Metoprolol, 1 mg/ml 5 pcs 5 pcs

Pharmacotherapeutic group:

β1-adrenoblocker selective

ATX:

C.07.A.B Selective beta1-adrenoblockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

In patients with myocardial infarction, intravenous metoprolol reduces chest pain and reduces the risk of atrial fibrillation and flutter. Intravenous metoprolol administration at the first symptoms (within 24 hours of the appearance of the first symptoms) reduces the risk of myocardial infarction.

Early initiation of metoprolol treatment leads to an improved further prognosis of myocardial infarction treatment.

A reduction in heart rate (HR) in paroxysmal tachycardia and atrial fibrillation (flutter) is achieved.

Metoprolol is a β1-adrenoblocker that blocks β1-receptors at doses significantly lower than those required to block p2-receptors. Metoprolol has little membrane-stabilizing effect and no partial agonist activity. Metoprolol reduces or inhibits the agonist effect that catecholamines produced by nervous and physical stress have on cardiac activity.

This means that metoprolol has the ability to inhibit the increase in heart rate, minute volume and myocardial contractility, as well as the rise in blood pressure (BP) caused by the sudden release of catecholamines.

Patients with symptoms of obstructive lung disease may be prescribed metoprolol in combination with β2-adrenomimetics if necessary. When co-administration with β2-adrenomimetics, metoprolol, in therapeutic doses, has less effect on bronchodilation induced by β2-adrenomimetics than non-selective β-adrenoblockers.

Metoprolol has less effect than non-selective β-adrenoblockers on insulin production and carbohydrate metabolism. The effect of Metoprolol on the response of the cardiovascular system (CVS) in hypoglycemia is significantly less pronounced compared to non-selective β-adrenoblockers. Improved quality of life during treatment with Metoprolol was observed in patients after myocardial infarction.

Pharmacokinetics:

Metoprolol undergoes oxidative metabolism in the liver with the formation of three main metabolites, none of which has clinically significant β-blocking effect. About 5% of the administered dose is excreted unchanged in the urine. The average blood plasma elimination half-life of metoprolol is about 3-5 hours.

Indications

Supraventricular tachycardia;

prevention and treatment of myocardial ischemia, tachycardia and pain during myocardial infarction or suspicion of it.

Pharmacological effect

Pharmacotherapeutic group:

Selective β1-blocker

ATX:

C.07.A.B Selective beta1-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

In patients with myocardial infarction, intravenous metoprolol reduces chest pain and reduces the risk of developing atrial fibrillation and flutter. Intravenous administration of metoprolol at the first symptoms (within 24 hours after the onset of the first symptoms) reduces the risk of myocardial infarction.

Early initiation of treatment with metoprolol leads to an improvement in the further prognosis of treatment of myocardial infarction.

A reduction in heart rate (HR) is achieved during paroxysmal tachycardia and atrial fibrillation (flutter).

Metoprolol is a β1-blocker that blocks β1 receptors in doses significantly lower than the doses required to block β2 receptors. Metoprolol has a slight membrane-stabilizing effect and does not exhibit partial agonist activity. Metoprolol reduces or inhibits the agonistic effect that catecholamines, produced during nervous and physical stress, have on cardiac activity.

This means that metoprolol has the ability to prevent an increase in heart rate, minute volume and increased myocardial contractility, as well as a rise in blood pressure (BP) caused by a sudden release of catecholamines.

Patients with symptoms of obstructive pulmonary diseases, if necessary, can be prescribed metoprolol in combination with β2-agonists. When used together with β2-adrenergic agonists, metoprolol, in therapeutic doses, has a lesser effect on the bronchodilation caused by β2-adrenergic agonists than non-selective β-blockers.

Metoprolol affects insulin production and carbohydrate metabolism to a lesser extent than non-selective β-blockers. The effect of Metoprolol on the response of the cardiovascular system (CVS) under conditions of hypoglycemia is significantly less pronounced compared to non-selective β-blockers. An improvement in the quality of life during treatment with Metoprolol was observed in patients after myocardial infarction.

Pharmacokinetics:

Metoprolol undergoes oxidative metabolism in the liver to produce three major metabolites, none of which have a clinically significant beta-blocking effect. About 5% of the dose taken is excreted unchanged in the urine. The average half-life of metoprolol from blood plasma is about 3-5 hours.

Special instructions

Patients taking β-blockers should not receive intravenous calcium channel blockers such as verapamil.

Patients with bronchial asthma or chronic obstructive pulmonary disease should be prescribed concomitant therapy with β2-agonists. If necessary, the dose of β2-adrenergic agonist should be increased.

When using β1-blockers, the risk of their influence on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly less than when using non-selective β-blockers.

In patients with chronic heart failure in the stage of decompensation, it is necessary to achieve a stage of compensation both before and during treatment with the drug. Non-selective β-blockers are not recommended for patients with Prinzmetal’s angina.

Very rarely, patients with impaired atrioventricular conduction may experience deterioration (a possible outcome is atrioventricular block). If bradycardia develops during treatment, the dose of metoprolol should be reduced.

Metoprolol may increase peripheral arterial circulatory disorders, mainly due to a decrease in blood pressure. Caution should be exercised when prescribing the drug to patients suffering from severe renal failure, metabolic acidosis, and co-administration with cardiac glycosides.

In patients taking β-blockers, anaphylactic shock occurs in a more severe form. Patients with pheochromocytoma should be prescribed an alpha-blocker simultaneously with Metoprolol. In case of surgery, the anesthesiologist should be informed that the patient is taking a beta-blocker.

It is not recommended to discontinue β-blocker therapy before surgery. In patients with risk factors for developing cardiovascular diseases, high doses of metoprolol should be avoided without prior titration of the dose during surgical interventions (except for heart surgery), due to the risk of bradycardia, arterial hypotension and stroke, including death.

If systolic blood pressure is below 100 mm Hg. Art., Metoprolol should be administered intravenously only if special precautions are taken due to the risk of developing a more pronounced decrease in blood pressure (for example, in patients with arrhythmias).

When treating patients with myocardial infarction or suspicion of it, it is necessary to evaluate the main hemodynamic parameters after each administration of the drug at a dose of 5 mg (see section “Dosage and Administration”).

A repeat dose should not be prescribed – the second or third dose if the heart rate is less than 40 beats/min, the PQ interval is more than 0.26 seconds. and systolic blood pressure less than 90 mm Hg. Art., as well as with increased shortness of breath or the appearance of cold sweat.

Impact on the ability to drive vehicles. Wed and fur.:

The effect of intravenous Metoprolol on the ability to drive vehicles and operate machinery has not been studied.

Active ingredient

Metoprolol

Composition

1 ml of solution contains:

Active ingredient:

Metoprolol tartrate – 1.0 mg.

Excipients:

Sodium chloride – 9.0 mg,

Water for injection – up to 1 ml.

Pregnancy

Pregnancy

Like most drugs, Metoprolol should not be prescribed during pregnancy and breastfeeding, unless the expected benefit to the mother outweighs the potential risk to the fetus. β-blockers reduce placental blood flow, which can lead to intrauterine growth retardation, intrauterine fetal death, spontaneous miscarriage and premature birth.

If Metoprolol is used during pregnancy, it is recommended to carry out appropriate monitoring of the condition of the patient and the fetus.

Like other antihypertensive drugs, beta-blockers can cause side effects, such as bradycardia in the fetus, newborns or breastfed children, and therefore special care should be taken when prescribing beta-blockers in the last trimester of pregnancy and immediately before birth.

Breastfeeding period

The amount of metoprolol excreted in breast milk and the β-blocking effect in a breastfed child (when the mother takes Metoprolol in therapeutic doses) are negligible.

Contraindications

Atrioventricular block II and III degrees, heart failure in the stage of decompensation, clinically significant sinus bradycardia, sick sinus syndrome (except for patients with a permanent pacemaker), cardiogenic shock, severe peripheral circulatory disorders, including the threat of gangrene, arterial hypotension;
metoprolol is contraindicated in patients with suspected acute myocardial infarction with a heart rate of less than 45 beats per minute, a PQ interval of more than 0.24 seconds, or a systolic blood pressure of less than 100 mmHg;
known hypersensitivity to metoprolol and its components or to other beta-blockers;
in the treatment of supraventricular tachycardia in patients with systolic blood pressure less than 110 mmHg;
In patients receiving β-blockers, intravenous administration of “slow” calcium channel blockers such as verapamil is contraindicated;
continuous or intermittent therapy with inotropic drugs acting as β-adrenergic agonists;
age under 18 years (efficacy and safety have not been established).
With caution:
First degree atrioventricular block;
Prinzmetal’s angina;
chronic obstructive pulmonary disease (pulmonary emphysema, chronic obstructive bronchitis, bronchial asthma);
diabetes mellitus;
severe renal failure.

Side Effects

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

As a result of clinical studies or when using the drug Metoprolol in clinical practice, the following undesirable side effects were described. In many cases, a causal relationship with treatment with Metoprolol has not been established.

WHO classification of adverse reactions by frequency of development: very often >1/10; often 1/10 – 1/100; infrequently 1/100 – 1/1000; rarely 1/1000 – 1/10000; very rare <1/10000, including isolated reports.From the cardiovascular system: often – bradycardia, postural disturbances (very rarely accompanied by fainting), a feeling of coldness in the extremities, a feeling of palpitations; uncommon – temporary increase in symptoms of heart failure, cardiogenic shock in patients with acute myocardial infarction; 1st degree atrioventricular block, swelling, pain in the heart area; rarely – other cardiac conduction disorders, arrhythmias; very rarely – gangrene in patients with previous severe peripheral circulatory disorders.From the central nervous system: very often – increased fatigue; often – dizziness, headache; uncommon – paresthesia, convulsions, depression, loss of attention, drowsiness or insomnia, nightmares; rarely – increased excitability, anxiety; very rarely – amnesia/memory impairment, depression, hallucinations.From the digestive system: often – nausea, abdominal pain, diarrhea, constipation; infrequently – vomiting; rarely – dryness of the oral mucosa, liver dysfunction; very rarely – hepatitis.From the skin: infrequently – rash (in the form of urticaria), increased sweating; rarely – alopecia; very rarely – photosensitivity, exacerbation of psoriasis.From the respiratory system: often – shortness of breath on exertion; uncommon – bronchospasm in patients with bronchial asthma; rarely – rhinitis.From the senses: rarely – visual disturbances, dryness and/or irritation of the eyes, conjunctivitis; very rarely – ringing in the ears, disturbances of taste.From the side of metabolism: infrequently – weight gain.From the musculoskeletal system: very rarely – arthralgia.From the hematopoietic organs: very rarely – thrombocytopenia.Other: rarely – impotence/sexual dysfunction.

Interaction

Co-administration of Metoprolol with the following drugs should be avoided:

Barbituric acid derivatives: barbiturates (study conducted with phenobarbital) slightly increase the metabolism of metoprolol due to enzyme induction.

Propafenone: it is possible to increase the plasma concentration of metoprolol by 2-5 times and develop side effects characteristic of metoprolol. The interaction is likely due to propafenone’s inhibition, like quinidine, of the metabolism of metoprolol via the cytochrome P4502D6 system.

Taking into account the fact that propafenone has the properties of a β-blocker, the joint administration of metoprolol and propafenone does not seem appropriate.

Verapamil: The combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and p-blockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.

The combination of Metoprolol with the following drugs may require dose adjustment:

Class I Antiarrhythmics: Class I antiarrhythmics and β-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and atrioventricular conduction disorder.

The interaction is described using disopyramide as an example.

Amiodarone: Concomitant use of amiodarone and metoprolol may result in severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), possible interactions should be considered long after discontinuation of amiodarone.

Diltiazem: Diltiazem and β-blockers mutually enhance the inhibitory effect on atrioventricular conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.

Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs reduce the antihypertensive effect of beta-blockers. This interaction is best documented for indomethacin and celecoxib. There is no reported interaction observed for sulindac. In studies with diclofenac, the described reaction was not observed.

Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.

Epinephrine (adrenaline): Severe hypertension and bradycardia may develop in patients taking non-selective beta-blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed.

This risk is expected to be much lower with cardioselective β-blockers.

Phenylpropanolamine: Phenylpropanolamine (norephedrine) in a single dose of 50 mg may cause an increase in diastolic blood pressure. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers may cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. It is possible to develop a hypertensive crisis while taking phenylpropanolamine.

Quinidine: Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden, approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased β-blockade. It is believed that a similar interaction is typical for other β-blockers in the metabolism of which cytochrome P4502D6 is involved.

Clonidine: Hypertensive reactions following abrupt discontinuation of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, in case of discontinuation of clonidine, discontinuation of β-blockers should begin several days before discontinuation of clonidine.

Rifampicin: Rifampicin may increase the metabolism of metoprolol, decreasing plasma concentrations of metoprolol.

Cimetidine, hydralazine, selective serotonin reuptake inhibitors (including paroxetine, fluoxetine, sertraline) increase the concentration of metoprolol in the blood plasma.

Medicines for inhalation anesthesia enhance the cardiodepressive effect of metoprolol.

Patients concomitantly taking metoprolol and other β-blockers (eye drops) or monoamine oxidase inhibitors (MAOIs) should be closely monitored.

When taking β-blockers, inhalational anesthetics enhance the cardiodepressive effect.

While taking β-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.

Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia. Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving metoprolol.

Iodine-containing x-ray contrast agents for intravenous administration increase the risk of anaphylactic reactions.

Overdose

Symptoms

In case of an overdose of metoprolol, a pronounced decrease in blood pressure, acute heart failure, bradycardia, bradyarrhythmia, intracardiac conduction disturbance and bronchospasm may be observed.

Treatment

Treatment should be carried out in a medical facility that has the equipment and conditions to support vital functions and monitor the patient’s condition.

For bradycardia and conduction disturbances, atropine and adrenergic agonists are used, and, if necessary, an artificial pacemaker is installed.

With a pronounced decrease in blood pressure, acute heart failure and shock, therapy should be carried out aimed at increasing the volume of circulating blood plasma; use glucagon by injection (then, if necessary, administer glucagon by intravenous infusion); Adrenergic agonists (such as dobutamine) should be administered intravenously along with α1-agonists if symptoms of vasodilation occur. Intravenous administration of drugs containing calcium ions is also possible.

To relieve bronchospasm, bronchodilators should be used.

Manufacturer

Moscow Endocrine Plant, Russia