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

active substance: metoprolol succinate (based on dry matter) 23.75 mg or 47.50 mg or 95.0 mg, calculated as metoprolol tartrate 25.0 mg or 50.0 mg or 100.0 mg;

Excipients: hypromellose (hydroxypropylmethylcellulose), hyethellosis (hydroxyethylcellulose), Kollidon SR [polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%], copovidone (copolyvidone), magnesium stearate

excipients for the shell: hypromellose (hydroxypropylmethylcellulose), macrogol 6000 (polyethylene glycol 6000), talc, titanium dioxide, dye quinoline yellow.

Description:

Tablets covered with a film coat of yellow color (at a dosage of 25 mg) and white or almost white (at a dosage of 50 mg and 100 mg); round, biconvex without risk (at a dosage of 25 mg and 50 mg) or biconvex, oblong with rounded ends at a risk (at a dosage of 100 mg).

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

Metoprolol-beta₁-adrenoblocker blocking beta₁-adrenoceptors at doses significantly lower than the doses required to block beta₂adrenoreceptors.

Metoprolol has an insignificant membrane-stabilizing effect and does not possess internal sympathomimetic activity.

Has antihypertensive, antianginal and antiarrhythmic action.

Blocking beta₁-adrenoceptors of the heart, reduces the stimulated catecholamines formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate, reduces the intracellular current of calcium ions, has a negative chrono, dromo-, batmo- and inotropic effect (reduces heart rate (heart rate), 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 after 1-3 days returns to the original, and with a long-term appointment - decreases.

The hypotensive effect is due to the reflex decrease in the minute volume of blood and the synthesis of renin, the inhibition of the activity of the renin-angiotensin-aldosterone system (is of greater importance in patients with initial renin hypersecretion) and the central nervous system (CNS), the sensitivity of the aortic baroreceptor sensitivity in response to a decrease in blood pressure (BP)) and, as a result, a decrease in peripheral sympathetic influences. Reduces elevated blood pressure at rest, with physical stress and stress. With arterial hypertension, the effect occurs after 2-5 days, a stable effect is observed after 1-2 months.

The antianginal effect is determined by the decrease in myocardial oxygen demand as a result of a decrease in heart rate (diastolic elongation and improvement in perfusionmyocardium) 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. By increasing the final diastolic pressure of the left ventricle and increasing the stretching of the muscle fibers of the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.

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

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

Prevents the development of migraine.

In contrast to nonselective beta-blockers, when given in average therapeutic doses, it has a less pronounced effect on organs containing beta₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism; the severity of atherogenic action does not differ from that of propranolol. When used in large doses (more than 100 mg / day) has a blocking effect on both subtypes of beta adrenoreceptors.

Pharmacokinetics:

Metoprolol is completely absorbed after oral administration (95%). Systemic bioavailability after oral administration of a single dose is approximately 30-40%.

The duration of the therapeutic effect after taking metoprolol in the dosage form of the sustained-release tablet is more than 24 hours, with a constant release rate of the active substance within 20 hours. The half-life period averages 3.5 hours.

Metoprolol is metabolized in the liver, 3 major metabolites do not have a clinically significant beta-adrenergic blocking effect.About 5% of the internal dose of the drug is excreted by the kidneys unchanged, the rest of the drug is excreted as metabolites.

The connection with plasma proteins is low, about 5-10%. Rapidly distributed in tissues, penetrates the blood-brain barrier. Penetrates into breast milk. It is not removed during hemodialysis.

Indications:

- Arterial hypertension;

- angina pectoris tension;

- stable symptomatic chronic heart failure II-IV functional class by classification NYHA;

- reduction in mortality and frequency of recurrent myocardial infarction after an acute phase of myocardial infarction;

- heart rhythm disturbances, including supraventricular tachycardia, reduced ventricular contraction rate in atrial fibrillation and ventricular extrasystole;

- functional disorders of cardiac activity accompanied by tachycardia;

- prevention of migraine attacks.

Contraindications:

- Hypersensitivity to metoprolol and its components or to other beta-blockers;

- atrioventricular blockade of II and III degree;

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

- Patients receiving long-term inotropic therapy or agents that affect beta-adrenergic receptors;

- clinically significant sinus bradycardia;

- syndrome of weakness of the sinus node;

- cardiogenic shock;

- arterial hypotension;

- patients with acute myocardial infarction at a heart rate of less than 45 beats / min, interval PQ more than 0.24 seconds. or systolic blood pressure less than 100 mm Hg;

- severe peripheral circulatory disturbances (with a threat of gangrene);

- simultaneous intravenous administration of blockers of "slow" calcium channels such as verapamil;

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

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

Carefully:

Atrioventricular block I prinzmetal angina, bronchial asthma, chronic obstructive pulmonary disease, diabetes mellitus, severe renal failure, severe hepatic insufficiency, metabolic acidosis, peripheral circulation disorders, psoriasis, depression (including in the anamnesis), myasthenia gravis, pheochromocytoma with simultaneous use of alpha adrenoblockers, thyrotoxicosis.

Pregnancy and lactation:

In pregnancy, the drug Metoprolol-OBL is prescribed if the benefit to the mother exceeds the risk to the fetus and / or newborn (due to possible development in a newborn bradycardia, arterial hypotension, hypoglycemia and respiratory arrest). Treatment should be interrupted for 48-72 hours before childbirth. In cases where this is not possible, it is necessary to ensure strict observation of newborns within 48-72 hours after delivery.

Metoprolol penetrates into breast milk (slightly), if you need to use the drug Metoprolol-OBL during lactation, breastfeeding should be discarded.

Dosing and Administration:

Metoprolol-OBL is intended for daily administration once a day, it is recommended to take the drug in the morning. The tablet of the drug Metoprolol-OBL should be swallowed whole, squeezed with liquid. Tablets (or tablets, divided in half) should not be chewed or crushed.

Arterial hypertension

50-100 mg once a day. If necessary, the dose can be increased to 100 mg per day or add another antihypertensive agent, preferably a diuretic and a "slow" calcium channel blocker (BCCC), a dihydropyridine derivative;

Angina of Stress

100-200 mg of metoprolol-OBL preparation once a day.If necessary, another antianginal agent may be added to therapy.

With angina pectoris, the metered dose of metoprolol-OBL should provide heart rate; at rest within the limits of 55-60 beats / min, at a load - no more than 110 beats / min.

Stable CHF II functional class according to NYHA classification

Patients should be in stable condition without episodes of exacerbation of CHF during the last 6 weeks and without changes in the main therapy within the last 2 weeks.

The development of CHF by beta-blockers can sometimes lead to a temporary worsening of the symptoms. In some cases, it is possible to continue therapy or reduce the dose, in some cases it may be necessary to cancel the drug.

In the case of development of arterial hypotension and / or bradycardia, correction of concomitant therapy or a decrease in the dose of the drug Metoprolol-OBL may be required. Arterial hypotension at the beginning of therapy does not necessarily indicate that this dose will not be tolerated by the patient with further long-term treatment. However, the dose should not increase until the patient's condition stabilizes. You may need to monitor kidney function.

The recommended initial dose of the drug is metoprolol-OBL for the first 2 weeks 25 mg once a day. After 2 weeks of therapy, the dose can be increased to 50 mg once a day, and then can be doubled every 2 weeks.

Supportive dose for long-term treatment of 200 mg of metoprolol-OBL preparation once a day.

Stable CHF III-IV NYHA functional class

The recommended initial dose for the first 2 weeks is 12.5 mg of the drug Metoprolol-OBL (the drug may be used metoprolol in the form of a tablet prolonged action of 25 mg with a risk) 1 time per day. The dose is selected individually. During the period of increasing the dose, the patient should be monitored, since in some patients the CHF may worsen.

After 1-2 weeks, the dose can be increased to 25 mg once a day. Then, after 2 weeks, the dose can be increased to 50 mg once a day. Patients who tolerate the drug well can double the dose every 2 weeks until a maximum dose of 200 mg of Metoprolol-OBL is given once a day.

Heart rhythm disturbances

100-200 mg once a day.

Supportive treatment after myocardial infarction 200 mg once a day.

Functional disorders of cardiac activity, accompanied by tachycardia

100 mg once a day. If necessary, the dose can be increased to a maximum daily dose of 200 mg.

Preventing migraine attacks

100-200 mg once a day.

Impaired renal function

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

Impaired liver function

Usually, due to the low degree of binding to plasma proteins, dose adjustment is not required. However, with severe liver dysfunction (in patients with severe cirrhosis or portocaval anastomosis), the possibility of reducing the dose of the drug should be considered.

Elderly age

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

Children

The experience of using the drug in children under 18 is limited.

Side effects:

To assess the frequency of cases, the following criteria were applied: very often (> 10%), often (1-9.9%), infrequently (0.1-0.9%), rarely (0.01-0.09%) and very rarely (<0.01%).

From the side of the cardiovascular system: often - sinus bradycardia, marked decrease in blood pressure, orthostatic hypotension (very rarely accompanied by syncope), cold extremities, palpitations; infrequently - the development (aggravation) of the course of CHF (edema of the feet and / or the lower part of the legs, shortness of breath),AV blockade of the 1st degree; Cardiogenic shock in patients with acute myocardial infarction; rarely - other violations of the conductivity of the myocardium, arrhythmia.

From the central nervous system: very often - increased fatigue; often - dizziness, headache; rarely - increased excitability, anxiety, impotence / sexual dysfunction; infrequently paresthesia in the extremities (in patients with "intermittent" lameness and Raynaud's syndrome), convulsions, depression, decreased concentration, drowsiness, insomnia, "nightmarish" dreams; very rarely - confusion or short-term memory loss, hallucinations, tremor, asthenia, myasthenia gravis, slowing of the speed of mental and motor reactions.

From the digestive system: often - nausea, abdominal pain, diarrhea, constipation; infrequently - vomiting; rarely - dryness of the oral mucosa, impaired liver function (dark urine, icteric sclera or skin, cholestasis); very rarely - hepatitis, a change in taste.

From the skin: infrequently - skin rash, itching, hives, increased sweating; rarely - reversible alopecia; very rarely - photosensitization, exacerbation of psoriasis, psoriasis-like skin reactions, skin hyperemia.

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

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

From the musculoskeletal system: very rarely - arthralgia, pain in the back or in the joints.

From the endocrine system: hyperglycemia (in patients with insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid status.

From the side of metabolism: infrequently, weight gain.

Laboratory indicators: very rarely - thrombocytopenia; agranulocytosis, leukopenia, increased activity of "hepatic" enzymes, hyperbilirubinemia.

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

Overdose:

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

Symptoms: when an overdose is most serious symptoms of the cardiovascular system, but sometimes, especially in children and adolescents, can predominate symptoms of the central nervous system, bradycardia, AV blockade I-III degree (up to the development of complete transverse blockade and cardiac arrest), pronounced sinus bradycardia, arrhythmia, ventricular extrasystole, asystole,marked decrease in blood pressure, weak peripheral perfusion, heart failure, cardiogenic shock; suppression of lung function, apnea, fatigue, dizziness, fainting, coma, cyanosis, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; impact on the kidneys; transient myasthenic syndrome; The concomitant intake of alcohol, antihypertensive drugs, quinidine or barbiturates can worsen a patient's condition.

Treatment: reception of activated charcoal, if necessary, gastric lavage.

Atropine (0.25-0.5 mg IV for adults, 10-20 μg / kg for children) should be prescribed before gastric lavage (because of the risk of stimulating the vagus nerve).

If it is necessary to maintain the patency of the airways, intubation is carried out and adequate ventilation is provided for the lungs. Replenishment of the volume of circulating blood and infusion of dextrose (glucose). ECG monitoring. If necessary, repeated administration of atropine, in a dose of 1.0-2.0 mg IV, is possible in the case of vagal symptoms.In the absence of a positive effect - dopamine, dobutamine.

As a follow-up, it is possible to administer glucagon 50-150 μg / kg IV with an interval of 1 minute. In some cases, the addition of norepinephrine (norepinephrine) may be effective. With arrhythmia and a broadened ventricular complex (QRS) infusion solutions of sodium (chloride or hydrogen carbonate). It is possible to install an artificial pacemaker. When cardiac arrest due to an overdose, resuscitation may be necessary for several hours. For cupping the bronchospasm can be applied salbutamol (inhalation). Treatment is symptomatic.

With convulsions - slow IV injection of diazepam. Hemodialysis is ineffective.

Interaction:

Metoprolol is a substrate of isoenzyme CYP2D6, in connection with which the preparations inhibiting the isoenzyme CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) can affect the plasma concentration of metoprolol.

Joint use with the following medicines should be avoided:

Derivatives of barbituric acid: Barbiturates (the study was conducted with pentobarbital) enhance metoprolol metabolism, due to the induction of microsomal liver enzymes.

Combinations with the following drugs may require dose adjustment:

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

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

Phenylpropanolamine: phenylpropanolamine in a single dose of 50 mg can cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure, caused by phenylpropanolamine. However, beta-adrenoblockers can cause reactions of paradoxical arterial hypertension in patients receiving high doses of phenylpropanolamine. Several cases of development of the hypertensive crisis against phenylpropanolamine were reported.

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

Patients simultaneously taking metoprolol and other beta-blockers (in dosage form, eye drops) or monoamine oxidase (MAO) inhibitors, should be closely monitored.

With simultaneous application with MAO inhibitors, due to a significant increase in antihypertensive effect, a break in treatment between the intake of MAO inhibitors and metoprolol should be at least 14 days.

Against the background of taking beta-blockers means for inhalation anesthesia (halogenated hydrocarbons) increase the cardiodepressant effect and the likelihood of lowering blood pressure.

Against the background of reception of beta-blockers to patients receiving hypoglycemic agents for oral administration, it may be necessary to adjust the dose of the latter.

The plasma concentration of metoprolol may increase with simultaneous admission cimetidine or hydralazine.

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.

Reduces ground clearance lidocaine and xanthines (except diprofilina) and increases their concentration in blood plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Cardiac glycosides, methyldopa, reserpine and guanfacine, BCCC (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV blockade, cardiac arrest and heart failure.

Diuretics, clonidine, sympatholytics, hydralazine, nifedipine and other antihypertensives can lead to excessive blood pressure lowering.

Lengthens the action Nondepolarizing muscle relaxants and anticoagulant effect coumarins.

Tri- and tetracyclic antidepressants, antipsychotics (antipsychotics), antipsychotics ethanol, sedatives and hypnotics increase the CNS depression.

Unhydrated alkaloids of ergot increase the risk of peripheral circulatory disorders.

Special instructions:

Control of patients taking beta-blockers,includes 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). 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.

It is possible to increase the severity of allergic reactions (against the background of a burdened allergic medical history) and the lack of the effect of the administration of usual doses of epinephrine (adrenaline).

In elderly patients, it is recommended that the kidney function is monitored (once every 4-5 months).

Metoprolol-OBL may exacerbate the symptoms of peripheral arterial circulation.

With arterial hypertension, the effect occurs after 2-5 days, a stable effect is observed after 1-2 months.

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

When combined therapy with metoprolol-OBL with clonidine, the latter should be discontinued a few days after the discontinuation of the drug Metoprolol-OBL, in order to avoid hypertensive crisis.

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

In diabetics, metoprolol-OBL can mask tachycardia caused by hypoglycemia. Unlike nonselective beta-blockers, it does not actually increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

If it is necessary to administer the drug Metoprolol-OBL to patients with bronchial asthma, as a concomitant therapy, use beta₂-adrenomimetics; at pheochromocytoma - alpha-adrenoblockers.

If it is necessary to perform a surgical procedure, it is necessary to warn the anesthetist about taking Metoprolol-OBL (choice of a means for general anesthesia with minimal negative inotropic effect), the drug cancellation is not recommended.

Reciprocal activation n.vagus can be eliminated in / in the administration of atropine (1-2 mg).

Sympatholytics (for example, reserpine), can enhance the action of beta-blockers, so patients who take such combinations of funds should be under constant observation of the doctor for the detection of excessive reduction in blood pressure or bradycardia.

In the case of increasing bradycardia (less than 50 / min), arterial hypotension (systolic blood pressure below 100 mm Hg) AV blockade, bronchospasm, ventricular arrhythmias, severe violations of the liver and kidneys, it is necessary to reduce the dose of the drug Metoprolol-OBL or discontinue treatment.

It is recommended to stop therapy with the appearance of skin rashes and the development of depression caused by the use of beta-blockers.

Cancellation of the drug Metoprolol-OBL is carried out gradually, reducing the dose within 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 withdrawal of the drug in patients with angina pectoris.

Patients using contact lenses should take into account that, against the background of beta-blocker therapy, tear production can be reduced.

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

During the treatment with Metoprolol-OBL, weakness, dizziness, convulsions, drowsiness and other side effects are possible, so care must be taken when driving vehicles and taking other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated, 25 mg, 50 mg and 100 mg.

Packaging:

For 10 or 14 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2 or 3 contour squares, together with the instructions for use, are placed in a pack of cardboard.

Storage conditions:

In a dry, 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005099/10

Date of registration:01.06.2010 / 15.08.2011

Expiration Date:Unlimited

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp10.05.2018

Illustrated instructions

Instructions

Metoprolol-OBL (Metoprolol-OBL )