Pharmacodynamics and pharmacokinetics
The active ingredient Betaloc reduces or eliminates the stimulating effect of catecholamines during stress and exercise, reduces myocardial contractility and cardiac output, reduces high blood pressure and heart rate. In addition, metoprolol reduces myocardial oxygen demand and prolongs diastole.
The drug may slightly increase TG levels and also slightly reduce HDL fractions and free fatty acid levels in the blood plasma.
The tablets are characterized by a delayed release of the active substance, so the concentration of the drug in the blood plasma remains unchanged, which ensures a stable clinical effect for a day or more. The drug is better tolerated than its analogues, and the risk of developing unwanted side effects is significantly reduced.
Betaloc ZOK is completely absorbed. Absorption does not depend on the timing of meals. The degree of connection with blood plasma proteins is 5-10%. The active substance is metabolized in the liver to form three metabolites without beta-blocking activity.
About 95% of the drug is excreted in the urine, the remaining amount remains unchanged. The half-life averages 3-4 hours.
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.
Indications for use
What are Betaloc ZOK tablets for? First of all, they are prescribed to patients with:
- arterial hypertension;
- heart rhythm disturbances;
- angina pectoris;
- functional disorders of the heart, which are accompanied by tachycardia .
As an element of therapy, the drug is used for chronic heart failure . In addition, Betaloc ZOK is used to reduce mortality and the likelihood of recurrent infarction after the acute phase of myocardial infarction , as well as as a prophylactic against migraine .
Contraindications
This drug is contraindicated in cases of atrioventricular block II-III degree, therapy with inotropic agents to activate beta-adrenergic receptors, sick sinus syndrome, peripheral arterial circulation disorders, heart failure in the decompensation phase, clinically significant sinus bradycardia , cardiogenic shock , as well as hypersensitivity to beta-adrenergic blockers and any component of the drug.
In addition, Betaloc ZOK is not suitable for patients with acute myocardial infarction with a heart rate less than 45 per minute, systolic blood pressure less than 100 mm Hg. Art. or the duration of the P-Q interval on the ECG is more than 0.24 s.
Composition and release form
Active substance: metoprolol tartrate 25 mg
- Excipients:
- lactose monohydrate;
- magnesium stearate;
- sodium carboxymethyl starch;
- anhydrous colloidal silicon dioxide;
- povidone.
Nosological classification (ICD-10)
- I21 Acute myocardial infarction
- I25 Chronic ischemic heart disease
- I47.1 Supraventricular tachycardia
- R00.0 Tachycardia, unspecified
- R07.2 Pain in the heart area
Description of the dosage form
Solution for intravenous administration: clear, colorless liquid.
Tablets: biconvex, round, white, scored and engraved A/mE on one side.
pharmachologic effect
Pharmacological action - antiarrhythmic, hypotensive, antianginal.
Indications for Betaloc®
arterial hypertension: lowering blood pressure and reducing the risk of cardiovascular and coronary death (including sudden death);
angina pectoris;
cardiac arrhythmias, including supraventricular tachycardia;
after myocardial infarction (in complex therapy);
functional disorders of cardiac activity accompanied by tachycardia;
prevention of migraine attacks;
hyperthyroidism (complex therapy).
Contraindications
known hypersensitivity to metoprolol and its components or to other beta-blockers;
AV block II and III degrees, heart failure in the stage of decompensation, clinically significant sinus bradycardia, sick sinus syndrome, cardiogenic shock, severe peripheral circulatory disorders, arterial hypotension;
patients with acute myocardial infarction with a heart rate of less than 45 beats per minute, a PQ interval of more than 0.24 s, or a blood pressure of less than 100 mm Hg;
In patients receiving β-blockers, the administration of “slow” calcium channel blockers such as verapamil is contraindicated.
serious peripheral vascular diseases (with the threat of gangrene);
age under 18 years (efficacy and safety have not been established).
Patients receiving long-term or intermittent therapy with inotropic agents acting on β-adrenergic receptors.
With caution: 1st degree AV block, Prinzmetal's angina, COPD (emphysema, chronic obstructive bronchitis, bronchial asthma), diabetes mellitus, severe renal failure.
Use during pregnancy and breastfeeding
Pregnancy
Like most drugs, Betaloc® should not be prescribed during pregnancy and breastfeeding, unless the expected benefit to the mother outweighs the potential risk to the fetus. Like other antihypertensive agents, beta-blockers may cause side effects such as bradycardia in the fetus, neonates, or breastfed children, and therefore particular caution should be exercised when prescribing beta-blockers in the last trimester of pregnancy and immediately before birth. .
Lactation period
The amount of metoprolol excreted in breast milk and the β-adrenergic blocking effect in a breastfed child (when the mother takes metoprolol in therapeutic doses) are insignificant.
Side effects
Betaloc® is well tolerated by patients, and side effects are mostly mild and reversible.
As a result of clinical studies or with the use of Betaloc® (metoprolol tartrate) in clinical practice, the following undesirable side effects have been described. In many cases, a cause-and-effect relationship with treatment with Betaloc® has not been established. The following criteria were used to assess the frequency of cases: very common (>10%), common (1–9.9%), uncommon (0.1–0.9%), rare (0.01–0.09%) and very rare (<0.01%).
From the cardiovascular system: often - bradycardia, postural disturbances (very rarely accompanied by fainting), coldness of the extremities, palpitations; uncommon - temporary increase in symptoms of heart failure, cardiogenic shock in patients with acute myocardial infarction, AV block of the first degree; rarely - other cardiac conduction disorders, arrhythmias; very rarely - gangrene in patients with previous severe peripheral circulatory disorders.
From the side of the central nervous system: very often - increased fatigue; often - dizziness, headache; uncommon - paresthesia, convulsions, depression, loss of attention, drowsiness or insomnia, nightmares; rarely - increased nervous excitability, anxiety, impotence/sexual dysfunction; very rarely - amnesia/memory impairment, depression, hallucinations.
From the gastrointestinal tract: often - nausea, abdominal pain, diarrhea, constipation; infrequently - vomiting; rarely - dry mouth.
From the skin: infrequently - rash (in the form of urticaria), increased sweating; rarely - hair loss; very rarely - photosensitivity, exacerbation of psoriasis.
From the liver: rarely - liver dysfunction.
From the respiratory system: often - shortness of breath with physical effort; uncommon - bronchospasm in patients with bronchial asthma; rarely - rhinitis.
From the senses: rarely - visual disturbances, dryness and/or irritation of the eyes, conjunctivitis; very rarely - ringing in the ears, disturbances of taste.
From the side of metabolism: infrequently - weight gain.
From the musculoskeletal system: very rarely - arthralgia.
From the blood system: very rarely - thrombocytopenia.
For tablets additionally
From the liver: very rarely - hepatitis.
Directions for use and doses
Inside, both with food and on an empty stomach.
Arterial hypertension
100–200 mg of Betaloc® once in the morning or in 2 divided doses; in the morning and in the evening. If necessary, the dose can be increased or another antihypertensive agent added.
Long-term antihypertensive therapy of 100–200 mg of Betaloc® per day can reduce overall mortality, including sudden death, as well as the incidence of cerebral strokes and coronary circulatory disorders in patients with arterial hypertension.
Angina pectoris
100–200 mg/day in 2 divided doses; in the morning and in the evening. If necessary, another antianginal drug may be added to therapy.
Heart rhythm disturbances
100–200 mg/day in 2 divided doses; in the morning and in the evening. If necessary, another antiarrhythmic drug may be added to therapy.
Maintenance therapy after myocardial infarction
The maintenance dose is 200 mg/day in 2 divided doses; in the morning and in the evening. Prescribing Betaloc® at a dose of 200 mg/day can reduce mortality in patients who have suffered a myocardial infarction and reduce the risk of developing a recurrent myocardial infarction (including in patients with diabetes mellitus).
Functional cardiac disorders accompanied by tachycardia
100 mg of Betaloc® 1 time per day, it is recommended to take the tablet in the morning. If necessary, the dose can be increased.
Preventing migraine attacks
100–200 mg/day in 2 divided doses; in the morning and in the evening.
Hyperthyroidism
150–200 mg/day in 3–4 doses.
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 liver cirrhosis or portacaval 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® in children is limited.
Overdose
Symptoms: the consequences of an overdose of Betaloc® can be a pronounced decrease in blood pressure, sinus bradycardia, AV block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impaired consciousness/coma, nausea, vomiting and cyanosis.
Concomitant use of alcohol, antihypertensive drugs, quinidine or barbiturates may worsen the patient's condition.
The first signs of overdose may appear within 20 minutes to 2 hours after taking the drug.
Treatment: administration of activated carbon, and, if necessary, gastric lavage. In case of a pronounced decrease in blood pressure, bradycardia, or the threat of heart failure, a β1-adrenergic agonist (for example, dobutamine) should be administered intravenously at intervals of 2–5 minutes or by infusion until a therapeutic effect is achieved. If a selective β1-agonist is not available, IV dopamine or atropine sulfate can be administered to block the vagus nerve.
If therapeutic effect is not achieved, other sympathomimetics such as dobutamine or norepinephrine can be used.
Glucagon can be administered at a dose of 1–10 mg. Sometimes it may be necessary to use a pacemaker. To relieve bronchospasm, a β2-adrenergic agonist should be administered intravenously.
It must be taken into account that the doses of antidotes required to eliminate the symptoms that occur with an overdose of β-blockers are much higher than therapeutic doses, since β-adrenergic receptors are bound to the β-blocker.
special instructions
Patients taking β-blockers should not be administered intravenous calcium channel blockers such as verapamil.
When using β1-blockers, the risk of their influence on carbohydrate metabolism or the possibility of masking hypoglycemia is significantly less than when using non-selective β-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.
Non-selective β-blockers are not recommended for patients suffering from Prinzmetal's angina.
Very rarely, patients with impaired atrioventricular conduction may experience deterioration (a possible outcome is AV block). If bradycardia develops during treatment, the dose of Betaloc® should be reduced. Metoprolol may worsen symptoms of peripheral arterial circulation disorders, mainly due to a decrease in blood pressure. Caution should be exercised when prescribing the drug to patients suffering from severe renal failure, metabolic acidosis, and co-administration with cardiac glycosides.
Patients suffering from pheochromocytoma should be prescribed an α-blocker in parallel with Betaloc®.
In case of surgery, the anesthesiologist should be informed that the patient is taking a beta-blocker.
In patients taking β-blockers, anaphylactic shock occurs in a more severe form.
Patients suffering from obstructive pulmonary disease are not recommended to prescribe β-blockers. In case of poor tolerance to other antihypertensive drugs or their ineffectiveness, metoprolol can be prescribed, since it is a selective drug. It is necessary to prescribe the minimum effective dose; if necessary, a β2-adrenergic agonist may be prescribed.
In patients with liver cirrhosis, the bioavailability of metoprolol increases.
Abrupt withdrawal of the drug should be avoided. If it is necessary to discontinue the drug, withdrawal should be carried out gradually. In most patients, the drug can be discontinued within 14 days. The dose of the drug is reduced gradually, in several doses, until a final dose of 25 mg is reached once a day. Patients with coronary artery disease should be closely monitored by a physician during drug withdrawal.
Impact on the ability to drive a car and operate technical devices. When using the drug, episodes of dizziness or general weakness are possible, and therefore it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
A comment
Before using the drug, you must read the instructions for use.
Conditions for dispensing from pharmacies
- On prescription.
Storage conditions for Betaloc®
- In a place protected from light, at temperatures below 25 °C.
- Keep out of the reach of children.
Shelf life of Betaloc®
- 5 years.
- Do not use after the expiration date stated on the package.
Side effects
As a rule, when used correctly, the medicine is well tolerated by patients to whom it is prescribed. Side effects are minor or easily reversible.
Cardiovascular system: bradycardia , coldness of the extremities, increased manifestations of heart failure , orthostatic hypotension , cardiogenic shock , edema, pain in the heart, fainting, palpitations, first degree atrioventricular block arrhythmia .
Gastrointestinal tract: nausea , diarrhea , vomiting , abdominal pain, constipation .
Skin: rash, increased sweating.
Metabolism: increased body fat.
CNS: increased fatigue, headache , convulsions, problems concentrating, insomnia , dizziness , paresthesia , depression , drowsiness , nightmares.
Respiratory organs: shortness of breath , bronchospasm .
In rare cases, when taking the drug, the following are possible:
- gangrene;
- increased nervous excitability;
- memory impairment;
- hallucinations;
- anxiety;
- depression;
- dryness of the oral mucosa;
- hepatitis;
- hair loss;
- exacerbation of psoriasis ;
- liver dysfunction;
- photosensitivity;
- rhinitis;
- visual impairment;
- conjunctivitis;
- taste disturbances;
- irritation and/or dry eyes;
- tinnitus;
- arthralgia;
- thrombocytopenia;
- impotence , sexual dysfunction .
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.
Instructions for use of Betaloc ZOK (Method and dosage)
Instructions for use of Betaloc ZOK include taking the drug once daily, regardless of meals (preferably in the morning). Tablets should not be crushed or chewed. During dosage selection, heart rate should be monitored.
Arterial hypertension : 50 mg per day (if the therapeutic effect is not achieved, the dose can be gradually increased to 100-200 mg per day, while Betaloc ZOK tablets, instructions for use, can be combined with other antihypertensive drugs).
Stable chronic heart failure of functional class III-IV : to begin with, a dosage is prescribed - 12.5 mg per day (1/2 tablet of 25 mg). If necessary, the dose is gradually increased, but this must be done strictly under the supervision of a doctor. After 14 days, the initial dosage is increased to 25 mg per day; after another 2 weeks, 50 mg per day can be prescribed. Thus, every 14 days the dose can be doubled until a maximum dosage of 200 mg is reached. However, the dose should not be increased until there is clear evidence that the patient is stable. Kidney function needs to be monitored.
Stable chronic heart failure of functional class II : at the beginning, a dose of 25 mg is prescribed. After the first 2 weeks, it can be increased to 50 mg per day, and then doubled every 14 days until a therapeutic effect is achieved. The maximum dosage is 200 mg per day.
For migraine prevention, 100–200 mg per day is prescribed.
For angina pectoris, 100–200 mg per day is prescribed (can be combined with other drugs for the treatment of angina pectoris).
For arrhythmia, 100–200 mg per day is prescribed.
Cardiac disorders with palpitations: 100 mg per day (if necessary, the dosage can be increased to 200 mg).
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.
Overdose
There are cases where, at a dosage of 7.5 g, the drug caused severe intoxication with a fatal outcome in an adult. At doses of 1.4 and 2.5 g, respectively, there was moderate and severe intoxication.
An overdose of this drug can lead to respiratory depression, atrioventricular block I–III degrees, decreased blood pressure, heart failure, bradycardia , asystole , weak peripheral perfusion , cardiogenic shock , apnea . In addition, Betaloc ZOK in increased doses can cause impairment of consciousness, tremor , excessive sweating and fatigue, bronchospasm , vomiting, hypoglycemia or hyperglycemia , renal impairment, loss of consciousness, convulsions, paresthesia , nausea, as well as esophageal spasm and hyperkalemia .
Initial signs of a drug overdose will be noticeable 20-120 minutes after administration.
Activated carbon is prescribed as treatment , as well as gastric lavage if necessary.
Depending on the manifestations of overdose, symptomatic treatment is carried out. So, you may need intubation and adequate ventilation, ECG monitoring, blood volume replenishment and glucose infusions. If necessary, Atropine (before gastric lavage) is administered intravenously 1-2 mg. For myocardial depression, Dobutamine or Dopamine . It is possible to use Glucagon intravenously at a dosage of 50–150 mcg per 1 kg of weight. In some cases, Adrenaline , terbutaline (to relieve bronchospasm ), as well as an artificial pacemaker, help. For arrhythmia and an extensive ventricular complex, a sodium solution is injected. Resuscitation measures may be necessary.
Betaloc Zok tab p/o 100 mg N30 (AstraZeneca)
Metoprolol is a CYP2D6 substrate. therefore, drugs that inhibit CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) may affect the plasma concentrations of metoprolol.
The combined use of Betaloc® ZOK with the following drugs should be avoided:
Barbituric acid derivatives
: Barbiturates (study conducted with pentobarbital) increase the metabolism of metoprolol due to enzyme induction.
Propaphenone
: When propafenone was prescribed to four patients treated with metoprolol, an increase in the plasma concentration 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 β-blocker properties. Co-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® ZOK with the following drugs may require dose adjustment:
Amiodarone
: Concomitant use of amiodarone and metoprolol can lead to severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.
Class I antiarrhythmic drugs:
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.
Nonsteroidal anti-inflammatory drugs (NSAIDs):
NSAIDs weaken the antihypertensive effect of β-blockers. This interaction has been documented for indomethacin. It is likely that the described interaction will not be observed with sulindac. Negative interactions have been noted in studies with diclofenac.
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.
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.
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 (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, 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-blockade. It is believed that a similar interaction is typical for other β-blockers, the metabolism of which involves cytochrome P4502D6.
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.
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.
Plasma concentrations of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Interaction
When using the drug Betaloc ZOK and other beta-adrenergic receptor blockers, as well as MAO inhibitors and ganglion blockers, strict medical supervision is required.
The drug should not be combined with Propafenone , Verapamil . When taking Diltiazem and/or antiarrhythmic drugs, a negative ino- and chronotropic effect may develop. When using inhalational anesthetics, the cardiodepressive effect is enhanced.
It is possible that inducers or inhibitors of microsomal liver enzymes may influence the content of the active substance Betaloc ZOK in the blood plasma. Its concentration is reduced when combined with Rifampicin or increased when taken simultaneously with Cimetidine , hydralazine , phenytoin , and serotonin .
When discontinuing clonidine, Betaloc ZOK must be discontinued several days before.
In combination with COX inhibitors, the antihypertensive effect of the drug may be reduced. Dosage adjustments of oral antidiabetic agents may also be necessary when administered concomitantly.
Betaloc® ZOK
Metoprolol is a CYP2D6 substrate. therefore, drugs that inhibit CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) may affect the plasma concentrations of metoprolol.
The combined use of Betaloc® ZOK with the following drugs should be avoided:
Barbituric acid derivatives: barbiturates (study conducted with pentobarbital) 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 β-blocker properties. Co-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® ZOK with the following drugs may require dose adjustment:
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.
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.
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs reduce the antihypertensive effect of beta-blockers. This interaction has been documented for indomethacin. It is likely that the described interaction will not be observed with sulindac. Negative interactions have been noted in studies with diclofenac.
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.
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.
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, 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-blockade. It is believed that a similar interaction is typical for other β-blockers, the metabolism of which involves cytochrome P4502D6.
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.
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.
Plasma concentrations of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Analogues of Betalok ZOK
Level 4 ATC code matches:
Biol
Metocard
Metozok
Nebilet
Nebilong
Betaxolol
Bisogamma
Aritel
Cordinorm
Vasocardin
Corvitol
Bidop
Bisoprolol
Nebivolol
Biprol
Bisoprol
Concor Cor
Lokren
Concor
Niperten
The following analogues of Betalok ZOK are sold in pharmacies:
- Betalok
- Egilok
- Metoprolol
- Metocard
- Metocore
- Serdol
- Azoprol Retard
- Vasocardin
- Corvitol
Reviews about analogues of Betalok ZOK are quite different. Some of them are almost as good as him, and some are of a fairly low level. So the price of analogs of this product, as well as their manufacturers, deserves special attention. To finally decide which medicine is best for each specific case, you should consult a doctor. In addition, before use, be sure to read the instructions.
Reviews of Betaloka ZOK
Reviews of Betalok ZOK indicate that quite often after its use undesirable symptoms occur. Thus, patients often report cases of rhinitis . Some also complain of irregular pulse and unstable blood pressure. Because of this, specialists prescribe additional medications that are designed to eliminate these side effects. However, it should be noted that most people still tolerate this medication easily.
In addition, reviews of Betalok ZOK draw attention to the fact that the selection of dosages should be approached with particular care. The patient’s condition must be constantly monitored and the danger of deterioration must be eliminated in a timely manner.
Betaloka ZOK price, where to buy
The average price of Betaloc ZOK 50 mg is about 250 rubles, the price of 25 mg is about 150 rubles, and the average cost of 100 mg of the drug is about 400 rubles.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
Pharmacy Dialogue
- Betalok Zok (tablet p/o 100 mg No. 30) Astra Zenesa/AstraZeneca Industries
424 rub. order - Betaloc Zok tablets 25 mg No. 14Astra Zenesa/AstraZeneca Industries
148 RUR order
- Betaloc Zok tablets 50 mg No. 30Astra Zenesa/AstraZeneca Industries
RUB 293 order
- Betalok Zok (tablet p/o 50 mg No. 30)Astra Zeneca/ZIO Health
RUB 279 order
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Pharmacy24
- Betaloc Zok 100 mg N30 Astra Zeneca AB, Sweden
199 UAH order - Betaloc Zok 50 mg N30 tablets Astra Zeneca AB, Sweden
142 UAH order
- Betaloc Zok 25 mg No. 14 tablets Astra Zeneca AB, Sweden
80 UAH order
