Pharmacological properties of the drug Betaloc zok
Metoprolol is a competitive cardioselective β1-adrenergic receptor blocker. It has a slightly pronounced membrane-stabilizing effect and does not have partial agonist activity. Metoprolol eliminates or reduces the stimulating effect of catecholamines on the heart during physical and psychoemotional stress, reduces heart rate, moderately reduces myocardial contractility and cardiac output, and also reduces high blood pressure. Reduces myocardial oxygen demand and increases diastole. At high concentrations of endogenous adrenaline, metoprolol affects blood pressure to a much lesser extent than non-selective beta-adrenergic receptor blockers. Unlike traditional tablet dosage forms, when using Betaloc ZOK tablets with a delayed release of the active substance, a constant concentration of the drug in the blood plasma is observed and a stable clinical effect is ensured (blockade of β1-adrenergic receptors) for more than 24 hours. Due to the absence of concentration peaks in the blood plasma Betaloc ZOK is characterized by better clinical tolerability than conventional tablet forms of β1-adrenergic receptor blockers - the potential risk of side effects that are observed at peak plasma concentrations of the drug, such as bradycardia and weakness in the lower extremities when walking, is significantly reduced. If necessary, Betaloc ZOK can be prescribed in combination with β2-adrenergic receptor agonists to patients with COPD. In therapeutic doses, metoprolol in combination with β2-adrenergic receptor agonists has a lesser effect on bronchial tone compared to non-selective β-adrenergic receptor blockers. Betaloc ZOK has a lesser effect on insulin release and carbohydrate metabolism than non-selective beta-adrenergic receptor blockers. The effect of Betaloc ZOK on the response of the cardiovascular system in conditions of hypoglycemia is much less pronounced than that of non-selective beta-adrenergic receptor blockers. Clinical studies have shown that Betaloc ZOK may cause a slight increase in TG levels and a decrease in plasma free fatty acid levels. In some cases, a slight decrease in the HDL fraction was noted, but it was less significant compared to taking non-selective β1-adrenergic receptor blockers. However, one long-term clinical study showed a significant reduction in total cholesterol levels after treatment with metoprolol for several years. In the MERIT-HF study (Effect of Metoprolol Therapy on Survival in NYHA Class II–IV Heart Failure with Reduced Ejection Fraction (≤40%)), which included 3991 patients, metoprolol therapy resulted in a reduction in mortality and hospitalization. With long-term treatment, patients showed an improvement in their condition and a decrease in the functional class of heart failure according to NYHA. Metoprolol therapy led to an increase in left ventricular ejection fraction and a decrease in left ventricular end-systolic and diastolic volumes. Betaloc ZOK is completely absorbed after oral administration. Absorption of the drug does not depend on food intake. Due to active metabolism during first pass through the liver, the systemic bioavailability of metoprolol after oral administration is approximately 50%. When the sustained-release formulation of metoprolol is used, its bioavailability is reduced by approximately 20–30% compared to conventional tablets, but this is not clinically significant because the sustained-release formulation has the same AUC as the conventional tablet. Metoprolol is characterized by a low degree of binding to plasma proteins (approximately 5–10%). Metoprolol is metabolized in the liver, producing three metabolites that do not have β-adrenergic blocking activity. More than 95% of the drug dose taken orally is excreted in the urine, 5% is excreted unchanged. In some cases, the amount of the drug that is excreted unchanged in the urine can reach 30%. The mean half-life is 3.5 hours (1–9 hours). The total plasma clearance is approximately 1 l/min. In elderly patients, significant changes in the pharmacokinetics of metoprolol are not observed. Systemic bioavailability and excretion of metoprolol do not change in patients with renal failure, but the excretion of metabolites in such patients is reduced. Significant accumulation of metabolites was observed in patients with a glomerular filtration rate of less than 5 ml/min. Such accumulation of metabolites does not have a β-adrenergic blocking effect. In patients with reduced liver function, the pharmacokinetics of metoprolol (due to low protein binding) changes slightly, however, in patients with severe liver cirrhosis or portacaval shunts, the bioavailability of metoprolol may be increased and overall clearance may be decreased. In patients with a portacaval shunt, the total clearance of metoprolol is approximately 0.3 l/min, and the AUC value is approximately 6 times higher than that in healthy individuals.
Betaloc Zok tab prolong release 25mg No. 14
Compound
Active substance: metoprolol tartrate - 25 mg. Excipients: ethylcellulose - 21.5 mg, hyprolose - 6.13 mg, hypromellose - 5.64 mg, microcrystalline cellulose - 94.9 mg, paraffin - 0.06 mg, macrogol - 1.41 mg, silicon dioxide - 14.6 mg, sodium stearyl fumarate - 0.241 mg, titanium dioxide - 1.41 mg.
Pharmacokinetics
Upon contact with liquid, the tablets quickly disintegrate, and the active substance is dispersed in the gastrointestinal tract. The rate of release 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 Betaloc® ZOK (slow-release tablets) is more than 24 hours, while a constant rate of release of the active substance is achieved within 20 hours. T1/2 averages 3.5 hours.
Betaloc® ZOK is completely absorbed after oral administration. Systemic bioavailability after oral administration of a single dose is approximately 30-40%.
Metoprolol undergoes oxidative metabolism in the liver. The three main metabolites of metoprolol did not exhibit a clinically significant β-blocking effect. About 5% of the oral dose of the drug is excreted unchanged in the urine, the rest of the drug is excreted in the form of metabolites. The binding to plasma proteins is low, approximately 5-10%.
Indications for use
- arterial hypertension;
- angina pectoris;
- stable symptomatic chronic heart failure with impaired left ventricular systolic function (as an adjuvant therapy to the main treatment of heart failure);
- to reduce mortality and the incidence of re-infarction after the acute phase of myocardial infarction;
- heart rhythm disturbances, including supraventricular tachycardia, decreased ventricular contraction frequency with atrial fibrillation and ventricular extrasystoles;
- functional disorders of cardiac activity accompanied by tachycardia;
- prevention of migraine attacks.
Contraindications
- AV block II and III degrees;
- heart failure in the stage of decompensation;
- continuous or intermittent therapy with inotropic agents acting on β-adrenergic receptors;
- clinically significant sinus bradycardia;
- SSSU;
- cardiogenic shock;
- severe disturbances of peripheral circulation (including with the threat of gangrene);
- arterial hypotension;
- patients with suspected acute myocardial infarction with a heart rate 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;
- hypersensitivity to metoprolol and other components of the drug or to other beta-blockers;
- intravenous administration of slow calcium channel blockers (like verapamil);
- age under 18 years (efficacy and safety have not been established).
Carefully
use the drug for AV blockade of the first degree, Prinzmetal's angina, bronchial asthma, COPD, diabetes mellitus, severe renal failure, metabolic acidosis, together with cardiac glycosides.
Directions for use and doses
Betaloc® ZOK is intended for daily use once a day; it is recommended to take the drug in the morning. The Betaloc® ZOK tablet should be swallowed with liquid. Tablets (or halved tablets) should not be chewed or crushed. Food intake does not affect the bioavailability of the drug.
When selecting a dose, it is necessary to avoid the development of bradycardia.
Arterial hypertension
50-100 mg 1 time/day. If necessary, the dose can be increased to 100 mg 1 time / day or Betaloc® ZOK can be used in combination with other antihypertensive agents, preferably a diuretic and a calcium channel blocker dihydropyridine derivative.
Angina pectoris
100-200 mg Betaloc® ZOK 1 time/day. If necessary, another antianginal drug may be added to therapy.
Stable symptomatic chronic heart failure with impaired left ventricular systolic function
Patients must be in stable chronic heart failure without episodes of exacerbation during the last 6 weeks and without changes in primary therapy during 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; in some cases, it may be necessary to discontinue the drug.
Stable chronic heart failure, functional class II
The recommended initial dose of Betaloc® ZOK for the first 2 weeks is 25 mg 1 time / day. After 2 weeks of therapy, the dose can be increased to 50 mg 1 time / day, and then can be doubled every 2 weeks.
Maintenance dose for long-term treatment: 200 mg Betaloc® ZOK 1 time/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 25 mg tablet) 1 time/day. The dose is selected individually. During the period of increasing the dose, the patient should be monitored, because In some patients, heart failure symptoms may worsen.
After 1-2 weeks, the dose can be increased to 25 mg Betaloc® ZOK 1 time / day. Then, after 2 weeks, the dose can be increased to 50 mg 1 time / day. For patients who tolerate the drug well, the dose can be doubled every 2 weeks until a maximum dose of 200 mg Betaloc® ZOK is reached 1 time / day.
In case of arterial hypotension and/or bradycardia, it may be necessary to reduce concomitant therapy or reduce the dose of Betaloc® ZOK. Arterial hypotension at the beginning of therapy does not necessarily indicate that a given dose of Betaloc® ZOK will not be tolerated during further long-term treatment. However, the dose should not be increased until the condition has stabilized. Monitoring of renal function may be required.
Heart rhythm disturbances
100-200 mg Betaloc® ZOK 1 time/day.
Maintenance treatment after myocardial infarction
200 mg Betaloc® ZOK 1 time/day.
Functional cardiac disorders accompanied by tachycardia
100 mg Betaloc® ZOK 1 time / day, if necessary, the dose can be increased to 200 mg / day.
Preventing migraine attacks
100-200 mg Betaloc® ZOK 1 time/day.
Renal dysfunction
There is no need to adjust the dose in patients with impaired renal function.
Liver dysfunction
Usually, due to the low degree of binding to plasma proteins, no dose adjustment of metoprolol is required. However, in severely impaired 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 the use of Betaloc® ZOK in children is limited.
Storage conditions
The drug should be stored out of the reach of children at temperatures above 30°C.
Best before date
3 years. Do not use after the expiration date.
special instructions
Patients receiving beta-blockers should not receive IV calcium channel blockers (like verapamil).
Patients with bronchial asthma or COPD should be prescribed concomitant therapy with a beta2-agonist. It is necessary to prescribe the minimum effective dose of Betaloc® ZOK, and an increase in the dose of the beta2-adrenergic agonist may be required.
It is not recommended to prescribe non-selective beta-blockers to patients with Prinzmetal's angina. Selective beta-blockers should be prescribed with caution in this group of patients.
When using beta1-blockers, the risk of their effect on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly less than when using non-selective beta-blockers.
In patients with chronic heart failure in the stage of decompensation, it is necessary to achieve a stage of compensation both before and during treatment with the drug.
Very rarely, patients with impaired AV conduction may worsen (a possible outcome is AV block). If bradycardia develops during treatment, the dose of the drug should be reduced or the drug should be gradually discontinued.
Betaloc® ZOK can aggravate the course of existing peripheral circulatory disorders, mainly due to a decrease in blood pressure.
Caution should be exercised when prescribing the drug to patients with severe renal failure, metabolic acidosis, and simultaneous use with cardiac glycosides.
In patients taking beta-blockers, anaphylactic shock occurs in a more severe form. The use of epinephrine (adrenaline) in therapeutic doses does not always lead to the achievement of the desired clinical effect while taking metoprolol.
Patients suffering from pheochromocytoma should be prescribed an alpha-blocker simultaneously with Betaloc® 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 done gradually over 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 tablet 25 mg) is reached, which should be taken as at least 4 days before the drug is completely discontinued. If symptoms appear (eg, increased symptoms of angina, increased blood pressure), a slower withdrawal regimen is recommended. Abrupt withdrawal of a beta-blocker may worsen the course of chronic heart failure and increase the risk of myocardial infarction and sudden death.
In case of surgery, the anesthesiologist should be informed that the patient is taking Betaloc® ZOK. In patients undergoing surgery, discontinuation of beta-blocker therapy is not recommended. Prescribing the drug in high doses without prior titration of the drug doses should be avoided in patients with cardiovascular risk factors undergoing non-cardiac surgery, due to the increased risk of bradycardia, arterial hypotension and stroke, incl. with fatal outcome.
Clinical trial data on efficacy and safety in patients with severe stable symptomatic chronic heart failure (NYHA class IV) are limited. Such patients should be treated by physicians with specialized knowledge and experience.
Patients with symptomatic heart failure combined with acute myocardial infarction and unstable angina were excluded from studies based on which indications for use were determined. The effectiveness and safety of the drug for this group of patients has not been described. Use in unstable heart failure in the decompensation stage is contraindicated.
Description
Beta1-adrenergic blocker selective.
Dosage form
White or off-white, oval, biconvex, film-coated tablets, sustained-release, scored on both sides and debossed with “A” over “β” on one side.
Use in children
The use of the drug is contraindicated in children and adolescents under the age of 18 (the effectiveness and safety of the drug have not been established).
Pharmacodynamics
Metoprolol is a beta1-adrenergic blocker that blocks β1-adrenergic receptors in doses significantly lower than the doses required to block β2-adrenergic receptors.
Metoprolol has a slight membrane-stabilizing effect and does not exhibit 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, cardiac output and increased contractility of the heart, as well as an increase in blood pressure caused by a sharp release of catecholamines.
Unlike conventional tablet dosage forms of selective beta1-blockers (including metoprolol tartrate), when using the drug Betaloc® ZOK, a constant concentration of the drug in the blood plasma is observed and a stable clinical effect (blockade of beta1-adrenergic receptors) is ensured for more than 24 hours.
Due to the absence of obvious peak plasma concentrations, clinically Betaloc® ZOK is characterized by better selectivity for β1-adrenergic receptors compared to conventional tablet forms of beta1-blockers. In addition, the potential risk of side effects observed at peak plasma concentrations, such as bradycardia and weakness in the legs when walking, is significantly reduced.
Patients with symptoms of obstructive pulmonary diseases, if necessary, can be prescribed Betaloc® ZOK in combination with beta2-agonists. When used together with beta2-adrenergic agonists, Betaloc® ZOK in therapeutic doses has a lesser effect on the bronchodilation caused by beta2-adrenergic agonists 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 much less pronounced compared to non-selective beta-blockers.
The use of the drug Betaloc® ZOK for 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 peripheral vascular resistance is observed. However, with long-term use, a decrease in blood pressure is possible due to a decrease in peripheral vascular resistance while cardiac output remains unchanged.
In the MERIT-HF study of survival in chronic heart failure (II-IV functional class according to the NYHA classification) with reduced ejection fraction (≤0.4), which included 3991 patients, Betaloc® ZOK showed an increase in survival and a decrease in the frequency of hospitalizations. With long-term treatment, patients achieved a general improvement in well-being and a decrease in the severity of symptoms (according to NYHA functional classes). Also, therapy with the drug Betaloc® ZOK showed an increase in left ventricular ejection fraction, a decrease in end-systolic and end-diastolic volumes of the left ventricle.
The quality of life does not deteriorate or improves during treatment with Betaloc® ZOK. An improvement in the quality of life during treatment with Betaloc® ZOK was observed in patients after myocardial infarction.
Side effects
Betaloc® ZOK is well tolerated by patients, side effects are mostly mild and reversible.
To assess the frequency of cases, the following criteria were used: very often (>10%), often (1-9.9%), infrequently (0.1-0.9%), rarely (0.01-0.09%), very rarely (<0.01%).
From the cardiovascular system: often - bradycardia, orthostatic arterial hypotension (very rarely accompanied by fainting), coldness of the extremities, palpitations; uncommon - temporary increase in symptoms of heart failure, AV block of the first degree, cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart area; rarely - other conduction disorders, arrhythmias; very rarely - gangrene (in patients with severe peripheral circulatory disorders).
From the side of the central nervous system: very often - increased fatigue; often - dizziness, headache; uncommon - paresthesia, convulsions, depression, decreased concentration, drowsiness or insomnia, nightmares; rarely - increased nervous excitability, anxiety; very rarely - memory impairment, amnesia, depression, hallucinations.
From the digestive system: often - nausea, abdominal pain, diarrhea, constipation; infrequently - vomiting; rarely - dryness of the oral mucosa.
From the liver: rarely - liver dysfunction; very rarely - hepatitis.
Dermatological reactions: uncommon - skin rash (such as psoriasis-like urticaria), increased sweating; rarely - hair loss; very rarely - photosensitivity, exacerbation of psoriasis.
From the respiratory system: often - shortness of breath on exertion; uncommon - bronchospasm; rarely - rhinitis.
From the senses: rarely - blurred vision, dryness and/or irritation of the eyes, conjunctivitis; very rarely - ringing in the ears, disturbances of taste.
From the musculoskeletal system: very rarely - arthralgia.
From the side of metabolism: infrequently - weight gain.
From the hematopoietic system: very rarely - thrombocytopenia.
Other: rarely - impotence, sexual dysfunction.
Use during pregnancy and breastfeeding
Like most drugs, Betaloc® ZOK should not be prescribed during pregnancy and breastfeeding, unless the expected benefit to the mother outweighs the potential risk to the fetus and/or child.
Like other antihypertensive agents, beta blockers may cause side effects such as bradycardia in the fetus, neonates, or breast-fed children. The amount of metoprolol excreted in breast milk and the beta-blocking effect in a breastfed baby (when the mother takes metoprolol in therapeutic doses) are negligible.
Interaction
Metoprolol is a CYP2D6 substrate, and therefore drugs that inhibit CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) may affect the plasma concentrations of metoprolol.
Combinations to Avoid
Barbituric acid derivatives: Barbiturates increase the metabolism of metoprolol due to enzyme induction (study conducted with phenobarbital).
Propafenone: when propafenone was prescribed to 4 patients treated with metoprolol, an increase in the plasma concentration of metoprolol was observed by 2-5 times, while 2 patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprolol via the CYP2D6 isoenzyme. Taking into account the fact that propafenone has beta-blocker properties, the co-administration of metoprolol and propafenone does not seem appropriate.
Verapamil: The combination of beta blockers (atenolol, propranolol and pindolol) and verapamil may cause bradycardia and lead to a decrease in blood pressure. Verapamil and beta-blockers have complementary inhibitory effects on AV conduction and sinus node function.
Combinations that may require dose adjustment of Betaloc® ZOK
Class I antiarrhythmic drugs: when combined with beta-blockers, the negative inotropic effect may be additive, resulting in serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with SSSS and impaired AV conduction. The interaction is described using disopyramide as an example.
Amiodarone: Concomitant use with metoprolol may lead to severe sinus bradycardia. Taking into account the extremely long T1/2 of amiodarone (50 days), the possible interaction should be considered long after discontinuation 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, cases of severe bradycardia were observed.
NSAIDs: NSAIDs reduce the antihypertensive effect of beta-blockers. This interaction has been reported in combination with indomethacin and is likely not to be observed in combination with sulindac. Negative interactions have been noted in studies with diclofenac.
Diphenhydramine: Diphenhydramine reduces the biotransformation of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.
Epinephrine (adrenaline): Ten cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta blockers (including pindolol and propranolol) and receiving epinephrine. The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. Apparently, this risk is much lower with the use of cardioselective beta-blockers.
Phenylpropanolamine: Phenylpropanolamine (norephedrine) in a single dose of 50 mg may increase diastolic blood pressure to pathological levels in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers may 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 the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased beta-adrenergic receptor blockade. It is believed that such an interaction is also typical for other beta-blockers, the metabolism of which involves the CYP2D6 isoenzyme.
Clonidine: Hypertensive reactions following abrupt withdrawal of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, if it is necessary to discontinue clonidine, discontinuation of beta-blockers should begin several days before discontinuation of clonidine.
Rifampicin: Rifampicin may increase the metabolism of metoprolol, reducing its plasma concentration. Patients concomitantly taking metoprolol and other beta-blockers (eye drops) or MAO inhibitors should be closely monitored.
While taking beta-blockers, inhalational anesthetics enhance the cardiodepressive effect.
While taking beta-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.
Plasma concentrations of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides, when used in combination with beta-blockers, can increase AV conduction time and cause bradycardia.
Overdose
Toxicity: 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. Administration of 1.4 g and 2.5 g of metoprolol to adults caused moderate and severe intoxication, respectively. Taking 7.5 g by adults resulted in extremely severe intoxication.
Symptoms: in case of an overdose of metoprolol, the most serious symptoms are those 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 may predominate. , poor peripheral perfusion, heart failure, cardiogenic shock; depression of pulmonary function, apnea, as well as increased fatigue, impaired consciousness, loss of consciousness, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; effects on the kidneys; granzitory myasthenic syndrome; concomitant use of alcohol, antihypertensive drugs, quinidine or barbiturates may worsen the patient's condition. The first signs of an overdose can be observed 20 minutes - 2 hours after taking the drug.
Treatment: administration of activated carbon, gastric lavage if necessary.
IMPORTANT!
Atropine (0.25-0.5 mg IV for adults, 10-20 mcg/kg for children) should be given before gastric lavage (due to the risk of vagus nerve stimulation). If necessary, maintain a patent airway (intubation) and provide adequate ventilation. Replenishment of circulating blood volume and glucose infusion. ECG monitoring. Atropine 1.0-2.0 mg IV, repeat administration if necessary (especially in case of vagal symptoms). In case of myocardial depression, infusion of dobutamine or dopamine is indicated.
You can also use glucagon 50-150 mcg/kg IV at 1-minute intervals. In some cases, adding epinephrine to therapy may be effective. For arrhythmia and a wide ventricular (QRS) complex, sodium solutions (chloride or bicarbonate) are infused. It is possible to install an artificial pacemaker. Cardiac arrest due to an overdose may require resuscitation for several hours. Terbutaline (injected or inhaled) can be used to relieve bronchospasm. Symptomatic treatment is carried out.
Impact on the ability to drive vehicles and operate machinery
When driving vehicles and engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions, it should be taken into account that dizziness and fatigue may occur when using Betalok® ZOK.
Indications for use of the drug Betaloc zok
- arterial hypertension (AH) (to reduce blood pressure and the risk of developing coronary and other cardiovascular complications, as well as cardiovascular and coronary death, including sudden death);
- angina pectoris;
- compensated chronic heart failure with impaired left ventricular systolic function (as an addition to the basic treatment of heart failure);
- in order to reduce mortality and the incidence of recurrent infarction after the acute phase of myocardial infarction;
- heart rhythm disturbances, including supraventricular tachycardia, as well as to reduce the frequency of ventricular contractions during atrial fibrillation and ventricular extrasystoles;
- functional disorders of cardiac activity;
- migraine prevention.
Use of the drug Betaloc zok
Betaloc ZOK is intended for daily use once a day, preferably in the morning. Tablets (or tablets split in half) should not be chewed or crushed. Food intake does not affect the bioavailability of the drug. During dose selection, heart rate should be monitored to prevent bradycardia. Hypertension (arterial hypertension) The recommended dose of Betaloc ZOK for patients with mild or moderate hypertension (arterial hypertension) is 50 mg 1 time per day. If the therapeutic effect is not achieved, the dose should be increased to 100–200 mg once a day or combined with other antihypertensive drugs. Angina pectoris The recommended dose is 100–200 mg Betaloc ZOK 1 time per day. If necessary, Betaloc ZOK can be combined with other drugs for the treatment of angina. Stable chronic heart failure with impaired left ventricular systolic function (as an addition to basic therapy) Patients must be in the stage of compensated chronic heart failure for at least 6 weeks; basic therapy should not change during the last 2 weeks. Treatment of heart failure with β-adrenergic blockers may lead to transient clinical deterioration. Further continuation of therapy or dose reduction is possible; in some cases, discontinuation of the drug may be necessary. Initiation of therapy with Betaloc ZOK in patients with severe heart failure (NYHA IV) should be carried out by an experienced physician experienced in treating patients with heart failure. Stable chronic heart failure, functional class II The recommended initial dose of Betaloc ZOK for the first 2 weeks is 25 mg (1 tablet of 25 mg or tablets of 50 mg) 1 time per day. After 2 weeks, the dose can be increased to 50 mg once a day and then can be doubled every 2 weeks. The optimal dose for long-term treatment is 200 mg Betaloc ZOK 1 time per day. Stable chronic heart failure, functional class III-IV The dose is selected individually. The recommended initial dose for the first 2 weeks is 12.5 mg Betaloc ZOK (1/2 tablet of 25 mg) 1 time per day. During the period of increasing the dose, the patient should be under the supervision of a physician, as in some cases the symptoms of heart failure may intensify. After 2 weeks of taking Betaloc ZOK at a dose of 12.5 mg, the dose can be increased to 25 mg (1 tablet of 25 mg or tablets of 50 mg) once a day. After 2 weeks, the dose can be increased to 50 mg once a day. For patients who tolerate higher doses well, the dose can be doubled every 2 weeks until a maximum dose of 200 mg Betaloc ZOK is reached once a day. In case of hypotension and/or bradycardia, it is necessary to reduce the dose of Betaloc ZOK or concomitant medications. Hypotension at the beginning of therapy does not necessarily indicate that such a dose of Betaloc ZOK will not be tolerated in the future. However, the dose should not be increased until the patient's condition has stabilized. Monitoring of kidney function is necessary. Cardiac arrhythmias The recommended dose is 100–200 mg Betaloc ZOK 1 time per day. Maintenance therapy after myocardial infarction It has been shown that as a result of long-term treatment with Betalok ZOK at a dose of 200 mg per day, the risk of death (including sudden death) is reduced, and the risk of recurrent myocardial infarction is reduced (including in patients with diabetes mellitus). Functional cardiac disorders accompanied by palpitations The recommended dose is 100 mg Betaloc ZOK 1 time per day. If necessary, the dose can be increased to 200 mg. Prevention of migraine The recommended dose is 100–200 mg Betaloc ZOK 1 time per day. Patients with impaired renal function No dose adjustment is required in patients with impaired renal function. Patients with impaired liver function Betaloc ZOK is usually prescribed to patients with liver cirrhosis at the same dose as patients with normal liver function. Only in case of severe liver failure is it possible to reduce the dose. Elderly patients No dose adjustment is required. Children Experience with the use of Betaloc ZOK in children is limited.
Betaloc Zok tablet with prolong release 50 mg x30
Trade name: Betaloc Zok International name: Metoprolol
Release forms: film-coated tablets with delayed release 50, 100 mg (polyethylene bottles)
Composition: metoprolol succinate 23.75/47.5/95 mg
Pharmacological group: selective beta1-adrenergic blocker
Pharmacological group according to ATK: C07AB02 (Metoprolol)
Pharmacological action: antianginal, antiarrhythmic, selective beta-adrenergic blocking, hypotensive,
Indications: IHD, exertional angina, unstable angina, myocardial infarction (acute phase, as well as secondary prevention). Arterial hypertension, hypertensive crisis. CHF (compensated) in combination with diuretics, ACE inhibitors and cardiac glycosides. Rhythm disturbances (including during general anesthesia) - sinus tachycardia, ventricular and supraventricular arrhythmias (including supraventricular tachycardia, atrial fibrillation, atrial flutter, atrial tachycardia, tachyarrhythmias caused by digitalis, catecholamines, ventricular extrasystole, arrhythmias on background of mitral valve prolapse), congenital long QT syndrome. Thyrotoxicosis (complex therapy), withdrawal syndrome, migraine (prevention), tremor (essential, senile), anxiety (auxiliary treatment), akathisia against the background of antipsychotics.
Dosage regimen: Orally, with food or immediately after a meal, the tablets can be divided in half, but not chewed and washed down with liquid; for long-acting dosage forms - swallow whole, do not crush, do not break (except for metoprolol succinate and tartrate), do not chew. For arterial hypertension, the average dose is 100-150 mg/day in 1-2 doses, if necessary - 200 mg/day. For angina pectoris - 50 mg 2-3 times a day. For hyperkinetic cardiac syndrome (including thyrotoxicosis) - 50 mg 1-2 times a day. For tachyarrhythmia - 50 mg 2-3 times a day, if necessary - 200-300 mg/day. Secondary prevention of myocardial infarction - 200 mg/day. Prevention of migraine - 100-200 mg/day in 2-4 doses. To relieve paroxysmal supraventricular tachycardia, it is administered parenterally in a hospital setting. Administer slowly, a dose of 2-5 mg (1-2 mg/min). If there is no effect, the administration can be repeated after 5 minutes. Increasing the dose above 15 mg usually does not lead to greater severity of action. After stopping the attack of arrhythmia, patients are transferred to oral administration at a dose of 50 mg 4 times a day, with the first dose taken 15 minutes after stopping the IV administration. In the acute stage of myocardial infarction, immediately after hospitalization of the patient (with constant monitoring of hemodynamics: ECG, heart rate, AV conduction, blood pressure), a bolus of 5 mg should be administered intravenously, the administration should be repeated every 2 minutes until a total dose of 15 mg is reached. If well tolerated, after 15 minutes - orally, 25-50 mg every 6 hours, for 2 days. Patients who do not tolerate the full IV dose should be started on oral administration, starting with a half dose. Maintenance therapy continues at doses of 200 mg/day (in 2 doses) for 3 months to 3 years. Elderly patients are recommended to start treatment with 50 mg/day. Renal failure does not require dose adjustment. In case of liver failure, it is advisable to prescribe other beta-blockers that are not metabolized in the liver.
Contraindications: Hypersensitivity, cardiogenic shock, AV block II-III stage, SA block, SSSU, sinus bradycardia (heart rate less than 50/min), acute HF or decompensated CHF, Prinzmetal's angina, arterial hypotension, acute myocardial infarction (PQ more than 0.24 s or systolic blood pressure less than 100 mm Hg), lactation period, simultaneous use of MAO inhibitors or simultaneous intravenous administration of verapamil.
Side effects: From the nervous system: increased fatigue, weakness, headache, slower speed of mental and motor reactions. Rarely: paresthesia in the extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor, convulsions, depression, anxiety, decreased attention, drowsiness, insomnia, nightmares, confusion or short-term memory loss, hallucinations, asthenia, myasthenia gravis . From the senses: rarely - decreased vision, decreased secretion of tear fluid, dry and sore eyes, conjunctivitis, tinnitus, decreased hearing. From the cardiovascular system: sinus bradycardia, decreased blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness). Rarely - decreased myocardial contractility, development (worsening) of CHF (edema, swelling of the feet and/or lower legs, shortness of breath), heart rhythm disturbances, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), myocardial conduction disturbances, cardialgia. Very rarely - worsening of pre-existing AV conduction disorders. From the digestive system: nausea, vomiting, abdominal pain, dry mouth, constipation or diarrhea, in some cases - impaired liver function (dark urine, yellowness of the sclera or skin, cholestasis), changes in taste. From the skin: skin rashes (exacerbation of psoriasis), psoriasis-like skin reactions, skin hyperemia, exanthema, photodermatosis, increased sweating, reversible alopecia. From the respiratory system: nasal congestion, bronchospasm when prescribed in high doses (loss of selectivity and/or in predisposed patients), shortness of breath. From the endocrine system: hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid state. Allergic reactions: urticaria, skin itching, rash. Laboratory indicators: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of liver enzymes, hyperbilirubinemia. Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia. Other: pain in the back or joints, weight gain, decreased libido and/or potency, with abrupt cessation of treatment - “smokers” syndrome; the effectiveness of beta-blockers is lower. In combination therapy with clonidine, the latter should be discontinued several days after metoprolol is discontinued in order to avoid a hypertensive crisis. At a dose above 200 mg/day, cardioselectivity decreases. Metoprolol may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can increase symptoms. In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal levels. If necessary, beta2-adrenergic stimulants are used as concomitant therapy for patients with bronchial asthma, and alpha-blockers for pheochromocytoma. If surgical intervention is necessary, it is necessary to warn the anesthesiologist about the therapy being performed (choosing a drug for general anesthesia with minimal negative inotropic effect); discontinuation of the drug is not recommended. Reciprocal activation of the n.vagus can be eliminated by intravenous administration of atropine (1-2 mg). Drugs that reduce catecholamine reserves (for example, reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect an excessive decrease in blood pressure or bradycardia. If elderly patients develop increasing bradycardia (less than 50/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or stop treatment . It is recommended to discontinue therapy if skin rashes appear and depression develops caused by taking beta-blockers. The drug is discontinued gradually, reducing the dose over 10 days. With abrupt cessation of treatment, intermittent claudication syndrome, Raynaud's syndrome), pregnancy, childhood (efficacy and safety have not been determined), and old age may occur.
Interactions: Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving metoprolol. Iodine-containing radiopaque drugs for intravenous administration increase the risk of developing anaphylactic reactions. Phenytoin with intravenous administration, drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of lowering blood pressure. Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure). Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking. The hypotensive effect is weakened by NSAIDs (Na+ retention and blockade of Pg synthesis by the kidneys), corticosteroids and estrogens (Na+ retention). Cardiac glycosides, methyldopa, reserpine and guanfacine, BMCC (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and HF. Nifedipine can lead to a significant decrease in blood pressure. Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure. Prolongs the effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins. Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase CNS depression. Concomitant use with MAO inhibitors is not recommended due to a significant increase in the hypotensive effect; the break in treatment between taking MAO inhibitors and metoprolol should be at least 14 days. Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.
Dispensed from pharmacies: Available with prescription
Drug registration number: P No. 013890/01-2002
Date of registration (re-registration) of the drug: 04/02/2002
Contraindications for Betaloc zok
AV blockade II–III degree; heart failure in the decompensation phase (pulmonary edema, hypoperfusion syndrome or arterial hypotension), simultaneous (long-term or periodic) therapy with inotropic agents aimed at stimulating β-adrenergic receptors; clinically significant sinus bradycardia, sick sinus syndrome, cardiogenic shock, severe peripheral arterial circulation disorders. Metoprolol should not be prescribed to patients with suspected acute myocardial infarction with a heart rate less than 45 per minute, a P-Q on the ECG of more than 0.24 s, or a systolic blood pressure level of less than 100 mmHg. Art. Hypersensitivity to any component of the drug or to other beta-adrenergic receptor blockers.
Side effects of the drug Betaloc zok
Well tolerated, side effects are usually mild and reversible. Side effects according to the frequency of occurrence are distributed as follows: very often - at least 10%, often - 1-9%, infrequently - 0.1%, rarely - 0.01-0.09%, very rarely - less than 0.01% . From the cardiovascular system Often: bradycardia, postural disturbances (extremely with dizziness), coldness of the extremities; uncommon: temporary worsening of symptoms of heart failure, 1st degree AV block, edema, pain in the heart area; rarely: sinoatrial conduction disturbance, arrhythmia; very rare: gangrene in patients with severe peripheral circulatory disorders. From the side of the central nervous system Very often: increased fatigue; often: dizziness, headache; uncommon: paresthesia, muscle cramps. From the gastrointestinal tract Often: nausea, abdominal pain, diarrhea, constipation; uncommon: vomiting; rarely: dry mouth. From the blood system : Very rare: thrombocytopenia. From the hepatobiliary system Rarely: changes in functional liver parameters; very rare: hepatitis. From the musculoskeletal system Very rare: arthralgia. Metabolic disorders : Uncommon: weight gain. Mental status: Uncommon: depression, decreased concentration, drowsiness or insomnia, nightmares; rarely: increased excitability, anxiety; very rarely: amnesia and other memory impairments, confusion, hallucinations. From the respiratory system Often: shortness of breath with physical effort; not often: bronchospasm; rarely: rhinitis. From the senses : Rarely: visual disturbances, dryness and/or irritation of the eyes, conjunctivitis; very rarely: taste disturbances, tinnitus. Skin disorders Uncommon: rash (urticaria, areas of skin dystrophy), increased sweating; rarely: hair loss; very rarely: photosensitivity, exacerbation of psoriasis. Other Impotence, sexual dysfunction.
Buy Betaloc solution for injection intravenously 1 mg/ml ampoule 5 ml No. 5 in pharmacies
Betaloc Buy Betaloc in pharmacies DOSAGE FORMS solution for intravenous administration 1 mg/ml
MANUFACTURERS AstraZeneca AB (Sweden) Senexi S.a.S. (France)
GROUP Beta1-blockers (cardioselective)
COMPOSITION Active substance - Metoprolol.
INTERNATIONAL NON-PROPENTED NAME Metoprolol
SYNONYMS Betaloc ZOK, Vasocardin, Corvitol 100, Corvitol 50, Methohexal, Metozok, Metocard, Metocor Adifarm, Metoprolol, Metoprolol Organics, Metoprolol-Acri, Metoprolol-Ratiopharm, Serdol, Egilok, Egilok retard, Egilok S, Emzok
PHARMACOLOGICAL ACTION Pharmacological action - hypotensive, antianginal, antiarrhythmic. Reduces cardiac output and systolic blood pressure, slows heart rate, weakens the stimulating effect of catecholamines on the myocardium during physical activity and mental stress, and prevents reflex orthostatic tachycardia. The antihypertensive effect is due to a decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin system and the central nervous system, restoration of baroreceptor sensitivity and, ultimately, a decrease in peripheral sympathetic influences. The hypotensive effect develops quickly (systolic blood pressure decreases after 15 minutes, maximum after 2 hours) and lasts for 6 hours. Diastolic blood pressure changes more slowly. The antianginal effect is a consequence of a decrease in the frequency and strength of heart contractions, energy costs and myocardial oxygen demand. Reduces the frequency and severity of attacks of ischemic heart disease. Has a moderate negative inotropic effect. Metoprolol tartrate is rapidly and almost completely absorbed when taken orally and undergoes intensive first-pass metabolism. It is quickly distributed in tissues, penetrates the blood-brain barrier, the placental barrier, and breast milk. Biotransforms in the liver, producing two active metabolites. It is excreted primarily by the kidneys in the form of metabolites. Pharmacokinetic parameters do not depend on the age of patients.
INDICATIONS FOR USE Moderate and moderate arterial hypertension (monotherapy or in combination with other antihypertensive drugs), coronary artery disease, hyperkinetic cardiac syndrome, heart rhythm disturbances (sinus tachycardia, ventricular and supraventricular arrhythmia, including paroxysmal tachycardia, supraventricular tachycardia, extrasystole, flutter and atrial fibrillation, atrial tachycardia), hypertrophic cardiomyopathy, mitral valve prolapse, myocardial infarction (prevention and treatment), migraine (prevention), thyrotoxicosis (complex therapy); treatment of akathisia caused by neuroleptics.
CONTRAINDICATIONS Hypersensitivity, AV block II and III degrees, sinoatrial block, acute or chronic (in the stage of decompensation) heart failure, sick sinus syndrome, severe sinus bradycardia (heart rate less than 60 beats/min), cardiogenic shock, arterial hypotension (systolic blood pressure less than 100 mm Hg), severe peripheral circulatory disorders, pregnancy, breastfeeding. Restricted for use in: diabetes mellitus, hypoglycemia, severe allergic history, metabolic acidosis, bronchial asthma, emphysema, non-allergic bronchitis, hyperthyroidism, psoriasis, pheochromocytoma, impaired liver and/or kidney function, myasthenia gravis, depression, general anesthesia, elderly and children age.
SIDE EFFECTS From the nervous system and sensory organs: weakness, dizziness and headache, decreased concentration, drowsiness/insomnia, nightmares, depression, muscle cramps, paresthesia, nervousness, anxiety, decreased libido, blurred vision, xerophthalmia, conjunctivitis, lethargy , increased fatigue, anxiety, confusion, amnesia/short-term memory loss, hallucinations, tinnitus, impaired taste. From the cardiovascular system and blood (hematopoiesis, hemostasis): bradycardia, palpitations, hypotension, cold extremities, heart failure, AV block, edema syndrome, chest pain, decreased myocardial contractility, arrhythmias, gangrene, impaired myocardial conduction, syncope, thrombocytopenia, leukopenia, agranulocytosis. From the gastrointestinal tract: nausea, abdominal pain, diarrhea or constipation, vomiting, dry mouth, liver dysfunction; flatulence, dyspepsia, heartburn, hepatitis. From the respiratory system: shortness of breath, bronchospasm, vasomotor rhinitis, dyspnea. From the skin: rash, degenerative skin changes, reversible alopecia, photosensitivity, exacerbation of psoriasis; itching, erythema, urticaria, hyperhidrosis. Other: weight loss, arthralgia, arthritis, myalgia, muscle weakness, Peyronie's disease.
INTERACTION Hypotension is potentiated by sympatholytics, nifedipine, nitroglycerin, diuretics, apressin and other antihypertensive drugs. Antiarrhythmic and anesthetic drugs increase the risk of bradycardia, arrhythmia, and hypotension. Digitalis preparations potentiate the slowing of AV conduction. Simultaneous intravenous administration of verapamil and diltiazem can provoke cardiac arrest. Beta-adrenergic agonists, aminophylline, cocaine, estrogens, indomethacin and other NSAIDs weaken the antihypertensive effect. Strengthens and prolongs the effect of antidepolarizing muscle relaxants. Combination with alcohol leads to a mutual strengthening of the inhibitory effect on the central nervous system. Allergens increase the risk of severe systemic allergic reactions or anaphylaxis. Changes the effectiveness of insulin and oral antidiabetic agents and increases the risk of hypoglycemia. Antacids, hydralazines, oral contraceptives, cimetidine, ranitidine, phenothiazines increase the level of metoprolol in the blood, rifampicin decreases it. Reduces the clearance of lidocaine and the effectiveness of beta2-adrenergic agonists (the dose of the latter must be increased). Incompatible with MAO type A inhibitors.
OVERDOSE Symptoms: arterial hypotension, acute heart failure, bradycardia, cardiac arrest, AV block, cardiogenic shock, bronchospasm, impaired breathing and consciousness/coma, nausea, vomiting, generalized convulsions, cyanosis (manifest 20 minutes - 2 hours after administration). Treatment: gastric lavage, symptomatic therapy: administration of atropine sulfate (0.5-2 mg intravenously quickly) - for bradycardia and impaired AV conduction; glucagon (1-10 mg IV, then IV drip 2-2.5 mg/h) and dobutamine - in case of decreased myocardial contractility; adrenomimetics (norepinephrine, adrenaline, etc.) - for arterial hypotension; diazepam (iv slowly) - to eliminate seizures; inhalation of beta-adrenergic agonists or intravenous injection of aminophylline to relieve bronchospastic reactions; cardiac stimulation.
SPECIAL INSTRUCTIONS In patients with chronic heart failure, myocardial contractility may deteriorate, necessitating the use of cardiac glycosides and/or diuretics with careful monitoring of hemodynamic status. Against the background of diabetes mellitus and hyperfunction of the thyroid gland, metoprolol can mask tachycardia caused by hypoglycemia or thyrotoxicosis. In patients with diabetes mellitus, dose adjustment of antidiabetic drugs and careful monitoring of glycemic levels is necessary. When performing surgery during treatment, the anesthetic agent with the least negative ionotropic effect should be the drug of choice. A more pronounced development of a hypersensitivity reaction and the absence of a therapeutic effect of usual doses of adrenaline against the background of a burdened allergic history are possible. In patients with pheochromocytoma, use is possible only in conjunction with alpha-adrenolytics. Stop taking metoprolol 2-3 days before birth (risk of developing bradycardia, hypotension and hypoglycemia in the newborn); in exceptional cases, newborns after birth should be under medical supervision for 48-72 hours. When discontinuing treatment, the dose should be reduced gradually over 10-14 days. Patients with coronary artery disease should be under close medical supervision during this period. Use with caution while working for vehicle drivers and people whose profession involves increased concentration. During treatment, test results may change during laboratory tests.
STORAGE CONDITIONS List B. In a place protected from light, at room temperature.
Special instructions for the use of the drug Betaloc zok
Patients taking beta-blockers should not receive intravenous verapamil-type calcium antagonists. As a rule, when treating patients with asthma, β2-adrenergic receptor agonists (in tablets or aerosol) are prescribed as concomitant therapy. In cases where these patients begin to take Betaloc ZOK, an increase in the dose of β2-adrenergic receptor agonists may be necessary. The risk that Betaloc ZOK will affect β2-adrenergic receptors is lower than in the case of the use of conventional non-selective β1-adrenergic receptor blockers in tablets. Betaloc ZOK has a lesser effect on insulin release and carbohydrate metabolism than non-selective beta-adrenergic receptor blockers. In patients with chronic heart failure, compensation for the disease should be achieved before starting the use of Betaloc ZOK, and during its use they should be under medical supervision. In extremely rare cases, the condition of patients with moderate AV conduction disorders may worsen (possible development of complete AV block). If bradycardia develops during treatment, the dose of Betaloc ZOK should be reduced or the use of the drug should be gradually discontinued. Betaloc ZOK may increase the severity of peripheral arterial circulatory disorders by reducing blood pressure. Patients with pheochromocytoma should be prescribed an α-adrenergic receptor blocker simultaneously with Betaloc ZOK. When performing surgery, it is necessary to warn the anesthesiologist that the patient is taking Betaloc ZOK. However, it is not recommended to discontinue treatment with beta-adrenergic blockers in patients scheduled for surgery. Data on the effectiveness and safety of the drug in patients with severe stable heart failure (NYHA functional class IV) are limited. These patients must be treated by physicians with specialized skills and experience. Abrupt discontinuation of β-adrenergic blockers should be avoided, as this may worsen heart failure and also increase the risk of myocardial infarction and sudden cardiac death. If treatment must be stopped, this should be done as gradually as possible, over a period of at least 2 weeks under medical supervision. The dose is reduced by half at each stage. The last dose (12.5 mg) should be taken for at least 4 days until the drug is completely discontinued. If symptoms return, it is recommended to slow down the dose reduction. Anaphylactic shock in patients taking metoprolol is more severe. Pregnancy and lactation Betaloc ZOK can be prescribed during pregnancy only if the expected therapeutic effect for the mother outweighs the potential risk to the fetus. β-adrenergic receptor blockers can cause the development of bradycardia in the fetus and newborn, which should be taken into account when prescribing the drug in the third trimester of pregnancy, as well as during childbirth. It is unlikely that metoprolol prescribed to the mother in therapeutic doses will have a negative effect on the infant. Effect on the ability to drive vehicles and work with potentially dangerous mechanisms Since dizziness and weakness may develop when using the drug, caution should be exercised when driving vehicles and working with potentially dangerous mechanisms.
Interactions of the drug Betaloc zok
Patients should be under medical supervision if other beta-adrenergic receptor blockers (for example, in the form of eye drops), ganglion blockers, or MAO inhibitors are simultaneously prescribed with Betaloc ZOK. Concomitant use with propafenone should be avoided. Propafenone inhibits the metabolism of metoprolol via cytochrome P450 2D6. The result of using this combination is unpredictable, since propafenone also has a β-adrenergic blocking effect. If clonidine is suddenly discontinued during treatment with beta-adrenergic blockers, blood pressure may increase. If it is necessary to discontinue concomitant therapy with clonidine, the β-adrenergic blocker should be discontinued several days before discontinuing clonidine. In patients taking calcium antagonists such as verapamil or diltiazem and/or antiarrhythmic drugs simultaneously with Betaloc ZOK, a negative ino- and chronotropic effect may develop. In patients taking β-adrenergic blockers, intravenous administration of verapamil is contraindicated (risk of cardiac arrest). β-adrenergic receptor blockers can enhance the negative ino- and chronotropic effects of antiarrhythmic drugs (quinidine analogues, amiodarone). In patients receiving treatment with beta-adrenergic blockers, the use of inhalational anesthetics increases the severity of the cardiodepressive effect. Inducers or inhibitors of microsomal liver enzymes may affect the concentration of metoprolol in blood plasma. Metoprolol plasma concentrations are reduced by concomitant use of rifampicin or may be increased by concomitant use of cimetidine, phenytoin, alcohol, hydralazine and serotonin reuptake inhibitors (paroxetine, fluoxetine and sertraline). With simultaneous use of indomethacin or other COX inhibitors, the antihypertensive effect of beta-adrenergic blockers may be reduced. Cardioselective beta-adrenergic blockers have a significantly lesser effect on blood pressure when patients are given epinephrine than non-selective beta-adrenergic blockers. When taking beta-adrenergic blockers concomitantly, dose adjustment of oral antidiabetic agents may be necessary.
Betaloc®
Co-administration of Betaloc ® with the following drugs should be avoided:
Barbituric acid derivatives: barbiturates (study conducted with phenofarbital) slightly increase the metabolism of metoprolol due to enzyme induction.
Propafenone: When propafenone was prescribed to four patients treated with metoprolol, an increase in plasma concentrations of metoprolol was observed by 2-5 times, while two patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprolol via the cytochrome P4502D6 system. Taking into account the fact that propafenone has the properties of a beta-blocker, the joint administration of metoprolol and propafenone does not seem appropriate.
Verapamil: The combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and β-blockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.
The combination of Betaloc® with the following drugs may require dose adjustment:
Class I Antiarrhythmics: Class I antiarrhythmics and β-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and impaired AV conduction. The interaction is described using disopyramide as an example.
Amiodarone: Concomitant use of amiodarone and metoprolol may result in severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.
Diltiazem: Diltiazem and β-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs reduce the antihypertensive effect of beta-blockers. This interaction is best documented for indomethacin. There is no reported interaction observed for sulindac. In studies with diclofenac, the described reaction was not observed.
Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.
Epinephrine (adrenaline): 10 cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta-blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.
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-blockers may 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 the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden, approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased beta-blockade. It is believed that a similar interaction is typical for other β-blockers in the metabolism of which cytochrome P4502D6 is involved.
Clonidine: Hypertensive reactions during abrupt withdrawal of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, if clonidine is discontinued, discontinuation of β-blockers should begin several days before discontinuation of clonidine.
Rifampicin: Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.
The concentration of metoprolol in the blood plasma may increase when combined with cimetidine, hydralazine, selective serotonin inhibitors such as paroxetine, fluoxetine and sertraline.
Patients concomitantly taking metoprolol and other β-blockers (eye drops) or monoamine oxidase inhibitors (MAOIs) should be closely monitored.
When taking β-blockers, inhalational anesthetics enhance the cardiodepressive effect.
While taking β-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.
Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Overdose of the drug Betaloc zok
Symptoms: severe arterial hypotension, sinus bradycardia, AV block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, disturbances of consciousness up to coma, nausea, vomiting, cyanosis of the extremities. Concomitant use of alcohol, antihypertensive drugs, quinidine or barbiturates may worsen the patient's condition. The first symptoms develop 20 minutes to 2 hours after an overdose. Treatment: gastric lavage, taking activated carbon. In cases of severe arterial hypotension, bradycardia, or the threat of developing heart failure, administration of a β1-adrenergic receptor agonist (for example, prenalterol) intravenously at intervals of 2–5 minutes or as an infusion is indicated until a therapeutic effect is achieved. In the absence of a selective β1-adrenergic receptor agonist, it can be replaced by intravenous dopamine or atropine sulfate to block the vagus nerve. If a therapeutic effect cannot be achieved, other sympathomimetics (dobutamine or norepinephrine) can be used. Administration of glucagon at a dose of 1–10 mg is indicated. It may be necessary to use a pacemaker. To relieve bronchospasm, a β2-adrenergic receptor agonist is administered intravenously. It should be borne in mind that the doses of antidotes that are necessary to eliminate the symptoms of an overdose of a β-adrenergic receptor blocker are much higher than therapeutic doses, since β-adrenergic receptors are bound by their blockers.
