Betaloc Zoc delayed-release pills 25mg, 14pcs

Composition

Active ingredient:

23.75 mg of metoprolol succinate, which corresponds to 19.5 mg of metoprolol and 25 mg of metoprolol tartrate.

Auxiliary substances:

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

Pharmacological action

Metoprolol is a beta-1 blocker that blocks beta-1 receptors at doses significantly lower than the doses required to block beta-2 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( HR), minute volume and increased contractility of the heart, as well as an increase in blood pressure (BP) caused by a sharp release of catecholamines.

Unlike conventional tablet dosage forms of selective beta-1-blockers (including metoprolol tartrate), when using the drug Betalok ZOK, a constant concentration of the drug in blood plasma is observed and a stable clinical effect (beta-1-blockade) is provided for more than 24 hours.

Due to the absence of obvious peak plasma concentrations, clinically Betalok ZOK is characterized by better beta-1 selectivity compared to conventional tablet forms of beta-1 blockers. In addition, the potential risk of side effects observed at peak plasma concentrations of the drug, such as bradycardia and weakness in the legs when walking, is significantly reduced. If necessary, patients with symptoms of obstructive pulmonary diseases can be prescribed Betalok ZOK in combination with beta-2-adrenomimetics. When combined with beta-2-adrenomimetics, Betaloc ZOK in therapeutic doses has a lesser effect on bronchodilation caused by beta-2-adrenomimetics than non-selective beta-blockers. Metoprolol affects insulin production and carbohydrate metabolism to a lesser extent than non-selective beta-blockers. The effect of the drug on the response of the cardiovascular system in conditions of hypoglycemia is significantly less pronounced compared to non-selective beta-blockers. The use of Betalok Zok in patients with arterial hypertension leads to a significant decrease in blood pressure for more than 24 hours, both in the supine and standing positions, and during exercise. At the beginning of metoprolol therapy, an increase in vascular resistance is noted. However, with prolonged use, blood pressure may decrease due to a decrease in vascular resistance with constant cardiac output.

In the MERIT-HF (NYHA Class II-IV Chronic Heart Failure Survival Study) and Reduced Cardiac Output fraction (Quality of life during treatment with Betaloc), ZOK did not worsen or improve. Improvement in the quality of life during treatment with Betalok ZOK was observed in patients after myocardial infarction.

Indications

• Arterial hypertension
• Angina pectoris.
• Stable symptomatic chronic heart failure with impaired left ventricular systolic function (as an adjunct therapy to the main treatment of chronic heart failure).
• Reduction of mortality and recurrent infarction after acute phase of myocardial infarction.
• Cardiac arrhythmias, including supraventricular tachycardia, decreased ventricular contraction in atrial fibrillation and ventricular extrasystoles.
• Functional disorders of cardiac activity accompanied by tachycardia.
• Prevention of migraine attacks.

Use during pregnancy and lactation

Like most medications, Betalok ZOK should not be administered during pregnancy or during breast-feeding, unless the expected benefit to the mother outweighs the potential risk to the fetus and / or child.

Like other antihypertensive agents, beta-blockers can cause side effects, such as bradycardia in the fetus, newborns, or children who are breastfed.

The amount of metoprolol released into breast milk and the beta-blocking effect in a breastfed child (when the mother takes metoprolol in therapeutic doses) are insignificant.

Contraindications

Atrioventricular block II and III degrees, heart failure in the stage of decompensation, constant or intermittent therapy with inotropic drugs acting on beta-adrenergic receptors, clinically significant sinus bradycardia, sinus node weakness syndrome, cardiogenic shock, severe peripheral circulatory disorders, including with the threat of gangrene, arterial hypotension. Betalok ZOK is contraindicated in patients with suspected acute myocardial infarction with a heart rate of less than 45 beats per minute, a PQ interval of more than 0.24 seconds, or a systolic blood pressure of less than 100 mm Hg.

Known hypersensitivity to metoprolol and its components or to other beta-blockers. Intravenous use of slow calcium channel blockers such as verapamil is contraindicated in patients receiving beta-blockers.

Age up to 18 years (efficacy and safety have not been established).

With caution: grade I atrioventricular block, Prinzmetal angina, bronchial asthma, chronic obstructive pulmonary disease, diabetes mellitus, severe renal failure, severe renal failure, metabolic acidosis, co-use with cardiac glycosides.

Side effects

Betalok ® ZOK is well tolerated by patients, with side effects generally mild and reversible.

The following criteria were used to assess the frequency of cases: very common (>10%), common (1-9.9%), infrequent (0.1-0.9%), rare (0.01-0.09%), very rare (>

From the cardiovascular system:  often-bradycardia, orthostatic hypotension (very rarely accompanied by syncope), cold extremities, palpitation sensation; infrequently-temporary increase in symptoms of heart failure, AV block I degree, cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart; rarely-other conduction disorders, arrhythmias; very rarely-gangrene (in patients with severe peripheral circulatory disorders).

From the central nervous system:  very often-increased fatigue; often-dizziness, headache; infrequently-paresthesia, convulsions, depression, decreased concentration, drowsiness or insomnia, nightmares; rarely-increased nervous excitability, anxiety; very rarely-memory disorders, amnesia, depression, hallucinations.

From the digestive system:  often – nausea, abdominal pain, diarrhea, constipation; infrequently-vomiting; rarely-dryness of the oral mucosa.

From the liver:  rarely-liver function disorders; very rarely-hepatitis.

Dermatological reactions:  infrequently-skin rash (such as psoriasis-like urticaria), increased sweating; rarely-hair loss; very rarely-photosensitization, exacerbation of psoriasis.

Respiratory system disorders:  often-shortness of breath during exercise; infrequently-bronchospasm; rarely-rhinitis.

From the side of the senses:  rarely-visual impairment, dryness and / or eye irritation, conjunctivitis; very rarely-ringing in the ears, impaired taste sensations.

Musculoskeletal disorders:  very rarely – arthralgia.

From the side of metabolism:  infrequently – weight gain.

From the hematopoietic system:  very rarely – thrombocytopenia.

Other services:  rarely-impotence, sexual dysfunction.

Interaction

Metoprolol is a CYP2D6 substrate, and therefore, drugs that inhibit CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) can affect the plasma concentration of metoprolol.

Combinations to avoid

Barbituric acid derivatives:  barbiturates increase the metabolism of metoprolol, due to the induction of enzymes (the study was conducted with phenobarbital).

Propafenone:  when propafenone was administered to 4 patients treated with metoprolol, there was a 2-5-fold increase in the plasma concentration of metoprolol, while 2 patients had side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. Probably, the interaction is caused by propafenone inhibition, like quinidine, of metoprolol metabolism by the CYP2D6 isoenzyme. Taking into account the fact that propafenone has beta-blocker properties, co-use of metoprolol and propafenone is not advisable.

Verapamil:  the combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and beta-blockers have a complementary inhibitory effect on AV conduction and sinus node function.

Combinations that may require dose adjustment of Betalok ® ZOK

Class I antiarrhythmic drugs: when combined with beta-blockers, the negative inotropic effect can be summed up, as a result of which serious hemodynamic side effects develop in patients with impaired left ventricular function. This combination should also be avoided in patients with SSSU and impaired AV conduction. The interaction is described on the example of disopyramide.

Amiodarone: concomitant use with metoprolol may result in severe sinus bradycardia. Taking into account the extremely long T1 / 2 of amiodarone (50 days), possible interactions should be considered long after the withdrawal of amiodarone.

Diltiazem: diltiazem and beta-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, there were cases of severe bradycardia.

NSAIDs: NSAIDs weaken the antihypertensive effect of beta-blockers. This interaction has been reported in combination with Indometacin and probably will not be observed in combination with sulindac. Negative interactions have been reported in studies with diclofenac.

Diphenhydramine: diphenhydramine reduces the biotransformation of metoprolol to alpha–hydroxymethoprolol by 2.5 times. At the same time, there is an increase in the effect of metoprolol.

Epinephrine (epinephrine): 10 cases of severe hypertension and bradycardia were reported in patients treated with non-selective beta-blockers (including pindolol and propranolol) and treated with epinephrine. Interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when using epinephrine together with local anesthetics in case of accidental contact with the vascular bed. Apparently, this risk is much lower when using cardioselective beta-blockers.

Phenylpropanolamine: phenylpropanolamine (norephedrine) in a single dose of 50 mg can increase diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers can cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported while taking phenylpropanolamine.

Quinidine: quinidine inhibits metoprolol metabolism in a special group of patients with rapid hydroxylation (approximately 90% of the population in Sweden), causing mainly a significant increase in the plasma concentration of metoprolol and increased beta-adrenergic blockade. It is believed that this interaction is also characteristic of other beta-blockers, in the metabolism of which the CYP2D6 isoenzyme is involved.

Clonidine: hypertensive reactions with abrupt withdrawal of clonidine may increase with simultaneous use of beta-blockers. When used together, if clonidine withdrawal is necessary, discontinuation of beta-blockers should begin several days before clonidine withdrawal.

Rifampicin: rifampicin may increase the metabolism of metoprolol, reducing its concentration in blood plasma. Patients taking metoprolol and other beta-blockers (eye drops) or MAO inhibitors at the same time should be carefully monitored.

While taking beta-blockers, inhaled anesthetics increase the cardiodepressive effect.

While taking beta-blockers, patients receiving oral hypoglycemic agents may need to adjust the dose of the latter.

The plasma concentration of metoprolol may increase when taking cimetidine or hydralazine.

Cardiac glycosides, when combined with beta-blockers, can increase the time of AV conduction and cause bradycardia.

How to take, course of use and dosage

Betalok ZOK is intended for daily use once a day, it is recommended to take the drug in the morning. The Betalok ZOK tablet should be swallowed with liquid. Tablets (or tablets divided in half) should not be chewed or crumbled. Food intake does not affect the bioavailability of the drug.

When selecting the dose, it is necessary to avoid the development of bradycardia.

Arterial hypertension

50-100 mg once a day. If necessary, the dose can be increased to 100 mg per day or add another antihypertensive agent, preferably a diuretic and a calcium antagonist of the dihydropyridine series.

Angina

pectoris 100-200 mg Betalok ZOK once a day. If necessary, another antianginal drug may be added to the therapy. Stable symptomatic chronic heart failure with impaired left ventricular systolic function Patients should be in a stable stage of chronic heart failure without episodes of exacerbation during the last 6 weeks and without changes in the main 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 cancel the drug. Stable chronic heart failure, functional class II

The recommended initial dose of Betalok ZOK for the first 2 weeks is 25 mg once a day. After 2 weeks of therapy, the dose can be increased to 50 mg once a day, and then it can be doubled every 2 weeks.

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

Stable chronic heart failure, functional class III-IV

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

After 1-2 weeks, the dose can be increased to 25 mg of Betalok ZOK once a day. Then, after 2 weeks, the dose can be increased to 50 mg once a day. Patients who tolerate the drug well can double the dose every 2 weeks until the maximum dose of 200 mg of Betalok ZOK once a day is reached.

In the case of hypotension and/or bradycardia, it may be necessary to reduce concomitant therapy or reduce the dose of Betalok ZOK. Arterial hypotension at the beginning of therapy does not necessarily indicate that this dose of Betalok ZOK will not be tolerated with further long-term treatment. However, the dose should not be increased until the condition stabilizes. Monitoring of renal function may be necessary.

Cardiac arrhythmias 100-200 mg Betalok ZOK once a day. Maintenance treatment after myocardial infarction 200 mg Betalok ZOK once a day. Functional disorders of cardiac activity, accompanied by tachycardia 100 mg Betalok ZOK once a day. If necessary, the dose can be increased to 200 mg per day. Prevention of migraine attacks 100-200 mg Betalok ZOK once a day. Impaired renal function There is no need to adjust the dose in patients with impaired renal function. Impaired liver function Usually, due to the low degree of binding to plasma proteins, no dose adjustment of metoprolol is required. However, in severe hepatic impairment (in patients with severe cirrhosis of the liver or portocaval anastomosis), a dose reduction may be required. Advanced age There is no need to adjust the dose in elderly patients. Children Experience with the use of Betalok ZOK in children is limited.

Overdose

Symptoms: overdose of metoprolol in the most severe symptoms of the cardiovascular system, but sometimes, especially in children and adolescents, can prevail symptoms of the Central nervous system and the suppression of lung function, bradycardia, AV blockade of I-III degree, asystole, marked reduction in blood pressure, weak peripheral perfusion, cardiac insufficiency, cardiogenic shock; inhibition of lung function, sleep apnea, as well as, fatigue, impairment of consciousness, loss of consciousness, tremor, convulsions, sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophagial spasm hypoglycaemia (particularly in children) or hyperglycemia, hyperkalemia; effects on the kidneys; a transient myasthenic syndrome; concomitant intake of alcohol, antihypertensive drugs, quinidine or barbiturates may impair the patient’s condition. The first signs of overdose may occur 20 minutes to 2 hours after taking the drug.

Treatment: use of activated charcoal, gastric lavage if necessary. IMPORTANT! Atropine (0.25-0.5 mg iv for adults,10-20 mcg / kg for children) should be administered before gastric lavage (due to the risk of vagus nerve stimulation). If necessary, maintain airway patency (intubation) and adequate ventilation of the lungs. Replenishment of circulating blood volume and glucose infusion. ECG monitoring. Atropine 1.0-2.0 mg IV, if necessary, repeat the use (especially in the case of vagal symptoms). In the case of (suppression) of myocardial depression, infusion of dobutamine or dopamine is indicated, and glucagon 50 – 150 mcg/kg IV can also be used at intervals of 1 minute. In some cases, adding epinephrine to therapy may be effective. In case of arrhythmia and extensive ventricular (QRS) complex, sodium (chloride or bicarbonate) solutions are infused. An artificial pacemaker can be installed. In case of cardiac arrest due to an overdose, resuscitation measures may be required for several hours.To stop bronchospasm, terbutaline can be used (by injection or by inhalation).

Symptomatic treatment is performed.

Special instructions

Patients receiving beta-blockers should not be given intravenous slow calcium channel blockers (such as verapamil).

Patients with asthma or COPD should receive concomitant beta-2-adrenomimetic therapy. It is necessary to prescribe the minimum effective dose of Betalok® ZOK, while an increase in the dose of beta-2-adrenomimetic may be required.

It is not recommended to prescribe non-selective beta-blockers to patients with Prinzmetal angina. Selective beta-blockers should be used with caution in this group of patients.

When using beta-1-blockers, the risk of their influence on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is significantly lower than when using non-selective beta-blockers.

In patients with chronic heart failure in the decompensation stage, it is necessary to achieve a compensation stage both before and during treatment with the drug.

Very rarely, patients with impaired AV conduction may experience deterioration (possible outcome-AV block). If bradycardia develops during treatment, the dose of the drug should be reduced or the drug should be gradually discontinued.

Betalok ® ZOK may worsen 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 insufficiency, metabolic acidosis, and concomitant use with cardiac glycosides.

In patients taking beta-blockers, anaphylactic shock occurs in a more severe form. The use of epinephrine (epinephrine) in therapeutic doses does not always lead to the achievement of the desired clinical effect against the background of taking metoprolol.

Patients with pheochromocytoma should be treated with an alpha-blocker concomitantly with Betalok ZOK.

Abrupt withdrawal of beta-blockers is dangerous, especially in high-risk patients, and should therefore be avoided. If necessary, discontinuation of the drug should be carried out gradually, for at least 2 weeks, with a two-fold reduction in the dose of the drug at each stage, until the final dose of 12.5 mg is reached (1/2 tab. 25 mg), which should be taken at least 4 days before complete discontinuation of the drug. If symptoms appear (for example, increased angina symptoms, increased blood pressure), a slower withdrawal regimen is recommended. Abrupt withdrawal of a beta-blocker can lead to a worsening of the course of chronic heart failure and an increased risk of myocardial infarction and sudden death.

In case of surgical intervention, the anesthesiologist should be informed that the patient is taking Betalok ® ZOK. Discontinuation of beta-blocker therapy is not recommended for patients undergoing surgery. Avoid prescribing the drug in high doses without prior titration of doses of the drug to patients with cardiovascular risk factors undergoing non-cardiological operations, due to the increased risk of bradycardia, hypotension and stroke, including those with a fatal outcome.

Data from clinical trials on efficacy and safety in patients with severe stable symptomatic chronic heart failure (NYHA class IV) are limited. Treatment of such patients should be carried out by doctors with special knowledge and experience.

Patients with symptomatic heart failure in combination with acute myocardial infarction and unstable angina were excluded from studies based on which indications for use were determined. The efficacy and safety of the drug for this group of patients is not described. Use in unstable heart failure in the decompensation stage is contraindicated.

Influence on the ability to drive motor vehicles and manage mechanisms

When driving vehicles and engaging in potentially dangerous activities that require increased attention and speed of psychomotor reactions, it should be borne in mind that when using Betalok® ZOK, dizziness and fatigue may occur.

Form of production

Slow-release, film-coated tablets.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Metoprolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Angina, Hypertension, Arrhythmia