Emzok (Tablets) Instructions for Use

Marketing Authorization Holder

Galena, a.s. (Czech Republic)

ATC Code

C07AB02 (Metoprolol)

Active Substance

Metoprolol (Rec.INN registered by WHO)

Dosage Forms

	Emzok	Film-coated tablets with prolonged release 50 mg: 30 or 100 pcs.
		Film-coated tablets with prolonged release 100 mg: 30 or 100 pcs.
		Film-coated tablets with prolonged release 200 mg: 30 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets with prolonged release, white, oblong, with a double-sided score line.

Excipients: microcrystalline cellulose, povidone, polyethylene oxide, talc, antioxidant (E321), dye (E171).

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Film-coated tablets with prolonged release, white, round, biconvex, with the number “100” embossed on one side and a double-sided score line.

Excipients: microcrystalline cellulose, povidone, polyethylene oxide, talc, antioxidant (E321), dye (E171).

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Film-coated tablets with prolonged release, white, round, biconvex, with a double-sided score line.

Excipients: microcrystalline cellulose, povidone, polyethylene oxide, talc, antioxidant (E321), dye (E171).

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

Beta₁-adrenergic blocker. It has antianginal, antihypertensive, and antiarrhythmic effects.

It reduces the automaticity of the sinus node, decreases heart rate, slows AV conduction, reduces myocardial contractility and excitability, decreases cardiac output, and reduces myocardial oxygen demand. It suppresses the stimulating effect of catecholamines on the heart during physical and psychoemotional stress.

Pharmacokinetics

The pharmacokinetics of metoprolol is directly dependent on the drug dose.

Absorption

After oral administration, Metoprolol is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is 50%. C_max in plasma is reached 6 hours after drug administration.

Distribution

Plasma protein binding is 11-12%. Metoprolol crosses the placental barrier, with metoprolol concentrations in maternal and fetal plasma being equal.

Metabolism

It is metabolized in the liver with the participation of microsomal enzymes of the cytochrome P₄₅₀ system.

Elimination

The T_1/2 of metoprolol is 8-12 hours.

It is excreted by the kidneys as metabolites – 95%, unchanged – about 5%.

Indications

• Arterial hypertension (as monotherapy or in combination with other antihypertensive agents);
• Prevention of angina attacks;
• Secondary prevention after myocardial infarction;
• Cardiac arrhythmias (supraventricular tachycardia, extrasystole);
• Chronic heart failure in the compensation stage (in patients receiving standard therapy, including diuretics, ACE inhibitors, cardiac glycosides);
• Migraine attack prevention.

ICD codes

Dosage Regimen

It is set individually depending on the tolerability and therapeutic efficacy of the drug.

Emzok is recommended to be taken once a day, preferably in the morning, regardless of meals, with water (at least 1/2 glass). The tablet can be divided into parts but should not be crushed or chewed. The maximum dose of 300 mg/day should not be exceeded.

For arterial hypertension, Emzok is prescribed at a dose of 50-200 mg once a day.

For prevention of angina attacks, the drug is used at a dose of 50-200 mg once a day; depending on the therapeutic effect, the dose can be increased to 300 mg/day.

For secondary prevention of myocardial infarction, the drug is prescribed at a dose of 200 mg once a day.

For chronic heart failure in the compensation stage, the dose for the first 4 days is 25 mg/day, then a stepwise weekly dose increase by 25 mg or 50 mg up to 200 mg/day is carried out.

For cardiac arrhythmias, 50-200 mg once a day is prescribed.

For migraine prevention, the drug is used at a dose of 100-200 mg once a day.

Elderly patients do not require dosage regimen adjustment. The drug is prescribed with caution to this category of patients due to the risk of a sharp decrease in blood pressure and heart rate.

Patients with impaired renal function or on hemodialysis do not require dosage regimen adjustment.

When prescribing the drug to patients with impaired liver function, an individual dose reduction is recommended due to increased bioavailability.

Adverse Reactions

From the digestive system nausea, vomiting, abdominal pain (in most cases, these reactions are temporary and disappear after reducing the therapeutic dose of the drug); rarely – diarrhea; in isolated cases – dry mouth, impaired liver function.

From the central and peripheral nervous system increased fatigue, dizziness, sleep disorders (in most cases, these reactions are temporary and disappear after reducing the therapeutic dose of the drug); rarely – paresthesia, muscle cramps, depression, attention disorders; extremely rarely – tinnitus; in isolated cases – dizziness, headaches.

From the cardiovascular system bradycardia, postural hypotension may occur; rarely – heart failure, palpitations, cardiac arrhythmias, Raynaud’s syndrome, peripheral edema, chest pain.

From the respiratory system rarely – shortness of breath; in isolated cases – bronchospasm, rhinitis.

From the organ of vision rarely – conjunctivitis, visual disturbances, xerophthalmia.

Dermatological reactions rarely – psoriasis-like rash, dystrophic skin changes, urticaria; in isolated cases – photosensitization, alopecia.

Other rarely – weight gain, thrombocytopenia, leukopenia; in isolated cases – increased sweating.

Emzok is generally well tolerated by patients, side effects are mild and reversible.

Contraindications

• Cardiogenic shock;
• AV block II and III degree;
• Arterial hypotension;
• Severe bradycardia;
• Sick sinus syndrome;
• Psoriasis;
• Severe peripheral circulatory disorders;
• Acute heart failure;
• Chronic heart failure stage IIB and III;
• Metabolic acidosis;
• Concomitant use with MAO inhibitors;
• Hypersensitivity to the drug.

During treatment with Emzok, intravenous administration of calcium channel blockers such as verapamil and diltiazem, or other antiarrhythmic agents (e.g., disopyramide) is contraindicated, except for patients in intensive care units.

The safety and efficacy of the drug in children have not been established.

Use in Pregnancy and Lactation

During pregnancy (especially in the first trimester), Emzok should be prescribed only in cases where the intended benefit to the mother outweighs the potential risk to the fetus, as there is currently insufficient clinical experience with its use during pregnancy. When used during pregnancy, the drug should be discontinued 48-72 hours before the onset of labor because newborns whose mothers took Emzok during pregnancy may develop bradycardia, arterial hypertension, and hyperglycemia. If discontinuation of the drug is not possible, the newborn should be under particularly careful observation for 48-72 hours after birth.

The use of Emzok during breastfeeding is not recommended, as Metoprolol passes into breast milk. The likelihood of creating a concentration of metoprolol in breast milk that poses a threat to the infant is very low; however, in such cases, the breastfed infant requires special medical supervision.

Use in Hepatic Impairment

When prescribing the drug to patients with impaired liver function, an individual dose reduction is recommended due to increased bioavailability.

Use in Renal Impairment

Patients with impaired renal function or on hemodialysis do not require dosage regimen adjustment.

Pediatric Use

The safety and efficacy of the drug in children have not been established.

Geriatric Use

Elderly patients do not require dosage regimen adjustment. The drug is prescribed with caution to this category of patients due to the risk of a sharp decrease in blood pressure and heart rate.

Special Precautions

Emzok is prescribed with caution to patients with diabetes mellitus (especially with a labile course), Raynaud’s disease, patients with other peripheral circulatory disorders, pheochromocytoma, severe liver and kidney dysfunction (when prescribing the drug to this category of patients, laboratory parameters of kidney and liver function should be carefully monitored).

The use of Emzok for heart failure is possible only after compensation is achieved and appropriate therapy with diuretics and/or cardiac glycosides that does not require correction is selected.

Although cardioselective beta-blockers have less effect on lung function compared to non-selective beta-blockers, Emzok is prescribed with caution to patients with COPD. In these cases, if it is necessary to prescribe Emzok, the possibility of using beta₂-adrenergic agonists as concomitant therapy should be considered.

Patients using contact lenses should consider that the use of Emzok may reduce tear fluid production.

Abrupt withdrawal of the drug is excluded. Discontinuation of therapy should be carried out with a gradual dose reduction over 7-10 days. Patients with coronary artery disease during this period should be under careful medical supervision.

Before surgery, the anesthesiologist must be informed that the patient is taking Emzok; if it is necessary to interrupt the course of therapy, the drug should be discontinued at least 48 hours in advance.

Effect on the ability to drive vehicles and mechanisms

Due to possible individual differences in the reaction to taking Emzok, some patients may have a reduced ability to drive a car.

Overdose

Symptoms arterial hypotension, bradycardia (up to cardiac arrest), heart failure, cardiogenic shock; in severe cases – difficulty breathing, bronchospasm, vomiting, impaired consciousness, generalized convulsive seizures.

Treatment drug withdrawal, if necessary – hospitalization in the ICU, monitoring of the patient’s condition, administration of atropine, glucagon, sympathomimetics (depending on body weight and the effect obtained – dopamine, dobutamine, isoprenaline, oxyprenaline or adrenaline). For severe bradycardia refractory to therapy, electrical cardiac pacing is possible. For bronchospasm – beta₂-adrenergic agonists in aerosol form (if the effect is insufficient – also intravenously) or aminophylline intravenously. For generalized convulsive seizures – diazepam (intravenously slowly).

Drug Interactions

With simultaneous use of Emzok and insulin or oral hypoglycemic agents, their action may be enhanced or prolonged, while symptoms of hypoglycemia (tachycardia and tremor) may be masked or disappear (if such a combination is necessary, regular monitoring of blood glucose levels is recommended).

With simultaneous use of Emzok with tricyclic antidepressants, barbiturates, phenothiazines, nitroglycerin, diuretics, vasodilators and other antihypertensive agents (e.g., prazosin), an enhancement of the hypotensive effect is possible.

With simultaneous use with calcium channel blockers (nifedipine), in addition to enhancing the hypotensive effect, the development of heart failure is possible; with verapamil and diltiazem or other antiarrhythmic drugs (e.g., disopyramide) – arterial hypotension, bradycardia, arrhythmias.

With simultaneous use with cardiac glycosides, reserpine, guanfacine, methyldopa and clonidine, severe bradycardia may occur.

With simultaneous use with norepinephrine, adrenaline or other sympathomimetics (including in the form of eye drops or as part of antitussives), an increase in blood pressure is possible.

With simultaneous use with indomethacin and rifampicin, a decrease in the antihypertensive effect of Emzok is possible.

With concomitant use with cimetidine, an enhancement of the effect of Emzok is possible.

With simultaneous use of Emzok with anesthetic agents, an enhancement of the hypotensive effect is possible; in this case, an additive negative inotropic effect of both drugs is manifested.

With concomitant use of Emzok with peripheral muscle relaxants (e.g., suxamethonium, tubocurarine), an enhancement of the neuromuscular blockade is possible.

With simultaneous use of Emzok and ethanol, an enhancement of the depressant effect on the central nervous system is possible.

In patients taking both Emzok and clonidine simultaneously, clonidine can be discontinued only several days after stopping therapy with Emzok.

Storage Conditions

The drug should be stored in a dry, light-protected place at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years.

Pharmacy supply conditions

The drug is dispensed by prescription.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.