Metoprolol - instructions for use, dose, side effects, contraindications

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

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

A decrease in the frequency of cardiac abbreviations (HR) with paroxysmal tachycardia and flicker (trembling) of the atria.

Metoprolol - β₁-adrenoblocker blocking β₁-receptors at doses significantly lower than the doses required to block p₂receptors. Metoprolol has an insignificant membrane-stabilizing effect and does not show activity of a partial agonist. Metoprolol reduces or inhibits agonistic action, which has on the cardiac activity catecholamines, formed with nervous and physical stress. It means that metoprolol has the ability to prevent an increase in heart rate, minute volume and increased myocardial contractility, as well as an increase in blood pressure (BP) caused by a sharp release of catecholamines.

Patients with symptoms of obstructive pulmonary disease, if necessary, can be prescribed metoprolol in combination with β₂-adrenomimetics. When combined with β₂-adrenomimetics metoprolol, in therapeutic doses, to a lesser extent affects the induced β₂-adrenomimetics bronchodilation, than non-selective β-adrenoblockers.

Metoprolol is less likely than non-selective β- adrenoblockers, affects insulin production and carbohydrate metabolism. Effect of the drug Metoprolol on the reaction of the cardiovascular system (CCS) under conditions of hypoglycemia is much less pronounced in comparison with non-selective β-adrenoblockers. Improving the quality of life in the treatment of the drug Metoprolol observed in patients after myocardial infarction.

Pharmacokinetics:

Metoprolol undergoes oxidative metabolism in the liver with the formation of three major metabolites, none of which has a clinically significant βblocking effect. About 5% of the dose is excreted unchanged in the urine. The average half-life of metoprolol from plasma is about 3-5 hours.

Indications:

- Nadzheludochkovaya tachycardia;

- prevention and treatment of myocardial ischemia, tachycardia and pain in case of myocardial infarction or suspected of it.

Contraindications:

- Atrioventricular blockade of II and III degree,heart failure in the decompensation stage, clinically significant sinus bradycardia, sinus node weakness syndrome (except for patients with a constant pacemaker), cardiogenic shock, severe peripheral circulation disorders, including those with a gangrene threat, arterial hypotension;

- metoprolol is contraindicated in patients with suspected acute myocardial infarction at a heart rate of less than 45 beats per minute, interval PQ more than 0.24 seconds or systolic blood pressure less than 100 mm Hg;

- known hypersensitivity to metoprolol and its components or to other β-blockers;

- in the treatment of supraventricular tachycardia in patients with systolic blood pressure less than 110 mm Hg;

- patients receiving β- adrenoblockers, intravenous administration of blockers of "slow" calcium channels such as verapamil is contraindicated;

- permanent or intermittent therapy with inotropic drugs acting as β-adrenomimetics;

- age to 18 years (efficacy and safety not established).

Carefully:

- Atrioventricular block of the 1st degree;

- angina of Prinzmetal;

- chronic obstructive pulmonary disease (emphysema, chronic obstructive bronchitis, bronchial asthma);

- diabetes;

- severe renal failure.

Pregnancy and lactation:

Pregnancy

Like most drugs, Metoprolol should not be prescribed during pregnancy and during breastfeeding, except when the expected benefit to the mother exceeds the potential risk to the fetus. β-adrenoconjugators reduce placental blood flow, which can lead to a delay in intrauterine development, intrauterine fetal death, spontaneous miscarriage and premature birth. In the case of using the drug Metoprolol during pregnancy, it is recommended that appropriate monitoring of the patient and fetus is performed. Like other antihypertensives, β-blockers can cause side effects, such as bradycardia in the fetus, newborns, or breast-fed infants, and therefore should be particularly careful when prescribing p- adrenoblockers in the last trimester of pregnancy and immediately before childbirth.

Breastfeeding period

The amount of metoprolol released into breast milk and the β-blocking effect of the infant breastfed (when taking Metoprolol's mother in therapeutic doses) are minor.

Dosing and Administration:

Nadzheludochkovaya tachycardia

Begin the administration with 5 mg (5 ml) of the drug Metoprolol at a rate of 1-2 mg / min. You can repeat the introduction with a 5-minute interval until the therapeutic effect is achieved. Usually the total dose is 10-15 mg (10-15 ml). The recommended maximum dose for intravenous administration is 20 mg (20 ml).

Prophylaxis and treatment of myocardial ischemia, tachycardia and pain with or suspected of myocardial infarction

Intravenous 5 mg (5 ml) of the drug. You can repeat the introduction with a 2-minute interval, the maximum dose is 15 mg (15 ml). 15 minutes after the last injection, Metoprolol for oral administration at a dose of 50 mg every 6 hours for 48 hours.

Impaired renal function

There is no need to adjust the dose in patients with impaired renal function.

Impaired liver function

Usually, due to the low degree of association with plasma proteins, dose adjustment is not required.However, in severe violations of the liver (in patients with portocaval anastomosis), a dose reduction may be required.

Elderly age

There is no need to adjust the dose in elderly patients.

Side effects:

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

As a result of clinical studies or with the use of the drug Metoprolol the following undesirable side effects have been described in clinical practice. In many cases, a causal relationship with drug treatment Metoprolol was not installed.

Classification of WHO adverse adverse reactions according to the frequency of development: Often >1/10; often 1/10 - 1/100; infrequently 1/100 - 1/1000; rarely 1/1000 - 1/10000; rarely <1/10000, including individual messages.

From the CCC side: often - bradycardia, postural disorders (very rarely accompanied by a syncope), cold feeling of the limbs, palpitation; infrequently - a temporary increase in cardiac symptoms deficiency, cardiogenic shock in patients with acute myocardial infarction; atrioventricular blockade of I degree, edema, pain in the heart; rarely - Other disorders of cardiac conduction, arrhythmia; rarely - gangrene in patients with previous severe impairment of peripheral circulation.

From the side of the central nervous system: very often - increased fatigue; often - dizziness, headache; infrequently - paresthesia, convulsions, depression, loss of attention, drowsiness or insomnia, nightmares; rarely - increased excitability, anxiety; rarely - Amnesia / memory disorders, depression, hallucinations.

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

On the part of the skin: infrequently - rash (in the form of urticaria), increased sweating; rarely - alopecia; rarely - photosensitivity, exacerbation of psoriasis.

From the respiratory system: often - shortness of breath when exercising; infrequently - bronchospasm in patients with bronchial asthma; rarely - Rhinitis.

From the senses: rarely - visual impairment, dryness and / or eye irritation, conjunctivitis; rarely - ringing in the ears, a violation of taste.

From the side of metabolism: infrequently - increase in body weight.

From the musculoskeletal system: very rarely - arthralgia.

On the part of the organs of hematopoiesis: very rarely - thrombocytopenia.

Other: rarely impotence / sexual dysfunction.

Overdose:

Symptoms

In case of metoprolol overdose, a marked decrease in blood pressure, acute heart failure, bradycardia, bradyarrhythmia, intracardiac conduction disorder and bronchospasm may be noted.

Treatment

Treatment should be carried out in a medical institution that has the equipment and conditions to support vital activity and monitor the patient's condition.

With bradycardia and conduction disorders apply atropine and adrenomimetics, if necessary - install an artificial pacemaker.

With a pronounced decrease in blood pressure, acute heart failure, and shock, follow therapy aimed at increasing the volume of circulating blood plasma; use glucagon in the form of injection (then, if necessary, enter glucagon in the form of intravenous infusion); intravenously administer adrenomimetics (such as dobutamine) together with α1-adrenomimetics in case of symptoms of vasodilation. It is also possible intravenous administration of drugs containing calcium ions.

To stop bronchospasm, bronchodilators should be used.

Interaction:

It is necessary to avoid co-administration of the drug Metoprolol with the following preparations:

Derivatives of barbituric acid: barbiturates (the study was conducted with phenobarbital) slightly increase metabolism of metoprolol, due to the induction of enzymes.

Propaphenon: it is possible to increase the plasma concentration of metoprolol by 2-5 times and the development of side effects characteristic of metoprolol. Probably, the interaction is due to the inhibition of propafenone, like quinidine, metoprolol metabolism through the cytochrome system P4502D6. Taking into account the fact that propafenone has the properties of β-blocker, the joint appointment of metoprolol and propafenone is not advisable.

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

Combination of the drug Metoprolol with the following drugs may require dose adjustment:

Class I antiarrhythmic drugs: Class I antiarrhythmics and beta-adrenoblockers can lead to a summation of the negative inotropic effect, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. Also, this combination should be avoided in patients with sinus node weakness syndrome and atrioventricular conduction disorder. The interaction is described by the example of disopyramide.

Amiodarone: The combined use of amiodarone and metoprolol can lead to severe sinus bradycardia. Taking into account the extremely long half-life of amiodarone (50 days), possible interaction should be considered after a long time after amiodarone withdrawal.

Diltiazem: Diltiazem and βadrenoblockers mutually enhance the inhibitory effect on atrioventricular conduction and sinus node function.In the combination of metoprolol with diltiazem, cases of severe bradycardia were noted.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs weaken the antihypertensive effect βadrenoblockers. This interaction is most documented for indomethacin and celecoxib. There was no marked interaction for sulindac. In the studies with diclofenac, the described reaction was not noted.

Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to α-hydroxymethoprolol by a factor of 2.5. At the same time there is an increase in the effect of metoprolol.

Epinephrine (adrenaline): the development of severe arterial hypertension and bradycardia in patients taking non-selective β-blockers (including pindolol and propranolol) and received epinephrine (adrenalin). It is assumed that similar reactions may occur and the application of epinephrine with local anesthetic together with a random contact with the bloodstream. It is assumed that this risk is much lower with the use of cardioselective β-adrenoblockers.

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, β-adrenoblockers can cause reactions of paradoxical arterial hypertension in patients receiving high doses of phenylpropanolamine. Perhaps the development of hypertensive crisis against the background of the use of phenylpropanolamine.

Quinidine: Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden about 90% of the population), mainly causing a significant increase in plasma concentrations of metoprolol and an increase in β-blockade. It is believed that this interaction is characteristic of other β-adrenoblockers in the metabolism of which cytochrome participates P4502D6.

Clonidine: Hypertensive reactions with abrupt cancellation of clonidine can be enhanced by joint admission of β-blockers. When combined, in the case of the withdrawal of clonidine, discontinuation of the adrenoblockers should be started several days before the withdrawal of clonidine.

Rifampicin: Rifampicin can enhance the metabolism of metoprolol, decreasing the plasma concentration of metoprolol.

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

Drugs for inhalation anesthesia increase the cardiodepressive effect of metoprolol.

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

Against the background of admission of β-adrenoblockers, inhalation anesthetics increase the cardiodepressive effect.

Against the background of taking beta-adrenoblockers, patients receiving oral hypoglycemic agents may require a dose adjustment of the latter. Cardiac glycosides when used together with βadrenoblockers can increase the time of atrioventricular conduction and cause bradycardia. Allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving metoprolol.

Iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions.

Special instructions:

Patients taking beta-adrenoblockers should not be administered intravenously blockers of "slow" calcium channels like verapamil.

Patients with bronchial asthma or chronic obstructive pulmonary disease should be assigned concomitant therapy with β₂-adrenomimetics. If necessary, increase the dose of β₂-adrenomimetics. When applying β₁adrenoblockers, the risk of their effect on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly less than with the use of nonselective β-blockers.

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

Very rarely, patients with impaired atrioventricular conduction may experience deterioration (a possible outcome is an atrioventricular block). If bradycardia develops against the background of treatment, the dose of metoprolol should be reduced. Metoprolol can increase the disturbance of peripheral arterial blood circulation mainly due to lowering blood pressure.Caution should be exercised in prescribing patients suffering from severe renal failure, metabolic acidosis, co-administration with cardiac glycosides. In patients taking beta-adrenoblockers, anaphylactic shock occurs in a more severe form. Patients with pheochromocytoma simultaneously with the drug Metoprolol should be prescribed alpha-blocker. In case of surgery, the anesthetist should be informed that the patient is taking a β-blocker. It is not recommended to cancel therapy β-adrenergic blocker before the operation. In patients with risk factors for CCC disease, high doses of metoprolol should be avoided, without prior titration of the dose in surgical interventions (with the exception of heart surgery), because of the risk of bradycardia, arterial hypotension and stroke, including fatalities.

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

When treating patients with myocardial infarction or suspected of it, it is necessary to evaluate the main parameters of hemodynamics after each injection of the drug at a dose of 5 mg (see section "Method of administration and dose").

Do not prescribe a second dose - the second or third at a heart rate of less than 40 beats / min, the interval PQ more than 0.26 seconds. and systolic blood pressure less than 90 mm Hg. st., as well as with increased dyspnea or the appearance of cold sweat.

Effect on the ability to drive transp. cf. and fur:Evaluation of drug effect Metoprolol at intravenous introduction on ability to operate vehicles and other mechanisms it was not studied.

Form release / dosage:

Solution for intravenous administration, 1 mg / ml.

Packaging:

5 ml of the drug in ampoules of colorless glass.

5 ampoules per contour cell packaging made of polyvinylchloride film and aluminum foil.

1 or 2 contourcell packs with instructions for use in a pack of cardboard or 20, 50 or 100 contour squares, together with an equal number of instructions for use, respectively, in a cardboard box or corrugated cardboard box (for inpatient).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004520

Date of registration:31.10.2017

Expiration Date:31.10.2022

The owner of the registration certificate:Endocrine technologies, LLCEndocrine technologies, LLC Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp23.11.2017

Illustrated instructions

Instructions

Metoprolol (Metoprolol)