Description
packaging 30 pcs
Pharmacological action
Selective beta1-blocker without internal sympathomimetic activity. It has a slight membrane stabilizing effect and does not show the activity of a partial agonist.
Metoprolol reduces or inhibits the agonistic effect that catecholamines, released during nervous and physical stresses, exert on the cardiac activity. This means that metoprolol has the ability to prevent an increase in heart rate, minute volume and increased contractility of the heart, as well as an increase in blood pressure caused by a sharp release of catecholamines.
Unlike conventional tablet dosage forms of selective beta1-blockers (including metoprolol tartrate), when using Betalok ® ZOK, a constant concentration of the drug in blood plasma is observed and a stable clinical effect (blockade of 1-adrenergic receptors) is maintained for more than 24 hours.
Due to the absence of apparent peak plasma concentrations, Betaloc ® ZOK is clinically characterized by better selectivity for β 1 -adrenoreceptors compared to conventional tablet forms of beta1-adrenergic 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.
Betalok ® ZOK in combination with beta2-adrenergic agonists may be prescribed to patients with symptoms of obstructive pulmonary disease. When combined with beta2-adrenergic agonists, Betaloc ® ZOK in therapeutic doses has a lesser effect on bronchodilation caused by beta2-adrenergic agonists than non-selective beta-blockers. Metoprolol to a lesser extent than non-selective beta-blockers, affects insulin production and carbohydrate metabolism. The effect of the drug on the reaction of the cardiovascular system under hypoglycemia is significantly less pronounced compared with non-selective beta-blockers.
The use of Betaloc ® ZOK for arterial hypertension leads to a significant decrease in blood pressure for more than 24 hours both in the supine and standing position, and during exercise. At the beginning of metoprolol therapy, an increase in OPSS is noted. With prolonged use, a decrease in blood pressure is possible due to a decrease in OPSS with a constant cardiac output.
In a MERIT-HF study of survival in chronic heart failure (NYHA Class II-IV functional class) with a reduced ejection fraction ( 0.4), which included 3991 patients, Betalok ® ZOK showed an increase in survival and a decrease in hospitalization rates.
With prolonged treatment, patients achieved a general improvement in well-being, a decrease in the severity of symptoms (according to the NYHA functional classes). Also, therapy with Betaloc ® ZOK showed an increase in the ejection fraction of the left ventricle, a decrease in the final systolic and final diastolic volumes of the left ventricle.
The quality of life during the treatment with Betalok ® ZOK does not deteriorate or improve. Improving the quality of life during treatment with Betaloc ® ZOK was observed in patients after myocardial infarction.
Indications
Arterial hypertension.
Angina pectoris.
Stable symptomatic chronic heart failure with impaired systolic function of the left ventricle (as an adjunct therapy to the main treatment for heart failure).
To reduce mortality and recurrence of heart attack after the acute phase of myocardial infarction.
Heart rhythm disturbances, including supraventricular tachycardia, decreased ventricular contractions with atrial fibrillation and ventricular extrasystoles.
Functional disorders of the heart, accompanied by tachycardia.
Prevention of migraine attacks.
Contraindications
AV block II and III degree.
Chronic heart failure in the decompensation stage.
Continuous or intermittent therapy with inotropic drugs aimed at stimulating -adrenoreceptors.
Clinically significant sinus bradycardia.
SSSU.
Cardiogenic shock.
Severe severe disturbances in peripheral arterial circulation (including with the threat of gangrene).
Arterial hypotension.
Patients with suspected acute myocardial infarction with a heart rate of less than 45 beats / min, a PQ interval of more than 0.24 s or a systolic blood pressure of less than 100 mmHg.
IV injection of slow calcium channel blockers (like verapamil).
Children and adolescents under 18 years of age (efficacy and safety not established).
Hypersensitivity to the drug.
Hypersensitivity to other beta-blockers.
Precautions: use the drug for grade I AV block, Prinzmetal angina, asthma, COPD, diabetes mellitus, severe renal failure, metabolic acidosis, together with cardiac glycosides.
Use during pregnancy and lactation
Like most Betalok ® ZOK preparations should not be prescribed during pregnancy and during breast-feeding, unless the expected benefit to the mother outweighs the potential risk to the fetus and / or baby.
Like other antihypertensive drugs, beta-blockers can cause side effects, such as bradycardia in the fetus, newborns or breastfed babies. The amount of metoprolol that is excreted in breast milk and the beta-blocking effect in a baby breast-fed (when the mother takes metoprolol in therapeutic doses), are negligible.
Composition
1 tablet contains:
Active substances:
metoprolol succinate – 47.5 mg, which corresponds to the content: metoprolol tartrate – 50 mg, metoprolol – 39 mg.
Excipients:
ethyl cellulose – 23 mg,
hypromellose – 7 mg,
hypromellose – 6.2 mg,
microcrystalline cellulose – 120 mg,
paraffin – 100 μg,
macrogol – 1.6 mg, silicon dioxide 12rd – srdlk mg,
sodium stearyl fumarate – 300 μg,
titanium dioxide – 1.6 mg.
Dosage and administration of
Bradycardia should be avoided when selecting a dose.
For arterial hypertension: the dose is 50-100 mg 1 time / day. If necessary, the dose can be increased to 100 mg 1 time / day or Betalok ® ZOK can be used in combination with other antihypertensive drugs (preferably a diuretic and a calcium channel blocker, a dihydropyridine derivative).
With angina pectoris: the dose is 100-200 mg 1 time / day. If necessary, Betalok ® ZOK can be used in combination with another antianginal drug.
In case of stable symptomatic chronic heart failure with impaired systolic function of the left ventricle: Betalok ® ZOK can be prescribed to patients who have not had exacerbation episodes during the last 6 weeks and have not had changes in the main therapy during the last 2 weeks. Therapy 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, and in some cases, it may be necessary to discontinue the drug.
In stable chronic heart failure of the II functional class: the recommended initial dose for the first 2 weeks is 25 mg 1 time / day. After 2 weeks, the dose can be increased to 50 mg 1 time / day and then can be doubled every 2 weeks. The maintenance dose for long-term treatment is 200 mg 1 time / day.
With stable chronic heart failure of the III and IV functional classes: the recommended initial dose for the first 2 weeks is 12.5 mg 1 time / day. The dose is selected individually. During the period of increasing the dose, the patient should be monitored, as in some patients, heart failure symptoms may worsen. After 1-2 weeks, the dose can be increased to 25 mg 1 time / day, then after another 2 weeks – up to 50 mg 1 time / day. With good tolerance, you can double the dose every 2 weeks until a maximum dose of 200 mg is reached 1 time / day.
In case of arterial hypotension and / or bradycardia: a reduction in concomitant therapy or a reduction in the dose of Betalok ® ZOK may be necessary. Arterial hypotension at the beginning of therapy does not necessarily indicate that this dose of Betalock ZOK will not be tolerated with further long-term treatment. However, the dose should not be increased until the condition is stabilized. Renal function monitoring may also be required.
In case of cardiac arrhythmias: the drug is prescribed in a dose of 100-200 mg 1 time / day.
For maintenance treatment after myocardial infarction: the drug is prescribed at a dose of 200 mg 1 time / day.
For functional disorders of cardiac activity accompanied by tachycardia: the dose is 100 mg 1 time / day, if necessary, the dose can be increased to 200 mg / day.
For the prevention of migraine attacks: prescribed in a dose of 100-200 mg 1 time / day.
Betalok ® ZOK is intended for daily use 1 time / day (preferably in the morning). The Betalok ® ZOK tablet should be swallowed with a liquid. Tablets can be divided in half, but should not be chewed or crumbled. Eating does not affect the bioavailability of the drug.
In patients with impaired renal function, as well as in elderly patients: there is no need to adjust the dose of the drug.
In patients with impaired liver function: usually dose adjustment is not required due to the low degree of binding of metoprolol to plasma proteins. However, in severely impaired liver function (in patients with severe cirrhosis or porto-caval anastomosis), a dose reduction may be required.
Side effects
From the cardiovascular system: often – bradycardia, orthostatic arterial hypotension (very rarely accompanied by fainting), cold extremities, palpitations are rare – a temporary increase in symptoms of heart failure, degree I AV block, cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart area are rare – other conduction disturbances, arrhythmias are very rare – gangrene (in patients with severe peripheral circulation disorders )
From the side of the central nervous system and peripheral nervous system: very often – increased fatigue often – dizziness, headache infrequently – paresthesias, cramps, depression, decreased ability to concentrate, drowsiness or insomnia, nightmares rarely – increased nervous irritability, anxiety very rarely – memory impairment, amnesia, depression, hallucinations.
From the digestive system: often – nausea, abdominal pain, diarrhea, constipation infrequently – vomiting is rare – dryness of the oral mucosa, impaired liver function is very rare – hepatitis.
From the hemopoietic system: very rarely – thrombocytopenia.
From the respiratory system: often – shortness of breath with physical exertion infrequently – bronchospasm rarely – rhinitis.
From the musculoskeletal system: very rarely – arthralgia.
On the part of the sensory organs: rarely – dryness and / or irritation of the eyes, conjunctivitis, visual impairment is very rare – ringing in the ears, disturbances in taste.
Dermatological reactions: infrequently – skin rash (like psoriasis-like urticaria), increased sweating rarely – hair loss is very rare – photosensitivity, exacerbation of psoriasis.
Other: sometimes – weight gain rarely – impotence, sexual dysfunction.
Betalok ® ZOK is well tolerated by patients, side effects are mostly mild and reversible.
Drug Interaction
Metoprolol is a CYP2D6 substrate and therefore CYP2D6 inhibitory drugs (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) may affect the plasma concentration of metoprolol.
Combinations to avoid
Barbituric acid derivatives: barbiturates enhance the metabolism of metoprolol due to enzyme induction (the study was conducted with phenobarbital).
Propafenone: In the administration of propafenone to 4 patients receiving metoprolol, there was a 2-5 fold increase in the concentration of metoprolol in blood plasma, with 2 patients experiencing side effects characteristic of metoprolol. This interaction was confirmed in a study of 8 volunteers. The interaction is likely due to the inhibition of propophenone, like quinidine, by metoprolol metabolism via the CYP2D6 isoenzyme. Considering the fact that propafenone has beta-blocker properties, the co-administration of metoprolol and propafenone does not seem appropriate.
Verapamil: A 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 complementary inhibitory effects 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, a negative inotropic effect is possible, resulting in serious hemodynamic adverse effects in patients with stroke. This combination should also be avoided in patients with CVD and AV-conduction disorders. The interaction is described by the example of disopyramide.
Amiodarone: Co-administration with metoprolol can lead to marked sinus bradycardia. Taking into account the extremely long T1 / 2 of amiodarone (50 days), the possible interaction after a long time after withdrawal of amiodarone should be considered.
Diltiazem: Diltiazem and beta-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. In combination with metoprolol with diltiazem, cases of marked bradycardia were noted.
NSAIDs: NSAIDs weaken the antihypertensive action of beta-blockers. This interaction has been reported in combination with indomethacin and is unlikely to be observed in combination with sulindac. Negative interaction was noted in studies with diclofenac. Diphenhydramine: Diphenhydramine reduces the biotransformation of metoprolol to β-hydroxymetoprolol by 2.5-fold. At the same time, there is an increase in the effect of metoprolol.
Epinephrine (epinephrine): 10 cases of overt hypertension and bradycardia have been reported in patients taking non-selective beta-blockers (including pindolol and propranolol) and receiving epinephrine. The interaction was also noted in the group of healthy volunteers. It is assumed that such reactions can be observed when using epinephrine in conjunction with local anesthetics in case of accidental entry into the vascular bed. This risk appears to be much lower when using cardioselective beta blockers. phenylpropanolamine: phenylpropanolamine (norephedrine) at a single dose of 50 mg may increase diastolic blood pressure to abnormal values in healthy volunteers. Propranolol generally prevents the rise in blood pressure caused by phenylpropanolamine. However, beta-blockers can cause paradoxical arterial hypertension in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported on the background of phenylpropanolamine intake.
Quinidine: quinidine inhibits the 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 an increase in β-adrenoceptor blockade. It is believed that this interaction is characteristic of other beta blockers, CYP2D6 isoenzyme involved in metabolism.
Clonidine: hypertensive reactions with abrupt withdrawal of clonidine may be exacerbated by the simultaneous administration of beta-blockers. When used jointly, if clonidine is required, discontinuation of beta-blockers should be initiated several days prior to clonidine withdrawal.
Rifampicin: rifampicin can increase the metabolism of metoprolol by reducing its concentration in blood plasma. Patients receiving concomitant metoprolol and other beta-blockers (eye drops) or MAO inhibitors should be closely monitored.
In the background of beta-blockers, inhaled anesthetics enhance cardio-depressive effects.
Against the background of beta-blockers, patients receiving oral hypoglycemic agents, the dose of the latter may be required.
Plasma concentrations of metoprolol may increase with cimetidine or hydralazine.
Cardiac glycosides when used together with beta blockers can increase AV conduction time and cause bradycardia.
Overdose
Metoprolol 7.5 g in an adult has caused fatal intoxication. In a 5 year old child taking 100 mg of metoprolol, no signs of intoxication were observed after gastric lavage. Taking 450 mg of metoprolol by a teenager for 12 years resulted in moderate intoxication. The intake of 1.4 g and 2.5 g of metoprolol in adults caused moderate and severe intoxication, respectively. The intake of 7.5 g by adults resulted in extremely severe intoxication.
Symptoms: The most serious are the symptoms from the cardiovascular system, but sometimes, especially in children and adolescents, symptoms from the CNS and pulmonary function suppression, bradycardia, AV-blockade of I-III degree, asystole, severe decrease in blood pressure may prevail weak peripheral perfusion, heart failure, cardiogenic shock, pulmonary depression, apnea, fatigue, impaired and loss of consciousness, tremor, convulsions, sweating, paraesthesia, bronchospasm, nausea, vomiting, esophageal Azmi, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia effect on the kidney transient myasthenic syndrome.
Concomitant use of alcohol, antihypertensive agents, quinidine or barbiturates may worsen the patient’s condition. The first signs of overdose can be observed 20 min-2 h after administration of the drug.
Treatment: Activation of activated charcoal, if necessary – gastric lavage.
Atropine at a dose of 0.25-0.5 mg / v for adults and 10-20 mcg / kg for children should be given before gastric lavage (due to the risk of vagus nerve stimulation).
Intubation and IVL are performed if necessary to maintain airway patency.
Terbutaline may be injected or inhaled for the relief of bronchospasm.
It is necessary to replace BCC, to carry out an infusion of glucose. Atropine 1.0-2.0 mg I / O, repeat the introduction if necessary (especially with vaginal symptoms). ECG monitoring.
Infusion of dobutamine or dopamine is indicated in case of myocardial depression. You can use glucagon 50-150 mcg / kg I / O at intervals of 1 min. In some cases, it may be effective to add epinephrine to therapy.
Sodium (chloride or bicarbonate) solutions are infused with arrhythmia and enlarged ventricular (QRS) complex. Installation of an artificial rhythm driver is possible.
Resuscitation may require several hours for heart failure due to overdose.
Symptomatic treatment is performed.
Storage conditions
Keep out of the reach of children at temperatures above 30 ° C.
The Expiration of
is 3 years.
Deystvuyuschee substances
Metoprolol
Pharmacy terms
Prescription
dosage form
dosage form
tablets
AstraZeneca, United Kingdom
