Composition
1 tablet contains:
Active ingredients:
metoprolol succinate – 95 mg, which corresponds to the content of: metoprolol tartrate-100 mg, metoprolol-78 mg.
Auxiliary substances:
ethylcellulose-46 mg,
hyprolose-13 mg,
hypromellose-9.8 mg,
microcrystalline cellulose-180 mg,
paraffin-200 mcg,
macrogol-2.4 mg,
silicon dioxide-24 mg,
sodium stearyl fumarate-500 mcg,4
titanium dioxide-2.4 mg
Pharmacological action
Selective beta-1-adrenoblocker without internal sympathomimetic activity. It has a slight membrane-stabilizing effect and does not show partial agonist activity.
Metoprolol reduces or inhibits the agonistic effect that catecholamines released during nervous and physical stress have on cardiac activity. This means that metoprolol has the ability to prevent an increase in heart rate, minute volume and increased contractility of the heart, as well as an increase in blood pressure caused by a sharp release of catecholamines.
In contrast to the usual tablet dosage forms of selective beta-1-blockers (including metoprolol tartrate), when using the drug Betalok ® ZOK, a constant concentration of the drug in blood plasma is observed and a stable clinical effect (blockade of beta-1-adrenergic receptors) is provided for more than 24 hours.
Due to the absence of obvious peak plasma concentrations, clinically Betalok ® ZOK is characterized by better selectivity for beta-1-adrenergic receptors compared to conventional tablet forms of beta-1-adrenergic blockers. In addition, the potential risk of side effects observed at peak plasma concentrations of the drug, such as bradycardia and weakness in the legs when walking, is significantly reduced.
If necessary, patients with symptoms of obstructive pulmonary disease can be prescribed Betalok ® ZOK in combination with beta-2-adrenomimetics. When combined with beta-2-adrenomimetics, Betaloc ® ZOK in therapeutic doses has a lesser effect on bronchodilation caused by beta-2-adrenomimetics than non-selective beta-blockers. Metoprolol affects insulin production and carbohydrate metabolism to a lesser extent than non-selective beta-blockers. The effect of the drug on the response of the cardiovascular system in conditions of hypoglycemia is significantly less pronounced compared to non-selective beta-blockers.
The use of Betalok ® ZOK in patients with arterial hypertension leads to a significant decrease in blood pressure for more than 24 hours, both in the supine and standing positions, and during exercise. At the beginning of metoprolol therapy, an increase in OPSS is noted. With prolonged use, a decrease in blood pressure is possible due to a decrease in OPSS with constant cardiac output.
In the MERIT-HF study of survival in chronic heart failure (NYHA functional class II-IV) with a reduced ejection fraction (≤ 0.4), which included 3991 patients, Betalok ® ZOK showed an increase in survival and a decrease in the frequency of hospitalizations. With long-term treatment, patients achieved an overall improvement in well-being, easing the severity of symptoms (according to NYHA functional classes). Also, therapy with Betalok ® ZOK showed an increase in the left ventricular ejection fraction, a decrease in the end systolic and end diastolic volumes of the left ventricle.
The quality of life during treatment with Betalok® ZOK does not worsen or improve. Improvement in quality of life during treatment with Betalok ® ZOK was observed in patients after myocardial infarction.
Indications
- Arterial hypertension.
- Angina pectoris.
- Stable symptomatic chronic heart failure with impaired left ventricular systolic function (as an adjunct therapy to the main treatment of heart failure).
- To reduce mortality and the frequency of recurrent infarction after the acute phase of myocardial infarction.
- Cardiac arrhythmias, including supraventricular tachycardia, decreased ventricular rate in atrial fibrillation and ventricular extrasystoles.
- Functional disorders of cardiac activity accompanied by tachycardia.
- Prevention of migraine attacks.
Use during pregnancy and lactation
As with most medications, Betalok ® ZOK should not be administered during pregnancy and lactation, unless the expected benefit to the mother outweighs the potential risk to the fetus and / or child.
Like other antihypertensive drugs, beta-blockers can cause side effects, such as bradycardia in the fetus, newborns, or children who are breastfed. The amount of metoprolol released into breast milk and the beta-blocking effect in a breastfed child (when the mother takes metoprolol in therapeutic doses) are insignificant.
Contraindications
- AV blockade of II and III degrees.
- Chronic heart failure in the stage of decompensation.
- Continuous or intermittent therapy with inotropic agents aimed at stimulating beta-adrenergic receptors.
- Clinically significant sinus bradycardia.
- SSSU.
- Cardiogenic shock.
- Severe pronounced disorders of peripheral arterial circulation (including with the threat of gangrene).
- Arterial hypotension.
- Patients with suspected acute myocardial infarction with a heart rate of less than 45 beats / min, a PQ interval of more than 0.24 seconds, or a systolic blood pressure of less than 100 mm Hg.
- Intravenous use of slow calcium channel blockers (similar to verapamil).
- Children and adolescents under 18 years of age (efficacy and safety have not been established).
- Hypersensitivity to the components of the drug.
- Hypersensitivity to other beta-blockers.
With caution: use the drug in patients with AV block I degree, Prinzmetal angina pectoris, bronchial asthma, COPD, diabetes mellitus, severe renal failure, metabolic acidosis, together with cardiac glycosides.
Side effects
The following criteria were used to assess the frequency of cases:
- Very often ( > 10%).
- Often (1-9.9%).
- Infrequently (0.1-0.9%).
- Rarely (0.01-0.09%).
- Very rare (
From the cardiovascular system: often-bradycardia, orthostatic arterial hypotension (very rarely accompanied by syncope), cold extremities, palpitation sensation; infrequently-temporary increase in symptoms of heart failure, AV block I degree, cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart; rarely-other conduction disorders, arrhythmias; very rarely-gangrene (in patients with severe peripheral circulatory disorders).
From the central nervous system and peripheral nervous system: very often-increased fatigue; often-dizziness, headache; infrequently-paresthesia, convulsions, depression, decreased ability to concentrate, drowsiness or insomnia, nightmares; rarely – increased nervous excitability, anxiety; very rarely – memory disorders, amnesia, depression, hallucinations.
From the digestive system: often – nausea, abdominal pain, diarrhea, constipation; infrequently-vomiting; rarely-dryness of the oral mucosa, liver function disorders; very rarely-hepatitis.
From the hematopoietic system: very rarely – thrombocytopenia.
From the respiratory system: often-shortness of breath during exercise; infrequently-bronchospasm; rarely-rhinitis.
Musculoskeletal disorders: very rare – arthralgia.
From the sensory organs: rarely-dryness and / or irritation of the eyes, conjunctivitis, visual impairment; very rarely-ringing in the ears, impaired taste sensations.
Dermatological reactions: infrequently-skin rash (like psoriasis-like urticaria), increased sweating; rarely-hair loss; very rarely-photosensitization, exacerbation of psoriasis.
Other: sometimes-weight gain; rarely-impotence, sexual dysfunction.
Betalok ® ZOK is well-tolerated by patients, and side effects are generally mild and reversible.
Interaction
Metoprolol is a CYP2D6 substrate, and therefore, drugs that inhibit CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) can affect the plasma concentration of metoprolol.
Combinations to avoid
Barbituric acid derivatives: barbiturates enhance the metabolism of metoprolol, due to the induction of enzymes (the study was conducted with phenobarbital).
Propafenone: when propafenone was administered to 4 patients treated with metoprolol, there was a 2-5-fold increase in the concentration of metoprolol in blood plasma, while 2 patients had side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. Probably, the interaction is caused by propafenone inhibition, like quinidine, of metoprolol metabolism by the CYP2D6 isoenzyme. Taking into account the fact that propafenone has beta-blocker properties, co-use of metoprolol and propafenone is not advisable.
Verapamil: a combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and beta-blockers have a complementary inhibitory effect on AV conduction and sinus node function.
Combinations that may require dose adjustment of Betalok ® ZOK
Class I antiarrhythmic drugs: when combined with beta-blockers, the negative inotropic effect can be summed up, as a result of which serious hemodynamic side effects develop in patients with impaired left ventricular function. This combination should also be avoided in patients with SSSU and impaired AV conduction. The interaction is described on the example of disopyramide.
Amiodarone: concomitant use with metoprolol may result in severe sinus bradycardia. Taking into account the extremely long T1 / 2 of amiodarone (50 days), possible interactions should be considered long after the withdrawal of amiodarone.
Diltiazem: diltiazem and beta-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, there were cases of severe bradycardia.
NSAIDs: NSAIDs weaken the antihypertensive effect of beta-blockers. This interaction has been reported in combination with Indometacin and probably will not be observed in combination with sulindac. Negative interactions have been reported in studies with diclofenac.
Diphenhydramine: diphenhydramine reduces the biotransformation of metoprolol to alpha-hydroxymethoprolol by 2.5 times. At the same time, there is an increase in the effect of metoprolol.
Epinephrine (epinephrine): 10 cases of severe hypertension and bradycardia were reported in patients treated with non-selective beta-blockers (including pindolol and propranolol) and treated with epinephrine. Interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when using epinephrine together with local anesthetics in case of accidental contact with the vascular bed. Apparently, this risk is much lower when using cardioselective beta-blockers.
Phenylpropanolamine: phenylpropanolamine (norephedrine) in a single dose of 50 mg can increase diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers can cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported while taking phenylpropanolamine.
Quinidine: quinidine inhibits metoprolol metabolism in a special group of patients with rapid hydroxylation (approximately 90% of the population in Sweden), mainly causing a significant increase in the plasma concentration of metoprolol and an increase in beta-adrenergic blockade. It is believed that this interaction is also characteristic of other beta-blockers, in the metabolism of which the CYP2D6 isoenzyme is involved.
Clonidine: hypertensive reactions with abrupt withdrawal of clonidine may increase with simultaneous use of beta-blockers. When used together, if clonidine withdrawal is necessary, discontinuation of beta-blockers should begin several days before clonidine withdrawal.
Rifampicin: rifampicin may increase the metabolism of metoprolol, reducing its concentration in blood plasma. Patients taking metoprolol and other beta-blockers (eye drops) or MAO inhibitors at the same time should be carefully monitored.
While taking beta-blockers, inhaled anesthetics increase the cardiodepressive effect.
While taking beta-blockers, patients receiving oral hypoglycemic agents may need to adjust the dose of the latter.
The plasma concentration of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides, when combined with beta-blockers, can increase the time of AV conduction and cause bradycardia.
How to take, course of use and dosage
When selecting the dose, it is necessary to avoid the development of bradycardia.
In case of arterial hypertension: the dose is 50-100 mg 1 time/day. If necessary, the dose can be increased to 100 mg 1 time / day or use Betalok ® ZOK in combination with other antihypertensive drugs (preferably a diuretic and a calcium channel blocker dihydropyridine derivative).
For angina pectoris: the dose is 100-200 mg 1 time/day. If necessary, Betalok ® ZOK can be used in combination with another antianginal drug.
In stable symptomatic chronic heart failure with impaired left ventricular systolic function: Betalok ® ZOK can be prescribed to patients who have not had any episodes of exacerbation in the last 6 weeks and have not changed the main therapy in the last 2 weeks. Treatment of heart failure with beta-blockers can sometimes lead to a temporary worsening of the symptomatic picture. In some cases, it is possible to continue therapy or reduce the dose, and in some cases, it may be necessary to cancel the drug.
With stable chronic heart failure of functional class II: The recommended starting dose for the first 2 weeks is 25 mg once a day. After 2 weeks, the dose can be increased to 50 mg 1 time / day and then doubled every 2 weeks. The maintenance dose for long-term treatment is 200 mg 1 time / day.
In stable chronic heart failure of functional classes III and IV: the recommended initial dose for the first 2 weeks is 12.5 mg 1 time/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 heart failure may worsen. After 1-2 weeks, the dose can be increased to 25 mg 1 time/day, then after another 2 weeks – to 50 mg 1 time/day. If well tolerated, the dose can be doubled every 2 weeks until a maximum dose of 200 mg once a day is reached.
In case of arterial hypotension and / or bradycardia: it may be necessary to reduce concomitant therapy or reduce the dose of Betalok® ZOK. 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. You may also need to monitor your kidney function.
In case of cardiac arrhythmias: the drug is prescribed at a dose of 100-200 mg 1 time/day.
For maintenance treatment after myocardial infarction: the drug is prescribed at a dose of 200 mg 1 time/day.
For functional cardiac disorders accompanied by tachycardia: the dose is 100 mg 1 time/day, if necessary, the dose can be increased to 200 mg/day.
For the prevention of migraine attacks: assign a dose of 100-200 mg 1 time/day.
Betalok ® ZOK is intended for daily use 1 time/day (preferably in the morning). A tablet of Betalok ® ZOK should be swallowed with liquid. Tablets can be divided in half, but should not be chewed or crumbled. Food intake does not affect the bioavailability of the drug.
In patients with impaired renal function, as well as in elderly patients: there is no need to adjust the dose of the drug.
In patients with impaired liver function: usually no dose adjustment is required due to the low degree of binding of metoprolol to plasma proteins. However, in severe hepatic impairment (in patients with severe cirrhosis or porto-caval anastomosis), a dose reduction may be required.
Overdose
Metoprolol at a dose of 7.5 g in an adult caused intoxication with a fatal outcome. A 5-year-old child who took 100 mg of metoprolol showed no signs of intoxication after gastric lavage. Taking 450 mg of metoprolol by a 12-year-old teenager resulted in moderate intoxication. Adults taking 1.4 g and 2.5 g of metoprolol caused moderate and severe intoxication, respectively. Taking 7.5 g to adults resulted in extremely severe intoxication.
Symptoms: the most serious are symptoms from the cardiovascular system, but sometimes, especially in children and adolescents, symptoms from the central nervous system and suppression of pulmonary function, bradycardia, AV block I-III degree, asystole, marked decrease in blood pressure, weak peripheral perfusion, heart failure, cardiogenic shock, depression of lung function, apnea, increased fatigue, impaired and loss of consciousness, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; effects on the kidneys; transient myasthenic syndrome.
Concomitant use of alcohol, antihypertensive drugs, quinidine, or barbiturates may worsen the patient’s condition. The first signs of overdose may occur 20 minutes-2 hours after taking the drug.
Treatment: taking activated charcoal, if necessary – gastric lavage.
Atropine at a dose of 0.25-0.5 mg iv for adults and 10-20 mcg / kg for children should be administered before gastric lavage (due to the risk of vagus nerve stimulation).
If it is necessary to maintain airway patency, intubation and mechanical ventilation are performed.
To stop bronchospasm, terbutaline can be used by injection or inhalation.
It is necessary to fill the BCC, conduct a glucose infusion. Atropine 1.0-2.0 mg IV, if necessary, repeat the use (especially with vagal symptoms). ECG monitoring.
In the case of myocardial depression, infusion of dobutamine or dopamine is indicated. You can use glucagon 50-150 mcg / kg iv with an interval of 1 min. In some cases, the addition of epinephrine to therapy may be effective.
In case of arrhythmia and dilated ventricular (QRS) complex, sodium solutions (chloride or bicarbonate) are infused. An artificial pacemaker can be installed.
In case of cardiac arrest due to an overdose, resuscitation measures may be required for several hours.
Symptomatic treatment is performed.
Special instructions
Patients receiving beta-blockers should not be given intravenous slow calcium channel blockers (such as verapamil).
Patients with asthma or COPD should receive concomitant beta-2-adrenomimetic therapy. Betalok ® ZOK should be administered at the lowest effective dose. In this case, it may be necessary to increase the dose of beta-2-adrenomimetic.
It is not recommended to prescribe non-selective beta-blockers to patients with Prinzmetal angina. Selective beta-blockers should be used with caution in this group of patients.
When using beta-1-blockers, the risk of their influence on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly lower than when using non-selective beta-blockers.
In patients with decompensated chronic heart failure, compensation should be achieved and maintained during treatment with Betalok® ZOK prior to prescribing.
Very rarely, during therapy with Betalok ® ZOK, patients with impaired conductivity may experience deterioration of the condition up to AV block. If bradycardia develops during treatment, the dose of the drug should be reduced or the drug should be gradually discontinued.
During the period of use of the drug, it is possible to increase the symptoms of peripheral arterial circulation disorders, mainly due to a decrease in blood pressure.
Caution should be exercised when prescribing the drug to patients with severe renal insufficiency, with metabolic acidosis, co-use with cardiac glycosides.
In patients taking beta-blockers, anaphylactic shock occurs in a more severe form. The use of epinephrine (epinephrine) in therapeutic doses does not always lead to the achievement of the desired clinical effect against the background of taking metoprolol.
Patients with pheochromocytoma should be treated with an alpha-blocker concomitantly with Betalok ZOK.
Abrupt withdrawal of beta-blockers is dangerous, especially in high-risk patients, and should therefore be avoided. If it is necessary to discontinue the drug, it should be carried out 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 is reached (1/2 tab. 25 mg), which should be taken at least 4 days before complete discontinuation of the drug. If symptoms appear (for example, increased angina symptoms, increased blood pressure), a slower withdrawal regimen is recommended. Abrupt withdrawal of a beta-blocker can lead to a worsening of the course of chronic heart failure and an increased risk of myocardial infarction and sudden death.
In case of surgical intervention, the anesthesiologist should be informed that the patient is taking Betalok ® ZOK. Discontinuation of beta-blocker therapy is not recommended for patients undergoing surgery. Avoid prescribing the drug in high doses without prior titration of doses of the drug to patients with cardiovascular risk factors undergoing non-cardiological operations, due to the increased risk of bradycardia, hypotension and stroke, including those with a fatal outcome.
Data from clinical trials on efficacy and safety in patients with severe stable symptomatic chronic heart failure (NYHA class IV) are limited. Treatment of such patients should be carried out by doctors with special knowledge and experience.
Patients with symptomatic heart failure in combination with acute myocardial infarction and unstable angina were excluded from studies based on which indications for use were determined. The efficacy and safety of the drug for this group of patients is not described. The use of the drug in unstable heart failure in the decompensation stage is contraindicated.
Use in pediatrics
Experience with the use of Betalok ® ZOK in children is limited.
Influence on the ability to drive motor vehicles and manage mechanisms
When driving vehicles and engaging in potentially dangerous activities that require increased attention and speed of psychomotor reactions, it should be borne in mind that dizziness and fatigue may occur when taking Betalok® ZOK.
Form of production
Coated tablets.
Storage conditions
At a temperature not exceeding 30 °C
Shelf life
3 years
Active ingredient
Metoprolol
Conditions of release from pharmacies
By prescription
Dosage form
Tablets
Purpose
For adults as prescribed by a doctor, for pregnant women as prescribed by a doctor
Indications
Hypertension, Angina, Arrhythmia, Migraine, Myocardial Infarction
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