Egilok S - instructions for use, dose, side effects, contraindications

active substance: 23.75 mg, 47.5 mg, 95 mg or 190 mg of metoprolol succinate, corresponding to 25 mg, 50 mg, 100 mg or 200 mg of metoprolol tartrate, respectively;

Excipients: cellulose microcrystalline 73,9 / 147,8 / 295,6 / 591,2 mg, methylcellulose 11,87 (23,75 / 47,5 / 95 mg, glycerol 0,24 / 0,48 / 0,95 / 1, 9 mg, starch corn 1.94 / 3.87 / 7.75 / 15.5 mg, ethyl cellulose 11.43 / 22.85 / 45.7 (91.4 mg, magnesium stearate 1.87 (3.75) 7.5 / 15 mg. The tablet shell (Sepiophilm LP 770 white) 3.75 / 7.5 / 15/30 mg: microcrystalline cellulose (5-15%), hypromellose (60-70%), stearic acid (8-12%), titanium dioxide (E-171) ( 10-20%).

Description:ABOUTdouble, biconvex tablets of white color, film-coated, with a risk on both sides.

Pharmacotherapeutic group:beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.02 Metoprolol

Pharmacodynamics:

Metoprolol - β₁-adrenoceptor blocking β₁-receptors at doses significantly lower than the doses required for blocking β₂receptors.

Metoprolol has an insignificant membrane-stabilizing effect and does not exhibit the activity of a partial agonist.

Metoprolol reduces or inhibits the agonistic effect that catecholamines exerted on nervous activity by nervous and physical stresses on cardiac activity. It means that metoprolol has the ability to prevent an increase in the heart rate (heart rate), a minute volume and increased heart contractility, as well as an increase in blood pressure (BP) caused by a sharp release of catecholamines.

In contrast to conventional tableted dosage forms of selective β₁-adrenoblockers (including metoprolol tartrate), with the use of the drug metoprolol succinate prolonged action, there is a constant concentration of the drug in the blood plasma and provides a stable clinical effect (β₁-blockade) for more than 24 hours.Due to the absence of significant maximum concentrations in blood plasma, the drug is characterized by a higher β₁-selectivity in comparison with conventional tableted forms of metoprolol. In addition, the potential risk of side effects observed at maximum drug concentrations in the blood plasma, for example, bradycardia and weakness in the legs when walking, is significantly reduced.

Patients with symptoms of obstructive pulmonary disease, if necessary, can be prescribed metoprolol succinate of prolonged action in combination with β₂-adrenomimetics. When combined with β₂-adrenomimetics metoprolol succinate prolonged action in therapeutic doses to a lesser extent affects the called β₂-adrenomimetics bronchodilation, than non-selective β-adrenoblockers.

Metoprolol, to a lesser extent than non-selective β-adrenoblockers, affects insulin production and carbohydrate metabolism. The effect of the drug on the cardiovascular system under conditions of hypoglycemia is much less pronounced compared with non-selective β-blockers.

The use of the drug with arterial hypertension leads to a significant decrease in blood pressure for more than 24 hours, both in the supine and standing position, and under physical exertion. At the beginning of metoprolol therapy, an increase in vascular resistance is noted. However, with long-term admission, it is possible to lower blood pressure due to a reduction in vascular resistance with unchanged cardiac output.

Pharmacokinetics:

In each tablet metoprolol succinate prolonged action contains a large number of micro pellets (pellets), allowing a controlled release of metoprolol succinate. Outside, each micro pellet (pellet) is coated with a polymer coating, which allows for a controlled release of the drug substance.

The effect of prolonged tablets comes quickly. In the gastrointestinal tract (GIT) the tablet disintegrates into separate micro pellets that act as independent units and provide a uniform controlled release of metoprolol (zero order kinetics) for more than 20 hours. The release rate of the active substance depends on the acidity of the medium.The duration of the therapeutic effect after taking the drug in the dosage form of the sustained-release tablet is more than 24 hours. The half-life of free metoprolol is 3.5-7 hours on average.

The drug is completely absorbed after ingestion. Systemic bioavailability after oral administration of a single dose is approximately 30-40%. Metoprolol is exposed to oxidative metabolism in the liver. The three main metabolites of metoprolol did not show a clinically significant βblocking effect. About 5% of the dose for oral administration 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%.

Indications:

Arterial hypertension.

Angina pectoris.

Stable chronic heart failure with the presence of clinical manifestations (II-IV functional class (FC) by classification NYHA) and a violation of the systolic function of the left ventricle (as an auxiliary therapy to the basic treatment of chronic heart failure).

Reduction of mortality and frequency of recurrent myocardial infarction after acute phase of myocardial infarction.

Heart rhythm disturbances, including supraventricular tachycardia, reduced ventricular contraction rate in atrial fibrillation and ventricular extrasystoles.

Functional disorders of cardiac activity, accompanied by tachycardia.

Prevention of migraine attacks.

Contraindications:

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

Atrioventricular blockade of II and III degree, heart failure in the stage of decompensation, patients receiving long-term or course therapy with inotropes and acting on beta-adrenoreceptors, clinically significant sinus bradycardia (heart rate less than 50 beats / min), sinus node weakness syndrome, cardiogenic shock, severe peripheral circulation disorders with the threat of gangrene development, arterial hypotension (systolic blood pressure less than 90 mm Hg), pheochromocytoma without simultaneous alpha-adrenoblockers.

Suspicion of acute myocardial infarction at a heart rate of less than 45 beats per minute, interval PQ more than 0.24 s, systolic blood pressure less than 100 mm Hg.

Simultaneous use of monoamine oxidase inhibitors (MAO) (with the exception of MAO-B inhibitors).

Intravenous administration of blockers of "slow" calcium channels such as verapamil.

Age to 18 years (efficiency and safety not established)

Carefully:Atrioventricular blockade of the first degree, angina of princemetal, bronchial asthma, chronic obstructive pulmonary disease, diabetes mellitus, severe renal failure, severe hepatic insufficiency, metabolic acidosis, concomitant use with cardiac glycosides, myasthenia gravis, pheochromocytoma (with simultaneous administration of alpha-adrenoblockers), thyrotoxicosis, depression, psoriasis, obliterating diseases of peripheral vessels ("intermittent" lameness, Raynaud's syndrome), elderly age.

Pregnancy and lactation:

Since no well-controlled studies on the use of metoprolol during pregnancy have been conducted, the use of the drug Egilok^®C in the treatment of pregnant women is possible only if the benefit to the mother exceeds the risks for the embryo / fetus.

Like other antihypertensives, β-blockers can cause side effects, for example,bradycardia in the fetus, newborns or children who are breastfed.

The amount of metoprolol released into breast milk and the β-blocking effect in a breastfed infant (when metoprolol is taken by the mother at therapeutic doses) are minor. Despite the fact that in children who are breast-feeding, when the therapeutic doses are prescribed, the risk of side effects is low (except for children with metabolic disorders), it is necessary to carefully monitor the appearance of signs of blockade of beta adrenoreceptors.

Dosing and Administration:

EHILOK^® Since it is intended for daily administration once a day, it is recommended to take the drug in the morning. Egilok Tablets^® C should be swallowed with a liquid. Tablets (or tablets, divided in half) should not be chewed or crushed. Eating does not affect the bioavailability of the drug. When choosing a dose, it is necessary to avoid the development of a bradycardia.

Arterial hypertension

50-100 mg once a day. If necessary, the dose can be increased to 200 mg per day or add another antihypertensive drug,preferably diuretic and blocker of "slow" calcium channels (BCCC). The maximum daily dose for AH is 200 mg / day.

Angina pectoris

100-200 mg of EGILOK^® From once a day. If necessary, another antianginal drug may be added to the therapy.

Stable chronic heart failure with the presence of clinical manifestations and a violation of the systolic function of the left ventricle

Patients should be in the stage of stable chronic heart failure without episodes of exacerbation during the last 6 weeks and without changes in the main therapy within the last 2 weeks.

Therapy of chronic heart failure with beta-blockers can sometimes lead to a temporary deterioration in the course of CHF. In some cases, it is possible to continue therapy or reduce the dose, in some cases it may be necessary to cancel the drug.

Stable chronic heart failure, II functional class

The recommended initial dose of Egilok^® From 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 can then be doubled every 2 weeks.

Supportive dose for long-term treatment 200 mg of EHILOK® C once a day.

Stable chronic heart failure, III-IV functional class

The recommended initial dose of the first 2 weeks is 12.5 mg of EHILOK^® C (1/2 tablets of 25 mg) once a day. The dose is selected individually. During the period of increasing the dose, the patient should be monitored, as in some patients the symptoms of chronic heart failure may progress.

After 1-2 weeks, the dose can be increased to 25 mg Egiloc^® From 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 to achieve a maximum dose of 200 mg of EHILOK^® From once a day.

In the case of arterial hypotension and / or bradycardia, it may be necessary to adjust the doses of the main therapy or to reduce the dose of EHILOK^® FROM.

Arterial hypotension at the beginning of therapy does not necessarily indicate that this dose of EHILOK^® C will not be tolerated with further long-term treatment. However, an increase in the dose is only possible after stabilization of the patient's condition. You may need to monitor kidney function.

Heart rhythm disturbances

100-200 mg once daily.

Supportive treatment after myocardial infarction

The target dose is 100-200 mg / day, in one (or two) doses.

Functional disorders of cardiac activity, accompanied by tachycardia

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

Preventing migraine attacks

100-200 mg once daily.

Impaired renal function

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

Impaired liver function

Usually, due to the low degree of association with plasma proteins, dose adjustment is not required. However, with a severe impairment of liver function (in patients with severe cirrhosis or portocaval anastomosis), a dose reduction may be required.

Elderly age

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

Side effects:

The drug is well tolerated by patients, side effects are mostly light and reversible.

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%).

The cardiovascular system: often - a bradycardia,Orthostatic hypotension (very rarely accompanied by syncope), cold extremities, palpitations; infrequently - peripheral edema, pain in the heart, temporary increase in symptoms of heart failure, AV blockade of the 1st degree; Cardiogenic shock in patients with acute myocardial infarction; rarely - other disorders of cardiac conduction, arrhythmia; very rarely - gangrene in patients with previous severe impairment of peripheral circulation.

central nervous system: very often - increased fatigue; often - dizziness, headache; infrequently - paresthesia, convulsions, depression, loss of attention, drowsiness or insomnia, nightmares; rarely - increased nervous excitability, anxiety, impotence / sexual dysfunction; very rarely - amnesia / memory disorders, depression, hallucinations.

Gastrointestinal tract: often - nausea, abdominal pain, diarrhea, constipation; infrequently - vomiting; rarely dryness of the oral mucosa.

Liver: rarely - violations of the liver function; very rarely - hepatitis.

Skin covers: infrequently - a rash (in the form of urticaria), increased sweating; rarely - hair loss; very rarely - photosensitivity, exacerbation of psoriasis.

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

Sense organs: rarely - visual impairment, dryness and / or eye irritation, conjunctivitis; very rarely - ringing in the ears, a violation of taste.

From the musculoskeletal system: very rarely - arthralgia.

Metabolism: infrequently, weight gain.

Blood: very rarely - thrombocytopenia.

Overdose:

Symptoms: with metoprolol overdose, the most serious symptoms are from the cardiovascular system, however sometimes, especially in children and adolescents, symptoms from the central nervous system and suppression of pulmonary function, bradycardia, AV blockade I-III degree, asystole, marked decrease in blood pressure, weak peripheral perfusion, heart failure, cardiogenic shock; oppression of lung function, apnea, as well as, increased fatigue, impaired consciousness, loss of consciousness, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophagic spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; impaired renal function; transient myasthenic syndrome; The concomitant intake of alcohol, antihypertensive drugs, quinidine or barbiturates can worsen a patient's condition.

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

Treatment: the appointment of activated carbon, 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 necessary, maintain airway patency (intubation) and adequate ventilation of the lungs. Replenishment of the volume of circulating blood and glucose infusion. ECG monitoring. Atropine 1,0-2,0 mg iv, if necessary, repeat the introduction (especially in case of vagal symptoms). In the case of (suppression) of myocardial depression, an infusion of dobutamine or dopamine is indicated. It can also be used glucagon 50-150 mcg / kg iv with an interval of 1 min. In some cases, it may be effective to add epinephrine (epinephrine) to therapy. With arrhythmias and extensive ventricular (QRS) a 0.9% solution of sodium chloride or sodium bicarbonate is injected infusion. It is possible to stage an artificial pacemaker. When cardiac arrest due to an overdose, resuscitation may be necessary for several hours. To stop bronchospasm, terbutaline can be used (by injection or by inhalation).Symptomatic treatment is performed.

Interaction:

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

Avoid joint use of the drug EHILOK^® FROM with the following medicines:

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

Propaphenon: when administering propafenone to four patients treated with metoprolol, an increase in plasma concentrations of metoprolol was observed in 2-5 times, while two patients had side effects typical of metoprolol. Probably, the interaction is due to the inhibition of propafenone, like quinidine, metabolism of metoprolol through the cytochrome P450 system of the CYP2D6 isoenzyme. Taking into account the fact that propafenone possesses the properties of Egilok^® With β-adrenoblocker, the combined use of metoprolol and propafenone is not recommended.

Verapamil: combination of Egilok^® With β-adrenoblockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and β-adrenoblockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.

The combination of ZILOK® C with the following preparations may require dose adjustment:

Amiodarone: The combined use of amiodarone and metoprolol can lead to severe sinus bradycardia. Taking into account the extremely long half-life of amiodarone (50 days), possible interaction should be considered after a long time after amiodarone withdrawal.

Class I antiarrhythmic drugs: Class I antiarrhythmics and beta-blockers can lead to the addition of a negative inotropic effect, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. Also, this combination should be avoided in patients with sinus node weakness syndrome and impaired AV conductivity.

The interaction is described by the example of disopyramide.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs impair antihypertensive effectβadrenoblockers. This interaction is documented for indomethacin. Probably, the described interaction will not be noted when interacting with sulindac. Negative interaction was noted in studies with diclofenac.

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

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

Epinephrine: There were reported 10 cases of severe arterial hypertension and bradycardia in patients taking non-selective β-adrenoconverters (including pindolol and propranolol) and received epinephrine. Interaction is noted in the group of healthy volunteers. It is assumed that similar reactions may occur and the application of epinephrine with local anesthetic together with a random contact with the bloodstream.It is assumed that this risk is much lower with the use of cardioselective βadrenoblockers.

Phenylpropanolamine: Phenylpropanolamine (norephedrine) 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. but β-adrenoconverters can cause reactions of paradoxical arterial hypertension in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported against phenylpropanolamine.

Quinidine: Quinidine inhibits the metabolism of metoprolol in a particular group of patients with rapid hydroxylation (in Sweden about 90% of the population), mainly causing a significant increase in plasma concentrations of metoprolol and an increase in β-blockade. It is believed that this interaction is characteristic of other β-adrenoblockers, in the metabolism of which cytochrome P450 isoenzyme CYP2D6.

Clonidine: Hypertensive reactions with a sharp abolition of clonidine can be enhanced by joint admission βadrenoblockers.When combined, in the case of withdrawal of clonidine, discontinuation of admission β-adrenoconverters should be started a few days before the withdrawal of clonidine.

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

Patients simultaneously taking metoprolol and others β- adrenoblockers (in the form of eye drops) or monoamine oxidase (MAO) inhibitors, should be carefully monitored. On the background of admission β-adreno-blockers inhalation anesthetics increase cardiodepressive effect. Against the background of admission of β-blockers, patients receiving hypoglycemic agents for ingestion may require a dose adjustment of the latter.

Plasma concentration of metoprolol may increase with the use of cimetidine or hydralazine.

Cardiac glycosides when used together with βadrenoblockers can increase the time of atrioventricular conduction and cause bradycardia.

Special instructions:

Patients receiving padrenoblockers, should not be administered intravenously blockers of "slow" calcium channels such as verapamil.

Patients with obstructive pulmonary disease should not be prescribed β-blockers. In case of poor tolerability of other antihypertensive drugs or their inefficiency, metoprololbecause it is a selective drug. It is necessary to prescribe a minimally effective dose, if necessary, the appointment of β₂-adrenomimetics.

It is not recommended to designate nonselective β- adrenoblockers in patients with Prinzmetal angina. This group of patients β-adrenoceptor selective should be administered with caution.

When applying β₁-adrenoblokatorov the risk of their influence on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly less than with the use of nonselective βadrenoblockers.

In patients with chronic heart failure in the stage of decompensation, it is necessary to achieve a compensation stage both before and during treatment with the drug Egilok^® FROM.

Very rarely in patients with impaired AV conductivity can be aggravated (possible outcome - AV blockade). If bradycardia develops against the background of treatment, the dose of the drug Egilok^® C should be reduced or the drug should be gradually withdrawn.

Metoprolol may worsen the symptoms of peripheral circulatory disorders mainly due to lowering blood pressure.

Care should be taken when prescribing the drug to patients with severe renal failure, metabolic acidosis, co-administration with cardiac glycosides.

In patients taking beta-adrenoblockers, anaphylactic shock occurs in a more severe form.

The use of epinephrine in therapeutic doses does not always lead to the desired clinical effect against metoprolol.

Patients with pheochromocytoma, in parallel with the drug Egilok^® C should be prescribed alpha-blocker.

In case of surgery, the anesthetist should be informed that the patient is taking EGILOK^® C. Patients who are undergoing surgery should not be treated with beta-blockers.

Data from clinical trials on efficacy and safety in patients with severe stable heart failure (grade IV class NYHA) are limited.

Patients with symptoms of heart failure in combination with acute myocardial infarction and unstable anginaexcluded from the studies, on the basis of which the indications for the appointment were determined. The efficacy and safety of the drug for this group of patients is not described. The use of heart failure in the stage of decompensation is contraindicated.

Sharp cancellation β-adrenoconstituent can lead to increased symptoms of CHF and an increased risk of myocardial infarction and sudden death, especially in high-risk patients, and therefore it should be avoided. If it is necessary to cancel the drug, it should be carried out gradually, for at least 2 weeks, with a twofold reduction in the dose of the drug at each stage, until the final dose of 12.5 mg (1/2 tablets of 25 mg), which should be taken at least 4 days before the complete withdrawal of the drug. When symptoms appear, a slower mode of drug cancellation is recommended.

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

Care must be taken when driving vehicles and engaging in potentially hazardous activities requiring increased concentration of attention, due to the risk of dizziness and fatigue when using Egiloc^® FROM.

Form release / dosage:Tablets of prolonged action, film-coated, 25 mg, 50 mg, 100 mg and 200 mg.

Packaging:

For 10 tablets in a blister of PVC / PE / PVDC / / aluminum foil.

3 or 10 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001351

Date of registration:13.12.2011 / 16.10.2014

Expiration Date:13.12.2016

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp24.07.2016

Illustrated instructions

Instructions

Egilok® С (Egilok® S)