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

Excipients: silicon dioxide colloidal anhydrous - 4.50 mg, microcrystalline cellulose - 88.50 mg, sodium carboxymethyl starch (type A) - 20.00 mg, magnesium stearate - 2.00 mg;

shell: hypromellose - 3.76 mg, polysorbate 80 - 0.16 mg, talc - 3.36 mg, titanium dioxide E 171 - 0.50 mg, dye crimson [Ponso 4R] - 0.22 mg.

1 tablet, film-coated, 100 mg, contains:

active substance: metoprolol tartrate - 100 mg;

Excipients: silicon dioxide colloidal anhydrous - 9,00 mg, microcrystalline cellulose - 177,00 mg, sodium carboxymethyl starch (type A) - 40,00 mg, magnesium stearate - 4,00 mg;

shell: hypromellose - 4.70 mg, polysorbate 80 - 0.20 mg, talc - 4.20 mg, titanium dioxide E 171 - 0.90 mg.

Description:

Tablets, film-coated, 50 mg: round, biconcave tablets, covered with a filmy coat of pinkish color, with a risk on one side.

Tablets coated with a film coating, 100 mg: round, biconvex tablets, covered with a film coat from white to yellowish white, with a risk on one side.

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, which do not possess internal sympathomimetic activity and membrane-stabilizing properties. Has antihypertensive, antianginal and antiarrhythmic action.

Blocking in low doses β₁-adrenoceptors of the heart, reduces catecholamine-stimulated cAMP production from ATP, reduces the intracellular current of Ca²⁺, has a negative chrono-, dromo-, batmo- and inotropic effect (it cuts the heart rate, inhibits conduction and excitability, reduces myocardial contractility).

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

The acute antihypertensive effect is due to a decrease in cardiac output, a stable antihypertensive effect develops within 2-3 weeks and is due to a decrease in renin synthesis and plasma renin accumulation, inhibition of renin-angiotensin system (important in patients with initial renin hypersecretion) and 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 blood pressure) and, as a result, sympathetic influences. Reduces high blood pressure at rest, with physical stress and stress.

The antianginal effect is determined by the reduction in myocardial oxygen demand as a result of a decrease in the heart rate (diastole lengthening and improvement of myocardial perfusion) and contractility,as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases the tolerance of exercise.

Arterial blood pressure is lowered after 15 minutes, the maximum - after 2 hour and is continued for 6 hours and diastolic blood pressure changes slower: a steady decline is observed after several weeks of continuous administration.

Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased sympathetic nervous system activity, increased cAMP levels, hypertension), decrease the rate of spontaneous excitation of the sinus and ectopic pacemaker and deceleration atrioventricular conduction (preferably antegrade and to a lesser extent, in the retrograde direction through the AVnode) and on additional paths.

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 average therapeutic doses, in contrast to non-selective beta-blockers, 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 β-adrenergic receptors.

Pharmacokinetics:

Metoprolol is absorbed rapidly and almost completely (95%) in the gastrointestinal tract. 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).

Bioavailability is 50% at the first intake and increases to 70% at repeated application. Food intake increases bioavailability by 20-40%. Bioavailability of metoprolol increases with cirrhosis of the liver.

The connection with plasma proteins is on average 10%.

The drug penetrates through blood-brain and placental barriers. Excreted in breast milk in small amounts.

Metabolised in the liver. Metabolites do not have pharmacological activity. Around 5% the drug is excreted unchanged by the kidneys.

Treatment of patients with decreased renal function does not require correction of the dose of the drug.

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

It is not removed during hemodialysis.

Indications:

- Arterial hypertension (as a monotherapy or in combination with other antihypertensive drugs), including hyperkinetic type, 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 beta-blockers;

- cardiogenic shock;

- atrioventricular (AV) blockade II-III degree;

- sinoatrial (SA) blockade;

- syndrome of weakness of the sinus node;

- pronounced bradycardia;

- heart failure in the stage of decompensation;

- Prinzmetal angina;

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

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

- simultaneous administration of MAO inhibitors or simultaneous intravenous administration of verapamil (see "Interaction with Other Drugs")

- age under 18 years (efficiency and safety not established).

Carefully:

Diabetes mellitus, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease (emphysema, chronic obstructive bronchitis), obliterating peripheral vascular disease ( "intermittent" claudication, Raynaud syndrome), chronic liver and / or kidney failure, myasthenia gravis, pheochromocytoma, AV blockade of the I degree, thyrotoxicosis, depression (including in the anamnesis), psoriasis, pregnancy, elderly age.

Pregnancy and lactation:

During pregnancy appoint strict conditions, taking into account the benefit / risk (in connection with the development of fetal bradycardia, hypotension, hypoglycemia). At the same time, careful monitoring is carried out, especially for fetal development. Strict observation of newborns is necessary within 48-72 hours after delivery.

Influence of metoprolol on a newborn when breastfeeding not studied, therefore, women receiving metoprolol, you should stop breastfeeding.

Dosing and Administration:

Tablets are taken orally with food or immediately after meals, without chewing and washing 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 additional prescription of other antihypertensive agents.

The maximum daily dose is 200 mg.

Angina pectoris, arrhythmias, prevention of migraine attacks

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

Secondary prevention of myocardial infarction

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).

In elderly patients, with violations of kidney function, as well as the need for hemodialysis do not change the dose.

With 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. Rarely: paresthesia in the extremities (in patients with "intermittent claudication" and Raynaud's syndrome), depression, anxiety, decreased attention, drowsiness, insomnia, nightmares, confusion or short-term memory impairment, muscle weakness.

From the sense organs: rarely - reduced vision, reduced secretion of tear fluid, dry and sore eyes, conjunctivitis, tinnitus.

From the side of the cardiovascular system: sinus bradycardia, palpitation, lowering of arterial pressure, orthostatic hypotension, dizziness, sometimes loss of consciousness). Seldom is myocardial contractility, temporary worsening of symptoms of chronic heart failure (edema, edema of the feet and / or lower leg, dyspnea), arrhythmias, manifestation of angiospasm (increased peripheral circulatory disturbance, lower extremities cooling, Raynaud's syndrome), myocardial conduction disturbance, cardialgia .

From the digestive system: nausea, vomiting, abdominal pain, dry mouth, diarrhea, constipation, impaired liver function, change in taste.

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, difficulty exhaling (bronchospasm in high doses - loss of selectivity and / or in predisposed patients), dyspnea.

From the endocrine system: hypoglycemia (in patients receiving insulin), rarely: hyperglycemia (in patients with diabetes mellitus), hypothyroidism.

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

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

Other: pain in the back or joints, like all beta-adrenoblockers in a few cases can cause a slight increase in body weight, a decrease in libido and / or potency.

Overdose:

Symptoms: severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked decrease in arterial pressure, arrhythmia, ventricular extrasystole, bronchospasm, syncope, in case of acute overdose - cardiogenic shock, loss of consciousness, coma, atrioventricular block (until the development of complete transverse blockade and stoppage heart), cardialgia.

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 marked decrease in blood pressure - the patient should be in the Trendelenburg position; in case of excessive reduction in blood pressure, bradycardia and heart failure - iv, with an interval of 2-5 min, beta-adrenostimulants - to achieve the desired effect or iv in 0.5-2 mg of atropine sulfate.

In the absence of a positive effect - dopamine, dobutamine or norepinephrine (norepinephrine).

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

When bronchospasm should be introduced in / in stimulants beta₂adrenoreceptors.

Metoprolol is poorly excreted by hemodialysis.

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.

Simultaneous iv injection of verapamil may provoke cardiac arrest.

Simultaneous administration of nifedipine leads to a significant reduction in blood pressure.

Means for inhalation anesthesia (derivatives of hydrocarbons) increase the risk of oppression of myocardial function and development of arterial hypotension.

Beta-adrenostimulants, theophylline, cocaine, etrogens (sodium retention), indomethacin and other non-steroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys) weaken the hypotensive effect.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), sedative and hypnotic drugs increase the CNS depression.

Increased oppressive effect on the central nervous system - with ethanol; summation of cardiodepressiveeffect - with anesthesia; increased risk of violations of peripheral circulation - with ergot alkaloids.

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

When combined with antihypertensives, diuretics, nitroglycerin or blockers "slow" calcium channels may develop sharp decrease in blood pressure), special caution is required in combination with prazosin); increase expression of deceleration of heart rate and depression of atrioventricular conduction - the application of metoprolol with verapamil, diltiazem, antiarrhythmics (amiodarone), reserpine, alpha-methyldopa, clonidine, guanfacine, means for general anesthesia and cardiac glycosides.

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 in the plasma.

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 substances 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 ethanol, the risk of a marked decrease in blood pressure increases.

Special instructions:

Control of patients taking beta-blockers includes regular monitoring of heart rate (heart rate) and blood pressure, blood glucose in diabetic patients.If necessary, for patients with diabetes mellitus, 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 a heart rate of less than 50 beats per minute.

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

With heart failure, metoprolol treatment begins only after the compensation stage has been 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).

Particular attention should be paid to patients with angina when removing the drug. 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 beta-blocker therapy, tear production can be reduced.

Metoprolol may mask certain clinical manifestations of hyperthyroidism (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. In contrast to nonselective beta-blockers, there is almost no increase in insulin-induced glycemia and does not delay the restoration of blood glucose to normal levels.

If it is necessary to prescribe to patients with bronchial asthma, as a concomitant therapy they use beta₂-adrenostimulators; when pheochromocytoma - alpha-adrenoblockers.

If it is necessary to perform a surgical procedure, it is necessary to warn the anesthesiologist about the therapy (choice of a means for general anesthesia with minimal negative inotropic action), drug discontinuation is not recommended.

Drugs that reduce catecholamine stocks (for example, reserpine), can enhance the action of beta-blockers, so patients taking such combinations of drugs should be under constant observation of the doctor for the detection of excessive lowering of blood pressure and bradycardia.

In elderly patients it is recommended to regularly monitor liver function. Correction of the dosing regimen is required only in the case of an elderly patient with an increasing bradycardia (less than 50 beats / min), a marked decrease in blood pressure (systolic blood pressure below 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, , sometimes it is necessary to stop treatment.

Patients with severe renal failure are advised to monitor kidney function.

Special monitoring should be carried out on the condition of patients with depressive disorders receiving metoprolol; In the case of development of depression caused by the use of beta-blockers, it is recommended to stop therapy.

Due to the lack of sufficient clinical data, the drug is not recommended for use in children.

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

At the beginning of metoprolol treatment, patients may experience dizziness, fatigue. In this case, they should refrain from driving vehicles and practicing potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. In the future, the definition of dose safety is carried out individually.

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

Packaging:

Tablets, film-coated, 50 mg: for 14 tablets, coated with a coating, in a blister of PVC / AL. 2 or 4 blisters together with instructions for use in a pack of cardboard.

Tablets, film-coated, 100 mg: 10 tablets per blister of PVC / AL. 3 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003093/08

Date of registration:24.04.2008

Expiration Date:Unlimited

The owner of the registration certificate:Hemofarm ADHemofarm AD Serbia

Manufacturer: & nbsp

HEMOFARM, A.D. Serbia

Representation: & nbspHEMOFARM A.D. HEMOFARM A.D. Serbia

Information update date: & nbsp10.05.2018

Illustrated instructions

Instructions

Metoprolol (Metoprolol )