Betalok ZOK - instructions for use, dose, side effects, contraindications

Excipients: ethyl cellulose 21.5 mg, giprolose 6.13 mg, hypromellose 5.64 mg, cellulose microcrystalline 94.9 mg, paraffin 0.06 mg, macrogene 1.41 mg, silicon dioxide 14.6 mg, sodium stearyl fumarate 0.241 mg, titanium dioxide 1.41 mg.

One Betaloc tablet® ZOK 50 mg contains:

Active substance: 47.5 mg of metoprolol succinate, corresponding to 39 mg of metoprolol and 50 mg of metoprolol tartrate.

Excipients: ethyl cellulose 23 mg, giprolose 7 mg, hypromellose 6.2 mg, microcrystalline cellulose 120 mg, paraffin 0.1 mg, macrogol 1.6 mg, silicon dioxide 12 mg, sodium stearyl fumarate 0.3 mg, titanium dioxide 1.6 mg.

One Betaloc tablet® ZOK 100 mg contains:

Active substance: 95 mg of metoprolol succinate, corresponding to 78 mg of metoprolol and 100 mg of metoprolol tartrate.

Excipients: ethylcellulose 46 mg, giprolose 13 mg, hypromellose 9.8 mg, microcrystalline cellulose 180 mg, paraffin 0.2 mg, macrogol 2.4 mg, silicon dioxide 24 mg, sodium stearyl fumarate 0.5 mg, titanium dioxide 2.4 mg.

Description:

Betalok® ZOK 25 mg: Oval biconvex tablets white or almost white, coated; with a notch on both sides and engraved A β on one side.

Betaloc® ZOK 50 mg: Round biconvex tablets white or almost white, coated; with a notch on one side and engraving A mabout on the other side.

Betaloc® ZOOC 100 mg: Round biconvex tablets white or almost white, coated; with a notch on one side and engraving A ms on the other side.

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 to block 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 medicinal forms of selective β₁-adrenoconverters (including metoprolol tartrate), with the use of the preparation Betalok® ZOK a constant concentration of the drug in the blood plasma is observed and a stable clinical effect is provided (β₁-blockade) for more than 24 hours.

Due to the lack of obvious peak plasma concentrations, Betaloc® ZOK is clinically better β₁-selectivity in comparison with conventional tableted forms β₁adrenoblockers. In addition, the potential risk of side effects observed at peak plasma concentrations of the drug, such as bradycardia and leg weakness during walking, is significantly reduced.

Patients with symptoms of obstructive pulmonary disease may, if necessary, be assigned Betalok® ZOK in combination with β₂- adrenomimetics. When combined with β₂- adrenomimetics Betalok® ZOK in therapeutic doses to a lesser extent affects the β₂- adrenomimetics bronchodilation, than non-selective β-adrenoceptor blockers. Metoprolol to a lesser extent than non-selective β -adrenoblockers, affects insulin production and carbohydrate metabolism. The effect of the drug on the response of the cardiovascular system in conditions of hypoglycemia is much less pronounced in comparison with nonselective β adrenoblockers.

The use of Betaloc® ZOK in arterial hypertension leads to a significant reduction in blood pressure for more than 24 hours, both in prone position and standing, and under load.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.

AT MERIT-HF (survival study for chronic heart failure (class II-IV by classification NYHA) and a reduced fraction of cardiac output (≤0.40), which included 3991 patients) Betaloc® ZOK showed an increase in survival rate and a decrease in the frequency of hospitalizations. With prolonged treatment, patients achieved a general improvement in symptoms (by class NYHA). Also, therapy with Betaloc® ZOK showed an increase in the left ventricular ejection fraction, a reduction in the final systolic and terminal diastolic volumes of the left ventricle.

The quality of life during the treatment with Betaloc® ZOK does not deteriorate or improve. Improvement of the quality of life in the treatment with Betaloc® ZOK was observed in patients after myocardial infarction.

Pharmacokinetics:

Upon contact with the liquid, the tablets disintegrate quickly, and the active substance is dispersed in the gastrointestinal tract.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 Betaloc® ZOK dosage form (sustained-release tablets) 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.

Betalok® ZOK is completely absorbed after ingestion. Systemic bioavailability after oral administration of a single dose is approximately 30-40%.

Metoprolol is subjected to oxidative metabolism in the liver. The three main metabolites of metoprolol did not show a clinically significant βblocking effect. About 5% of the oral dose of the drug is excreted in the urine unchanged, the rest of the drug is excreted as metabolites. The association with plasma proteins is low, about 5-10%.

Indications:

- Arterial hypertension;

- fromangina pectoris;

- fromtamily symptomatic chronic heart failure with a violation of systolic function of the left ventricle (as an auxiliary therapy to the main treatment of chronic heart failure);

- fromthe mortality and frequency of recurrent myocardial infarction after the acute phase of myocardial infarction;

- Mr.cardiac rhythm disturbances, including supraventricular tachycardia, a reduction in ventricular contraction rate in atrial fibrillation and ventricular extrasystoles;

- ffunctional disorders of cardiac activity, accompanied by tachycardia;

- Pprevention of migraine attacks.

Contraindications:

Atrioventricular blockade of II and III degree, heart failure in the stage of decompensation, permanent or intermittent therapy with inotropic drugs acting on beta-adrenergic receptors, clinically significant sinus bradycardia, sinus node weakness syndrome, cardiogenic shock, severe peripheral circulatory disturbances, including under threat gangrene, arterial hypotension.

Betalok® ZRO is contraindicated in patients with suspected acute myocardial infarction at a heart rate of less than 45 beats per minute, PQ interval greater than 0.24 seconds, or systolic blood pressure less than 100 mmHg.

Known hypersensitivity to metoprolol and its components or to other βadrenoblockers.

Patients receiving β-adrenoblockers are contraindicated intravenous administration of blockers of "slow" calcium channels such as verapamil.

Age to 18 years (effectiveness and safety not established).

Carefully:

Atrioventricular block I degrees, angina pectoris, bronchial asthma, chronic obstructive pulmonary disease, diabetes mellitus, severe hepatic insufficiency, severe renal failure, metabolic acidosis, joint appointment with cardiac glycosides.

Pregnancy and lactation:

As with most Betaloc® ZOK preparations, you should not prescribe during pregnancy and during breastfeeding, except when the expected benefit to the mother exceeds the potential risk to the fetus and / or the baby. Like other antihypertensive drugs, β-adrenoconjugators 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.

Dosing and Administration:

Betalok® ZOK is designed for daily administration once a day, it is recommended to take the drug in the morning. The Betaloc® ZOK tablet 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 100 mg per day or add another antihypertensive agent, preferably diuretic and calcium antagonist dihydropyridine series.

Angina pectoris

100-200 mg Betaloc® ZOK once a day. If necessary, another antianginal drug may be added to the therapy.

Stable symptomatic chronic heart failure with a violation of left ventricular systolic function

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.

The therapy of heart failure with beta-blockers can sometimes lead to a temporary worsening of the symptomatic pattern.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 Betaloc® ZOC is 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.

The maintenance dose for long-term treatment is 200 mg Betaloc® ZOK once a day.

Stable chronic heart failure, III-IV functional class

The recommended initial dose for the first 2 weeks is 12.5 mg Betaloc® ZOK (half a tablet of 25 mg) once a day. The dose is selected individually. During the period of increasing the dose, the patient should be monitored, since in some patients the symptoms of heart failure may worsen.

After 1-2 weeks, the dose may be increased to 25 mg Betaloc® ZOK 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 Betaloc® ZOK is given once a day.

In the case of arterial hypotension and / or bradycardia, a reduction in concomitant therapy or a decrease in the dose of Betaloc® ZOK may be necessary. Arterial hypotension at the beginning of therapy does not necessarily indicate that this dose of Betaloc® ZOK will not be tolerated with further long-term treatment. However, the dose should not be increased until the condition stabilizes. Control of kidney function may be required.

Heart rhythm disturbances

100-200 mg Betaloc® ZOK once a day.

Supportive treatment after myocardial infarction

200 mg Betaloc® ZOK once a day.

Functional disorders of cardiac activity, accompanied by tachycardia

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

Preventing migraine attacks

100-200 mg Betaloc® ZOK once a day.

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 binding to plasma proteins, dose correction of metoprolol 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.

Children

Experience with Betalok® ZOK in children is limited.

Side effects:

Betalok® ZOK 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: bradycardia, orthostatic hypotension (very rarely accompanied by syncope), coldness of the extremities, palpitation;

Infrequent: a temporary increase in symptoms of heart failure, AV blockade of the 1st degree; cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart;

Rarely: other conduction disorders, 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, decreased concentration of attention, drowsiness or insomnia, nightmares;

Rarely: increased nervous excitability, anxiety;

Very rarely: amnesia / memory disorders, depression, hallucinations.

Gastrointestinal tract

Often: nausea, abdominal pain, diarrhea, constipation;

Infrequent: vomiting;

Rarely: dryness of the oral mucosa.

Liver

Rarely: liver dysfunction;

Very rarely: hepatitis.

Skin covers

Infrequent: skin rash (by the type of psoriasis-like urticaria), increased sweating;

Rarely: hair loss;

Very rarely: photosensitization, exacerbation of psoriasis.

Respiratory system

Often: dyspnoea with physical exertion;

Infrequent: bronchospasm;

Rarely: rhinitis.

Sense organs

Rarely: visual disturbances, dryness and / or eye irritation, conjunctivitis;

Very rarely: ringing in the ears, a violation of taste.

From the musculoskeletal system

Very rarely: arthralgia.

Metabolism

Infrequent: weight gain.

Blood

Very rarely: thrombocytopenia.

Other

Rarely: impotence / sexual dysfunction.

Overdose:

Toxicity: metoprolol in a dose of 7.5 g in an adult caused intoxication with a fatal outcome. In a 5-year-old child who took 100 mg of metoprolol, no signs of intoxication were noted after gastric lavage. Admission of 450 mg metoprolol by a teenager of 12 years resulted in moderate intoxication.Admission 1.4 g and 2.5 g metoprolol in adults caused mild and severe intoxication, respectively. Admission 7.5 grams to adults led to extremely severe intoxication.

Symptoms: with metoprolol overdose, the most serious are the symptoms of the cardiovascular system, but sometimes, especially in children and adolescents, the symptoms of 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, unconsciousness, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophagial 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. The first signs of an overdose can be observed in 20 minutes - 2 hours after taking the drug.

Treatment: the appointment of activated carbon, if necessary, gastric lavage. IMPORTANT! 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 minute. In some cases, there may be an effective addition to adrenaline therapy. With arrhythmias and extensive ventricular (QRS) complex infusion is introduced solutions of sodium (chloride or bicarbonate). It is possible to install 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 CYP2D6, in this connection, drugs inhibiting CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) can affect the plasma concentration of metoprolol.

It is necessary to avoid the joint use of Betalok® OCK with the following medicines:

Derivatives of barbituric acid: Barbiturates (the study was conducted with pentobarbital) increases the 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. This interaction was confirmed during the study on 8 volunteers. Probably, the interaction is due to the inhibition of propafenone, like quinidine, metabolism of metoprolol through the cytochrome P4502D6 system. Taking into account the fact that propafenone has properties βadrenoblocker, co-administration of metoprolol and propafenone is not advisable.

Verapamil: a combination of β-blockers (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 Betaloc® ZOK with the following drugs 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: Antiarrhythmics of Class I and βadrenoblockers can lead to a summation 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 AV conduction disorder. The interaction is described by the example of disopyramide.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs impair antihypertensive effect of β-blockers. 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 clearance 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 β-adrenoblockers 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 (adrenaline): There were reported 10 cases of severe arterial hypertension and bradycardia in patients taking non-selective β-blockers (including pindolol and propranolol) and received epinephrine (adrenalin). Interaction is noted in the group of healthy volunteers. It is suggested that similar reactions can be observed when epinephrine is used in conjunction with local anesthetics in case of accidental exposure tothe vascular bed. It is assumed that this risk is much lower with the use of cardioselective β-adrenoblockers.

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. However, β-adrenoblockers 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 special 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 participates P4502D6.

Clonidine: Hypertensive reactions with abrupt cancellation of clonidine can be enhanced by joint admission of β-blockers.When combined, in the case of the withdrawal of clonidine, discontinuation of the adrenoblockers should be started several 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-adrenoconjunctivators (eye drops) or monoamine oxidase inhibitors (MAO), should be carefully monitored.

Against the background of taking β-blockers, inhalational anesthetics increase the 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 taking beta-adrenoblockers should not be administered intravenously blockers of "slow" calcium channels like verapamil.

Patients with bronchial asthma or chronic obstructive pulmonary disease should be assigned concomitant therapy with β₂adrenomimetic. It is necessary to prescribe a minimally effective dose of Betaloc® ZOK, and an increase in the dose of β₂-adrenomimetics.

It is not recommended to prescribe non-selective β-adrenoblockers to patients with Prinzmetal angina. To this group of patients, β-selective adrenoblockers should be administered with caution.

When applying β₁adrenoblockers, the risk of their effect on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly less than with the use of nonselective β-adrenoblockers.

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.

Very rarely in patients with AV conduction disorder, deterioration may occur (the possible outcome is AV blockade).

If bradycardia develops against the background of treatment, the dose of the drug should be reduced or the drug should be gradually withdrawn.

Betalok® ZOK can aggravate the course of existing 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, concomitant use with cardiac glycosides.

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

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

Patients with pheochromocytoma simultaneously with the preparation Betalok® ZOK should be prescribed alpha-blocker.

Abrupt withdrawal of beta-blockers is dangerous, especially in patients at high risk, and therefore it should be avoided. If it is necessary to cancel the drug, it should be done gradually, for at least 2 weeks, with a two-fold reduction in the dose of the drug at each stage, until the final dose of 12.5 mg (1/2 tablet of 25 mg), which should be taken as a minimum 4 days before the drug is completely discontinued. When symptoms appear (eg, increased symptoms of angina pectoris, increased blood pressure), a slower cancellation is recommended.

Abrupt withdrawal of the beta-blocker may lead to an increase in the course of chronic heart failure and an increased risk of myocardial infarction and sudden death.

In case of surgery, the anesthetist should be informed that the patient is taking Betaloc® ZOK. Patients who are undergoing surgery should not be discontinued with beta-blockers. High doses should be avoided without preliminary titration of the doses of the drug in patients with cardiovascular risk factors undergoing non-cardiac surgery, due to an increased risk of bradycardia, arterial hypotension and stroke, including fatalities.

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

The treatment of such patients should be carried out by physicians with special knowledge and experience.

Patients with symptomatic heart failure in combination with acute myocardial infarction and unstable angina were excluded from the studies,on the basis of which the indications to the appointment were determined. The efficacy and safety of the drug for this group of patients is not described.

The use in unstable heart failure in the stage of decompensation is contraindicated.

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

When driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, it should be borne in mind that when using Betaloc® ZOK, dizziness and fatigue can occur.

Form release / dosage:Tablets with delayed release, coated with a coating, 25 mg, 50 mg and 100 mg.

Packaging:

Tablets 25 mg: 14 tablets in aluminum / PVC blister, in a cardboard box with instructions for use.

Tablets 50 mg and 100 mg: 30 tablets in a plastic bottle with a screwed plastic lid with the control of the first opening, 1 bottle is placed in a cardboard box with instructions for use.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013890 / 01

Date of registration:05.09.2007 / 29.01.2016

Expiration Date:Unlimited

The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

ZIO-HEALTH, JSC Russia

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

Betalok® ZOK (Betaloc® ZOK)