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

Excipients: cellulose microcrystalline 55,0 / 110,0 mg; corn starch 43.2 / 86.4 mg; croscarmellose sodium; 11.6 / 23.2 mg; Copovidone 5.0 / 10.0 mg; silicon colloidal dioxide 1.9 / 3.8 mg; magnesium stearate 3.3 / 6.6 mg.

Description:Bround, biconvex tablets with a risk on one side and engraving "M" on the other.

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 β₁adrenoreceptors. Has an insignificant membrane-stabilizing effect and does not possess an internal sympathomimeticactivity. It has antihypertensive, antianginal and antiarrhythmic action.

Blocking in low doses β₁-adrenoceptors heart stimulated by catecholamines reduces the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces intracellular calcium ion current has a negative chronotropic, dromo-, BATM and inotropic effects (heart rate slows, inhibits conduction and excitability and reduces contractility of the myocardium). Total peripheral resistance at the beginning of application β₁(in the first 24 hours after ingestion) increases (as a result of the reciprocal increase in the activity of α-adrenergic receptors and elimination of stimulation β₂-adrenoreceptors), which after 1-3 days returns to the original, and with prolonged use - decreases.

Antihypertensive action is associated with a decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin-aldosterone system (important in patients with initial renin hypersecretion) and the central nervous system, restoration of the sensitivity of the aortic arch baroreceptorsactivity in response to a decrease in blood pressure) and, ultimately, a decrease in peripheral sympathetic influences. Reduces elevated blood pressure (BP) at rest, with physical stress and stress. The antihypertensive 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.

Antianginal action is determined by a decrease in myocardial oxygen demand as a result of a decrease in the heart rate (diastole 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 the tolerance of exercise. By increasing the end diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles, the myocardial oxygen demand may increase, especially in patients with chronic heart failure (CHF).

The antiarrhythmic effect is caused by 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 conduction (mainly in antegrade and, to a lesser extent, retrograde atrioventricular node and by additional routes).

If supraventricular tachycardia, atrial fibrillation, sinus tachycardia with functional heart disease and hyperthyroidism slows the heart rate and may even lead to the restoration of sinus rhythm.

Prevents the development of migraine.

When used in the middlex therapeutic doses, in contrast to nonselective βadrenoblockers, has a less pronounced effect on organs containing β₂-adrenoceptors (pancreas, skeletal muscles and 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 of β-adrenoreceptors.

Pharmacokinetics:

Suction. Ingestion metoprolol almost completely absorbed (about 95%) from the gastrointestinal tract. It is subjected to intensive presystemic metabolism, therefore the system bioavailability is about 35%. The maximum concentration in the blood plasma is achieved after 1.5-2 hours after administration.

Distribution. The connection with blood proteins is 10%. The volume of distribution is 5.5 l / kg. Penetrates through blood-brain and placental barriers. Excreted in breast milk in small amounts.

Metabolism. Metoprolol almost completely metabolized in the liver, inmainly, with, the participation of the isoenzyme, CYP2D6. The half-life of metoprolol is between 3 and 4 hours, but in slow metabolizers it can increase to 7-8 hours. Metabolites of o-desmethylmethoprolol and α-hydroxymetoprolol have weak β-adrenoblocking activity.

Excretion. It is excreted mainly by the kidneys (about 95%), about 10% is excreted unchanged. It is not excreted by hemodialysis.

In patients with cirrhosis of the liver and portocaval anastomosis, bioavailability increases, and clearance decreases.Patients with portocaval anastomosis AUC (the area under the concentration-time curve) can increase by a factor of 6, and the clearance can be reduced to 0.3 ml / min.

Indications:

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

- 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 drpre-componentsrat, β-blockers;

- chronic heart failure in the stage of decompensation;

- cardiogenic shock;

- syndrome of weakness of the sinus node;

- Sinoatrial blockade;

- atrioventricular block II-III degree (without artificial pacemaker);

- severe bradycardia (heart rate less than 50 beats / min.);

- severe forms of bronchial asthma and chronic obstructive pulmonary disease;

metabolic acidosis;

severe violations of peripheral circulation;

- Prinzmetal angina;

- arterial hypotension (in the case of secondary prevention of myocardial infarction - systolic blood pressure less than 100 mm Hg);

- Acute myocardial infarction (heart rate less than 45 bpm, interval PQ more than 0.24 seconds. or systolic blood pressure less than 100 mm Hg);

- Patients receiving long-term or intermittent therapy with inotropic agents and acting on β-adrenergic receptors,

- chronic obstructive pulmonary disease in the acute stage;

- pheochromocytoma (without simultaneous use αadrenoblockers);

- the period of breastfeeding;

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

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- simultaneous intravenous administration of blockers of "slow" calcium channels (BCCC) such as verapamil (see section "Interaction with other drugs").

Carefully:

Diabetes mellitus, metabolic acidosis, impaired liver function, kidneys (creatinine clearance less than 40 ml / min), myasthenia gravis, atrioventricular block I degree, thyrotoxicosis, depression (incl.and in anamnesis), psoriasis, a burdened allergic anamnesis (it is possible to increase sensitivity to allergens, weighty arterial hypertension, and decrease the therapeutic response to epinephrine), bronchial asthma, chronic obstructiveI am a lung disease, onRdo notreefcrocheted bloodration ("intermittent" lameness, Raynaud's syndrome), elderly age.

Pregnancy and lactation:

In pregnancy the drug Metoprolol-Teva is prescribed only on strict indications if the intended benefit for the mother exceeds the potential risk to the fetus (due to the possible development of fetal bradycardia, arterial hypotension, hypoglycemia). β-adrenoblockers reduce the permeability of the placenta, which can lead to premature birth or intrauterine fetal death.

The risk of cardiac or pulmonary complications increases in the postpartum period in those newborns who have been exposed to metoprolol in utero. The drug should be discontinued 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure thorough medical supervision of newborns within 48-72 hours after birth.

Metoprolol penetrates into breast milk. If you need to use the drug Metoprolol-Teva during lactation Breastfeeding should be discontinued.

Dosing and Administration:

The drug Methrollol-teva should be taken orally, during or immediately after meals, the tablets can be divided in half (but not chewed) and washed down with liquid.

With arterial hypertension the initial dose - 50-100 mg 1-2 times a day (morning and evening), with insufficient therapeutic effect, the daily dose can be increased to 100-200 mg or additionally use other antihypertensive agents. The maximum daily dose is 200 mg.

At an arrhythmia, long prophylaxis of an attack of a stenocardia and a migraine - 100-200 mg 1-2 times a day (morning and evening).

Secondary prevention of myocardial infarction - 200 mg per day, divided into 2 doses (morning and evening).

With functional disorders of cardiac activity, accompanied by tachycardia - 100 mg per day in 2 divided doses (morning and evening).

With hyperthyroidism - 150-200 mg per day in 3-4 sessions (morning and evening).

Elderly patients it is recommended to start treatment with 50 mg per day.

Renal insufficiency does not require dose adjustment.

With hepatic insufficiency a dose adjustment may be required depending on the clinical condition.

If there is a need to interrupt or stop treatment with the drug Methprolol-Teva after prolonged therapy, the dose of the drug must be gradually reduced by 2 times for a minimum of 2 weeks. When there is a syndrome of "cancellation", reduce the dose gradually. A sharp discontinuation of the drug may cause myocardial ischemia and may lead to exacerbation of angina or myocardial infarction, and also to increase arterial hypertension.

Side effects:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%.

On the part of the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia.

From the immune system: rarely an anaphylactic reaction.

From the endocrine system: rarely hypo-, hyperglycemia in patients with type 1 diabetes mellitus, masking the symptoms of thyrotoxicosis.

From the side of metabolism and nutrition: infrequently - weight gain; rarely - aggravation of the course of latent diabetes mellitus.

From the central nervous system: often fatigue, headache, dizziness; infrequent asthenic syndrome, slowing of the speed of mental and motor reactions, paresthesia, anxiety, nervousness, convulsions in the extremities (in patients with "intermittent" lameness and Raynaud's syndrome), depression, anxiety, decreased attention, drowsiness, frustration, sleep, "nightmarish" dreams, more frequent and / or more vivid dreams, confusion, muscle weakness; very rarely - emotional lability, short-term memory impairment.

From the side of the organ of vision: rarely - conjunctivitis, reduced secretion of tear fluid, decreased vision.

From the side of the hearing organ and labyrinthine disorders: rarely - hearing loss and noise in the ears.

From the side of the cardiovascular system: often - "a feeling of palpitation," bradycardia, orthostatic hypotension (dizziness, loss of consciousness), coldness of the lower limbs; infrequently - atrioventricular blockade of the 1st degree, pericardial pain; rarely a marked decrease in blood pressure,impairment of atrioventricular conduction or worsening of heart failure with peripheral edema and / or dyspnoea with exercise, increased complaints in patients with peripheral circulatory disorders (including patients with Reynaud's syndrome). Very redco - in patients with angina pectoris attacks.

On the part of the respiratory system, the organs of the thorax and the mediastinum: often - shortness of breath in a patientin c beforelocation to the development of bronchospasm; infrequently - nasal congestion, difficulty exhaling (bronchospasm in high doses - loss of selectivity and / or in predisposed patients); rarely allergic rhinitis.

From the gastrointestinal tract: often - nausea, vomiting, abdominal pain, diarrhea, constipation; infrequent - dryness of the oral mucosa; rarely - a violation of taste.

From the liver and biliary tract: rarely - increased activity of "liver" transaminases; very rarely - hepatitis.

From the skin and subcutaneous tissues: infrequently - skin hyperemia, skin itching, increased sweating; rarely - alopecia; very rarely - the reaction of photosensitization, psoriasis skin reaction.

From the musculoskeletal and connective tissue: infrequently - muscle spasm; very rarely - arthralgia, muscle weakness.

From the genitals and breast: rarely - a decrease in libido and potency, Peyronie's disease.

Laboratory indicators: very rarely - a decrease in high-density cholesterol and an increase in triglyceride levels in blood plasma.

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, atrioventricular block (until the development of complete transverse blockade and cardiac arrest) , angina pectoris, hypoglycaemia, hyperkalemia, convulsions, respiratory arrest.

The first signs of an overdose appear after 20 minutes - 2 hours after taking the drug. In case of an overdose or a threatening decrease in heart rate and / or blood pressure, treatment with Metoprolol-Teva should be stopped immediately.

Treatment: gastric lavage and intake of adsorbing agents; symptomatic therapy; with a marked decrease in blood pressure - the patient should be in the Trendelenburg position; in case of excessive decrease in blood pressure,bradycardia and heart failure - intravenously (intravenously) with an interval of 2-5 min β-adrenomimetiki - until the desired effect is achieved or in / in 0.5-2 mg of atropine. In the absence of a positive effect - dopamine, dobutamine or norepinephrine (norepinephrine).

When bronchospasm should be introduced in / in β₂- adrenomimetics. With convulsions - slow IV injection of diazepam.

Hemodialysis is ineffective.

Interaction:

It is not recommended simultaneous use with MAO inhibitors due to a significant increase in antihypertensive action. 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 blocking prostaglandin synthesis by the kidneys) weaken the antihypertensive 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, angiotensin converting enzyme inhibitors, nitroglycerin or blockers of "slow" calcium channels, can lead to a significant reduction in blood pressure (special 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; pronounced decrease in heart rate and inhibition of AV-conduction up to complete blockade - with metoprolol with verapamil, diltiazem, reserpine, methyldopa, clonidine, guanfacin and cardiac glycosides, means for general anesthesia (along with cardiodepressive and antihypertensive effects).

Drugs that induce or inhibit CYP2D6, may affect the level of metoprolol in the plasma. The concentration of metoprolol in plasma can increase with simultaneous admission with other drugs that are a substrate for CYP2D6, for example antiarrhythmics, antihistamines, antagonists of H₂-receptors, antidepressants (selective serotonin reuptake inhibitors eg, paroxetine, fluoxetine, sertraline), neuroleptics and cyclooxygenase-2 inhibitors.

Antiarrhythmic drugs of the first class can lead to the summation of a negative inotropic effect with pdevelopment of pronounced hemodynamic side effects in patients with left ventricular dysfunction (this combination should be avoided in patients with sinus node weakness syndrome and atrioventricular conduction disturbancethe).

Quinidine inhibitsMetoprolol metabolism in fast metabolizers, leading to a significant increase in the concentration of metoprolol in plasma and an increase in its β-adrenergic blocking effect.

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 allergen extracts 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 developing 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 drugs with hypnotic activity, the antihypertensive effect is enhanced, with ethanol - the risk of a pronounced decrease in blood pressure increases and the depressing effect on the central nervous system increases.

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

When used simultaneously with aldesleukinincreased risk of a sharp decline in blood pressure.

With simultaneous use, the effectiveness of alprostadil decreases.

Special instructions:

Β-adrenoceptor blockers may enhance sensitivity to allergens and severity of anaphylactic reactions, however in patients with the presence of severe hypersensitivity reactions in history and in patients undergoing a course desensitizing therapy, there is a danger of anaphylactic reactions expressed.

In severe renal impairment, and in some cases it reported worsening of renal function in the treatment of β-adrenoceptor blockers. AT such cases, the use of the drug metoprolol-Teva should be accompanied by appropriate monitoring of renal function.

Control of patients taking beta-adrenoblockers includes regular monitoring of heart rate and blood pressure, blood glucose concentration in patients with diabetes mellitus (1 time in 4-5 months).

If necessary, for patients with diabetes, the dose of insulin or hypoglycemic drugs administered orally should be selected individually.

It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at heart rate less than 50 beats per minute. When taking a dose above 100 mg per day, cardioselectivity decreases.

With heart failure, Metoprolol-Teva begins treatment only after reaching the compensation stage.

Avoid sudden discontinuation of the drug. Cancellation of the drug should be spend gradually, within 2 weeks. The dose decreases gradually, in several steps, until the final dose is reached - 25 mg once a day.

If surgical intervention is required, the surgeon / anesthesiologist should be alerted to the therapy to select a general anesthetic agent with minimal negative lyotropic effect, however, the discontinuation of the drug before surgery is not recommended.Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1 -2 mg).

It can intensify the symptoms of peripheral arterial circulation.

With angina pectoris, the selected dose of the drug should provide a heart rate at rest in the range of 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 β-adrenoblockers, tear production can be reduced.

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

In diabetes mellitus can mask tachycardia caused by hypoglycemia. In contrast to non-selective β-blockers metoprolol to a much lesser extent affects insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

If it is necessary to prescribe the drug Metoprolol-Teva, patients with bronchial asthma as a concomitant therapy are used β₂-adrenomimetics; with pheochromocytoma - αadrenoblockers.

Drugs that reduce catecholamine stocks (for example, reserpine), may increase the effect of β-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect excessive decrease in blood pressure and bradycardia.

It is recommended to stop therapy when skin rashes caused by the use of beta-blockers occur.

In elderly patients, it is recommended to regularly monitor liver function. Correction of the dosing regimen is required only if the patient develops an aging bradycardia (less than 50 beats / minute) in elderly patients, a marked decrease in blood pressure (systolic blood pressure below 100 mmHg), atrioventricular blockade, bronchospasm, ventricular arrhythmia, severe liver function disorders, sometimes it is necessary to stop treatment.

Special monitoring of the condition of patients with depressive disorders taking metoprolol should be carried out: in the case of depression caused by the use of β-blockers. is necessary Precycle thosepapiu.

When taking Metoprolol-Teva should refrain from drinking alcohol.

In smokers, the effectiveness of beta-blockers is lower.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

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

Packaging:

For 10 tablets in a PVC / Al-foil blister.

For 3, 5 or 10 blisters with instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N011845 / 01

Date of registration:25.10.2011 / 03.08.2017

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

MERCKLE, GmbH Germany

Representation: & nbspTeva Teva Israel

Information update date: & nbsp10.05.2018

Illustrated instructions

Instructions

Metoprolol-Teva (Metoprolol-Teva)