Betaloc Zoc, 50 mg 30 pcs

Indications

Arrhythmia, Visual disturbances, Migraine, Hypertension (high blood pressure), Cardialgia (heart pain), Headache – Arterial hypertension.
– Angina.
– Stable symptomatic chronic heart failure with impaired left ventricular systolic function (as adjuvant therapy to the main treatment of chronic heart failure).
– Reduction of mortality and recurrent infarction rate after the acute phase of myocardial infarction.
– Cardiac rhythm disorders, including supraventricular tachycardia, reduction of ventricular contraction rate in atrial fibrillation and ventricular extrasystoles.
– Functional disorders of cardiac activity accompanied by tachycardia.
– Prevention of migraine episodes.

Active ingredient

Metoprolol

Composition

One tablet Betaloc® ZOC 25 mg contains:
Tablet core: Active ingredient: 23.75 mg metoprolol succinate, corresponding to 19.5 mg metoprolol and 25 mg metoprolol tartrate.
Excipients: ethylcellulose 21.5 mg, hyprolose 6.13 mg, microcrystalline cellulose 94.9 mg, silica 14.6 mg, sodium stearyl fumarate 0.241 mg; tablet glaze: hypromellose 5.64 mg, paraffin 0.06 mg, macrogol 1.41 mg, titanium dioxide 1.41 mg.

One tablet Betaloc® ZOC 50 mg contains:
Tablet core: Active ingredient: 47.5 mg metoprolol succinate, corresponding to 39 mg metoprolol and 50 mg metoprolol tartrate.
Excipients: ethyl cellulose 23 mg, hyprolose 7 mg, microcrystalline cellulose 120 mg, silica 12 mg, sodium stearyl fumarate 0.3 mg; tablet glaze: hypromellose 6.2 mg, paraffin 0.1 mg, macrogol 1.6 mg, titanium dioxide 1.6 mg.

One tablet Betaloc® ZOC 100 mg contains:
Tablet core: Active ingredient: 95 mg metoprolol succinate, corresponding to 78 mg metoprolol and 100 mg metoprolol tartrate.
Excipients: ethyl cellulose 46 mg, hyprolose 13 mg, microcrystalline cellulose 180 mg, silica 24 mg, sodium stearyl fumarate 0.5 mg;

Tablet glaze: 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.

The therapy of heart failure with β-adrenoblockers may sometimes lead to 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 Betalock® 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

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

The co-administration of Betaloc® ZOC with the following drugs should be avoided:

Barbituric acid derivatives: barbiturates (studied with pentobarbital) increase metabolism of metoprolol, due to induction of enzymes.

Propafenone:Propafenone administration to four patients treated with metoprolol showed a 2-5-fold increase in metoprolol plasma concentration, with two patients experiencing side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is probably due to the inhibition of metoprolol metabolism by the cytochrome P4502D6 system with propafenone, similar to quinidine. Taking into account the fact that propafenone has the properties of a b-adrenoblocker, joint administration of metoprolol and propafenone is not advisable.

Verapamil:The combination of b-adrenal blockers (atenolol, propranolol and pindolol) and verapamil may cause bradycardia and lead to a decrease in BP. Verapamil and b-adrenoblockers have complementary inhibitory effects on atrioventricular conduction and sinus node function.

Combination of Betaloc® ZOC with the following drugs may require dose adjustment:
Amiodarone: The combined use of amiodarone and metoprolol may result in marked sinus bradycardia. Taking into account the extremely long half-life of amiodarone (50 days), a possible interaction long after amiodarone withdrawal should be considered.

Class I antiarrhythmic agents: Class I antiarrhythmic agents and b-adrenoblockers may result in summation of negative inotropic effects, which may lead to serious hemodynamic side effects in patients with impaired left ventricular function. Such combination should also be avoided in patients with sinus node weakness syndrome and impaired AV conduction. The interaction is described by the example of disopyramide.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs weaken antihypertensive effect of b-adreno-blockers. This interaction is documented for indomethacin. It is likely that the described interaction will not be noted in interactions with sulindac. Negative interaction was noted in studies with diclofenac.
Diphenhydramine: Diphenhydramine decreases clearance of metoprolol to b- hydroxymethoprolol by 2.5 times. At the same time, there is an increase in the action of metoprolol.

Diltiazem: Diltiazem and b-adrenoblockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When combining metoprolol with diltiazem, there have been cases of marked bradycardia.

Epinephrine (adrenaline): There have been 10 reported cases of marked arterial hypertension and bradycardia in patients taking nonselective b-adrenoblockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). Interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions may also be observed when epinephrine is used together with local anesthetics in case of accidental ingestion into the vascular bed. This risk is thought to be much lower with the use of cardioselective b-adrenoblockers.

Phenylpropanolamine: Phenylpropanolamine (norephedrine) in a single dose of 50 mg may cause diastolic BP to increase to abnormal values in healthy volunteers. Propranolol generally interferes with the BP elevation induced by phenylpropanolamine. However, b-adrenoblockers may cause paradoxical arterial hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported with phenylpropanolamine.

Chinidine: Chinidine inhibits metabolism of metoprolol in a special group of patients with rapid hydroxylation (approximately 90% of the population in Sweden), causing mainly a significant increase in plasma metoprolol concentration and increased b-blockade. A similar interaction is believed to be characteristic of other b-adrenoblockers whose metabolism involves cytochrome P4502D6.

Clonidine: Hypertensive reactions when clonidine is abruptly withdrawn may be enhanced by co-administration of b-adrenoblockers. When used concomitantly, if clonidine is withdrawn, discontinuation of b-adrenal blockers should be initiated several days before clonidine withdrawal.

Rifampicin: Rifampicin may increase metabolism of metoprolol, decreasing plasma concentrations of metoprolol.
Patients taking metoprolol and other b-adrenoblockers (eye drops) or monoamine oxidase inhibitors (MAOIs) simultaneously should be closely monitored. Against the background of taking b-adrenoblockers, inhaled anesthetics increase the cardiodepressant effect. During administration of b-adrenoblockers, patients receiving hypoglycemic agents for oral administration may require correction of the dose of the latter.
Plasma concentration of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides in co-administration with b-adrenoblockers may increase atrioventricular conduction time and cause bradycardia.

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 b2-adrenomimetics. The lowest effective dose of Betaloc® ZOC should be administered, and the dose of b2-adrenomimetic may need to be increased.
Non-selective b-adrenoblockers are not recommended for patients with Prinzmetal angina. Caution should be exercised when prescribing b-selective adrenoblockers to this group of patients.
When using b1-adrenoblockers the risk of their effect on carbohydrate metabolism or the possibility of masking hypoglycemic symptoms is significantly lower than when using non-selective b-adrenoblockers.
In patients with decompensated chronic heart failure it is necessary to reach the compensation stage both before and during the drug treatment.
Very rarely in patients with AV conduction disturbance it may worsen (possible outcome – AV blockade). If bradycardia developed during treatment, the drug dose should be reduced or the drug should be gradually withdrawn.
Betaloc® ZOC may aggravate the course of existing peripheral circulatory disorders mainly due to decreased blood pressure.
Caution should be exercised when prescribing the drug in patients with severe renal insufficiency, in metabolic acidosis, concomitant use with cardiac glycosides.
In patients taking b-adrenoblockers anaphylactic shock occurs in a more severe form. Epinephrine (adrenaline) usage in therapeutic doses does not always lead to the desired clinical effect during metoprolol administration. In patients with pheochromocytoma, an alpha-adrenoblocker should be administered simultaneously with Betaloc® ZOC.
Abrupt withdrawal of β-adrenoblockers is dangerous, especially in high-risk patients, therefore, it should be avoided. If withdrawal is necessary, it should be done gradually, over at least 2 weeks, with the drug dose reduced twice at each step, until a final dose of 12.5 mg (1/2 of a 25 mg tablet) is reached, which should be taken for at least 4 days before complete withdrawal. If symptoms occur (e.g., increased symptoms of angina, increased blood pressure), a slower withdrawal regimen is recommended. Abrupt withdrawal of β-adrenoblocker may worsen the course of chronic heart failure and increase the risk of myocardial infarction and sudden death.

In case of surgical intervention, inform the anesthesiologist that the patient is taking Betalok® ZOC. In patients undergoing surgery, discontinuation of therapy with b-adrenoblockers is not recommended. Administration of high doses without prior titration of the drug in patients with cardiovascular risk factors undergoing noncardiac surgery should be avoided due to increased risk of bradycardia, arterial hypotension and stroke, including 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 performed by physicians with special knowledge and experience.
Patients with symptomatic heart failure combined with acute myocardial infarction and unstable angina pectoris were excluded from trials, based on which indications for prescription were determined. Efficacy and safety of the drug for this group of patients have not been described. Use in unstable heart failure in decompensation stage is contraindicated.

Impact on the ability to drive vehicles, mechanisms
When driving motor transport and engaging in potentially dangerous activities that require high concentration and rapid psychomotor reactions, it should be noted that dizziness and fatigue may be observed when using Betaloc® ZOC.

Synopsis

Betaloc® ZOK 25 mg: Oval biconvex white or almost white film-coated tablets; with notches on both sides and engraving on one side.

Betaloc® ZOK 50 mg: Round biconvex white or almost white film-coated tablets; with notches on one side and engraving on the other side.

Betaloc® ZOC 100 mg: Round biconvex white or almost white coated tablets; with notches on one side and engraving on the other side.

Contraindications

– Atrioventricular block of II and III degree.
– Heart failure in decompensation stage.
– Permanent or intermittent therapy with inotropic drugs acting on beta-adrenoreceptors.
– Clinically significant sinus bradycardia.
– Syndrome of weak sinus node.
– Cardiogenic shock.
– Severe peripheral circulatory disorders, including at risk of gangrene.
– Arterial hypotension (systolic blood pressure less than 100 mm Hg).
– Betaloc® ZOC is contraindicated in patients with suspected acute myocardial infarction with HR less than 45 beats per minute, PQ interval greater than 0.24 seconds or systolic blood pressure less than 100 mm Hg.
– Known hypersensitivity to metoprolol, to other b-adrenoblockers or to excipients included in the drug.
– Patients receiving b-adrenoblockers are contraindicated by intravenous administration of “slow” calcium channel blockers such as verapamil.
– Age under 18 years (effectiveness and safety has not been established).
– Pheochromocytoma (without simultaneous use of alpha-adrenoblockers).
– Breast-feeding period.

With caution: Grade I atrioventricular blockade, Prinzmetal angina, bronchial asthma, chronic obstructive pulmonary disease, diabetes mellitus, severe renal failure, severe hepatic failure, metabolic acidosis, concurrent use with cardiac glycosides, pheochromocytoma (with concurrent use of alpha-adrenoblockers), pregnancy, thyrotoxicosis, psoriasis, old age, depression (including

, peripheral arterial occlusive disease (intermittent claudication), Raynaud’s syndrome.

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.

Respiratory 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. Administration of 7.5 g to 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.

WARNING: Atropine (0.25-0.5 mg I/V for adults, 10-20 mcg/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 carried out.