Egilok

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EGILOK® (EGILOK®)

Composition:

Active substance: metoprolol;

1 tablet contains 25 mg, 50 mg, or 100 mg of metoprolol tartrate;

Excipients: magnesium stearate, povidone, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), microcrystalline cellulose.

Pharmaceutical form. Tablets.

Main physicochemical properties:

25 mg: white or almost white, round, biconvex tablets with a cross-shaped dividing line and double bevel («double bevel») on one side and engraved stylized letter «E» and number 435 on the other side, odorless or almost odorless;

50 mg: white or almost white, round, biconvex tablets with a line on one side and engraved stylized letter «E» and number 434 on the other side, odorless or almost odorless;

100 mg: white or almost white, round, biconvex tablets with bevelled edge, a line on one side and engraved stylized letter «E» and number 432 on the other side, odorless or almost odorless.

The break line on the tablet is intended only to facilitate splitting and swallowing, and not for dividing the dosage into equal parts.

Pharmacotherapeutic group.

Selective β-adrenoreceptor blockers.

ATC code C07AB02.

Pharmacological Properties

Pharmacodynamics

Metoprolol is a cardioselective β1-adrenoreceptor blocker. It does not exhibit membrane-stabilizing activity and has no intrinsic sympathomimetic activity.

It suppresses cardiac effects of enhanced sympathetic activity, significantly reducing heart rate, myocardial contractility, cardiac output, and arterial blood pressure.

In arterial hypertension, metoprolol reduces arterial blood pressure in patients both in the standing and supine positions. The sustained antihypertensive effect of the drug is associated with a gradual reduction in total peripheral vascular resistance.

In patients with arterial hypertension, long-term administration of metoprolol leads to a statistically significant reduction in left ventricular mass and improvement in left ventricular diastolic function.

In men with mild to moderate arterial hypertension, metoprolol reduces mortality due to cardiovascular diseases (primarily by reducing the incidence of sudden death, fatal myocardial infarctions, and strokes).

By reducing systemic arterial pressure, heart rate, and myocardial contractility, metoprolol decreases myocardial oxygen demand. By reducing heart rate and thereby prolonging diastole duration, metoprolol improves perfusion and oxygenation of myocardial areas with impaired blood supply.

Additionally, the drug reduces the frequency, duration, and severity of angina attacks, as well as asymptomatic ischemia, and increases exercise tolerance.

In myocardial infarction, metoprolol reduces the risk of sudden death. This effect is primarily related to prevention of ventricular fibrillation. Reduced mortality is observed regardless of whether metoprolol was administered in the early or late stages of the disease, as well as in high-risk patients and in patients with diabetes mellitus.

When administered after myocardial infarction, metoprolol reduces the likelihood of recurrent infarction.

In chronic heart failure resulting from dilated cardiomyopathy, metoprolol, initially administered at a low dose (2 × 5 mg daily) and gradually increased, improves cardiac function, quality of life, and physical performance; it also reduces hospitalizations due to heart failure and the need for heart transplantation.

In supraventricular tachycardia, atrial fibrillation, and ventricular extrasystoles, metoprolol reduces ventricular rate and the number of extrasystoles.

At therapeutic doses, the peripheral vasoconstrictive and bronchoconstrictive effects of metoprolol are less pronounced than those of non-selective β-blockers.

Compared to non-selective β-blockers, metoprolol has a significantly lesser effect on insulin secretion and carbohydrate metabolism. It only slightly alters the cardiovascular response to hypoglycemia or slightly prolongs the duration of a hypoglycemic episode.

In short-term clinical studies, metoprolol induced a slight increase in triglyceride levels and a slight decrease in serum free fatty acid levels. In some cases, a slight reduction in HDL-C (high-density lipoprotein cholesterol) levels was also observed, although this reduction was less pronounced than with non-selective β-blockers. However, in long-term clinical studies, a significant reduction in serum total cholesterol levels was demonstrated after several years of metoprolol treatment.

Pharmacokinetics

Metoprolol is rapidly and almost completely absorbed from the gastrointestinal tract. The pharmacokinetic parameters of metoprolol are linear within the therapeutic dose range.

Maximum plasma concentration is reached within 1.5–2 hours after administration. Following absorption, metoprolol undergoes first-pass metabolism. The bioavailability of metoprolol is approximately 50% after a single dose and nearly 70% after repeated administration.

Concomitant food intake may increase metoprolol bioavailability by 30–40%.

Plasma protein binding is low, approximately 5–10%.

Metoprolol is widely distributed in tissues and has a high volume of distribution (5.6 L/kg).

Metoprolol is metabolized in the liver by cytochrome P450 enzymes. The metabolites do not contribute to the clinical effect.

The elimination half-life (t_1/2) averages 3.5 hours (ranging from 1 to 9 hours).

Total clearance is approximately 1 L/min.

More than 95% of the administered dose is recovered in the urine, with 5% excreted unchanged. In some cases, the unchanged fraction may increase up to 30%.

Pharmacokinetic parameters of metoprolol are not significantly altered in elderly patients.

Renal impairment does not affect systemic bioavailability or elimination of metoprolol. However, excretion of metabolites is reduced. Significant accumulation of metabolites has been observed in severely ill patients with renal impairment (glomerular filtration rate of 5 mL/min). Nevertheless, metabolite accumulation does not increase the degree of β-blockade.

Hepatic impairment has only a minor effect on the pharmacokinetic parameters of metoprolol. However, in cases of severe cirrhosis and following portacaval shunt surgery, metoprolol bioavailability may increase and total clearance decrease. In patients after portacaval shunt surgery, total clearance decreased to approximately 0.3 L/min, and the area under the concentration-time curve increased about sixfold compared to healthy individuals.

Clinical characteristics.

Indications.

• Arterial hypertension.
• Angina pectoris (including postinfarction).
• Arrhythmia (including supraventricular tachycardia).
• Prevention of cardiac death and recurrent myocardial infarction after the acute phase of myocardial infarction.
• As part of complex therapy in thyrotoxicosis.
• Prophylaxis of migraine attacks.

Contraindications.

• Hypersensitivity to any component of the medicinal product or to other β-blockers;
• Second- or third-degree atrioventricular block (AV block), sinoatrial block;
• Sick sinus syndrome;
• Decompensated heart failure (pulmonary edema, hypoperfusion syndrome, or arterial hypotension); long-term or intermittent inotropic therapy with β-receptor agonists;
• Marked bradycardia (heart rate ≤ 45 beats per minute);
• Cardiogenic shock;
• Severe peripheral circulatory disorders with pain or trophic changes;
• Arterial hypotension (systolic blood pressure < 100 mm Hg);
• Metabolic acidosis;
• Untreated pheochromocytoma;
• Long-term or intermittent inotropic therapy with β-receptor agonists;
• Concomitant therapy with monoamine oxidase-A inhibitors (MAO-A inhibitors);
• Severe bronchial asthma, severe form of chronic obstructive pulmonary disease;
• Metoprolol is contraindicated in patients receiving intravenous administration of calcium antagonists of the verapamil or diltiazem type, or other antiarrhythmic agents (such as disopyramide).

Metoprolol should not be administered to patients with suspected acute myocardial infarction if heart rate is less than 45 beats per minute, PQ interval > 0.24 seconds, or systolic blood pressure < 100 mm Hg.

Note. In patients with decompensated heart failure who tolerate other medications well, metoprolol may be used with individual dose titration.

Interaction with other medicinal products and other types of interactions.

Metoprolol is a substrate of the CYP 2D6 enzyme. The plasma concentration of metoprolol may be affected by drugs that inhibit CYP 2D6, such as: quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone, and diphenhydramine. At the beginning of treatment with these drugs, a reduction in the dose of the medicinal product Egilok® may be necessary.

Barbituric acid derivatives: barbiturates (particularly pentobarbital) stimulate the metabolism of metoprolol via enzyme induction.

Concomitant use of Egilok® with the following medicinal products should be avoided.

Patients should be under close monitoring if they are taking ganglion blockers, other β-blockers (e.g., eye drops), or monoamine oxidase inhibitors (MAOIs) concomitantly with Egilok®.

Propafenone: concomitant administration with propafenone should be avoided. It has been reported that in 4 patients receiving metoprolol, plasma concentrations of metoprolol increased 2–5 times after administration of propafenone, and 2 patients developed adverse effects typical of metoprolol. This interaction has been confirmed in 8 healthy volunteers. This interaction may be explained by the fact that propafenone, like quinidine, inhibits the metabolism of metoprolol via cytochrome P450 2D6. The outcome of such a combination is unpredictable, as propafenone also possesses β-blocking properties.

Concomitant use of Egilok® with the following medicinal products may require dose adjustment.

Clonidine: abrupt withdrawal of clonidine during β-blocker therapy may lead to an increase in blood pressure. If concomitant clonidine therapy needs to be discontinued, the β-blocker should be withdrawn several days before stopping clonidine.

In patients who are concomitantly taking calcium antagonists of the verapamil or diltiazem type and/or antiarrhythmic agents with Egilok®, negative inotropic and chronotropic effects may occur. Intravenous verapamil should not be administered to patients receiving β-blockers due to the risk of cardiac arrest. β-blockers may potentiate the negative inotropic and chronotropic effects of antiarrhythmic agents (quinidine analogs or amiodarone).

Amiodarone: clinical case reports confirm that pronounced sinus bradycardia may develop in patients taking amiodarone when used concomitantly with metoprolol. Amiodarone has an extremely long elimination half-life (approximately 50 days), meaning that interactions may occur for a prolonged period after discontinuation of the drug.

Class I antiarrhythmic agents: class I antiarrhythmic agents and β-blockers have additive negative inotropic effects, which may lead to serious hemodynamic adverse effects in patients with impaired left ventricular function. The use of this combination should also be avoided in sick sinus syndrome and disturbances of atrioventricular conduction. This interaction is best documented with disopyramide.

Nonsteroidal anti-inflammatory/antirheumatic drugs (NSAIDs): NSAIDs have been shown to antagonize the antihypertensive effect of β-blockers. Indomethacin has been primarily studied. This interaction is unlikely with sulindac. A negative interaction has been reported with diclofenac.

In patients receiving β-blocker therapy, inhaled anesthetics may potentiate the cardiodepressant effect. Inducers or inhibitors of metabolism may affect the plasma concentration of metoprolol.

The plasma concentration of metoprolol decreases with rifampicin or may increase with cimetidine, phenytoin, alcohol, hydralazine, and serotonin reuptake inhibitors (paroxetine, fluoxetine, and sertraline).

When used concomitantly with indomethacin or other drugs that inhibit prostaglandin synthetase, the antihypertensive effect of β-blockers may be reduced.

Cardioselective β-blockers have a significantly lesser effect on blood pressure when adrenaline is administered compared to nonselective β-blockers.

Diltiazem: diltiazem and β-receptor blockers have additive inhibitory effects on AV conduction and sinus node function, potentially leading to marked bradycardia.

Epinephrine: in patients who have been using nonselective β-receptor blockers (including pindolol and propranolol), administration of epinephrine (adrenaline) has led to marked arterial hypertension and bradycardia (approximately 10 reports). Additionally, epinephrine present in local anesthetics may provoke these reactions if inadvertently administered intravascularly. The risk is likely lower when cardioselective β-receptor blockers are used.

Phenylpropanolamine: phenylpropanolamine (norephedrine) at a single dose of 50 mg may cause pathological elevation of diastolic blood pressure in healthy volunteers. Propranolol generally counteracts the blood pressure increase caused by phenylpropanolamine. β-receptor blockers may provoke paradoxical hypertensive reactions in patients taking high doses of phenylpropanolamine. Hypertensive crisis has been reported in two cases during treatment with phenylpropanolamine alone.

In patients receiving β-blockers, dose adjustments of oral antidiabetic agents may be required. Concomitant use of β-blockers with insulin or oral antidiabetic agents may potentiate or prolong their effects. Symptoms of hypoglycemia (particularly tachycardia and tremor) may be masked or absent. In such cases, regular monitoring of blood glucose levels is necessary.

Concomitant use with barbiturates should be avoided, as barbiturates (studied with pentobarbital) stimulate the metabolism of metoprolol via enzyme induction.

The plasma concentration of metoprolol may be affected by drugs that inhibit CYP 2D6, such as: quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone, and diphenhydramine. At the beginning of treatment with these drugs, dose reduction of metoprolol may be necessary.

Digitalis glycosides: concomitant use of digitalis glycosides and β-receptor blockers may increase atrioventricular conduction time and cause bradycardia.

Diphenhydramine: diphenhydramine reduces (by 2.5 times) the clearance of metoprolol to α-hydroxymetoprolol via the CYP 2D6 system in individuals who are rapid hydroxylators. The effects of metoprolol are enhanced. Diphenhydramine may also inhibit the metabolism of other CYP 2D6 substrates.

Rifampicin: rifampicin may stimulate the metabolism of metoprolol, leading to reduced plasma levels.

Caution should be exercised when combining with nitrates due to the risk of arterial hypotension and/or bradycardia.

Patients receiving ganglionic blockers concomitantly with metoprolol should be under close supervision.

Metoprolol may interfere with the elimination of lidocaine.

Metoprolol should be prescribed with caution in patients using β2- and β1-receptor stimulants as well as dihydropyridines.

Caution is required when using metoprolol concomitantly with ergotamine.

Combining metoprolol with other antihypertensive agents should be done cautiously.

Special precautions for use.

When taking metoprolol tartrate, as with other β-blockers, heart rate (HR) and blood pressure (BP) should be monitored (initially daily, then once a month).

Patients receiving β-blockers should not be administered intravenous calcium antagonists of the verapamil type.

In general, patients with asthma who are treated with β₂-agonists (in tablets or aerosol) may require an increased dose of β₂-agonists when starting this medication. The risk of the drug affecting β₂-receptors is lower than with conventional non-selective oral β₁-blockers.

Particular medical supervision is required when treating patients with diabetes mellitus (monitoring blood glucose levels), patients with unstable blood sugar levels, or those on strict diets involving fasting. During treatment with metoprolol, the risk of affecting carbohydrate metabolism or masking hypoglycemia is minimal compared to therapy with non-selective β-blockers.

Metoprolol may mask certain clinical signs of thyrotoxicosis (e.g., tachycardia). Abrupt discontinuation of the drug is contraindicated in patients with thyrotoxicosis due to the risk of exacerbating symptoms.

Patients undergoing treatment for heart failure should be stabilized before initiating metoprolol therapy and throughout its continuation.

Very rarely, pre-existing A-V conduction disturbances may progress to more severe degrees of A-V block. Patients with first-degree A-V block should be treated with this drug with extreme caution.

Sudden withdrawal of beta-blockers is dangerous, especially in high-risk patients, and may worsen chronic heart failure, increase the risk of myocardial infarction, and sudden cardiac death. Therefore, discontinuation of Egilok® for any reason should be gradual whenever possible, over a period of at least 2 weeks, with the dose halved at each step until the final dose of 25 mg is reached. The last dose should be taken for at least 4 days before complete discontinuation. If symptoms recur, the dose reduction should be slowed.

Metoprolol should be used with caution in patients with myasthenia gravis.

Metoprolol may exacerbate pre-existing bradycardia. In case of bradycardia development (HR less than 50–55 beats/min) during treatment, the dose should be reduced and/or the drug gradually withdrawn.

Due to its hypotensive effect, the drug may worsen symptoms of peripheral circulatory disorders such as intermittent claudication.

If metoprolol is administered to patients with pheochromocytoma, an α-adrenergic blocking agent should be used concomitantly.

Before general anesthesia, the anesthesiologist must be informed that the patient is taking Egilok®. In case of surgical intervention, it should be communicated that the patient is receiving metoprolol. Discontinuation of beta-blocker therapy before surgery is not recommended. If discontinuation of metoprolol is considered necessary, it should be initiated at least 48 hours before general anesthesia whenever possible. Acute administration of high doses of metoprolol to patients after non-cardiac surgery should be avoided, as it may lead to bradycardia, arterial hypotension, and stroke, including fatal outcomes in patients with cardiovascular risk factors.

However, in some patients, beta-blockers may be beneficial as premedication. In such cases, an anesthetic with minimal negative inotropic effect should be selected to minimize the risk of myocardial depression.

Discontinuation of the drug should be gradual, reducing the dose over 10 days down to 25 mg. Treatment should not be stopped abruptly due to the risk of withdrawal syndrome (increased angina attacks, elevated arterial pressure).

Metoprolol may cause a slight increase in triglyceride levels and a reduction in free fatty acids in blood. In some cases, a slight decrease in low-density lipoprotein (LDL) levels has been observed, which was significantly less pronounced than with non-selective β₂-blockers. However, in one long-term study, a significant reduction in total cholesterol levels was observed after several years of metoprolol treatment.

Experience with metoprolol use in patients with heart failure and concomitant conditions such as unstable heart failure (NYHA IV classification by the New York Heart Association); acute myocardial infarction or unstable angina within the previous 28 days; renal or hepatic impairment; patient age over 80 or under 40 years; hemodynamically significant valvular disease; hypertrophic obstructive cardiomyopathy; or within 4 months after cardiac surgery is limited. Treatment of such patients should be managed by physicians with specialized skills and experience.

If discontinuation of therapy is necessary and feasible, it should be done over 10–14 days, with a daily reduction of 25 mg during the last 6 days. Special attention should be paid to patients with ischemic heart disease during this period. The risk of cardiac events, including sudden cardiac death, may increase during discontinuation of beta-blocker therapy.

In patients with Prinzmetal's angina, the frequency and severity of angina attacks may increase due to α-receptor-mediated coronary vasoconstriction. Therefore, non-selective β-blockers are contraindicated in these patients, and selective β₁-blockers should be used with caution.

In patients receiving β-blockers, epinephrine may increase blood pressure and cause (reflex) bradycardia; this reaction is less likely with selective β-blockers.

Since metoprolol should be discontinued before surgery, discontinuation should occur no later than 48 hours before the procedure, except in special cases such as thyrotoxicosis or pheochromocytoma.

However, in some cases, preoperative administration of beta-blockers may be beneficial, as they may reduce arrhythmogenic effects and decrease coronary blood flow during surgical stress caused by increased sympathetic tone. If a beta-blocker is administered for these reasons, an anesthetic with weak negative inotropic activity should be selected to reduce the risk of myocardial depression.

Very rarely, pre-existing moderate atrioventricular conduction disturbances may worsen, sometimes progressing to atrioventricular block.

Anaphylactic shock may be more severe in patients receiving beta-blocker therapy.

Patients with a history of severe allergic reactions require caution when treated with metoprolol. Particular attention should also be paid to patients undergoing allergen immunotherapy (desensitization therapy). The effect of standard epinephrine doses may be diminished.

Patients using contact lenses should be aware that the drug may reduce tear secretion.

Metoprolol therapy should be prescribed to patients with psoriasis or a history of depressive disorders only after careful assessment of benefit-risk ratio.

Metoprolol bioavailability may be increased in patients with liver cirrhosis.

Special attention should be given to patients with severe renal impairment, serious acute conditions associated with metabolic acidosis, and those receiving concomitant digitalis therapy.

Use during pregnancy or breastfeeding.

Egilok®, like other medicinal products, should not be used during pregnancy or breastfeeding unless absolutely necessary. Like other β-adrenergic blockers, metoprolol may cause adverse effects such as bradycardia and hypoglycemia in the fetus or newborn, or in infants during breastfeeding.

Generally, beta-blockers may impair placental blood flow, potentially leading to fetal growth retardation. Metoprolol may cause bradycardia, arterial hypotension, hypoglycemia, and respiratory depression in newborns; therefore, its use should be discontinued 48–72 hours before expected delivery. If this is not possible, the newborn should be closely monitored for 48–72 hours after birth.

On the other hand, the amount of metoprolol transferred to the infant through breast milk is generally insufficient to produce significant β-adrenergic blockade effects when maternal doses are within the normal therapeutic range. However, breastfed infants should be carefully monitored for potential signs of β-blockade.

Ability to influence reaction speed when driving or operating machinery.

Metoprolol may affect activities requiring high speed of mental and physical reactions and quick decision-making (e.g., driving vehicles, operating machinery, working at heights). Therefore, during treatment, patients should refrain from driving, operating machinery, or working at heights.

Dosage and Administration.

Egilok® is intended for daily use, preferably in the morning. Tablets should be taken independently of food. Swallow the tablet whole with sufficient amount of drinking water.

The score line on the tablet is intended only to facilitate breaking and swallowing, not for dividing the dose into equal parts.

The dosage should be individually determined and gradually increased to avoid excessive bradycardia. During dose titration, heart rate should be monitored to prevent bradycardia. The maximum daily dose is 400 mg.

Arterial hypertension

The recommended dose is 100 mg (once daily in the morning or in two divided doses – morning and evening). If the therapeutic effect is not achieved at this dosage, the daily dose may be increased to 200 mg (once daily in the morning or in two divided doses – morning and evening) or the drug may be combined with other antihypertensive agents.

Angina pectoris

The recommended dose is 50–100 mg 2–3 times daily. If necessary, the drug may be combined with other antianginal agents.

Arrhythmia

The recommended dose is 50 mg 2–3 times daily. If necessary, the daily dose may be increased to 300 mg, divided into 2–3 doses.

Myocardial infarction (treatment should preferably be initiated within the first 12 hours after onset of chest pain)

The recommended dose is 50 mg every 6 hours for 48 hours; the recommended maintenance daily dose is 200 mg, divided into two doses. The treatment course should last for at least 3 months.

Hyperthyroidism (thyrotoxicosis)

The recommended dose is 50 mg 4 times daily. Once the therapeutic effect is achieved, the dose should be gradually reduced.

Prophylaxis of migraine attacks

The recommended daily dose is 100–200 mg daily, in two divided doses.

Patients with renal impairment

Dosage adjustment is not required.

Patients with hepatic impairment

Dosage adjustment (reduction of metoprolol dose) is usually necessary in patients with impaired liver function (e.g., patients with liver cirrhosis).

Elderly patients

Dosage adjustment is not required.

Arterial hypertension: For mild to moderate hypertension, the initial dose is 25 mg.

Children

The use of this medicinal product in children is contraindicated.

Overdose.

Toxicity. In adults, ingestion of a 7.5 g dose has resulted in fatal intoxication. Ingestion of 100 mg by a 5-year-old child did not result in symptoms of intoxication after gastric lavage. A dose of 450 mg caused moderate intoxication in a 12-year-old child, and a dose of 1.4 g caused moderate intoxication in an adult. A dose of 2.5 g caused severe intoxication in an adult, and 7.5 g caused very severe intoxication.

Symptoms. The most severe symptoms are cardiovascular; however, in some cases, especially in children and young individuals, central nervous system (CNS) symptoms and respiratory depression may predominate. Arterial hypotension, sinus bradycardia, first- to third-degree AV block, QT interval prolongation (rare), heart failure, cardiogenic shock, asystole, nausea, vomiting, bronchospasm, cyanosis, hypoglycemia, loss of consciousness, coma, and in some cases, hypokalemia. Respiratory depression, respiratory arrest.

Other symptoms: fatigue, confusion, fine tremor, seizures, sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia. Renal effects. Transient myasthenic syndrome. Initial signs of overdose may appear 20 minutes to 2 hours after ingestion of an excessive dose.

Concomitant alcohol intake, use of antihypertensive agents, quinidine, or barbiturates may worsen the patient's condition.

Treatment. Intensive therapy and close monitoring of the patient are required (circulatory and respiratory parameters, renal function, blood glucose, serum electrolytes). If the drug has been recently ingested, further absorption can be reduced by gastric lavage, induction of emesis, and administration of activated charcoal.

NB! Atropine (0.25–0.5 mg intravenously for adults, 10–20 mcg/kg body weight for children) should be administered prior to gastric lavage (due to the risk of vagal stimulation). Intubation and mechanical ventilation may be necessary; adequate volume restoration; glucose infusion; ECG monitoring; repeated intravenous administration of atropine 1–2 mg (mainly for vagal symptoms). In case of myocardial depression: infusion of dobutamine or dopamine and calcium gluconate 9 mg/mL, 10–20 mL.

Glucagon 50–150 mcg/kg body weight may be administered intravenously over 1 minute, as well as amrinone. In some cases, addition of adrenaline (epinephrine) has been effective.

Infusion of sodium (chloride or bicarbonate) in case of QRS complex widening and arrhythmia. A cardiac pacemaker may be used. In case of circulatory arrest, resuscitation measures may be required for several hours. In case of bronchospasm, terbutaline (injection or inhalation) should be administered. Symptomatic therapy.

Adverse reactions.

Metoprolol is well tolerated by patients, and adverse effects that occur are usually mild and transient.

In the table below, adverse reactions to metoprolol are grouped according to the MedDRA organ system classification:

Table

*The frequency of such adverse effects as skin reactions or eye irritation is low, and symptoms usually resolve after discontinuation of therapy.

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 25 ºC in a place inaccessible to children.

Incompatibilities.

Unknown.

Packaging. 60 tablets (25 mg and 50 mg); 60 or 30 tablets (100 mg) in a glass bottle in a cardboard box.

Prescription status. Prescription only.

Manufacturer. EGIS Pharmaceuticals Ltd., Hungary / EGIS Pharmaceuticals PLC, Hungary.

Address of the manufacturer and location of business operations.

1165 Budapest, Bokenyfoldi ut. 118-120, Hungary / 1165 Budapest, Bokenyfoldi ut. 118-120, Hungary.

9900, Kormend, Matyas kiraly ut. 65, Hungary / 9900, Kormend, Matyas kiraly ut. 65, Hungary