Metokor Adifarm - instructions for use, doses, side effects, contraindications

Cardioselective beta₁-adrenergic blocker. Metoprolol has an insignificant membrane-stabilizing action and does not possess internal sympathomimetic activity. It has antihypertensive, antianginal and antiarrhythmic action.

Blocking beta₁-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect (reduces heart rate (HR), inhibits conduction and excitability, reduces myocardial contractility).

The total peripheral vascular resistance - at the beginning of beta-blockers (in the first 24 hours after ingestion) increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), which returns to the initial one after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is due to the reflex decrease in the minute volume of blood and the synthesis of renin, inhibition of the activity of the renin-angiotensin-aldosterone system (more important in patients with initial renin hypersecretion) and the central nervous system, restoration of the sensitivity of the aortic artery baroreceptors (there is no increase in their activity in response to lowering blood pressure (BP)) and ultimately reducing peripheral sympathetic influences.

The antianginal effect is determined by the decrease in myocardial oxygen demand as a result of the decrease in heart rate (diastolic elongation and improvement of myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to sympathetic innervation.

Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular (AV) of carrying out (mainly in antegrade and to a lesser extent in the retrograde direction through AV node) and on additional paths.

In contrast to nonselective beta-blockers, when given in average therapeutic doses, it has a less pronounced effect on organs containing beta₂-adrenoceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus). When used in large doses (more than 100 mg / day) has a blocking effect on both subtypes of beta adrenoreceptors.

With myocardial infarction IVI reduces the severity of chest pain, reduces the risk of flicker and atrial flutter. At the first symptoms of myocardial infarction (within 24 hours after their appearance) reduces the risk of further progression of myocardial infarction. The early onset of treatment improves the future prognosis of myocardial infarction.

With iv infusion of metoprolol for 10 min or more, the maximum effect develops after 20 minutes, the decrease in heart rate at doses of 5 and 10 mg is 10 and 15%, respectively.

Pharmacokinetics:

The time to reach the maximum concentration in the blood plasma is 20 minutes - after intravenous administration.

Connection with blood plasma proteins - 10%.

The maximum concentration is achieved in the blood plasma after 1 h after iv injection of 20 mg - 200 nmol / l.

Rapidly distributed in tissues, penetrates through the blood-brain and placental barrier. Penetrates into breast milk (concentration is higher than in blood plasma). Metabolized in the liver, 2 metabolites have beta-adrenoblocking activity. The isozyme CYP2D6 participates in the metabolism of the drug. Over 95% of the IV dose is given by the kidneys, 5% - unchanged. The half-life period is from 3 to 5 hours with IV introduction.Systemic clearance with iv injection - 1 l / min. It is not removed during hemodialysis.

A significant accumulation of metabolites is observed in patients with a creatinine clearance of 5 ml / min, while the beta-adrenergic blocking activity of the drug does not increase.

Bioavailability increases with cirrhosis of the liver, while its overall clearance decreases (patients with superimposed portocaval anastomosis have a total clearance after intravenous administration of about 300 ml / min, and the area under the concentration-time curve is 6 times higher than in healthy volunteers).

Indications:

- Nadzheludochkovaya tachycardia;

- prevention and treatment of myocardial ischemia, tachycardia and pain syndrome with myocardial infarction or with suspected of it.

Contraindications:

- Hypersensitivity to the drug or to other β-blockers;

- Acute myocardial infarction (heart rate less than 45 beats / min, PQ interval more than 0.24 s, systolic blood pressure less than 100 mmHg);

- cardiogenic shock;

- atrioventricular block II-III degree;

- syndrome of weakness of the sinus node;

- clinically significant sinus bradycardia;

- chronic heart failure (in the stage of decompensation);

- arterial hypotension (for the treatment of supraventricular tachycardia - systolic blood pressure less than 110 mm Hg);

- severe violations of peripheral circulation, threat of gangrene;

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

- pheochromocytoma (without simultaneous use of alpha-blockers);

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

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

Carefully:

AV-blockade I degrees, angina of prinzmetal, chronic obstructive pulmonary disease, diabetes mellitus, severe renal failure.

Pregnancy and lactation:

Like most drugs, Metokor Adifarm should not be administered during pregnancy and lactation, unless the expected benefit to the mother outweighs the potential risk to the fetus. Beta-blockers reduce placental blood flow, which may lead to intrauterine development, fetal death, spontaneous abortion and premature birth. When using Metocor Adipharm during pregnancy, appropriate monitoring of the patient and fetus is recommended.Like other antihypertensives, beta-blockers can cause side effects, such as bradycardia in the fetus, newborns or breastfed babies, and therefore should be especially careful when using beta-blockers in the last trimester of pregnancy and immediately before childbirth .

Metoprolol in small amounts excreted in breast milk.

Application in the lactation period is not recommended.

Dosing and Administration:

Parenteral administration of Metocor Adipharm should be carried out by specially trained personnel, with cardiorespiratory control and the possibility of resuscitation.

For arresting paroxysmal supraventricular tachycardia is administered parenterally, under hospital conditions, iv slowly in a dose of 2-5 mg (1-2 mg / min). If there is no therapeutic effect, the administration can be repeated after 5 minutes. Increasing the dose above 15 mg usually does not lead to a greater severity of the action.

After arresting an attack of arrhythmia, patients are taken to the drug inside at a dose of 50 mg 4 times a day, with the first dose being taken 15 minutes after stopping the IV.

In the acute stage of myocardial infarction immediately after hospitalization of the patient (with constant monitoring of hemodynamics: ECG, heart rate, AV conductivity, AD) should be administered iv bolus 5 mg, if necessary, the administration is repeated every 2 minutes until a total dose of 15 mg is reached.

15 minutes after the last iv administration and with good tolerability, it is necessary to appoint metoprolol for oral administration - 50 mg metoprolol every 6 hours for 2 days.

Use in patients with renal insufficiency

Correction of the dose is not required.

Use in patients with hepatic impairment

Usually, patients with cirrhosis do not undergo a dose adjustment; In case of severe liver dysfunction, a dose reduction may be necessary.

Use in elderly patients

Correction of the dose is not required.

Side effects:

The incidence of adverse events is classified according to the recommendations of the World Health Organization. To assess the frequency of cases, the following criteria were used: very often (more than 10%), often (1-10%), infrequently (0.1-1%), rarely (0.01-0.1%), very rarely (less 0.1%).

From the side of the cardiovascular system: often - bradycardia, orthostatic hypotension (including fainting), coldness of the lower limbs, a feeling of palpitations; infrequent - temporary enhancement of symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, AV blockade of I degree, edema, pain in the heart; rarely - conduction disorders, arrhythmia; very rarely - gangrene (in patients with peripheral circulatory disorders).

From the nervous system: very often - increased fatigue; often - dizziness, headache; rarely - increased nervous excitability, anxiety, impotence / sexual dysfunction; infrequently - paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, "nightmarish" dreams; very rarely - amnesia / memory disorders, depression, hallucinations.

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

From the side of the digestive tract: often - nausea, abdominal pain, constipation or diarrhea; infrequently - vomiting; rarely - dryness of the oral mucosa, impaired liver function; very rarely - hepatitis.

From the skin: infrequently - hives, increased sweating; rarely - alopecia; very rarely - photosensitivity, exacerbation of psoriasis.

From the respiratory system: often - shortness of breath with physical effort; infrequently - bronchospasm in patients with bronchial asthma; rarely rhinitis.

Other: infrequent increase in body weight; very rarely - arthralgia, thrombocytopenia.

Overdose:

Symptoms: severe severe sinus bradycardia, dizziness, AV block (up to the full development of cross-blockade and heart failure), marked reduction in blood pressure, poor peripheral perfusion, fatigue, fainting, arrhythmia, ventricular premature beats, congestive heart failure, cardiogenic shock, inhibition of lung function, sleep apnea, asystole, bronchospasm, impairment of consciousness , up to its loss, tremor, convulsions, increased sweating, paresthesia, coma, nausea, vomiting, hypo- or hyperglycemia, hyperkalemia, transient muscle weakness. The first signs of an overdose appear after 20 minutes - 2 hours after the administration of the drug.

Treatment: symptomatic.

With a marked decrease in blood pressure - the patient should be in the Trendelenburg position; in case of excessive reduction of blood pressure, bradycardia and heart failure - in / in, with an interval of 2-5 minutes,beta-adrenomimetics - to achieve the desired effect or iv in 0.5-2 mg of atropine. In the absence of a positive effect - dopamine, dobutamine or norepinephrine.

As a follow-up, it is possible to use 1-10 mg of glucagon, the setting of a transvenous intracardiac electrostimulator.

When bronchospasm should be introduced in / in stimulants beta₂-adrenomimetics. With convulsions - slow IV injection of diazepam.

Hemodialysis is ineffective.

Interaction:

Barbiturates increase metabolism of metoprolol due to the induction of microsomal liver enzymes.

Propaphenone raises the plasma concentration of metoprolol 2-5 times (probably as a result of propafenone inhibition of the isoenzyme CYP2D6).

Simultaneous iv injection of verapamil can cause bradycardia and marked decrease in blood pressure.

Class I antiarrhythmics may result in the summation of a negative inotropic effect with the development of severe hemodynamic side effects in patients with left ventricular dysfunction (this combination should be avoided in patients with sinus node weakness syndrome and violation AV conductivity).

Amiodarone - the risk of developing severe sinus bradycardia (including after a long time after the abolition of amiodarone, due to its long half-life).

Diltiazem - the risk of development of severe bradycardia (mutual enhancement of the inhibitory effect on AV conduction and sinus node function).

Antihypertensive effect weaken non-steroidal anti-inflammatory drugs (sodium retention and blockade of prostaglandin synthesis by the kidneys).

Diphenhydramine reduces the clearance of metoprolol, enhancing its effect.

Epinephrine - the risk of a pronounced decrease in blood pressure and bradycardia.

Phenylpropanolamine in high doses - a paradoxical increase in blood pressure (right up to the hypertensive crisis).

Quinidine inhibits the metabolism of metoprolol in fast acetylators, leading to a significant increase in the concentration of metoprolol in the blood plasma and enhancing its beta-adrenergic blocking effect.

Clonidine - the risk of a marked increase in blood pressure with a sharp abolition of clonidine on a background of simultaneous reception of beta-blockers, so in the case of withdrawal of clonidine, the gradual cessation of beta-blockers should start a few days before it is canceled.

Rifampicin - increases the metabolism of metoprolol, reducing the concentration in the plasma.

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.

Care should be taken when using other beta-blockers in eye drops and monoamine oxidase inhibitors.

Against the background of the use of metoprolol may require correction of doses of hypoglycemic agents for oral administration.

Cardiac glycosides increase the risk of developing a 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:

With combined therapy with clonidine, the latter should be discontinued a few days after the withdrawal of Metocor Adipharm in order to avoid a hypertensive crisis.

If it is necessary to use in patients with concomitant bronchial asthma, it is necessary to additionally apply betaa₂-adrenomimetics; at pheochromocytoma - alpha-adrenoblockers.

If it is necessary to perform a surgical procedure, the anesthesia doctor should be warned about the therapy (choice of a medicament for general anesthesia with minimal negative inotropic effect).

It is not recommended to cancel beta-blocker therapy before surgery. It should avoid the appointment of high doses of metoprolol immediately without prior titration to patients undergoing non-cardiac surgery, as in patients with cardiovascular risk factors it was associated with bradycardia, arterial hypotension and stroke, including fatal.

In patients with initial impairment AV conductivity against the background of treatment with metoprolol may be impaired (possible outcome - AV blockade). With the development of bradycardia, its dose is reduced.

Metokor Adipharm can worsen the symptoms of peripheral circulation, mainly due to lower blood pressure.

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

Patients taking beta-blockers should not be injected with iv BMPC of verapamil type (see section "Contraindications").

In patients with chronic heart failure in the stage of decompensation, it is necessary to achieve a compensation stage both before and during therapy with the drug.

Patients with angina prinzmetal, it is not recommended to appoint non-selective beta-blockers.

Care should be taken when using the drug in patients with severe renal failure, with metabolic acidosis, concomitant use with cardiac glycosides.

In patients taking beta-adrenoblockers, anaphylactic shock occurs in a more severe form.

If the systolic blood pressure is below 100 mm Hg, metoprolol should be administered iv only if special precautions are observed, since with this route of administration, there is a risk of further reduction in blood pressure (for example, in patients with arrhythmias).

When treating patients with confirmed myocardial infarction or suspected of it, it is necessary to assess the patient's hemodynamic status after each of the three 5 mg doses administered.

With the use of beta-blockers, the risk of their effect on carbohydrate metabolism or the possibility of masking hypoglycemia is significantly less than when using non-selective beta-blockers.

Effect on the ability to drive transp. cf. and fur:

Since dizziness and weakness may develop during application, caution should be exercised when driving vehicles and working with potentially dangerous mechanisms.

Form release / dosage:

Solution for intravenous administration, 1 mg / ml.

Packaging:

5 ml of solution in an ampoule.

10 ampoules per blister.

1 blister with instructions for use in a cardboard package.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000022

Date of registration:01.11.2010 / 04.03.2016

Expiration Date:Unlimited

The owner of the registration certificate:Adifarm, EADAdifarm, EAD Bulgaria

Manufacturer: & nbsp

ADIPHARM, EAD Bulgaria

Representation: & nbspADIFARMADIFARMBulgaria

Information update date: & nbsp09.05.2018

Illustrated instructions

Instructions

Metocor Adipharm (Metocor Adipharm)