Metoprolol-OBL

General characteristics. Structure:

Active ingredient: 25 mg, 50 mg or 100 mg of a metoprolol (in the form of succinate) in 1 tablet.

Excipients: gipromelloz (gidroksipropilmetiltsellyuloz), gietelloza (hydroxyethylcellulose), Kollidon SR [polyvinyl acetate of 80%, povidone of 19%, sodium lauryl sulfate of 0,8%, silicon dioxide of 0,2%], коповидон (кополивидон), magnesium stearate

Excipients for a cover: gipromelloz (gidroksipropilmetiltsellyuloz), macrogoal 6000 (polyethyleneglycol 6000), talc, titanium dioxide, dye quinolinic yellow.

Pharmacological properties:

Pharmacodynamics. Metoprolol – the beta1-adrenoblocker blocking beta1-adrenoceptors in doses considerably smaller than the doses which are required for blocking of beta2-adrenoceptors.

Metoprolol possesses insignificant membrane stabilizing action and has no internal sympathomimetic activity.

Possesses hypotensive, anti-anginal and antiarrhytmic action.

Blocking in heart beta1-adrenoceptors, reduces stimulated catecholamines formation of cyclic adenosinemonophosphate (tsAMF) from adenosinetriphosphate, reduces intracellular current of calcium ions, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat the heart rate (HR), conductivity and excitability oppresses, reduces contractility of a myocardium).

The general peripheric vascular resistance at the beginning of use of beta adrenoblockers (in the first 24 h after intake) increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors) which in 1-3 days is returned to initial, and at long appointment - decreases.

Hypotensive action is caused by reflex reduction of minute volume of blood and synthesis of a renin, activity oppression system renin-angiotensin-aldosteronovoy (has bigger value at patients with initial hypersecretion of a renin) and the central nervous system (CNS), recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to a lowering of arterial pressure (ABP)) and as a result reduction of peripheral sympathetic influences. Reduces raised by the ABP at rest, at a physical tension and a stress. At arterial hypertension the effect occurs in 2-5 days, stable action is noted in 1-2 months.

The anti-anginal effect is defined by decrease in need of a myocardium for oxygen as a result of reduction of ChSS (lengthening of a diastole and improvement of perfusion of a myocardium) and contractility, and also decrease in sensitivity of a myocardium to influence of a sympathetic innervation. Reduces number and weight of attacks of stenocardia and increases portability of an exercise stress. Due to increase in end diastolic pressure of a left ventricle and increase in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with chronic heart failure.

The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of atrioventricular (AV) carrying out (it is preferential in antegrade and to a lesser extent in retrograde the directions through an atrioventricular node) and on additional ways.

At supraventricular tachycardia, atrial fibrillation, sinus tachycardia at functional heart diseases and a thyrotoxicosis urezhat ChSS or can even lead to recovery of a rhythm.

Prevents development of migraine.

Unlike non-selective beta adrenoblockers at appointment in average therapeutic doses exerts less expressed impact on the bodies containing beta2-adrenoceptors (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism; expressiveness of atherogenous action does not differ from effect of propranolol. At use in high doses (more than 100 mg/days) renders the blocking effect on both subtypes of beta adrenoceptors.

Pharmacokinetics. Metoprolol is completely absorbed after intake (95%). System bioavailability after intake of a single dose makes about 30 - 40%.

Duration of therapeutic effect after reception of a metoprolol in a dosage form of a tablet of the prolonged action makes more than 24 hours, at the same time the constant speed of release of active agent within 20 hours is reached. The elimination half-life averages 3,5 hours.

Metoprolol is metabolized in a liver, 3 main metabolites have no clinically significant beta and adrenoceptor blocking effect. About 5% of the dose of drug accepted inside are removed by kidneys in not changed look, other part of drug is removed in the form of metabolites.

Communication with proteins of a blood plasma of low, about 5-10%. It is quickly distributed in fabrics, gets through a blood-brain barrier. Gets into breast milk. Is not removed at a hemodialysis.

Indications to use:

- Arterial hypertension;

- Angina of exertion;

- Stable symptomatic chronic heart failure of the II-IV functional class on NYHA classification;

- Decline in mortality and frequencies of a repeated heart attack after an acute phase of a myocardial infarction;

- Disturbances of a cordial rhythm, including supraventricular tachycardia, decrease in frequency of reduction of ventricles at fibrillation of auricles and ventricular premature ventricular contraction;

- The functional disturbances of cordial activity which are followed by tachycardia;

- Prevention of attacks of migraine.

Route of administration and doses:

Lidalok is intended for daily reception of 1 times a day, it is recommended to accept drug in the morning. The drug tablet Lidalok should be swallowed entirely, washing down with liquid. Tablets (or the tablets halved) should not be chewed or crumbled.

Arterial hypertension. 50-100 mg once a day. If necessary it is possible to increase a dose to 100 mg a day or to add other anti-hypertensive means, diuretic and a blocker of "slow" calcium channels (BMKK), derivative are more preferable than a dihydropyridinic row.

Angina of exertion. 100-200 mg of drug Lidalok of 1 time a day. If necessary other anti-anginal means can be added to therapy.

At an angina of exertion the picked-up dose of drug of Lidalok has to provide ChSS at rest within 55-60 beats/min, at loading - no more than 110 beats/min.

Stable HSN II of a functional class on NYHA classification. Patients have to be in a stable state without episodes of an aggravation of a current of HSN within the last 6 weeks and without changes in the main therapy within the last 2 weeks.

Therapy of HSN beta adrenoblockers can sometimes lead to temporary deterioration in symptomatology. Continuation of therapy or a dose decline is in certain cases possible, in some cases there can be a need of drug withdrawal.

In case of development of arterial hypotension and/or bradycardia correction of the accompanying therapy or a dose decline of drug Lidalok can be required. Arterial hypotension at the beginning of therapy not necessarily specifies that this dose will not be transferred by the patient at further prolonged treatment. However the dose should not increase until the condition of the patient is not stabilized. Control of function of kidneys can be required.

The recommended initial dose of drug Lidalok the first 2 weeks of 25 mg of 1 times a day. After 2 weeks of therapy the dose can be increased to 50 mg of 1 times a day, and further can double each 2 weeks.

Maintenance dose for prolonged treatment of 200 mg of drug Lidalok of 1 time a day.

Stable HSN III-IV of a functional class on NYHA classification. The recommended initial dose the first 2 weeks of 12,5 mg of drug Lidalok (drug use метопролол in a dosage form of a tablet of the prolonged action on 25 mg with risky is possible) 1 time a day. The dose is selected individually. During increase in a dose the patient has to be under observation as at some patients deterioration in a current of HSN is possible.

In 1-2 weeks the dose can be increased to 25 mg of 1 times a day. Then, after 2 weeks, the dose can be increased to 50 mg of 1 times a day. Patients who well transfer drug can double a dose each 2 weeks before achievement of the maximum dose of 200 mg of drug Lidalok of 1 time a day.

Disturbances of a heart rhythm. 100-200 mg of 1 times a day.

The supporting treatment after a myocardial infarction. 200 mg of 1 times a day.

The functional disturbances of cordial activity which are followed by tachycardia. 100 mg of 1 times a day. If necessary a dose it is possible to increase 200 mg to the maximum daily dose.

Prevention of attacks of migraine. 100-200 mg of 1 times a day.

Renal failure. There is no need to adjust a drug dose at patients with a renal failure.

Abnormal liver function. Usually because of low extent of communication with proteins of plasma of dose adjustment it is not required. However at a heavy abnormal liver function (at patients with a severe form of cirrhosis or a porto-caval anastomosis) it is necessary to consider the possibility of a dose decline of drug.

Advanced age. There is no need to adjust a drug dose at patients of advanced age.

Children. Experience of use of drug for children up to 18 years is limited.

Features of use:

Use at pregnancy and in the period of a lactation: At pregnancy drug Lidalok is appointed if the advantage for mother exceeds risk for a fruit and/or the newborn (in connection with possible development in the newborn of bradycardia, arterial hypotension, a hypoglycemia and an apnoea). Treatment needs to be interrupted for 48-72 h before childbirth. When it is impossible, it is necessary to provide strict observation of newborns during 48-72 h after delivery.

Metoprolol gets into breast milk (slightly), in need of drug use Lidalok in the period of a lactation, breastfeeding needs to be cancelled.

Control of the patients accepting beta adrenoblockers includes observation of ChSS and the ABP (at the beginning of reception - daily, then 1 time in 3-4 months), concentration of glucose in blood at patients with a diabetes mellitus (1 time in 4-5 months). It is necessary to train the patient in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS less than 50 уд. / min.

Strengthening of expressiveness of allergic reactions (against the background of the burdened allergological anamnesis) and lack of effect of introduction of usual doses of Epinephrinum (adrenaline) is possible.

At elderly patients it is recommended to exercise control of function of kidneys (1 times in 4-5 months).

Lidalok can strengthen symptoms of disturbance of peripheric arterial circulation.

At arterial hypertension the effect occurs in 2-5 days, stable action is noted in 1-2 months.

At "smokers" efficiency of beta adrenoblockers is lower.

At a combination therapy of drug Lidalok with a clonidine reception of the last should be stopped in several days after drug withdrawal Lidalok, in order to avoid hypertensive crisis.

Lidalok can mask some clinical displays of a thyrotoxicosis (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology.

At a diabetes mellitus Lidalok can mask the tachycardia caused by a hypoglycemia. Unlike non-selective beta adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of concentration of glucose in blood to normal level does not detain.

In need of purpose of drug Lidalok to patients with bronchial asthma, as the accompanying therapy, use beta2-adrenomimetik; at a pheochromocytoma - alpha adrenoblockers.

In need of carrying out surgical intervention it is necessary to warn the anesthesiologist about administration of drug Lidalok (the choice of means for the general anesthesia with the minimum negative inotropic effect), drug withdrawal is not recommended.

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

Sympatholytics (for example, Reserpinum), can strengthen effect of beta adrenoblockers therefore the patients accepting such combinations of means have to be under constant observation of the doctor regarding identification of excessive decrease in the ABP or bradycardia.

In case of the accruing bradycardia (less than 50/mines), arterial hypotension (systolic the ABP is lower than 100 mm hg), AV of blockade, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions and kidneys it is necessary to reduce a drug dose Lidalok or to stop treatment.

It is recommended to stop therapy at emergence of skin rashes and development of the depression caused by reception of beta adrenoblockers.

Drug withdrawal Lidalok is carried out gradually, reducing a dose within 10 days. At the sharp termination of treatment there can be a syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP). Special attention at drug withdrawal needs to be paid to patients with an angina of exertion.

The patients using contact lenses have to consider that against the background of treatment by beta adrenoblockers reduction of products of the lacrimal liquid is possible.

Influence on ability to manage motor transport and to work with technical devices. During treatment by drug Lidalok weakness, dizziness, spasms, drowsiness, etc. side effects in this connection, it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions are possible.

Side effects:

Applied the following criteria to assessment of frequency of cases: very often (> 10%), it is frequent (1-9,9%), infrequently (0,1-0,9%), is rare (0,01-0,09%) and is very rare (<0,01%).

From cardiovascular system: often - a sinus bradycardia, the expressed decrease in the ABP, the orthostatic hypotension (which is very seldom followed by a faint), a cold snap of extremities, heartbeat; infrequently - development (aggravation) of a current of HSN (puffiness of feet and/or the lower part of shins, an asthma), AV blockade of the I degree; cardiogenic shock at patients with an acute myocardial infarction; seldom - other disturbances of conductivity of a myocardium, arrhythmia.

From the central nervous system: very often - increased fatigue; often - dizziness, a headache; seldom - hypererethism, uneasiness, impotence / sexual dysfunction; infrequently – paresthesias in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), spasms, a depression, decrease in concentration of attention, drowsiness, sleeplessness, "dreadful" dreams; very seldom – confusion of consciousness or short-term loss of memory, a hallucination, a tremor, an adynamy, a myasthenia, delay of speed of mental and motor reactions.

From the alimentary system: often - nausea, an abdominal pain, diarrhea, a lock; infrequently - vomiting; seldom - dryness of a mucous membrane of an oral cavity, an abnormal liver function (dark urine, yellowness of scleras or skin, a cholestasia); very seldom – hepatitis, taste change.

From integuments: infrequently - skin rash, an itch, a small tortoiseshell, the increased sweating; seldom – a reversible alopecia; very seldom - a photosensitization, an aggravation of a course of psoriasis, psoriazopodobny skin reactions, a dermahemia.

From respiratory system: often - an asthma at physical effort; infrequently - a bronchospasm; seldom - rhinitis.

From sense bodys: seldom - vision disorders, dryness and/or irritation of eyes, conjunctivitis; very seldom - a ring in ears.

From a musculoskeletal system: very seldom – an arthralgia, a dorsodynia or in joints.

From endocrine system: a hyperglycemia (at patients with a non-insulin-dependent diabetes mellitus), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

From a metabolism: infrequently - increase in body weight.

Laboratory indicators: very seldom – thrombocytopenia; agranulocytosis, leukopenia, increase in activity of "hepatic" enzymes, hyperbilirubinemia.

Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.

Interaction with other medicines:

Metoprolol is CYP2D6 isoenzyme substrate in this connection, the drugs inhibiting CYP2D6 isoenzyme (quinidine, тербинафин, пароксетин, fluoxetine, sertraline, целекоксиб, пропафенон and дифенгидрамин) can influence plasma concentration of a metoprolol.

It is necessary to avoid combined use with the following medicines:

Derivatives of barbituric acid: barbiturates (the research was conducted with pentobarbital) strengthen metabolism of a metoprolol, owing to induction of microsomal enzymes of a liver.

Combination with the following drugs can demand dose adjustment:

Difengidramin: дифенгидрамин reduces clearance of a metoprolol to an alpha gidroksimetoprolola by 2,5 times. Strengthening of action of a metoprolol is at the same time observed.

Diltiazem: diltiazem and beta adrenoblockers mutually strengthen the inhibiting effect on AV conductivity and function of a sinus node. At a combination of a metoprolol with diltiazem cases of the expressed bradycardia were noted.

Fenilpropanolamin: фенилпропаноламин in a single dose of 50 mg can cause increase in the diastolic ABP to pathological values in healthy volunteers. Propranolol generally interferes with the increase in the ABP caused fenilpropanolaminy. However beta adrenoblockers can cause reactions of paradoxical arterial hypertension in the patients receiving high doses of a fenilpropanolamin. It was reported about several cases of development of hypertensive crisis against the background of reception of a fenilpropanolamin.

Rifampicin: rifampicin can strengthen metabolism of a metoprolol, reducing plasma concentration of a metoprolol.

The patients who are at the same time accepting метопролол and other beta adrenoblockers (in a dosage form of a drop eye) or inhibitors of a monoaminooxidase (MAO), have to be under careful observation.

At simultaneous use with MAO inhibitors, owing to considerable strengthening of hypotensive action, having rummaged in treatment between reception of MAO inhibitors and a metoprolola has to make not less than 14 days.

Against the background of reception of beta adrenoblockers of means for inhalation anesthesia (halogenated hydrocarbons) are strengthened by cardiodepressive action and probability of decrease in the ABP.

Against the background of reception of beta adrenoblockers dose adjustment of the last can be required by the patients receiving hypoglycemic means for intake.

Plasma concentration of a metoprolol can increase at a concomitant use of Cimetidinum or a gidralazin.

The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving метопролол.

Iodinated X-ray contrast means for in/in introductions increase risk of development of anaphylactic reactions.

Reduces clearance of lidocaine and xanthines (except a diprofillin) and increases their concentration in a blood plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.

Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, BMKK (verapamil, diltiazem), Amiodaronum and other antiarrhytmic means increase risk of development or aggravation of bradycardia, AV of blockade, a cardiac standstill and heart failure. Diuretics, a clonidine, sympatholytics, гидралазин, can lead nifedipine and other antihypertensives to excessive decrease in the ABP.

Extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.

Rub - and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedative and hypnagogues strengthen oppression of TsNS.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.

Contraindications:

- hypersensitivity to a metoprolol and its components or to other beta adrenoblockers;
- atrioventricular block of II and III degrees;
- acute and the chronic heart failure (CHF) in a decompensation stage;
- the patients receiving the long inotropic therapy or means influencing beta adrenoceptors;
- clinically significant sinus bradycardia;
- sick sinus syndrome;
- cardiogenic shock;
- arterial hypotension;
- patients with an acute myocardial infarction at ChSS less than 45 уд. / mines, PQ interval more than 0,24 sec. or the systolic ABP less than 100 mm рт.ст;
- the expressed disturbances of peripheric circulation (at threat of gangrene);
- simultaneous intravenous administration of blockers of "slow" calcium channels like verapamil;
- a pheochromocytoma (without simultaneous use of alpha adrenoblockers);
- age up to 18 years (efficiency and safety are not established).

With care: an atrioventricular block of the I degree, Printsmetal's stenocardia, bronchial asthma, a chronic obstructive pulmonary disease, a diabetes mellitus, the expressed renal failure, a heavy liver failure, a metabolic acidosis, disturbances of peripheric circulation, psoriasis, a depression (including in the anamnesis), a myasthenia, a pheochromocytoma at simultaneous use of alpha adrenoblockers, a thyrotoxicosis.

Overdose:

The first signs of overdose are shown in 20 min. - 2 h after administration of drug.

Symptoms: at overdose by the most serious symptoms from cardiovascular system are, however sometimes, especially at children and teenagers, symptoms from TsNS can prevail, bradycardia, AV blockade of the I-III degree (up to development of total cross block and a cardiac standstill), the expressed sinus bradycardia, arrhythmia, ventricular premature ventricular contraction, an asystolia, the expressed decrease in the ABP, weak peripheral perfusion, heart failure, cardiogenic shock; oppression of function of lungs, an apnoea, increased fatigue, dizziness, a syncope, a coma, cyanosis, a tremor, spasms, the increased sweating, paresthesias, a bronchospasm, nausea, vomiting, the ezofagealny spasm, a hypoglycemia (especially at children) or a hyperglycemia, a hyperpotassemia is possible; impact on kidneys; tranzitorny myasthenic syndrome; the accompanying alcohol intake, anti-hypertensive means, quinidine or barbiturates can worsen a condition of the patient.

Lecheniye:pry of absorbent carbon, in case of need gastric lavage.

Atropine (0,25-0,5 mg in/in for adults, 10-20 mkg/kg for children) has to be appointed to a gastric lavage (because of risk of stimulation of a vagus nerve).

In need of maintenance of passability of respiratory tracts carry out an intubation and provide adequate ventilation of the lungs. Completion of volume of the circulating blood and infusion of a dextrose (glucose). Control of an ECG. If necessary, repeated administration of atropine, in a dose of 1,0-2,0 mg in/in perhaps in case of vagal symptoms. In the absence of positive effect – a dopamine, Dobutaminum.

As the subsequent measures purpose of a glucagon of 50-150 mkg/kg in/in at an interval of 1 minute is possible. Addition to therapy of Norepinephrinum (noradrenaline) can be in certain cases effective. At arrhythmia and the widened ventricular complex (QRS) infusionally enter sodium solutions (chloride or a hydrocarbonate). Installation of an artificial pacemaker is possible. At a cardiac standstill owing to overdose resuscitation actions within several hours can be necessary. Salbutamol can be applied to stopping of a bronchospasm it (is inhalation). Symptomatic treatment.

At spasms - slow in/in administration of diazepam. The hemodialysis is inefficient.

Storage conditions:

In the dry place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated 25 mg, 50 mg, 100 mg. On 10 or 14 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2 or 3 blister strip packagings together with the application instruction place in a pack from a cardboard.