpha-blockers.

Due to insufficient clinical data, Egiolok ® is contraindicated in acute heart attack myocardium, accompanied by a heart rate below 45 beats/min, with a PQ interval of more than 240 ms, and systolic blood pressure below 100 mm Hg.

Diabetes, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease (COPD), renal/liver failure, myasthenia gravis, pheochromocytoma (with simultaneous use with alpha-blockers), thyrotoxicosis, AV block of the first degree, depression (including a history), psoriasis, obliterating diseases peripheral vessels(“intermittent” claudication, Raynaud’s syndrome), pregnancy, lactation, elderly age, in patients with a burdened allergic history (possibly a decreased response when using adrenaline).

USE IN PREGNANCY AND LACTATION

The use of the drug is not recommended during pregnancy. The use of the drug is possible only when the benefit to the mother exceeds potential risk for the fetus. If taking the drug is necessary, you should carefully monitor the fetus and then the newborn for several days (48 - 72 hours) after birth, as bradycardia, respiratory depression, decreased blood pressure and hypoglycemia may develop.

Despite the fact that when taking therapeutic doses of metoprolol, only small amounts of the drug are released into the breast milk, the newborn should be kept under observation (bradycardia is possible). The use of the drug during lactation is not recommended. If it is necessary to use the drug during lactation, it is recommended to stop breastfeeding.

METHOD OF APPLICATION AND DOSES

Egilok ® tablets are taken orally. The tablets can be taken with food or without regard to meals. If necessary, the tablet can be broken in half. The dose should be adjusted gradually and individually to avoid excessive bradycardia. Maximum daily dose is 200 mg. Recommended doses:

Arterial hypertension

For mild or moderate arterial hypertension, the initial dose is 25-50 mg twice a day (morning and evening). If necessary, the daily dose can be gradually increased to 100-200 mg/day or another antihypertensive agent can be added.

Angina pectoris

The initial dose is 25-50 mg two to three times a day. Depending on the effect, this dose can be gradually increased to 200 mg per day or another antianginal drug can be added.

Maintenance therapy after myocardial infarction

The usual daily dose is 100 - 200 mg/day, divided into two doses (morning and evening).

Heart rhythm disturbances

Initial dose is 25 to 50 mg two or three times daily. If necessary, the daily dose can be gradually increased to 200 mg/day or another antiarrhythmic drug. Hyperthyroidism

The usual daily dose is 150-200 mg per day in 3 to 4 doses.

Functional heart disorders accompanied by palpitations The usual daily dose is 50 mg 2 times a day (morning and evening); if necessary, it can be increased to 200 mg in two doses.

Preventing migraine attacks

The usual daily dose is 100 mg/day in two divided doses (morning and evening); if necessary, it can be increased to 200 mg/day in 2 divided doses.

Special patient groups

If renal function is impaired, no change in dosage regimen is required.

In liver cirrhosis, a dose change is usually not required due to the low binding of metoprolol to plasma proteins (5-10%). For severe liver failure(for example, after portacaval shunt surgery), it may be necessary to reduce the dose of Egilok ®.

In elderly patients, no dose adjustment is required.

Egilok ® is usually well tolerated by patients. Side effects are usually mild and reversible. The following side effects have been reported in clinical trials and with the therapeutic use of metoprolol. In some cases, the connection between an adverse event and the use of the drug has not been reliably established. Frequency parameters listed below side effects defined as follows: very common: > 10%), common: 1-9.9%, uncommon: 0.1-0.9%, rare: 0.01-0.09%, very rare (including isolated reports) :< 0,01 %.

From the nervous system: very often - increased fatigue; often - dizziness, headache; rarely - increased excitability, anxiety, impotence/sexual dysfunction; uncommon - paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, nightmares; very rarely - amnesia/memory impairment, depression, hallucinations.

From the outside of cardio-vascular system: often - bradycardia, orthostatic hypotension(in some cases syncope is possible), cold snap lower limbs, feeling of heartbeat; uncommon - temporary increase in symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, first degree atrioventricular block; rarely - conduction disturbances, arrhythmia; very rarely - gangrene (in patients with peripheral circulatory disorders). From the outside digestive system: often - nausea, abdominal pain, constipation or diarrhea; infrequently - vomiting; rarely - dryness of the oral mucosa, impaired liver function.

From the outside skin: uncommon - urticaria, increased sweating; rarely - alopecia; very rarely - photosensitivity, exacerbation of psoriasis. From the outside respiratory system: often - shortness of breath during physical effort; uncommon - bronchospasm in patients with bronchial asthma; rarely - rhinitis.

From the senses: rarely - blurred vision, dryness and/or irritation of the eyes, conjunctivitis; very rarely - ringing in the ears, disturbance of taste. Other: infrequently - weight gain; very rarely - arthralgia, thrombocytopenia. Taking Egilok ® should be discontinued if any of the above effects reaches a clinically significant intensity, and its cause cannot be reliably determined.

Symptoms: marked decrease in blood pressure, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, asystole, nausea, vomiting, bronchospasm, cyanosis, hypoglycemia, loss of consciousness, coma. The symptoms listed above may worsen with simultaneous administration ethanol, antihypertensive drugs, quinidine and barbiturates.
The first symptoms of overdose appear 20 minutes -2 hours after taking the drug.

Treatment: Careful monitoring of the patient is necessary (monitoring blood pressure, heart rate, respiratory rate, renal function, blood glucose concentration, serum electrolytes) in the intensive care unit. If the drug has been taken recently, gastric lavage using activated carbon may reduce further absorption of the drug (if rinsing is not possible, vomiting can be induced if the patient is conscious).

In case of excessive decrease in blood pressure, bradycardia and the threat of heart failure - intravenously, at intervals of 2-5 minutes, beta-adrenergic agonists - until the desired effect is achieved or intravenously 0.5-2 mg of atropine. With absence positive effect- dopamine, dobutamine or norepinephrine (norepinephrine). For hypoglycemia - administration of 1-10 mg of glucagon, installation of a temporary pacemaker. For bronchospasm, beta2-agonists should be administered. For convulsions - slow intravenous administration of diazepam. Hemodialysis is ineffective.

INTERACTIONS WITH OTHER MEDICINES

Antihypertensive effects of Egilok ® and others antihypertensive drugs usually intensify. To avoid hypotension, careful monitoring of patients receiving combinations of these drugs is necessary. However, the summation of the effects of antihypertensive drugs can be used, if necessary, to achieve effective blood pressure control.

Simultaneous use of metoprolol and slow blockers calcium channels such as diltiazem and verapamil can lead to increased negative inotropic and chronotropic effects. Intravenous administration of calcium channel blockers such as verapamil should be avoided in patients receiving beta-blockers.

Caution should be exercised when taken concomitantly with the following drugs:

Oral antiarrhythmic drugs(such as quinidine and amiodarone) - risk of bradycardia, atrioventricular block.

Cardiac glycosides (risk of bradycardia, conduction disorders; metoprolol does not affect the positive inotropic effect of cardiac glycosides).

Other antihypertensive drugs(especially the guanethidine, reserpine, alpha-methyldopa, clonidine and guanfacine groups) due to the risk of hypotension and/or bradycardia.

Stopping the simultaneous use of metoprolol and clonidine should definitely begin by stopping metoprolol, and then (after a few days) clonidine; If clonidine is first discontinued, a hypertensive crisis may develop.

Some drugs acting on the central nervous system, for example: sleeping pills, tranquilizers, tri- and tetracyclic antidepressants, antipsychotics and ethanol increase the risk of arterial hypotension. Anesthesia (risk of cardiac depression).

Alpha and beta sympathomimetics (risk of arterial hypertension, significant bradycardia; possibility of cardiac arrest). Ergotamine (increased vasoconstrictor effect). Beta-2 sympathomimetics (functional antagonism).

Nonsteroidal anti-inflammatory drugs (for example, indomethacin) may weaken the antihypertensive effect.

Estrogens (possibly reducing the antihypertensive effect of metoprolol). Oral hypoglycemic agents and insulin (metoprolol may enhance their hypoglycemic effects and mask the symptoms of hypoglycemia). Curare-like muscle relaxants (increased neuromuscular blockade). Enzyme inhibitors (for example, cimetidine, ethanol, hydralazine; selective serotonin reuptake inhibitors, for example, paroxetine, fluoxetine and sertraline) - enhance the effects of metoprolol due to an increase in its concentration in the blood plasma. Enzyme inducers (rifampicin and barbiturates): the effects of metoprolol may be reduced due to increased hepatic metabolism.

Concomitant use of sympathetic ganglion blockers or other beta blockers (for example: eye drops) or monoamine oxidase inhibitors requires close medical supervision.

Monitoring of patients taking beta-blockers includes regular measurement of heart rate (HR) and blood pressure, blood glucose concentration in patients with diabetes mellitus. If necessary, for patients with diabetes mellitus, the dose of insulin or hypoglycemic agents for oral administration should be selected individually. The patient should be taught how to calculate heart rate and instructed about the need medical consultation at heart rate less than 50 beats/min. When taking a dose above 200 mg per day, cardioselectivity decreases.

In case of heart failure, treatment with Egilok ® begins only after reaching the stage of compensation of cardiac function.

Possible increased severity of reactions hypersensitivity and the lack of effect from the administration of usual doses of epinephrine (adrenaline) in patients with a history of allergic reactions.

Anaphylactic shock may be more severe in patients taking Egilok ® . May increase symptoms of peripheral arterial circulation disorders. Should be avoided abrupt end taking the drug Egilok ®. The drug should be discontinued gradually by reducing doses over approximately 14 days. Abrupt withdrawal may worsen angina symptoms and increase the risk of coronary events. Special attention when discontinuing the drug, care must be taken in patients with disease coronary arteries. For exertional angina, the selected dose of Egilok ® should ensure the heart rate at rest is within 55-60 beats/min, and during exercise - no more than 110 beats/min. Patients using contact lenses, should take into account that during treatment with beta-blockers, a decrease in the production of tear fluid is possible. Egilok may mask some clinical manifestations hyperthyroidism (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated as it can increase 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 recovery of blood glucose concentrations to normal level. When prescribing Egilok ® to patients with diabetes mellitus, the concentration of blood glucose should be monitored and, if necessary, the dose of insulin or oral hypoglycemic agents should be adjusted (see section “Interaction with other drugs”).

If necessary, beta2-adrenergic stimulants are prescribed to patients with bronchial asthma; for pheochromocytoma - alpha-blockers.

If necessary surgical intervention it is necessary to warn the surgeon/anesthesiologist about the therapy being performed (choice of drug for general anesthesia with minimal negative inotropic effects), discontinuation of the drug is not recommended. 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.

In elderly patients, regular monitoring of liver function is recommended. Correction of the dosage regimen is required only if an elderly patient develops increasing bradycardia (less than 50 beats/min), a pronounced decrease in blood pressure (systolic blood pressure below 100 mm Hg), atrioventricular block, bronchospasm, ventricular arrhythmias, severe violations liver function, sometimes it is necessary to stop treatment. Patients with severe renal failure It is recommended to monitor renal function.

Special monitoring of the condition of patients with depressive disorders taking metoprolol; in case of development of depression caused by taking beta-blockers, it is recommended to discontinue therapy.

If progressive bradycardia occurs, the dose should be reduced or the drug discontinued.

Due to lack sufficient quantity According to clinical data, the drug is not recommended for use in children.

Impact on the ability to drive vehicles and complex equipment.

Caution must be exercised when driving and engaging in potentially dangerous activities. dangerous species activities requiring increased concentration attention (risk of dizziness and increased fatigue).

Tablets 25 mg: 60 tablets in a brown glass bottle with a PE cap with an accordion shock absorber, with first opening control. 1 bottle along with instructions for use is packed in a cardboard box. Or 20 tablets in a blister made of PVC/PVDC//al. foil. 3 blisters along with instructions for use are packed in a cardboard box.

ATTENTION!!! Nothing in this information can be considered as a recommendation to a citizen (patient) for the diagnosis and treatment of any diseases and cannot serve as a substitute for consultation with medical worker.

Nothing in this information should be interpreted as an appeal to a citizen (patient) to independently purchase or use any of the above medicines.

This information cannot be used by a citizen (patient) to independently make a decision on the medical use of any of the above medicines and/or a decision to change the procedure for the medical use of any of the above medicines recommended by a medical professional.

Egilok - Tablets

INSTRUCTIONS
By medical use drug

Read these instructions carefully before starting to take the drug.

- Save this sheet. You may need to read it again.
- If you have any further questions, consult your doctor orpharmacist
- This medicine is prescribed specifically for you and you should not give it to you.it to other persons. It can harm them even if they have the samesymptoms of the disease.

EGILOK tablets 25 mg, 50 mg, 100 mg

Each tablet contains 25 mg, 50 mg or 100 mg active substance metoprolol tartrate.

Other components: magnesium stearate, polyvidone, anhydrous colloidal silicon dioxide, sodium starch glycolate, microcrystalline cellulose.

1. WHAT IS EGILOK AND WHAT IS IT USED FOR?

Metoprolol belongs to a group of medicines called beta blockers. They are used to treat high blood pressure and prevent heart pain due to angina pectoris. Metoprolol is also used to treat arrhythmias (irregular or accelerated heart rhythm), as maintenance therapy after myocardial infarction, and for the prevention of migraines.

Indications for use

• Hypertension - used as monotherapy or (if necessary) in combination with other antihypertensive drugs; reduces mortality from cardiovascular and coronary diseases(including the incidence of sudden death) in patients with hypertension.
• Angina pectoris. The drug can be used as monotherapy and in combination with other antianginal agents.
• Maintenance therapy - for secondary prevention - after myocardial infarction.
• Heart rhythm disturbances ( sinus tachycardia, supraventricular tachycardia, ventricular extrasystoles).
• Hyperthyroidism (to reduce heart rate).
• Prevention of migraine attacks.
• Functional heart disorders with palpitations.

2. BEFORE TAKING EGILOK TABLETS

Do not take these tablets if you have

• Hypersensitivity to metoprolol or any other component of the drug, as well as other beta blockers
• Atrioventricular block II or III degree
• Clinically significant sinus bradycardia (significant decrease in heart rate
• Sick sinus syndrome
• Severe peripheral arterial circulation disorder
• Heart failure in the stage of decompensation.

Due to limited clinical data, the use of metoprolol is contraindicated in acute myocardial infarction if:

• heart rate below 45 beats per minute,
• P-Q interval exceeds 240 ms,
• systolic blood pressure below 100 mmHg.
• Treatment with beta-agonists.

The use of EGILOK requires special caution in the following conditions:

• conduction disorders (atrioventricular) in the heart,
• bradycardia (decreased heart rate),
• peripheral circulatory disorders.

EGILOK should be withdrawn gradually by gradually reducing doses over approximately 14 days. Abrupt withdrawal may worsen angina symptoms and increase the risk of coronary events.

Although cardioselective beta blockers have a weaker effect on breathing than non-selective beta blockers, it is still recommended that they not be prescribed to patients with chronic obstructive diseases if possible. respiratory tract. If it is necessary to prescribe metoprolol to patients bronchial asthma Co-administration of B2-agonists (in tablet and/or aerosol form) or a change in the dose of previously used B2-agonists may be required.

Despite the fact that selective beta blockers relatively rarely affect carbohydrate metabolism or mask the symptoms of hyperglycemia, if EGILOK is prescribed to patients diabetes condition should be checked more often carbohydrate metabolism and, if necessary, adjust the dose of insulin or oral antidiabetic agents.

When treating patients pheochromocytoma metoprolol should be combined with alpha blockers.

The anesthesiologist should be warned that the patient is taking metoprolol before any surgical operation, however, it is not recommended to stop treatment with EGILOK.

Taking EGILOK tablets with food and drinks

EGILOK can be taken with or without food, since food does not affect the absorption or effectiveness of metoprolol.

Pregnancy and breastfeeding

When metoprolol was administered to animals, no harmful effects were found on their offspring.

Human studies

The use of the drug requires a careful assessment of risks and benefits. If the administration of the drug is unavoidable, the fetus and newborn should be closely monitored for several days (48-72 hours) after birth since a decrease in uteroplacental blood flow can affect fetal growth and, penetrating into the fetal bloodstream, cause bradycardia, respiratory depression, and decreased blood pressure. pressure and hypoglycemia.

Although therapeutic doses of metoprolol pass into breast milk little and

The likelihood of a beta-blocking effect on the fetus is small, but the child should still be examined more carefully (bradycardia is possible).

Check with your doctor before taking any medicine if you are pregnant or breastfeeding.

Transport and machinery management

Metoprolol affects the patient's ability to drive vehicles and perform work with increased risk accidents, especially at the beginning of treatment and while taking alcohol (dizziness and fatigue may develop). Therefore, the dose at which driving and performing dangerous work, should be determined individually.

Taking other medications

Please tell your doctor or pharmacist if you are currently takingtime or recently took any medicines, no furtherrecipe.

Please note that this also applies to medications taken previously or planned to be taken in the future.

The antihypertensive effects of EGILOK and other antihypertensive drugs are usually cumulative. Patients receiving combinations of these drugs should be closely monitored to avoid hypotension. However, the additive effects of antihypertensive drugs can be used, if necessary, to achieve more effective blood pressure control.

The simultaneous use of metoprolol and verapamil and/or other calcium channel blockers such as diltiazem leads to increased negative inotropic and chronotropic effects. Not recommended intravenous administration calcium channel blockers such as verapamil in patients receiving beta blockers.

Should be careful at combinations with the following:

• Oral antiarrhythmic drugs (such as quinidine and amiodarone), as well as parasympathomimetics (risk of hypotension, bradycardia, atrioventricular block).
• Digitalis glycosides (risk of bradycardia, conduction disturbances; metoprolol does not affect the positive inotropic effect of digitalis drugs).
• Other antihypertensive drugs (especially the guanethidine, reserpine, alpha-methyldopa, clonidine and guanfacine groups) due to the risk of hypotension and/or bradycardia.
• When combined with clonidine, treatment should be discontinued, making sure to first stop metoprolol and then (after a few days) clonidine. If clonidine is first stopped, a hypertensive crisis may occur.
• Some drugs acting on the central nervous system (hypnotics, tranquilizers, tri- and tetracyclic antidepressants, antipsychotics) and alcohol (risk of hypotension).
• Drugs (risk of cardiac depression).
• Ergotamine (increased vasoconstrictor effect).
• Rg-sympathomimetics (functional antagonism).
• Non-steroidal anti-inflammatory drugs, such as indomethacin (possibly enhancing the antihypertensive effect).
• Estrogens (possibly reducing the antihypertensive effect of metoprolol).
• Oral antidiabetic drugs and insulin (metoprolol may enhance their hypoglycemic effects and mask the symptoms of hypoglycemia).
• Muscle relaxants such as curare (increased neuromuscular blockade).
• Enzyme inhibitors (such as cimetidine, alcohol, hydralazine; selective serotonin reuptake inhibitors, such as paroxetine, fluoxetine and sertraline) - enhance the effects of metoprolol due to an increase in its plasma concentration.
• Enzyme inducers (such as rifampicin and barbiturates) - the effects of metoprolol may be reduced due to increased hepatic metabolism.
• Concomitant use of sympathetic ganglion blockers or other beta blockers (such as eye drops) or MAO inhibitors requires close medical monitoring.

3. HOW TO TAKE EGILOK TABLETS

Always take EGILOK strictly as prescribed by your doctor. For anyIf in doubt, consult your doctor or pharmacist.

The tablets can be taken regardless of meals.
If necessary, the tablet can be broken in half.
The dose should be individualized to avoid excessive bradycardia.

Hypertension: For moderate or moderate hypertension, the initial dose is 25 - 50 mg twice a day (morning and evening). If necessary, the daily dose can be gradually increased to 2 x 100 mg or another antihypertensive agent can be added.

Angina: The initial dose is 25-50 mg two to three times a day. Depending on the effect, this dose can be gradually increased to 200 mg per day or another antianginal drug can be added.

Maintenance therapy after myocardial infarction: The usual dose is 50 - 100 mg twice a day (morning and evening).

Arrhythmias: The initial dose is 25-50 mg two or three times a day. If necessary, the daily dose can be gradually increased to 200 mg or another antiarrhythmic agent can be added.

Hyperthyroidism: The usual daily dose is 150 - 200 mg in 3 - 4 doses.

Functional heart disorders with palpitations:

Preventing migraine attacks: The usual daily dose is 2 x 50 mg (morning and evening); if necessary, the dose can be increased to 2 x 100 mg.

Special patient groups:

At kidney diseases The dose of the drug does not need to be specified.
In case of liver diseases, dose changes are usually also not required due to the low binding of metoprolol to plasma proteins (5-10%). In severe liver failure (for example, after bypass surgery), it may be necessary to reduce the dose of metoprolol.

In elderly patients, dose adjustment is not required.

The drug should not be prescribed to children (no clinical experience).

If you feel that EGIL01S has too much or too little effect, consult your doctor or pharmacist.

If you accepted more pills EGILOK" than prescribed, and if anyone accidentally takes any amount of these tablets, contact the department immediately emergency assistance the nearest hospital. Take these instructions and any remaining tablets with you to show your doctor.

Overdose symptoms: hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, asystole, nausea, vomiting, bronchospasm, cyanosis, hypoglycemia, loss of consciousness, coma.

The symptoms listed above may be exacerbated by the simultaneous administration of alcohol, antihypertensive drugs, quinidine and barbiturates. The first symptoms of an overdose appear 20 minutes - 2 hours after taking the drug.

Among other measures to treat overdose, it is necessary intensive therapy and careful monitoring of the patient (circulatory and respiratory parameters, renal function, blood glucose, serum electrolytes). If the drug was taken not too long ago, gastric lavage (if lavage is not possible, you can induce vomiting in the presence of an experienced medical personnel and if the patient is conscious) with the introduction of activated carbon can reduce further absorption of the drug.

For severe hypotension, bradycardia and risk of heart failure, B 1 -agonists should be administered intravenously at intervals of 2-5 minutes or by infusion until the desired effect is achieved. In the absence of selective B 1 -agonists, atropine or dopamine can be administered intravenously. If the desired effect is not achieved, other sympathomimetics (dobutamine or norepinephrine) should be used. Administration of glucagon in doses of 1 to 10 mg may help reverse the effects of strong beta blockade. In cases of severe bradycardia that are resistant to pharmacotherapy, implantation of a cardiac pacemaker may be required. Bronchospasm can be relieved by intravenous administration of a B 2 -agonist (for example, terbutaline). These antidotes can be used in doses exceeding therapeutic ones. Metoprolol cannot be effectively removed by hemodialysis.

If youforgot to take EGILOK

Do not take double the dose to make up for missed doses.
The doctor will inform you about the required duration of treatment with EGILOK. Be sure to follow your doctor's instructions.

4. POSSIBLE SIDE EFFECTS

Like everyone else medications, EGILOKG may cause side effects.

If any of the following occur, stop taking EGILOK and immediately contact your doctor or department emergency care nearest hospital:

• Swelling of the lips or throat with difficulty swallowing or breathing
• Collapse

These side effects are very serious but are rare. Their appearance may mean that you have a severe allergic reaction on EGILOK. You may need emergency health care or hospitalization.

Metoprolol is usually well tolerated by patients. Side effects are usually mild and reversible. The following side effects have been reported in clinical trials and during therapeutic use of metoprolol. In some cases, the connection between an adverse event and the use of the drug has not been reliably established.

Nervous system: fatigue, dizziness, headache. In rare cases - depression, drowsiness, insomnia, nightmares, emotional stress, sexual dysfunction; very rarely - memory impairment and confusion.

The cardiovascular system: bradycardia (decreased heart rate), orthostatic hypotension, cold extremities, palpitations, in rare cases, heart pain, arrhythmias.

Gastrointestinal tract: nausea, abdominal pain, diarrhea, constipation, in rare cases, vomiting, dry mouth, liver dysfunction.

Kooyua: rash, sweating, in rare cases photosensitivity, progressive psoriasis.

Respiratory system: dyspnea.

Sense organs: rarely - visual impairment, tinnitus.

Increased body weight; in very rare cases - joint pain.

Taking EGILOK should be discontinued if any of the above effects reaches a clinically significant intensity, and its cause cannot be reliably determined.

If you notice any side effects not listed in thisinstructions, please consult your doctor or pharmacist.

5. APPEARANCE AND PACKAGING OF THE DRUG

Description of the drug EGILOK 25 mg: White or almost white, round, biconvex tablets with a cross-shaped dividing line and a double bevel (double snap shape) on one side and engraved with a stylized letter "E" and the number 435 on the other side, without or almost without smell.

Description of the drug EGILOK 50 mg: White or almost white, round, biconvex tablets, scored on one side and engraved with the stylized letter “E” and number 434 on the other side, odorless or almost odorless.

Description of the drug EGILOK "100 mg: White or almost white, round, biconvex tablets, chamfered, scored on one side and engraved with the stylized letter "E" and number 432 on the other side, without or almost odorless.

30 tablets (only for the drug EGILOK 100 mg tablets) or 60 tablets in brown glass bottles are packed in a cardboard box along with instructions for use.

6. STORAGE CONDITIONS

Store at room temperature(15 - 25°C). Keep the drug out of the reach of children!

7. EXPIRATION DATE

The expiration date is indicated on the packaging.
Do not use the drug after the expiration date indicated on the package.

8. CONDITIONS OF VACATION FROM PHARMACIES

On prescription.

9. MANUFACTURER

JSC PHARMACEUTICAL PLANT EGIS
1106 Budapest, st. Keresturi, 30-38
HUNGARY
Phone: (36-1) 265-5555
Fax: (36-1) 265-5529

Beta 1 adrenergic blocker

Active substance

Release form, composition and packaging

Pills white or almost white, round, biconvex, with a cross-shaped dividing line and a double bevel ("double step" shape) on one side and an engraving "E435" on the other side, odorless.

Excipients: microcrystalline cellulose - 41.5 mg, sodium carboxymethyl starch (type A) - 7.5 mg, colloidal anhydrous silicon dioxide - 2 mg, K90 - 2 mg, magnesium stearate - 2 mg.

20 pcs. - blisters (3) - cardboard packs.

Pills white or almost white, round, biconvex, with a mark on one side and an engraving “E434” on the other side, odorless.

Excipients: microcrystalline cellulose - 83 mg, sodium carboxymethyl starch (type A) - 15 mg, colloidal anhydrous silicon dioxide - 4 mg, povidone K90 - 4 mg, magnesium stearate - 8 mg.

15 pcs. - blisters (4) - cardboard packs.
60 pcs. - dark glass jars (1) - cardboard packs.

Pills white or almost white, round, biconvex, chamfered, with a mark on one side and engraved “E432” on the other side, odorless.

Excipients: microcrystalline cellulose - 166 mg, sodium carboxymethyl starch (type A) - 30 mg, colloidal anhydrous silicon dioxide - 8 mg, povidone K90 - 8 mg, magnesium stearate - 8 mg.

30 pcs. - dark glass jars (1) - cardboard packs.
60 pcs. - dark glass jars (1) - cardboard packs.

pharmachologic effect

Cardioselective β-adrenergic receptor blocker.

Metoprolol suppresses the effect of increased activity of the sympathetic system on the heart, and also causes a rapid decrease in heart rate, contractility, output and blood pressure.

For arterial hypertension, metoprolol reduces blood pressure in patients in a standing and lying position. The long-term antihypertensive effect of the drug is associated with a gradual decrease in peripheral vascular resistance. In arterial hypertension, long-term use of the drug leads to a statistically significant decrease in the mass of the left ventricle and an improvement in its diastolic function. In men with mild or moderate hypertension, metoprolol reduces mortality from cardiovascular causes (primarily sudden death, fatal and non-fatal heart attack and stroke).

- functional disorders of cardiac activity, accompanied by tachycardia;

— IHD (secondary prevention of myocardial infarction, prevention of angina attacks);

- heart rhythm disturbances (supraventricular arrhythmias, ventricular extrasystole);

- hyperthyroidism (as part of complex therapy);

- prevention of migraine attacks.

Contraindications

- cardiogenic shock;

— AV blockade II and III degrees;

- sinoatrial block;

- sinus bradycardia (HR<50 уд./мин);

— heart failure in the stage of decompensation;

- severe peripheral circulatory disorders;

- age under 18 years (due to the lack of sufficient clinical data);

- simultaneous intravenous administration of verapamil;

- severe form of bronchial asthma;

- pheochromocytoma without simultaneous use of alpha-blockers;

- hypersensitivity to metoprolol or any other component of the drug;

- increased sensitivity to other beta-blockers.

Due to insufficient clinical data, Egiolok is contraindicated in acute myocardial infarction accompanied by heart rate<45 уд./мин, с интервалом PQ >240 ms, and systolic blood pressure<100 мм рт.ст.

Carefully the drug should be prescribed for diabetes mellitus; metabolic acidosis; bronchial asthma; COPD; renal/liver failure; myasthenia gravis; pheochromocytoma (when used simultaneously with alpha-blockers); thyrotoxicosis; AV blockade of the first degree, depression (including a history); psoriasis; obliterating diseases of peripheral vessels (intermittent claudication, Raynaud's syndrome); pregnancy; during lactation; elderly patients; patients with a history of allergic reactions (possible decreased response when using adrenaline).

Dosage

The drug should be taken orally during or regardless of meals. If necessary, the tablet can be broken in half.

The dose should be adjusted gradually and individually to avoid the development of excessive bradycardia. The maximum daily dose is 200 mg.

At mild or moderate arterial hypertension The initial dose is 25-50 mg 2 times a day (morning and evening). If necessary, the dose can be gradually increased to 100-200 mg/day or another antihypertensive agent can be added.

At angina pectoris the initial dose is 25-50 mg 2-3 times/day. Depending on the effect, the dose can be gradually increased to 200 mg/day or another antianginal drug can be added.

At heart rhythm disturbances the initial dose is 25-50 mg 2-3 times/day. If necessary, the daily dose can be gradually increased to 200 mg/day or another antiarrhythmic agent can be added.

At hyperthyroidism the usual daily dose is 150-200 mg in 3-4 doses.

At functional heart disorders accompanied by palpitations the usual dose is 50 mg 2 times / day (morning and evening); if necessary, the dose can be increased to 200 mg in 2 doses.

For prevention of migraine attacks The recommended dose is 100 mg/day in 2 divided doses (morning and evening); if necessary, the dose can be increased to 200 mg/day in 2 divided doses.

U patients with renal dysfunction no change in dosage regimen is required.

In liver cirrhosis, dose changes are usually not required due to the low binding of metoprolol to plasma proteins. At severe liver failure(for example, after portacaval shunting), it may be necessary to reduce the dose of Egilok.

U elderly patients no dose adjustment is required.

Side effects

Egilok is usually well tolerated by patients. Side effects are usually mild and reversible. The following side effects have been reported in clinical trials and during therapeutic use of metoprolol. In some cases, the connection between an adverse event and the use of the drug has not been reliably established. The frequency of side effects listed below is defined as follows: very common (>10%), common (1-9.9%), uncommon (0.1-0.9%), rare (0.01-0.09%), very rare, including isolated messages (<0.01%).

From the nervous system: very often - increased fatigue; often - dizziness, headache; rarely - increased excitability, anxiety; uncommon - paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, nightmares; very rarely - amnesia/memory impairment, depression, hallucinations.

From the cardiovascular system: often - bradycardia, orthostatic hypotension (in some cases syncope is possible), coldness of the lower extremities, palpitations; uncommon - temporary increase in symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, AV block of the first degree; rarely - conduction disturbances, arrhythmia; very rarely - gangrene (in patients with peripheral circulatory disorders).

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

From the digestive system: often - nausea, abdominal pain, constipation or diarrhea; infrequently - vomiting; rarely - dryness of the oral mucosa, impaired liver function.

From the skin: uncommon - urticaria, increased sweating; rarely - alopecia; very rarely - photosensitivity, exacerbation of psoriasis.

From the senses: rarely - blurred vision, dryness and/or irritation of the eyes, conjunctivitis; very rarely - ringing in the ears, disturbance of taste.

From the reproductive system: rarely - impotence/sexual dysfunction.

Others: infrequently - weight gain; very rarely - arthralgia, thrombocytopenia.

The use of Egilok should be discontinued if any of the above effects reaches a clinically significant intensity, and its cause cannot be reliably determined.

Overdose

Symptoms: marked decrease in blood pressure, sinus bradycardia, AV block, heart failure, cardiogenic shock, asystole, nausea, vomiting, bronchospasm, cyanosis, hypoglycemia, loss of consciousness, coma. The symptoms listed above may increase when used simultaneously with ethanol, antihypertensive drugs, quinidine and barbiturates.

The first symptoms of overdose appear 20 minutes to 2 hours after taking the drug.

Treatment: Careful monitoring of the patient is necessary (monitoring blood pressure, heart rate, respiratory rate, renal function, blood glucose concentration, serum electrolytes) in the intensive care unit. If the drug has been taken recently, gastric lavage with activated charcoal may reduce further absorption of the drug (if lavage is not possible, vomiting may be induced if the patient is conscious). In case of excessive decrease in blood pressure, bradycardia and threat of heart failure - intravenous administration of beta-adrenergic agonists (until the desired effect is achieved) or intravenous administration of 0.5-2 mg of atropine at intervals of 2-5 minutes. If there is no positive effect, dopamine, dobutamine or norepinephrine (norepinephrine). For hypoglycemia - administration of 1-10 mg of glucagon, installation of a temporary pacemaker. For bronchospasm - administration of beta 2-adrenergic agonists. For convulsions - slow intravenous administration of diazepam. Hemodialysis is ineffective.

Drug interactions

The antihypertensive effects of Egilok are usually enhanced when used concomitantly with other antihypertensive drugs. To avoid hypotension, careful monitoring of patients receiving combinations of these drugs is necessary. However, the summation of the effects of antihypertensive drugs can be used, if necessary, to achieve effective blood pressure control.

The simultaneous use of metoprolol and slow calcium channel blockers such as diltiazem and verapamil can lead to increased negative inotropic and chronotropic effects. IV administration of the verapamil type should be avoided in patients receiving beta-blockers.

Combinations requiring caution

Oral antiarrhythmic drugs (such as quinidine and amiodarone): risk of bradycardia, AV block.

Cardiac glycosides: risk of developing bradycardia, conduction disorders; metoprolol does not affect the positive inotropic effect of cardiac glycosides.

Other antihypertensive drugs (especially the guanethidine, reserpine, alpha-methyldopa, clonidine and guanfacine groups): risk of developing arterial hypotension and/or bradycardia.

Discontinuation of the simultaneous use of metoprolol and clonidine should be started by discontinuing metoprolol, and then (after a few days) clonidine; If clonidine is first discontinued, a hypertensive crisis may develop.

Some drugs acting on the central nervous system (for example, hypnotics, tranquilizers, tri- and tetracyclic antidepressants, antipsychotics and ethanol): risk of developing arterial hypotension.

Anesthesia: risk of cardiac depression.

Alpha and beta sympathomimetics: risk of developing arterial hypertension, significant bradycardia, possible cardiac arrest.

Ergotamine: increased vasoconstrictor effect.

Beta 2 sympathomimetics: functional antagonism.

NSAIDs (for example, indomethacin): the antihypertensive effect may be weakened.

Estrogens: the antihypertensive effect of metoprolol may be reduced.

Oral hypoglycemic agents and insulin: metoprolol may enhance their hypoglycemic effects and mask the symptoms of hypoglycemia.

Curare-like muscle relaxants: increased neuromuscular blockade.

Enzyme inhibitors (for example, cimetidine, ethanol, hydralazine; selective serotonin reuptake inhibitors, for example, paroxetine, fluoxetine and sertraline): the effects of metoprolol may be enhanced due to an increase in its concentration in the blood plasma.

Enzyme inducers (rifampicin and barbiturates): the effects of metoprolol may be reduced due to increased hepatic metabolism.

Concomitant use of sympathetic ganglion blockers or other beta blockers (eg, eye drops) or MAO inhibitors requires close medical monitoring.

special instructions

When prescribing Egilok, heart rate and blood pressure should be regularly monitored. The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation in case of heart rate<50 уд./мин.

In patients with diabetes mellitus, blood glucose levels should be regularly monitored and, if necessary, the dose of insulin or oral hypoglycemic drugs should be adjusted.

When using the drug at a dose exceeding 200 mg/day, cardioselectivity decreases.

Prescribing Egilok to patients with chronic heart failure is possible only after reaching the compensation stage.

In patients taking Egilok, the severity of hypersensitivity reactions may increase (against the background of a burdened allergic history) and there may be no effect from the administration of usual doses of epinephrine (adrenaline).

Anaphylactic shock may be more severe in patients taking Egilok.

The use of Egilok may worsen the symptoms of peripheral circulatory disorders.

Egilok should be discontinued gradually, gradually reducing its dose over 14 days. Abrupt cessation of treatment may increase angina attacks and the risk of developing coronary disorders. During drug withdrawal, patients with coronary artery disease should be under close medical supervision.

For exertional angina, the selected dose of Egilok should ensure the heart rate at rest is within the range of 55-60 beats/min, and during exercise - no more than 110 beats/min.

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.

Egilok may mask some clinical manifestations of hyperthyroidism (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.

In diabetes mellitus, taking Egilok 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 levels.

When prescribing metoprolol to patients with bronchial asthma, simultaneous use of beta 2-adrenergic agonists is necessary.

In patients with pheochromocytoma, Egilok should be used in combination with alpha-blockers.

Before performing any surgical intervention, it is necessary to inform the surgeon/anesthesiologist about the therapy being carried out with Egilok (choosing a drug for general anesthesia with minimal negative inotropic effect); discontinuation of the drug is not required.

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.

When prescribing the drug to elderly patients, liver function should be regularly monitored. Correction of the dosage regimen is required only if increasing bradycardia appears in elderly patients (<50 уд./мин), выраженного снижения АД (систолическое АД <100 мм рт.ст.), AV-блокады, бронхоспазма, желудочковых аритмий, тяжелых нарушений функции печени. Иногда необходимо прекратить лечение.

In patients with severe renal failure, monitoring of renal function is recommended.

Special monitoring of the condition of patients with depressive disorders should be carried out. If depression occurs due to the use of beta-blockers, therapy should be discontinued.

If progressive bradycardia occurs, the dose should be reduced or the drug discontinued.

Use in pediatrics

Due to the lack of sufficient clinical data, the drug is not recommended for use in children and adolescents under 18 years of age.

Impact on the ability to drive vehicles and operate machinery

Caution must be exercised when driving vehicles and when engaging in potentially hazardous activities that require increased concentration (risk of dizziness and fatigue).

Pregnancy and lactation

The use of the drug is not recommended during pregnancy. The use of the drug is possible only when the expected benefit to the mother outweighs the potential risk to the fetus. If it is necessary to prescribe the drug during pregnancy, careful monitoring of the condition of the fetus and newborn is necessary for 48-72 hours after birth, since bradycardia, arterial hypotension, hypoglycemia and respiratory depression may develop.

Despite the fact that when using the drug in therapeutic doses, only a small amount of metoprolol is excreted in breast milk, the condition of the newborn should be monitored (bradycardia is possible). The use of the drug during lactation is not recommended. If it is necessary to use Egilok during lactation, breastfeeding should be stopped.

Severe liver failure

Egilok (active ingredient metoprolol) is a popular Hungarian beta-1-blocker of selective action without its own sympathomimetic activity. It has antihypertensive, antianginal (anti-ischemic) and antiarrhythmic effects. Suppresses the automaticity of the first order pacemaker, reduces the heart rate, slows down atrioventricular conduction, reduces the excitability and contractility of the heart muscle, reduces cardiac output, and reduces the heart's need for oxygen. Reduces the stimulating effect of catecholamine neurotransmitters on the heart during physical and psycho-emotional stress. The antihypertensive effect of Egilok stabilizes by the end of the second week of the drug course. For exertional angina, the drug reduces the frequency and severity of attacks. In the event of a myocardial infarction, Egilok limits the area of ​​ischemic damage, reduces the risk of developing life-threatening arrhythmias and the likelihood of recurrent myocardial infarction. When used in moderate doses, it affects the smooth muscles of the bronchial tree and peripheral arteries less than non-selective beta-blockers. After oral administration, egilok is quickly and completely absorbed from the gastrointestinal tract. The maximum concentration of the active substance in the blood is observed after 1-2 hours. The half-life from blood plasma is 3-4 hours.

Egilok is available in tablets. The recommended daily dose of the drug is 100 mg for 1-2 doses with the possibility of gradually increasing to 200 mg. The maximum daily dose should not exceed 400 mg. The drug has been very well researched, incl. Russian scientists. Thus, in one of the studies, domestic cardiologists studied the effectiveness of Egilok in the treatment of arterial hypertension in patients suffering from diabetes. The relevance of this issue is due to the fact that about 70% of patients suffering from non-insulin-dependent diabetes mellitus die from one or another cardiovascular complications, and strict control of blood pressure can significantly reduce mortality rates, even to a greater extent than glycemic control.

The advisability of using beta-blockers in such patients has been questioned for a long time. There was an opinion that they significantly increase the risk of hypoglycemia, hide its signs, inhibit the rate of recovery of glucose concentrations after a hypoglycemic episode and worsen the lipid profile. As it turned out, such fears were unfounded. Returning to the above study, it should be noted that systolic and diastolic blood pressure decreased in both groups, but the decrease was more pronounced in the diabetic group. In addition, therapy with Egilok led to a decrease in the level of total and “bad” cholesterol, triglycerides and had virtually no effect on carbohydrate metabolism. Another study examined the drug's effectiveness in coronary heart disease. A number of clinicians have complained that some antianginal drugs can effectively relieve pain while providing only minor anti-ischemic effects. This can mask the danger signal given by a heart attacked by ischemia (so-called silent ischemia). The study involved patients with exertional angina. As a result of treatment with Egilok, the frequency of angina attacks decreased by half. Confirmation of the anti-ischemic activity of the drug is the improvement in exercise tolerance. Beta-blockers and, in particular, Egilok are used not only for therapeutic, but also for prophylactic purposes, including the prevention of ischemic complications in post-infarction patients. The drug can also be used to treat patients suffering from coronary heart disease in combination with broncho-obstructive syndrome, which in itself is a contraindication to the use of beta-blockers.

Pharmacology

Cardioselective beta 1-blocker without intrinsic sympathomimetic activity. It has hypotensive, antianginal and antiarrhythmic effects. Reduces the automaticity of the sinus node, reduces heart rate, slows AV conduction, reduces myocardial contractility and excitability, reduces cardiac output, and reduces myocardial oxygen demand. Suppresses the stimulating effect of catecholamines on the heart during physical and psycho-emotional stress.

Causes a hypotensive effect, which stabilizes by the end of the 2nd week of course use. For angina pectoris, metoprolol reduces the frequency and severity of attacks. Normalizes heart rate during supraventricular tachycardia and atrial fibrillation. In case of myocardial infarction, it helps to limit the ischemia zone of the heart muscle and reduces the risk of developing fatal arrhythmias, and reduces the possibility of relapses of myocardial infarction. When used in average therapeutic doses, it has a less pronounced effect on the smooth muscles of the bronchi and peripheral arteries than non-selective beta-blockers.

Pharmacokinetics

After oral administration, metoprolol is quickly and almost completely absorbed from the gastrointestinal tract, the Cmax of the active substance in the blood plasma is reached within 1-2 hours. After absorption, metoprolol is largely subject to the “first pass” effect through the liver. Intensively metabolized in the liver with the participation of isoenzymes of the cytochrome P450 system with the formation of non-catative metabolites. T1/2 of metoprolol from plasma is 3-4 hours and does not change during the course of treatment. More than 95% of the dose taken is excreted by the kidneys, of which only 3% is unchanged.

Release form

The tablets are white or almost white, round, biconvex, with a cross-shaped dividing line and a double bevel on one side and engraved “E435” on the other side, odorless.

Excipients: microcrystalline cellulose, sodium starch glycolate, colloidal anhydrous silicon dioxide, povidone K90, magnesium stearate.

30 pcs. - dark glass jars (1) - cardboard packs.
60 pcs. - dark glass jars (1) - cardboard packs.

Dosage

When taken orally, the average dose is 100 mg/day in 1-2 doses. If necessary, the daily dose is gradually increased to 200 mg. When administered intravenously, a single dose is 2-5 mg; if there is no effect, repeated administration is possible after 5 minutes.

Maximum doses: when taken orally, the daily dose is 400 mg, when administered intravenously, a single dose is 15-20 mg.

Interaction

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 Cmax in the blood plasma and the AUC of metoprolol increase. 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 half-life, so the likelihood of drug interaction remains even several days after discontinuation of fluoxetine.

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.

Side effects

From the cardiovascular system: bradycardia, arterial hypotension, AV conduction disturbances, and symptoms of heart failure are possible.

From the digestive system: at the beginning of therapy, dry mouth, nausea, vomiting, diarrhea, constipation are possible; in some cases - liver dysfunction.

From the central nervous system and peripheral nervous system: at the beginning of therapy, weakness, fatigue, dizziness, headache, muscle cramps, feeling of cold and paresthesia in the extremities are possible; possible decrease in the secretion of tear fluid, conjunctivitis, rhinitis, depression, sleep disturbances, nightmares.

From the hematopoietic system: in some cases - thrombocytopenia.

From the endocrine system: hypoglycemic conditions in patients with diabetes mellitus.

From the respiratory system: in predisposed patients, symptoms of bronchial obstruction may appear.

Allergic reactions: skin rash, itching.

Indications

Arterial hypertension, prevention of angina attacks, heart rhythm disturbances (supraventricular tachycardia, extrasystole), secondary prevention after myocardial infarction, hyperkinetic cardiac syndrome (including with hyperthyroidism, NCD). Prevention of migraine attacks.

Contraindications

AV blockade II and III degrees, sinoatrial blockade, bradycardia (heart rate less than 50 beats/min), CVS, arterial hypotension, chronic heart failure stage IIB-III, acute heart failure, cardiogenic shock, metabolic acidosis, severe peripheral circulatory disorders, hypersensitivity to metoprolol.

Features of application

Use during pregnancy and breastfeeding

Use during pregnancy is possible only when the expected benefit to the mother outweighs the potential risk to the fetus. Metoprolol penetrates the placental barrier. Due to the possible development of bradycardia, arterial hypotension, hypoglycemia and respiratory arrest in the newborn, metoprolol should be discontinued 48-72 hours before the planned date of delivery. After delivery, it is necessary to ensure strict monitoring of the newborn’s condition for 48-72 hours.

Metoprolol is excreted in breast milk in small quantities. Use during lactation is not recommended.

Use for liver dysfunction

Use with caution in patients with severe liver dysfunction.

Use for renal impairment

Use with caution in patients with severe renal impairment.

special instructions

Use with caution in patients with chronic obstructive respiratory diseases, diabetes mellitus (especially with a labile course), Raynaud's disease and obliterating diseases of the peripheral arteries, pheochromocytoma (should be used in combination with alpha-blockers), severe renal and liver dysfunction.

During treatment with metoprolol, there may be a decrease in the production of tear fluid, which is important for patients who use contact lenses.

Completion of a long course of treatment with metoprolol should be carried out gradually (over a minimum of 10 days) under the supervision of a physician.

In combination therapy with clonidine, the latter should be discontinued several days after metoprolol is discontinued in order to avoid a hypertensive crisis. When used simultaneously with hypoglycemic agents, correction of their dosage regimen is required.

A few days before anesthesia, it is necessary to stop taking metoprolol or select an anesthetic agent with minimal negative inotropic effect.

Impact on the ability to drive vehicles and operate machinery

In patients whose activities require increased attention, the issue of using metoprolol on an outpatient basis should be decided only after assessing the patient's individual response.

Latin name: Egilok S

ATX code: C07AB02

Active substance: metoprolol

Manufacturer: Intas Pharmaceuticals, Ltd. (Intas Pharmaceuticals, Ltd.) (India)

Updating the description and photo: 30.11.2018

Egilok S is a beta 1-adrenergic blocker with selective action.

Release form and composition

Dosage form – long-acting tablets, film-coated: biconvex, oval, white, with a score on both sides (10 pieces in a blister, in a cardboard pack of 3 or 10 blisters and instructions for use of Egilok S).

Composition of 1 tablet:

• active substance: metoprolol succinate – 25, 50, 100 or 200 mg;
• auxiliary components: ethylcellulose, methylcellulose, microcrystalline cellulose, glycerol, magnesium stearate, corn starch;
• film shell: Sepifilm LP 770 white (hypromellose, titanium dioxide E171, stearic acid, microcrystalline cellulose).

Pharmacological properties

Pharmacodynamics

The active substance of Egilok S, metoprolol succinate, is a beta 1-adrenergic blocker that is capable of blocking β 1 -adrenergic receptors when using significantly lower doses than required to block β 2 -adrenergic receptors.

Egilok S has insignificant membrane-stabilizing activity and is not a partial agonist.

Metoprolol is able to reduce or suppress the agonistic effect exerted on cardiac activity by catecholamines, which are released during physical and nervous stress. This means that the drug can prevent an increase in cardiac output and heart rate (HR), increased cardiac contractility and an increase in blood pressure (BP) due to a sharp release of catecholamines.

Unlike conventional tablet selective beta 1 blockers (including metoprolol tartrate), extended-release metoprolol succinate provides a constant plasma concentration of the drug and a stable clinical effect (beta 1 blockade) for at least 24 hours. As a result of the absence of significant maximum plasma concentrations of metoprolol succinate has higher β 1 -selectivity than conventional tablet forms of metoprolol. In addition, Egilok S significantly reduces the potential risk of side effects that often occur at maximum plasma concentrations, such as weakness in the legs when walking or bradycardia.

For concomitant obstructive pulmonary diseases, Egilok S can be prescribed in addition to beta 2 adrenergic agonists. Metoprolol succinate has less effect on the bronchodilation they cause compared to non-selective beta-blockers.

Metoprolol succinate has less effect than non-selective beta-blockers on carbohydrate metabolism and insulin production, as well as on the cardiovascular system under conditions of hypoglycemia.

In case of arterial hypertension, Egilok S significantly reduces blood pressure, this effect persists for at least 24 hours, both in a lying and standing position, and during physical activity. At the beginning of drug use, an increase in vascular resistance is observed. However, with prolonged use of metoprolol succinate, a decrease in blood pressure is possible due to a decrease in vascular resistance, while cardiac output does not change.

Pharmacokinetics

Each Egilok S tablet contains a large number of microgranules (pellets) coated with a polymer shell, due to which the controlled release of the active substance is carried out.

The effect of the drug occurs quickly. Once in the gastrointestinal tract (GIT), the tablets are disintegrated into separate pellets, each of which acts separately, and together they provide a uniform release of metoprolol succinate for more than 20 hours. The rate of release depends on the acidity of the gastric environment. Thus, the duration of action of Egilok S is more than 24 hours.

Metoprolol succinate is completely absorbed from the gastrointestinal tract. After a single dose, systemic bioavailability is approximately 30–40%.

The substance is characterized by low binding to plasma proteins – 5–10%.

The drug is metabolized in the liver by oxidation to form three main metabolites that do not have clinically significant activity. It is excreted mainly in the form of metabolites, only about 5% of the dose is eliminated unchanged by the kidneys.

The half-life of free metoprolol is ~3.5–7 hours.

Indications for use

• stable chronic heart failure, accompanied by clinical manifestations (II–IV functional class according to the NYHA classification) and impaired left ventricular systolic function (as an additional drug as part of the main treatment of chronic heart failure);
• arterial hypertension;
• heart rhythm disturbances, including supraventricular tachycardia, decreased ventricular contraction frequency during ventricular extrasystoles and atrial fibrillation;
• angina pectoris;
• functional disorders of cardiac activity accompanied by tachycardia;
• reduction in the incidence of re-infarction and mortality after the acute phase of myocardial infarction;
• prevention of migraine attacks.

Contraindications

Absolute:

• arterial hypotension at systolic blood pressure< 90 мм рт. ст.;
• sick sinus syndrome (SSNS);
• atrioventricular block II and III degrees;
• clinically significant sinus bradycardia with heart rate< 50 уд/мин;
• decompensated heart failure;
• P-Q interval > 0.24 sec;
• suspicion of acute myocardial infarction at heart rate< 45 уд/мин;
• cardiogenic shock;
• severe peripheral circulatory disorders with the threat of gangrene;
• pheochromocytoma (if alpha-blockers are not used simultaneously);
• age under 18 years;
• intravenous (IV) administration of slow calcium channel blockers such as verapamil;
• simultaneous use of monoamine oxidase inhibitors (MAO) (except type B);
• long-term or course use of inotropic agents and drugs acting on β-adrenergic receptors;
• hypersensitivity to any component of the drug or other beta-blockers.

Egilok S tablets should be used with caution in the following cases (a careful assessment of the benefit-risk ratio is required):

• Prinzmetal's angina;
• atrioventricular block of the first degree;
• obliterating diseases of peripheral vessels (intermittent claudication, Raynaud's syndrome);
• metabolic acidosis;
• severe renal/liver failure;
• chronic obstructive pulmonary disease;
• bronchial asthma;
• diabetes;
• thyrotoxicosis;
• psoriasis;
• myasthenia gravis;
• depression;
• pheochromocytoma (with simultaneous use of alpha-blockers);
• simultaneous use of cardiac glycosides;
• elderly age.

Egilok S, instructions for use: method and dosage

Egilok S is taken orally, 1 time per day (regardless of the prescribed dose), preferably in the morning. The tablets must be swallowed whole, without chewing or crumbling, and washed down with a sufficient amount of liquid. Meal times don't matter.

The optimal dose is selected individually by the doctor, with caution to avoid the development of bradycardia.

Treatment of stable chronic heart failure (CHF) with clinical manifestations and impaired left ventricular systolic function begins only if the patient is in a stable condition without episodes of exacerbation during the last 6 weeks. However, during the last 2 weeks the main therapy regimen cannot be changed.

In some cases, beta-blockers (including Egilok S) can cause a temporary worsening of chronic heart failure. Sometimes it is possible to extend therapy or reduce the dose, but some patients require discontinuation of metoprolol.

For functional class II CHF, 25 mg is prescribed at the beginning of therapy; after 2 weeks, if necessary, the dose is increased to 50 mg. If in this case the effect is not enough, further doubling of the dose is possible at intervals of 2 weeks. For long-term treatment, the maintenance dose is usually 200 mg.

For CHF of functional classes III and IV, Egilok S is prescribed in the first two weeks at a daily dose of 12.5 mg (½ tablet at a dosage of 25 mg). The optimal maintenance dose is selected individually under close medical supervision, since progression of heart failure symptoms is possible. After 1–2 weeks, if necessary, increase the daily dose to 25 mg, after another 2 weeks – to 50 mg. If the therapeutic effect is insufficient, but provided the drug is well tolerated, it is possible to double the dose at intervals of 2 weeks until the maximum is reached - 200 mg.

If arterial hypotension and/or bradycardia develops, it may be necessary to adjust the main therapy regimen or reduce the dose of Egilok S. The development of arterial hypotension during dose selection does not always indicate intolerance to the drug at this dose when treatment is continued. However, the dose can be further increased only after the patient’s condition has stabilized. Sometimes monitoring of the functional state of the kidneys is required.

• arterial hypertension: 50–100 mg. If the effect is insufficient, increase the daily dose to a maximum of 200 mg or add another antihypertensive drug to therapy (preference is given to diuretics and slow calcium channel blockers);
• heart rhythm disturbances: 100–200 mg;
• angina: 100–200 mg. If the therapeutic effect is insufficient, another antianginal agent is added to therapy;
• functional disorders of cardiac activity accompanied by tachycardia: 100 mg, if necessary, the daily dose is increased to 200 mg;
• maintenance therapy after myocardial infarction: 100–200 mg (in this case, the daily dose can be divided into 2 doses);
• prevention of migraine attacks: 100–200 mg.

Elderly persons, patients with impaired renal function and patients with moderate impairment of liver function do not need to adjust the dose.

In case of severe functional disorders of the liver (severe cirrhosis, portocaval anastomosis), it may be necessary to reduce the dose of Egilok S.

Side effects

Egilok S is generally well tolerated. If adverse reactions occur, they are usually mild and reversible.

Possible side effects (classified as follows: very often -> 10% of cases; often - 1-9.9%; infrequently - 0.1-0.9%; rarely - 0.01-0.09%; very rarely -< 0,01%):

• from the cardiovascular system: often - palpitations, orthostatic hypotension (very rarely accompanied by fainting), bradycardia, cold extremities; uncommon – temporary increase in symptoms of heart failure, pain in the heart area, peripheral edema, first degree atrioventricular block, cardiogenic shock in patients with acute myocardial infarction; rarely - other cardiac conduction disorders, arrhythmias; very rarely in patients with previous severe peripheral circulatory disorders - gangrene;
• from the digestive system: often – abdominal pain, constipation, diarrhea, nausea; infrequently - vomiting; rarely – dryness of the oral mucosa, functional liver disorder; very rarely - hepatitis;
• from the central nervous system: very often – increased fatigue; often – headache, dizziness; uncommon – insomnia/drowsiness, nightmares, decreased attention, paresthesia, depression, convulsions; rarely - anxiety, increased nervous excitability, sexual dysfunction/impotence; very rarely - depression, memory impairment/amnesia, hallucinations;
• from the senses: rarely - dryness and/or irritation of the eyes, visual disturbances, conjunctivitis; very rarely - taste disturbances, ringing in the ears;
• from the respiratory system: often – shortness of breath with physical effort; uncommon – bronchospasm; rarely – rhinitis;
• from the musculoskeletal system: very rarely - arthralgia;
• from the skin: infrequently – urticaria, increased sweating; rarely – hair loss; very rarely - exacerbation of psoriasis, photosensitivity;
• other: infrequently - weight gain; very rarely - thrombocytopenia.

Overdose

The most serious symptoms of metoprolol succinate overdose are disorders of the cardiovascular system, but sometimes suppression of pulmonary function and predominance of symptoms from the central nervous system are possible.

Possible symptoms: marked decrease in blood pressure, AV block I–III degree, bradycardia, weak peripheral perfusion, asystole, cardiogenic shock, heart failure, apnea, depression of pulmonary function, bronchospasm, impairment or loss of consciousness, increased fatigue, increased sweating, tremor, paresthesia, convulsions, esophageal spasm, nausea, vomiting, renal dysfunction, hyperkalemia, hyperglycemia, hypoglycemia (especially in children), transient myasthenic syndrome. Concomitant use of alcohol, barbiturates, antihypertensive drugs or quinidine may worsen the patient's condition. The first symptoms of overdose may occur 20–120 minutes after taking high doses of Egilok S.

First aid measures: taking activated carbon, and, if necessary, gastric lavage. Before gastric lavage, due to the risk of stimulating the vagus nerve, atropine is prescribed (adults - 0.25–0.5 mg). If required, ensure airway patency (by intubation) and adequate ventilation. It is necessary to administer glucose, replenish the volume of circulating blood, and monitor the electrocardiogram. Atropine is also administered at a dose of 1–2 mg intravenously; the administration is repeated as necessary (especially in the presence of vagal symptoms). For depression (suppression) of the myocardium, an infusion of dopamine or dobutamine is given. In addition, it is possible to administer glucagon intravenously at 50–150 mcg/kg at intervals of 1 minute. In some cases, it is advisable to add epinephrine (adrenaline) to therapy. For arrhythmia and dilated ventricular complex, infusion of 0.9% sodium chloride solution or sodium bicarbonate is indicated. If necessary, an artificial pacemaker is installed. To relieve bronchospasm, terbutaline is used (injection or inhalation). In case of cardiac arrest, appropriate resuscitation measures are carried out.

special instructions

Beta blockers are not recommended for patients with obstructive pulmonary disease. If other antihypertensive drugs are poorly tolerated or do not have the desired therapeutic effect, Egilok S can be used, but the minimum effective dose should be prescribed. If necessary, beta 2-adrenergic agonists are used.

Compared to non-selective beta-blockers, selective beta 1-blockers have a lesser effect on carbohydrate metabolism and mask the symptoms of hypoglycemia, but the risk of such an effect cannot be completely excluded.

In case of decompensated chronic heart failure, the stage of compensation should be achieved before starting treatment, and it should be maintained during therapy.

Data from clinical studies on the safety and effectiveness of Egilok S in severe stable heart failure (NYHA class IV) are limited.

Metoprolol succinate may worsen symptoms of peripheral circulatory disorders (usually due to a decrease in blood pressure).

For patients with concomitant pheochromocytoma, Egilok S is prescribed simultaneously with an alpha-blocker.

In rare cases, if atrioventricular conduction is impaired, it may worsen (even to AV block). If bradycardia develops, the dose of metoprolol succinate should be reduced or gradually discontinued.

Patients undergoing surgery should warn the anesthesiologist about taking Egilok S. It is not recommended to discontinue beta-blockers.

Anaphylactic shock that develops during therapy with beta-blockers occurs in a more severe form. However, the use of adrenaline in standard therapeutic doses does not always produce the desired effect.

The effectiveness and safety of Egilok S in patients with symptoms of heart failure in combination with acute myocardial infarction and unstable angina have not been established.

If the drug is abruptly discontinued, symptoms of chronic heart failure may increase, and the risk of myocardial infarction and sudden death may increase, especially in high-risk patients. For this reason, it is not recommended to suddenly stop taking Egilok S. This should be done gradually, over a minimum of 2 weeks, reducing the dose by half at each stage, until the final dose of 12.5 mg is reached - it should be taken for at least 4 days until the drug is completely discontinued. If undesirable symptoms appear with this regimen, a slower withdrawal of therapy is recommended.

Impact on the ability to drive vehicles and complex mechanisms

Egilok S can cause dizziness and increased fatigue, so patients receiving the drug should be careful when driving vehicles and performing potentially hazardous types of work.

Use during pregnancy and lactation

Adequate controlled studies on the use of metoprolol succinate in pregnant women have not been conducted. As a result, Egilok S can only be used in women for whom the expected benefits of therapy outweigh the possible risks.

Beta blockers may cause some side effects in fetuses, newborns, and infants, such as bradycardia.

Metoprolol passes into mother's milk in small quantities, so the risk of adverse reactions is low. However, infants whose mothers receive Egilok S during lactation should be under close medical supervision for possible signs of β-adrenergic receptor blockade.

Use in childhood

Egilok S is contraindicated under 18 years of age, since its effectiveness and safety in pediatric patients have not been established.

For impaired renal function

For patients with chronic renal failure, Egilok S is prescribed with caution.

Correction of the dosage regimen for functional renal impairment and hemodialysis is not required.

For liver dysfunction

For patients with liver failure, Egilok S is prescribed with caution. The doctor selects the dose individually, based on the clinical condition.

Use in old age

For the treatment of elderly patients, Egilok S tablets are used with precautions.

Drug interactions

• verapamil: high risk of developing bradycardia and lowering blood pressure, there is a complementary inhibitory effect on AV conduction and sinus node function;
• barbituric acid derivatives: increases the metabolism of metoprolol;
• propafenone: plasma concentration of metoprolol increases significantly (2–5 times), side effects may develop.

Combinations that require caution and may require dose adjustment:

• Class I antiarrhythmic drugs: the negative inotropic effect may be additive, which can lead to the development of serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with AV conduction defects and sick sinus syndrome;
• non-steroidal anti-inflammatory drugs (with the possible exception of sulindac): the antihypertensive effect of metoprolol is weakened;
• cardiac glycosides: AV conduction time increases, bradycardia develops;
• clonidine: after its abrupt withdrawal, hypertensive reactions may increase (it is recommended to start stopping beta-blockers several days before stopping the use of clonidine);
• quinidine: in patients with rapid hydroxylation, the metabolism of metoprolol is inhibited, which causes a significant increase in its plasma concentration and increased beta-blockade (similar reactions are possible when using other beta-blockers, the metabolism of which involves the CYP2D6 isoenzyme);
• Rifampicin: it is possible to increase the metabolism of metoprolol and reduce its plasma concentration;
• oral hypoglycemic agents: there is a possibility of a change in their effect, which may require dose adjustment;
• inhalation anesthetics: increased cardiodepressive effect;
• Amiodarone: severe sinus bradycardia may develop. Amiodarone has a long half-life, so interactions may occur long after discontinuation;
• epinephrine: there is a risk of bradycardia and severe arterial hypertension;
• diltiazem: there is a mutual enhancement of the inhibitory effect on the conductivity and function of the sinus node, there are known cases of the development of severe bradycardia;
• phenylpropanolamine (norephedrine): it is possible to increase diastolic blood pressure to pathological values ​​and develop a hypertensive crisis (even after using a single dose of 50 mg);

Dispensed by prescription.