Betaloc^® (Tablets, Solution) Instructions for Use

ATC Code

C07AB02 (Metoprolol)

Active Substance

Metoprolol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

Cardioselective beta₁-adrenergic blocker without intrinsic sympathomimetic activity. It has antihypertensive, antianginal, and antiarrhythmic effects. It lowers the automaticity of the sinus node, reduces heart rate, slows AV conduction, decreases myocardial contractility and excitability, reduces cardiac output, and lowers myocardial oxygen demand. It suppresses the stimulating effect of catecholamines on the heart during physical and psychoemotional stress.

It causes an antihypertensive effect that stabilizes by the end of the 2nd week of course use. In stable angina, Metoprolol reduces the frequency and severity of attacks. It normalizes heart rhythm in supraventricular tachycardia and atrial fibrillation. In myocardial infarction, it helps to limit the area of myocardial ischemia and reduces the risk of fatal arrhythmias, decreasing the possibility of recurrent myocardial infarction. It prevents the development of migraine.

When used in average therapeutic doses, unlike non-selective beta-blockers, it has a less pronounced effect on organs containing β₂-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi, and uterus) and on carbohydrate metabolism. With long-term use, it reduces the concentration of cholesterol in the blood. When used in high doses (more than 100 mg/day), it has a blocking effect on both subtypes of beta-adrenergic receptors.

Pharmacokinetics

After oral administration, Metoprolol is rapidly and almost completely absorbed from the gastrointestinal tract; the C_max of the active substance in blood plasma is reached after 1-2 hours. After absorption, Metoprolol undergoes a significant first-pass effect through the liver. Binding to plasma proteins is low, about 5-10%. V_d is 5.6 L/kg. It is rapidly distributed in tissues, penetrates the blood-brain barrier, and the placental barrier. It is excreted in breast milk. Metoprolol undergoes oxidative metabolism in the liver (mainly with the participation of the isoenzyme CYP2D6) with the formation of 3 main metabolites, none of which has a clinically significant beta-blocking effect. The plasma T_1/2 of metoprolol is 3-4 hours and does not change during the course of treatment. More than 95% of the administered dose is excreted by the kidneys, about 5% of the administered dose is excreted by the kidneys unchanged.

Indications

Arterial hypertension, prevention of angina attacks, cardiac arrhythmias (supraventricular tachycardia, extrasystole), secondary prevention after myocardial infarction, hyperkinetic cardiac syndrome (including in hyperthyroidism, neurocirculatory dystonia). Prevention of migraine attacks.

ICD codes

Dosage Regimen

Tablets, Solution

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. For IV administration, 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; for IV administration, a single dose is 15-20 mg.

Adverse Reactions

From the cardiovascular system: frequent – sinus bradycardia, decreased blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness), postural disorders (very rarely accompanied by fainting); rare – decreased myocardial contractility, development (worsening) of chronic heart failure (edema, swelling of the feet and/or lower legs, shortness of breath), cardiac arrhythmias, impaired myocardial conduction, cardialgia, manifestation of angiospasm (increased peripheral circulatory disorders, cold lower extremities, Raynaud’s syndrome); very rare – worsening of pre-existing AV conduction disorders, gangrene in patients with previous severe peripheral circulatory disorders.

From the nervous system: very frequent – increased fatigue; frequent – weakness, headache, slowing of mental and motor reactions; rare – paresthesia, convulsions, tremor, seizures, depression, anxiety, decreased attention, drowsiness, insomnia, nightmares, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, impotence/sexual dysfunction, Peyronie’s disease; very rare – amnesia/memory impairment, depression, hallucinations.

From the respiratory system: frequent – nasal congestion; infrequent – bronchospasm when prescribed in high doses (loss of selectivity in predisposed patients), shortness of breath; rare – rhinitis.

From the digestive system: frequent – nausea, vomiting, abdominal pain, dry mouth, constipation or diarrhea; rare – dryness of the oral mucosa; very rare – taste change.

From the liver and biliary tract: rare – impaired liver function (dark urine, jaundice of the sclera or skin, cholestasis), increased activity of liver transaminases.

From the organ of vision: rare – decreased vision, decreased tear secretion, dry and sore eyes, conjunctivitis.

From the organ of hearing and labyrinthine disorders: rare – tinnitus, hearing loss.

From the endocrine system: rare – hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid state.

From the skin and subcutaneous tissues: infrequent – skin rashes (exacerbation of psoriasis), psoriasis-like skin reactions, skin hyperemia, exanthema, photodermatosis, increased sweating, reversible alopecia.

Allergic reactions: infrequent – urticaria.

General reactions: rare – back or joint pain, weight gain, decreased libido and/or potency, with abrupt discontinuation of treatment – withdrawal syndrome (increased angina attacks, increased blood pressure).

Laboratory data: rare – thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, hyperbilirubinemia.

Contraindications

Hypersensitivity to metoprolol or other beta-blockers; AV block II and III degree (without a pacemaker); decompensated heart failure; patients receiving long-term or intermittent therapy with inotropic agents and agents acting on beta-adrenergic receptors; clinically significant sinus bradycardia; sick sinus syndrome; cardiogenic shock; severe peripheral circulatory disorders, including threat of gangrene; arterial hypotension (systolic BP less than 100 mm Hg); patients with acute myocardial infarction (heart rate less than 45 beats/min, PQ interval duration more than 0.24 sec or systolic BP less than 100 mm Hg); for the treatment of supraventricular tachycardia with systolic BP less than 110 mm Hg; IV administration of calcium channel blockers of the verapamil and diltiazem type; simultaneous use of MAO inhibitors; severe forms of bronchial asthma and COPD; pheochromocytoma (without simultaneous use of alpha-blockers); breastfeeding period; children under 18 years of age.

With caution

AV block I degree; Prinzmetal’s angina; COPD and mild bronchial asthma; diabetes mellitus; severe renal failure.

Use in Pregnancy and Lactation

Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. Metoprolol crosses 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 delivery date. After delivery, strict monitoring of the newborn’s condition for 48-72 hours is necessary.

It is excreted in breast milk. Contraindicated for use during breastfeeding.

Use in Hepatic Impairment

Use with caution in patients with severe liver dysfunction.

Use in Renal Impairment

Use with caution in patients with severe renal failure.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

In elderly patients, it is recommended to start treatment with a dose of 50 mg/day, as a sharp decrease in blood pressure or increasing bradycardia may be more pronounced.

Special Precautions

Use with caution in patients with chronic obstructive airway diseases, diabetes mellitus (especially with labile course), Raynaud’s disease and obliterating peripheral arterial diseases, pheochromocytoma (should be used in combination with alpha-blockers), severe renal and hepatic impairment.

During treatment with metoprolol, a decrease in tear production is possible, which is important for patients using contact lenses.

Discontinuation of a long course of metoprolol treatment should be carried out gradually (for at least 10 days) under medical supervision.

Simultaneous use of metoprolol with MAO inhibitors is not recommended.

During combination therapy with clonidine, the latter should be discontinued several days after discontinuation of metoprolol to avoid a hypertensive crisis. With simultaneous use with hypoglycemic agents, adjustment of their dosage regimen is required.

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

Influence on the ability to drive vehicles and mechanisms

For patients whose activities require increased attention, the issue of outpatient use of metoprolol should be decided only after assessing the individual patient’s response.

Drug Interactions

With simultaneous use with antihypertensive agents, diuretics, antiarrhythmic agents, nitrates, there is a risk of developing severe arterial hypotension, bradycardia, AV block.

With simultaneous use with barbiturates, the metabolism of metoprolol is accelerated, which leads to a decrease in its effectiveness.

With simultaneous use with hypoglycemic agents, the effect of hypoglycemic agents may be enhanced.

With simultaneous use with NSAIDs, the antihypertensive effect of metoprolol may be reduced.

With simultaneous use with opioid analgesics, the cardiodepressive effect is mutually enhanced.

With simultaneous use with peripheral muscle relaxants, neuromuscular blockade may be enhanced.

With simultaneous use with agents for inhalation anesthesia, the risk of myocardial function depression and development of arterial hypotension increases.

With simultaneous use with oral contraceptives, hydralazine, ranitidine, cimetidine, the concentration of metoprolol in blood plasma increases.

With simultaneous use with amiodarone, arterial hypotension, bradycardia, ventricular fibrillation, asystole are possible.

With simultaneous use with verapamil, the C_max in plasma and AUC of metoprolol increase. Cardiac output and stroke volume, heart rate, and arterial hypotension decrease. The development of heart failure, dyspnea, and sinus node block is possible.

With IV administration of verapamil against the background of metoprolol intake, there is a threat of cardiac arrest.

With simultaneous use, bradycardia caused by digitalis glycosides may be enhanced.

With simultaneous use with dextropropoxyphene, the bioavailability of metoprolol increases.

With simultaneous use with diazepam, a decrease in clearance and an increase in the AUC of diazepam are possible, which may lead to an enhancement of its effects and a decrease in the speed of psychomotor reactions.

With simultaneous use with diltiazem, the concentration of metoprolol in plasma increases due to inhibition of its metabolism under the influence of diltiazem. The effect on heart activity is additively depressed due to the slowing of impulse conduction through the AV node caused by diltiazem. There is a risk of developing severe bradycardia, a significant decrease in stroke and minute volume.

With simultaneous use with lidocaine, the excretion of lidocaine may be impaired.

With simultaneous use with mibefradil in patients with low activity of the CYP2D6 isoenzyme, an increase in the concentration of metoprolol in plasma and an increase in the risk of toxic effects are possible.

With simultaneous use with norepinephrine, epinephrine, other adreno- and sympathomimetics (including in the form of eye drops or as part of antitussives), some increase in blood pressure is possible.

With simultaneous use with propafenone, the concentration of metoprolol in 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.

With simultaneous use with reserpine, guanfacine, methyldopa, clonidine, the development of severe bradycardia is possible.

With simultaneous use with rifampicin, the concentration of metoprolol in plasma decreases.

Metoprolol may cause a slight decrease in the clearance of theophylline in smoking patients.

Fluoxetine inhibits the CYP2D6 isoenzyme, this leads to inhibition of metoprolol metabolism and its accumulation, which can enhance the cardiodepressive effect and cause bradycardia. A case of lethargy has been described.

Fluoxetine and mainly its metabolites are characterized by a long T_1/2, so the likelihood of drug interaction persists even several days after discontinuation of fluoxetine.

There are reports of a decrease in the clearance of metoprolol from the body with simultaneous use with ciprofloxacin.

With simultaneous use with ergotamine, peripheral circulatory disorders may be enhanced.

With simultaneous use with estrogens, the antihypertensive effect of metoprolol decreases.

With simultaneous use, Metoprolol increases the concentration of ethanol in the blood and prolongs its excretion.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

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.