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

Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, silicon dioxide methylated, povidone K 25, silicon dioxide colloid, calcium stearate, sodium carboxymethyl starch.

Description:

Round, flat tablets from white to white with a creamy shade of color with a facet, and a risk on one side. Light marble is allowed.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

Metoprolol refers to cardioselective blockers of β-adrenergic receptors that do not possess internal sympathomimetic activity and membrane-stabilizing properties. Has antihypertensive, anti-anginal and antinhythmic action. Blocking in low doses β₁-adrenoceptors of the heart, reduces the 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 action (urezhaet heart rate (heart rate), inhibits conduction, excitability and reduces myocardial contractility).

The total peripheral vascular resistance at the beginning of the use of β-blockers (within the first 24 hours after ingestion) increases (as a result of the reciprocal increase in activity α-adrenoceptors and removal of stimulation β₂- adrenoreceptors), which after 1-3 days returns to the original, and for a long-term administration - decreases.

The hypotensive effect is due to a decrease in cardiac output and renin synthesis in the kidneys,inhibition of the activity of the renin-angiotensin system (more important in patients with initial renin hypersecretion) and the central nervous system, restoration of the sensitivity of the aortic arch baroreceptors (there is no increase in their activity in response to a decrease in arterial pressure) and, ultimately, a decrease in peripheral sympathetic influences. Reduces elevated blood pressure (BP) at rest, with physical stress and stress.

The hypotensive effect develops rapidly (systolic blood pressure decreases after 15 minutes, maximum after 2 hours) and lasts for 6 hours, the diastolic blood pressure changes more slowly: a stable decrease is observed after several weeks of regular intake of the drug.

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. Reduces the number and severity of angina attacks and increases exercise tolerance.

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

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and hyperthyroidism, the heart rate decreases or even lead to the restoration of sinus rhythm.

Prevents the development of migraine.

When used in average therapeutic doses, in contrast to non-selective β-adrenoblockers, it exerts a less pronounced effect on organs containing β₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism.

When used in large doses (more than 100 mg / day) has a blocking effect on both subtypes βadrenoreceptors.

Pharmacokinetics:

Absorption when taken orally is complete (95%). The maximum concentration in the blood plasma is achieved 1-2 hours after ingestion. The half-life period on the average is 3.5 hours (ranging from 1 hour to 9 hours).It is subjected to intensive presystemic metabolism, bioavailability is 50% at the first ingestion and increases to 70% at repeated application. Eating increases bioavailability by 20-40%. Bioavailability of metoprolol increases with cirrhosis of the liver. Connection with blood plasma proteins - 10%. Penetrates through the blood-brain and placental barrier. Excreted in breast milk in small amounts. Metabolized in the liver, 2 metabolites possess β-adrenergic blocking activity. In the metabolism of the drug takes part isoenzyme CYP2D6. About 5% the drug is excreted unchanged by the kidneys.

Treatment of patients with reduced renal function does not require dose adjustment.

Disturbance of liver function slows the metabolism of the drug, and in cases of insufficient liver function, the dose of the drug should be reduced.

e is removed during hemodialysis.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);

- functional disorders of cardiac activity accompanied by tachycardia;

- ischemic heart disease: myocardial infarction (secondary prevention - complex therapy), prevention of angina attacks;

- heart rhythm disturbances (supraventricular tachycardia, ventricular extrasystole);

- hyperthyroidism (complex therapy);

- prevention of migraine attacks.

Contraindications:

- Hypersensitivity to metoprolol or other components of the drug, other β-blockers;

- cardiogenic shock;

- AV blockade II - III degree (without artificial pacemaker);

- sinoatrial (SA) blockade;

- syndrome of weakness of the sinus node (SSSU);

- sinus bradycardia (heart rate less than 50 beats per minute);

- chronic heart failure in the stage of decompensation;

- angina of Prinzmetal;

- arterial hypotension (in case of use in secondary prevention of myocardial infarction - systolic blood pressure less than 100 mmHg heart rate less than 45 beats / min);

- acute myocardial infarction (heart rate less than 45 beats per minute, interval PQ more than 0.25 seconds, systolic blood pressure less than 100 mm Hg);

- hereditary diseases such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose in the composition);

- lactation period (see section "Pregnancy and lactation period");

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- simultaneous intravenous administration of blockers of "slow" calcium channels (BCCC) of veralamsht type (see Fig.section "Interaction with other drugs");

- age under 18 years (effectiveness and safety not established);

- pheochromocytoma (without simultaneous use αadrenoblockers);

- marked violations of peripheral circulation.

Carefully:FROMdiabetes mellitus, metabolic acidosis, impaired hepatic function, kidney function (creatinine clearance less than 40 ml / min), myasthenia gravis, AV blockade of the first degree, thyrotoxicosis, depression (including history), psoriasis, allergic reactions in the anamnesis (it is possible to increase sensitivity to allergens, weighty arterial hypertension and reduce the therapeutic response to adrenaline), bronchial asthma, chronic obstructive pulmonary disease, emphysema, chronic obstructive bronchitis, obliterating peripheral vascular diseases ("intermittent" lameness, Raynaud's syndrome), elderly age.

Pregnancy and lactation:

In pregnancy Metoprolol Zentiva is prescribed according to strict indications if the intended benefit for the mother exceeds the potential risk for the fetus (due to the possible development of fetal bradycardia, arterial hypotension, hypoglycemia).At the same time, careful monitoring is carried out, especially for fetal development. Strict monitoring of newborns is necessary within 48-72 hours after delivery.

If taking Metoprolol Zentiva is necessary during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Tablets are taken orally at the same time as eating or immediately after eating, the tablets can be divided in half, but not chewed and washed down with liquid.

Arterial hypertension

The initial daily dose is 50-100 mg in 1-2 doses (morning and evening). With insufficient therapeutic effect, the daily dose can be gradually increased to 100-200 mg and / or additionally prescribed other antihypertensive agents. The maximum daily dose is 200 mg.

Secondary prevention of myocardial infarction 200 mg per day in two divided doses (morning and evening).

Angina pectoris, arrhythmia, prevention of migraine attacks

100-200 mg per day in two divided doses (morning and evening).

Functional disorders of cardiac activity, accompanied by tachycardia

100 mg per day in two divided doses (morning and evening).

With hyperthyroidism

150-200 mg per day in 3-4 divided doses.

In elderly patients, with violations of kidney function (CC less than 40 ml / min), and if hemodialysis is necessary, the dose is not changed.

When expressed violations of liver function the dose of the drug should be reduced depending on the clinical condition.

Side effects:

Side effects depend on the individual sensitivity of the patient. Usually they are minor and disappear after the drug is discontinued.

From the nervous system: increased fatigue, weakness, headache, slowing of the speed of mental and motor reactions, convulsions, paresthesia in the extremities (in patients with "intermittent claudication" and Raynaud's syndrome), depression, anxiety, depression, increased nervous excitability, anxiety, decreased concentration, drowsiness, insomnia, "nightmarish dreams", confusion, amnesia or short-term memory impairment, hallucinations, muscle weakness.

From the sense organs: decreased vision, decreased secretion of tear fluid, dryness and soreness of the eyes, conjunctivitis, tinnitus.

From the side of the cardiovascular system: sinus bradycardia, palpitations, marked decrease in blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness), cardiogenic shock in patients with myocardial infarction, AV blockade of the first degree, reduction of myocardial contractility, temporary worsening of symptoms of chronic heart failure (edema of the feet and / or lower legs, shortness of breath), arrhythmias, angiospasm manifestation (increased peripheral circulation disturbance, lower extremities cooling, Raynaud's syndrome, gangrene) .

From the digestive system: nausea, vomiting, abdominal pain, dryness of the oral mucosa, diarrhea, constipation, taste change, hepatitis, a violation of liver function.

From the skin: urticaria, skin itch, rash, exacerbation of psoriasis, psoriasis-like skin reactions, skin hyperemia, exanthema, photodermatosis, increased sweating, reversible alopecia.

From the respiratory system: nasal congestion, rhinitis, difficulty exhaling (bronchospasm in high doses - loss of selectivity and / or in predisposed patients), dyspnea.

From the endocrine system: hypo-, hyperglycemia (rarely) in patients with type I diabetes mellitus.

Laboratory indicators: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of "hepatic enzymes," hyperbilirubinemia.

Influence on the fetus: possible intrauterine growth retardation, hypoglycemia, bradycardia.

Other: pain in the back or joints, arthralgia, like all β-adrenoblockers in a few cases can cause a slight increase in body weight, decreased libido and / or potency, sexual dysfunction.

Overdose:

Symptoms: severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked decrease in blood pressure, arrhythmia, ventricular extrasystole, bronchospasm, fainting, with acute overdose - cardiogenic shock, loss of consciousness, coma, AV (up to the development of complete transverse blockade and cardiac arrest), cardialgia, hypoglycemia, hyperkalemia, convulsions, respiratory arrest.

The first signs of an overdose appear after 20 minutes - 2 hours after taking the drug.

Treatment: gastric lavage and administration of adsorptive agents; symptomatic therapy: with a pronounced decrease in blood pressure - the patient should be in the Trendelenburg position; in case of excessive reduction in blood pressure, bradycardia and heart failure - intravenously, with an interval of 2-5 minutes, β-adrenostimulators - until the desired effect is achieved or intravenously, 0.5-2 mg of atropine sulfate.In the absence of a positive effect - dopamine, dobutamine or norepinephrine (norepinephrine). As a follow-up, it may be the administration of 1-10 mg of glucagon, the setting of a transvenous intracardiac electrostimulator.

When bronchospasm should be administered intravenously stimulants β₂adrenoreceptors.

Hemodialysis is ineffective.

Interaction:

It is not recommended simultaneous use with MAO inhibitors due to a significant increase in antihypertensive effect. A break in treatment between taking MAO inhibitors and metoprolol should be at least 14 days,

β-adrenostimulators, theophylline, cocaine, glucocorticoids, estrogens (sodium ion retention), indomethacin and other non-steroidal anti-inflammatory drugs (sodium ion delay and blockage of prostaglandin synthesis by the kidneys) weaken the hypotensive effect of metoprolol.

When combined with hypoglycemic agents for oral administration, a decrease in their effect is possible; with insulin - increased risk of developing hypoglycemia, increasing its severity and duration, masking some of the symptoms of hypoglycemia (tachycardia, increased sweating, increased blood pressure).

When combined with antihypertensive drugs, diuretics, ACE inhibitors, nitroglycerin or BCCC, nifedipine can lead to a significant reduction in blood pressure (extra caution is necessary when combined with prazosin); increased risk of bradycardia when combined with mefloquine; marked decrease in blood pressure and bradycardia when combined with epinephrine; marked decrease in heart rate and depression AV conductivity up to complete blockade - with metoprolol with verapamil, diltiazem, reserpine, α-methyldopa, clonidine, guanfacin and cardiac glycosides, means for general anesthesia (along with cardiodepressive and hypotensive effects).

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

Class I antiarrhythmic drugs can lead to a summation of the negative inotropic effect with the development of pronounced hemodynamic side effects in patients with left ventricular dysfunction (this combination should be avoided in patients with SSSU and violation AV conductivity).

Quinidine inhibits the metabolism of metoprolol in fast acetylarates, leading to a significant increase in the concentration of metoprolol in plasma and its enhancement β-adrenoblocking action.

The combination with amiodarone increases the risk of pronounced sinus bradycardia (including after a long time after the abolition of amiodarone, due to its long half-life).

If metoprolol and clonidine take simultaneously, then with the cancellation of metoprolol clonidine cancellation after a few days (due to the risk of the syndrome of "withdrawal").

Inductors of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of metoprolol, a decrease in the concentration of metoprolol in the blood plasma and a decrease in the effect. Inhibitors (cimetidine, oral contraceptives, phenothiazines) - increase the concentration of metoprolol in the blood plasma.

Diphenhydramine reduces the clearance of metoprolol, enhancing its effect.

Joint reception with high doses of phenylpropanolamine can lead to a paradoxical increase in blood pressure (right up to the hypertensive crisis).

Allergens used for immunotherapy,or extracts of allergens for skin tests when combined with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions,

Reduces the clearance of xanthine (except diphylline), especially with the initially elevated clearance of theophylline under the influence of smoking.

Reduces the clearance of lidocaine, increases the concentration of lidocaine in the blood plasma.

Strengthens and prolongs the effect of antidepolarizing muscle relaxants; prolongs the anticoagulant effect of coumarins.

When combined with anxiolytics and hypnotics, the hypotensive effect is enhanced, with ethanol - the risk of a pronounced decrease in blood pressure and an increase in the inhibitory effect on the central nervous system increase.

There is an increased risk of peripheral circulatory disorders - with ergot alkaloids.

Special instructions:

It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at a heart rate of less than 50 beats per minute.

Control of patients taking Metoprolol Zentiva,includes regular monitoring of heart rate and blood pressure (at the beginning of administration - every day, then once every 3-4 months), the concentration of glucose in the blood in patients with diabetes mellitus (1 every 4-5 months).

For patients with diabetes, it may be necessary to adjust the dose of insulin or hypoglycemic agents administered internally.

Metoprolol Zentiva can mask tachycardia caused by hypoglycemia. In contrast to nonselective β-adrenoblockers, Metoprolol Zentiva does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to a normal value.

When taking a dose above 200 mg per day, cardioselectivity decreases.

In "smokers" the effectiveness of β-blockers is lower.

In chronic heart failure Metoprolol Zentiva is appointed only after the stage of compensation is reached.

It is possible to increase the severity of reactions of hypersensitivity (against a background of a burdened allergic anamnesis) and the absence of the effect of the administration of usual doses of epinephrine (epinephrine).

It can intensify the symptoms of peripheral arterial circulation.

Cancellation of the drug is carried out gradually, reducing the dose for 10 days.With a sharp cessation of treatment, there may be a "cancellation" syndrome (increased angina attacks, increased blood pressure).

With angina pectoris, the selected dose of the drug should provide a heart rate at rest within 55-60 beats / min, with a load - no more than 110 beats / min.

Patients using contact lenses should take into account that, against the background of treatment with the drug Metoprolol Zentiva, a decrease in the production of tear fluid is possible.

Metoprolol Zentiva may mask certain clinical manifestations of hyperthyroidism (eg, tachycardia). Sharp abolition in patients with the drug Metoprolol Zentiva with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

In bronchial asthma, chronic obstructive pulmonary disease, emphysema, chronic obstructive bronchitis, the drug is prescribed in a minimally effective dose and only if other hypotensive agents are poorly tolerated or ineffective. If it is necessary to prescribe to patients with bronchial asthma, as a concomitant therapy, β₂-adrenostimulators; with pheochromocytoma - α-adrenoblockers.

If surgery is necessary, an anesthesiologist should be warned aboutthe ongoing therapy with the drug Metoprolol Zentiva (for the choice of a means for general anesthesia with a minimum negative inotropic effect).

Drugs that reduce catecholamine stocks (for example, reserpine), and Metoprolol Zentiva can cause excessive reduction in blood pressure and bradycardia, so patients taking such combinations of drugs should be under constant medical supervision.

In elderly patients, it is recommended to regularly monitor liver function.

In the case of an elderly patient with a growing bradycardia (less than 50 beats per minute), a marked decrease in blood pressure (systolic blood pressure below 100 mm Hg). in the case of AV blockade, bronchospasm, ventricular arrhythmias, severe liver dysfunction, correction of the dosing regimen or discontinuation of treatment is required.

Patients with severe renal failure (CC less than 40 ml / min) are recommended to monitor kidney function.

Special monitoring of the condition of patients with depressive disorders taking Metoprolol Zentiva should be carried out, in the case of development of depression caused by taking the drug Metoprolol Zentiva, it is recommended to stop therapy.

During treatment with the drug Metoprolol Zentiva, excessive insolation should be avoided, since the drug can cause an allergic reaction to the sun.

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

At the beginning of treatment with Metoprolol Zentiva, patients may experience dizziness, fatigue - caution should be exercised when driving vehicles and engaging in potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage: Tablets, 50 mg and 100 mg.

Packaging:

10 tablets in a PVC / A blisterl.

By 2, 3, 5 or 6 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of 15 ° C to 25 ° C, in a dry, protected from light place.

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:П N013374 / 01

Date of registration:07.04.2010 / 12.02.2014

Expiration Date:Unlimited

The owner of the registration certificate:Zentiva as.Zentiva as. Czech Republic

Manufacturer: & nbsp

Saneca Pharmaceuticals a.s. The Slovak Republic

Representation: & nbspZENTIVA PHARMA, LLCZENTIVA PHARMA, LLC

Information update date: & nbsp10.05.2018

Illustrated instructions

Instructions

Metoprolol Zentiva (Metoprolol Zentiva)