Betaloc Zoc, 25 mg 14 pcs

Pharmacotherapeutic group: beta1-adrenoblocker selective

ATX code: C07AB02

Pharmacological properties Pharmacodynamics

Metoprolol is a b1-adrenoblocker that blocks b1-receptors at doses much lower than those required to block b2-receptors.

Metoprolol has little membrane-stabilizing effect and no partial agonist activity.

Metoprololol reduces or inhibits the agonist effect that catecholamines released during nervous and physical stress have on cardiac activity. This means that metoprolol has the ability to inhibit the increase in heart rate (HR), minute volume, and increased cardiac contractility and blood pressure (BP) caused by the sudden release of catecholamines.

In contrast to the common tablet forms of selective b1-adrenoblockers (including metoprolol tartrate), Betaloc® ZOC has consistent plasma concentrations and produces a sustained clinical effect (b1-blockade) for greater than 24 hours.

With no apparent peak plasma concentrations, clinically, Betaloc® ZOC has better b1-selectivity than conventional tablet forms of b1-adrenoblockers. In addition, the potential risk of side effects observed at peak plasma concentrations of the drug, such as bradycardia and weakness in the legs when walking, is significantly reduced.

Patients with symptoms of obstructive pulmonary disease may be prescribed Betaloc® ZOC in combination with b2-adrenomimetics if necessary. When used in combination with b2-adrenomimetics, Betaloc® ZOC in therapeutic doses has less effect on b2-adrenomimetic-induced bronchodilation than non-selective b-adrenoblockers. Metoprolol affects insulin production and carbohydrate metabolism to a lesser extent than non-selective b-adrenoblockers. The effect of the drug on cardiovascular response in hypoglycemia is significantly less pronounced compared to non-selective b-adrenoblockers.

The use of Betaloc® ZOC in arterial hypertension leads to a significant reduction of blood pressure for more than 24 hours, both when lying and standing and under load. At the beginning of metoprolol therapy, an increase in vascular resistance is noted. However, with long-term therapy, BP may decrease due to decreased vascular resistance while cardiac output remains unchanged.

In MERIT-HF (chronic heart failure survival study (NYHA class II-IV) and reduced cardiac output fraction (£ 0.40) including 3991 patients) Betaloc® ZOC showed increased survival and reduced hospitalization rate. With long-term treatment, patients achieved an overall improvement in symptoms (according to NYHA grades). Also, therapy with Betaloc® ZOC showed increased left ventricular ejection fraction and decreased left ventricular end-systolic and end-diastolic volumes.

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

Pharmacokinetics

The tablets disintegrate rapidly on contact with liquid, with dispersion of the active ingredient in the gastrointestinal tract. The rate of release of the active substance depends on the acidity of the environment. The duration of therapeutic effect after using Betaloc® ZOC (sustained release tablets) is more than 24 hours, while a constant rate of active substance release is achieved over 20 hours. The half-life is an average of 3.5 hours.

Betaloc® ZOC 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 major metabolites of metoprololol showed no clinically significant b-blocking effect. About 5% of the oral dose of the drug is excreted unchanged in the urine, the rest of the drug is excreted as metabolites. Binding to blood plasma proteins is low, about 5-10%.

Indications

Active ingredient

Composition

One Betaloc® ZOC 25 mg tablet contains:

Pill nucleus: The active ingredient: 23.75 mg metoprolol succinate, corresponding to 19.5 mg metoprolol and 25 mg metoprolol tartrate.

Auxiliary substances: ethylcellulose 21.5 mg, hyprolose 6.13 mg, microcrystalline cellulose 94.9 mg, silicon dioxide 14.6 mg, sodium stearyl fumarate 0.241 mg; Pill shell: hypromellose 5.64 mg, paraffin “0.06 mg, macrogol 1.41 mg, titanium dioxide 1.41 mg.

One tablet Betaloc® ZOC 50 mg contains:

Pill nucleus: Active ingredient: 47.5 mg metoprolol succinate, corresponding to 39 mg metoprolol and 50 mg metoprolol tartrate.

Auxiliary substances: ethylcellulose 23 mg, hyprolose 7 mg, microcrystalline cellulose 120 mg, silicon dioxide 12 mg, sodium stearyl fumarate 0.3 mg; Pill shell: hypromellose 6.2 mg, paraffin “0.1 mg, macrogol 1.6 mg, titanium dioxide 1.6 mg.

One tablet of Betaloc® ZOC 100 mg contains:

Pill nucleus: Active ingredient: 95 mg metoprolol succinate, which corresponds to 78 mg metoprolol and 100 mg metoprolol tartrate.

Auxiliary substances: ethylcellulose 46 mg, hyprolose 13 mg, microcrystalline cellulose 180 mg, silicon dioxide 24 mg, sodium stearyl fumarate 0.5 mg;

the tablet shell: hypromellose 9.8 mg, paraffin “0.2 mg, macrogol 2.4 mg, titanium dioxide 2.4 mg.

How to take, the dosage

Betaloc® ZOC is intended to be taken once daily and is recommended to be taken in the morning. The Betaloc® ZOC tablet should be swallowed with fluids. Tablets (or tablets divided in half) should not be chewed or crumbled. Food intake does not affect the bioavailability of the drug.

The development of bradycardia should be avoided when adjusting the dose.

Arterial hypertension

50-100 mg once daily. If necessary, the dose may be increased to 200 mg daily or another antihypertensive agent may be added, preferably a diuretic and a dihydropyridine-type slow calcium channel blocker.

Stenocardia

100-200 mg of Betaloc® ZOC once daily. 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 an episode of exacerbation within the past 6 weeks and without changes in underlying therapy within the past 2 weeks.

Therapy of heart failure with β-adrenoblockers may sometimes result in a temporary worsening of the symptomatic picture. In some cases, continuation of therapy or reduction of the dose may be possible; in some cases it may be necessary to discontinue the drug.

Stable chronic heart failure, functional class II

The recommended starting dose of Betalok® ZOC for the first 2 weeks is 25 mg once daily. After 2 weeks of therapy, the dose may be increased to 50 mg once daily and may be doubled every 2 weeks thereafter.

The maintenance dose for long-term treatment is 200 mg of Betaloc® ZOC once daily.

Stable chronic heart failure, functional class III-IV The recommended starting dose for the first 2 weeks is 12.5 mg of Betaloc® ZOC (half tablet 25 mg) once daily. The dose is adjusted individually. During the period of dose increase the patient should be monitored, because in some patients the symptoms of heart failure may worsen.

After 1 to 2 weeks, the dose may be increased to 25 mg of Betaloc® ZOC once daily. Then, after 2 weeks, the dose may be increased to 50 mg once daily. In patients who tolerate the drug well the dose may be doubled every 2 weeks up to a maximum dose of 200 mg of Betaloc® ZOC once daily.

In cases of arterial hypotension and/or bradycardia, it may be necessary to reduce concomitant therapy or decrease the dose of Betaloc® ZOC. Arterial hypotension at the start of therapy does not necessarily indicate that a given dose of Betaloc® ZOC will not be tolerated with continued long-term treatment. However, the dose should not be increased until the condition has stabilized. Renal function may need to be monitored.

Heart rhythm disorders

100-200 mg of Betaloc® ZOC once daily. Supportive treatment after myocardial infarction 200 mg of Betaloc® ZOC once daily.

Functional cardiac disorders with tachycardia

100 mg of Betaloc® ZOC once daily. If necessary, the dose can be increased to 200 mg daily.

Prevention of migraine attacks

100-200 mg of Betaloc® ZOC once daily.

Renal dysfunction

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

Hepatic dysfunction

Because of the low degree of binding to plasma proteins, no dose adjustment of metoprolol is usually required. However, in severe liver function impairment (in patients with severe cirrhosis or portocaval anastomosis), dose reduction may be required.

Elderly age

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

Children

Limited experience with Betaloc® ZOC in children.

Interaction

Toxicity: metoprolol at a dose of 7.5 g in an adult caused intoxication with fatal outcome. A 5-year-old child who took 100 mg metoprololol showed no signs of intoxication after gastric lavage. Administration of 450 mg metoprolol to a 12-year-old adolescent resulted in moderate intoxication. Administration of 1.4 g and 2.5 g metoprolol to adults caused moderate and severe intoxication, respectively. Intake of 7.5 g in adults resulted in extremely severe intoxication.

Symptoms: In metoprolol overdose, cardiovascular symptoms are most serious, but sometimes, especially in children and adolescents, CNS symptoms and pulmonary function suppression, bradycardia, grade I-III AV blockade, asystole, marked BP decrease, poor peripheral perfusion, heart failure, cardiogenic shock may predominate; depression of lung function, apnea, as well as, increased fatigue, impaired consciousness, loss of consciousness, tremors, seizures, increased sweating, paresthesias, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; effects on the kidneys; transient myasthenic syndrome; concomitant administration of alcohol, antihypertensives, quinidine, or barbiturates may worsen the patient’s condition. The first signs of overdose may be observed 20 minutes to 2 hours after taking the drug.

Treatment: Appointment of activated charcoal, if necessary, gastric lavage. IMPORTANT: Atropine (0.25-0.5 mg i.v. for adults, 10-20 µg/kg for children) should be given before gastric lavage (due to risk of vagus nerve stimulation). If necessary, maintenance of airway patency (intubation) and adequate pulmonary ventilation. Replenishment of circulating blood volume and glucose infusion. ECG monitoring. Atropine 1.0-2.0 mg v/v, repeat administration if necessary (especially in case of vagus symptoms). In case of myocardial depression, infusion of dobutamine or dopamine is indicated. Glucagon 50-150 mcg/kg IV at 1-minute intervals may also be used. In some cases, the addition of adrenaline to therapy may be effective. In arrhythmia and extensive ventricular (QRS) complex, sodium solutions (chloride or bicarbonate) are infused. Installation of an artificial pacemaker is possible. In case of cardiac arrest due to overdose, resuscitation measures may be required for several hours. Terbutaline may be used to relieve bronchospasm (by injection or inhalation). Symptomatic treatment is given.

Special Instructions

Patients taking b-adrenoblockers should not receive intravenous calcium channel blockers such as verapamil.

Patients with bronchial asthma or chronic obstructive pulmonary disease should be prescribed concomitant therapy with a b2-adrenomimetic. The lowest effective dose of Betaloc® ZOC should be administered, and an increased dose of b2-adrenomimetic may be required.

Non-selective b-adrenoblockers are not recommended for patients with Prinzmetal angina. B-selective adrenoblockers should be prescribed with caution in this group of patients.

When using b1-adrenoblockers, 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 b-adrenoblockers.

In patients with decompensated chronic heart failure, a stage of compensation should be achieved both before and during treatment with the drug.

Very rarely, patients with AV conduction abnormality may worsen (possible outcome is AV blockade). If bradycardia develops with treatment, the drug dose should be reduced or the drug should be gradually withdrawn.

Betaloc® ZOC may worsen the course of existing peripheral circulatory disorders mainly due to decreased blood pressure.

Patients with severe renal impairment, metabolic acidosis, concomitant use with cardiac glycosides should be cautioned when prescribing the drug.

Patients taking b-adrenoblockers have a more severe anaphylactic shock. Administration of epinephrine (adrenaline) in therapeutic doses does not always lead to the desired clinical effect with metoprolol. In patients with pheochromocytoma, an alpha-adrenoblocker should be administered simultaneously with Betaloc® ZOC.

The abrupt withdrawal of β-adrenoblockers is dangerous, especially in high-risk patients, and therefore should be avoided. If withdrawal is necessary, it should be done gradually over at least 2 weeks, with twice the dose of the drug at each step, until a final dose of 12.5 mg (1/2 25 mg tablets) is reached, which should be taken for at least 4 days until complete withdrawal of the drug. If symptoms occur (e.g., increased symptoms of angina, increased blood pressure), a slower withdrawal regimen is recommended. Abrupt withdrawal of a β-adrenoblocker may worsen the course of chronic heart failure and increase the risk of myocardial infarction and sudden death.

In case of surgery, inform the anesthesiologist that the patient is taking Betaloc® ZOC. In patients undergoing surgery, discontinuation of therapy with b-adrenoblockers is not recommended. High-dose administration without prior titration of the drug should be avoided in patients with cardiovascular risk factors undergoing non-cardiac surgery due to increased risk of bradycardia, arterial hypotension and stroke, including fatal outcomes.

The data from clinical trials on efficacy and safety in patients with severe stable symptomatic chronic heart failure (NYHA class IV) are limited. Treatment of these patients should be performed by physicians with special knowledge and experience.

Patients with symptomatic heart failure combined with acute myocardial infarction and unstable angina were excluded from studies that determined indications for administration. Efficacy and safety of the drug for this group of patients have not been described. The use in unstable heart failure in decompensation stage is contraindicated.

When driving motor transport and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reaction, it should be noted that dizziness and fatigue may be observed when using Betaloc® ZOC.

Synopsis

Contraindications

Side effects

Betaloc® ZOC is well tolerated by patients; side effects are mostly mild and reversible.

The following criteria were used to assess incidence: very common (>10%), common (1-9.9%), infrequent (0.1-0.9%), rare (0.01-0.09%), and very rare (<0.01%).

Cardiovascular System

Often: bradycardia, orthostatic hypotension (very rarely accompanied by syncope), coldness of extremities, palpitations;

Infrequent: Temporary worsening of heart failure symptoms, grade I AV block; cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart region;

Rare: other conduction disorders, arrhythmias;

Very rare: gangrene in patients with previous severe peripheral circulatory disturbances.

Central nervous system

Very common: increased fatigue; Frequent: dizziness, headache;

Infrequent: paresthesia, seizures, depression, decreased concentration, drowsiness or insomnia, nightmares;

Rare: increased nervous excitability, anxiety;

Very rare: amnesia/memory disturbances, depression, hallucinations.

Gastrointestinal tract

Often: nausea, abdominal pain, diarrhea, constipation; Infrequent: vomiting;

Rarely: dry oral mucosa.

Liver

Rarely: disorders of liver function; Very rare: hepatitis.

Skin

Infrequent: skin rash (similar to psoriasis-like urticaria), increased sweating;

Rare: Hair loss;

Very rare: photosensitization, exacerbation of psoriasis.

Breathing organs

Often: shortness of breath on exercise; Infrequent: bronchospasm;

Rarely: rhinitis.

Sensory organs

Rarely: visual disturbances, dry and/or irritated eyes, conjunctivitis; Very rare: ringing in the ears, taste disturbances.

Skeletal and muscular system

Very rare: arthralgia.

Metabolism

Infrequent: weight gain.

blood

Very rare: thrombocytopenia.

Others

Rarely: impotence/sexual dysfunction.

Overdose

Toxicity: metoprolol at a dose of 7.5 g in an adult caused intoxication with fatal outcome. A 5-year-old child who took 100 mg metoprololol showed no signs of intoxication after gastric lavage. Administration of 450 mg metoprolol to a 12-year-old adolescent resulted in moderate intoxication. Administration of 1.4 g and 2.5 g metoprolol to adults caused moderate and severe intoxication, respectively. Intake of 7.5 g in adults resulted in extremely severe intoxication.

Symptoms: In metoprolol overdose, cardiovascular symptoms are most serious, but sometimes, especially in children and adolescents, CNS symptoms and pulmonary function suppression, bradycardia, grade I-III AV blockade, asystole, marked BP decrease, poor peripheral perfusion, heart failure, cardiogenic shock may predominate; depression of lung function, apnea, as well as, increased fatigue, impaired consciousness, loss of consciousness, tremors, seizures, increased sweating, paresthesias, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; effects on the kidneys; transient myasthenic syndrome; concomitant administration of alcohol, antihypertensives, quinidine, or barbiturates may worsen the patient’s condition. The first signs of overdose may be observed 20 minutes to 2 hours after taking the drug.

Treatment: Appointment of activated charcoal, if necessary, gastric lavage. IMPORTANT: Atropine (0.25-0.5 mg i.v. for adults, 10-20 µg/kg for children) should be given before gastric lavage (due to risk of vagus nerve stimulation). If necessary, maintenance of airway patency (intubation) and adequate pulmonary ventilation. Replenishment of circulating blood volume and glucose infusion. ECG monitoring. Atropine 1.0-2.0 mg v/v, repeat administration if necessary (especially in case of vagus symptoms). In case of myocardial depression, infusion of dobutamine or dopamine is indicated. Glucagon 50-150 mcg/kg IV at 1-minute intervals may also be used. In some cases, the addition of adrenaline to therapy may be effective. In arrhythmia and extensive ventricular (QRS) complex, sodium solutions (chloride or bicarbonate) are infused. Installation of an artificial pacemaker is possible. In case of cardiac arrest due to overdose, resuscitation measures may be required for several hours. Terbutaline may be used to relieve bronchospasm (by injection or inhalation). Symptomatic treatment is given.

Pregnancy use

Similarities