Properties
What is it?
Trade name: Betaloc International Nonproprietary Name: Metoprolol Dosage form: Solution for injection for intravenous administration Composition 1 ml of solution contains: Active substance: 1 mg Metoprolol tartrate Excipients for injection: Sodium chloride for injection 9 mg, Water for injection up to 1 ml. Description Clear, colorless solution Pharmacotherapeutic group: Selective beta-1 adrenoceptor blocker ATC code: С07АВ02 Pharmacological properties Pharmacodynamics In patients with myocardial infarction, intravenous administration of metoprolol reduces chest pain and lowers the risk of developing atrial flutter and fibrillation. At the first symptoms, intravenous administration of metoprolol (within 24 hours after the onset of the first symptoms) reduces the risk of developing myocardial infarction. Early initiation of metoprolol treatment improves the prognosis after myocardial infarction. In paroxysmal tachycardia and atrial flutter (fibrillation), a reduction in heart rate (HR) is achieved. Metoprolol is a beta-1 adrenoceptor blocker that blocks beta-1 receptors at lower doses than are required to block beta-2 receptors. Metoprolol has a minor membrane-stabilizing effect and does not exhibit partial agonist activity. Metoprolol reduces or inhibits the agonist effect of catecholamines produced during nervous and physical stress on the cardiovascular system. This means that metoprolol can counteract the increase in heart rate, cardiac output, and myocardial contractility, as well as the increase in blood pressure caused by a sharp release of catecholamines. In patients with obstructive pulmonary disease, metoprolol can be prescribed with beta-2 adreno-mimetics if necessary. When used at therapeutic doses with beta-2 adreno-mimetics, Betaloc has less effect on beta-2 adreno-mimetics-induced bronchodilation than non-selective adreno-blockers. Metoprolol has less effect on insulin production and carbohydrate metabolism than non-selective beta-adreno-blockers. The effect of Betaloc on the cardiovascular system's response to hypoglycemia is significantly less pronounced compared to non-selective beta-adreno-blockers. An improvement in quality of life was observed in patients after myocardial infarction during treatment with Betaloc. Pharmacokinetics Metoprolol undergoes oxidative metabolism in the liver, forming three main metabolites, none of which have clinically significant beta-blocking activity. Approximately 5% of the administered dose is excreted unchanged in the urine. The mean half-life of metoprolol is approximately 5 hours. See blog: Betaloc - A drug for cardiovascular diseases Indications Supraventricular tachycardia Prevention and treatment of myocardial ischemia, tachycardia, and pain during or suspected myocardial infarction. Contraindications Atrioventricular block of II and III degree, heart failure in the decompensation stage, continuous or intermittent treatment with inotropic agents that act as beta-adreno-mimetics, clinically significant sinus bradycardia, sick sinus syndrome (except in patients with a permanent pacemaker), cardiogenic shock, severe peripheral circulatory disorders, including risk of gangrene, arterial hypotension. Betaloc is contraindicated in patients with suspected myocardial infarction and HR less than 45 beats/min, PQ interval greater than 0.24 seconds, or systolic blood pressure less than 100 mm Hg. Known hypersensitivity to metoprolol and its components or other beta-adreno-blockers. Treatment of supraventricular tachycardia in patients with systolic blood pressure less than 110 mm Hg. Intravenous administration of "slow" calcium channel blockers or verapamil is contraindicated in patients taking beta-adreno-blockers. Age under 18 years (efficacy and safety not established). Use with caution: Atrioventricular block of I degree, Prinzmetal's angina, chronic obstructive pulmonary disease (pulmonary emphysema, chronic obstructive bronchitis, bronchial asthma), diabetes mellitus, severe renal insufficiency. Use during pregnancy and breastfeeding Pregnancy As with most drugs, Betaloc should not be prescribed during pregnancy and breastfeeding, except when the expected benefit to the mother outweighs the potential risk to the fetus. Beta-adreno-blockers reduce placental blood flow, which can lead to intrauterine growth retardation, intrauterine fetal death, spontaneous abortion, and premature birth. When Betaloc is used during pregnancy, appropriate monitoring of the patient and fetus is recommended. Like other antihypertensive agents, beta-adreno-blockers can cause side effects, such as bradycardia in the fetus, newborns, and breastfed infants, so special caution is required when prescribing beta-adreno-blockers in the last trimester of pregnancy and immediately before and during labor. Breastfeeding The amount of metoprolol excreted in breast milk and the beta-blocking effect in breastfed infants (when the mother takes metoprolol at therapeutic doses) are insignificant. Method of administration and dosage Supraventricular tachycardia Begin by administering Betaloc 5 mg at a rate of 1-2 mg/min. Administration can be repeated at 5-minute intervals until a therapeutic effect is achieved. The total dose is usually 10-15 mg (10-15 ml). The recommended maximum dose for intravenous administration is 20 mg (20 ml). Prevention and treatment of myocardial ischemia, tachycardia, and pain during or suspected myocardial infarction. Administer 5 mg (5 ml) of the drug intravenously. Administration can be repeated at 2-minute intervals. Maximum dose - 15 mg (15 ml). 15 minutes after the last injection, metoprolol is administered orally at a dose of 50 mg (Betaloc) every 6 hours for 48 hours. Renal impairment Dose adjustment is not necessary in patients with impaired renal function. Hepatic impairment Dose adjustment is usually not necessary due to low plasma protein binding. However, in severe hepatic impairment (in patients with portocaval anastomosis), dose reduction may be necessary. Elderly patients Dose adjustment is not necessary in elderly patients. Children The use of Betaloc in children is limited. Side effects Betaloc is well tolerated, and side effects are generally mild and reversible. The following adverse side effects have been reported in clinical trials or in clinical practice with Betaloc (metoprolol tartrate). In many cases, a causal relationship with Betaloc treatment has not been established. The following criteria were used to describe the frequency of events: very common (>10%), common (1-9.9%), uncommon (0.1-0.9%), rare (0.01-0.09%), very rare (<0.01%). Cardiovascular system Common: bradycardia, postural disorders (very rarely accompanied by shock), cold extremities, palpitations. Uncommon: temporary worsening of heart failure symptoms, cardiogenic shock in patients with acute myocardial infarction, atrioventricular block of grade I, edema, chest pain. Rare: other conduction disturbances, arrhythmias. Very rare: gangrene in patients with severe peripheral circulatory disorders. Central nervous system Very common: increased fatigue. Common: dizziness, headache. Uncommon: paresthesia, cramps, worsening of depression, decreased concentration, drowsiness or insomnia, nightmares. Rare: increased excitability, anxiety. Very rare: amnesia/memory impairment, feeling of depression, hallucinations. Gastrointestinal tract Common: nausea, abdominal pain, diarrhea, constipation. Uncommon: vomiting. Rare: dry mouth, impaired liver function. Very rare: hepatitis. Skin and subcutaneous tissue Uncommon: rash (urticarial), increased sweating. Rare: alopecia. Very rare: photosensitivity, worsening of psoriasis. Respiratory system Common: shortness of breath on exertion. Uncommon: bronchospasm in patients with bronchial asthma. Rare: rhinitis. Sensory organs Rare: visual disturbances, dry and/or irritated eyes, conjunctivitis. Very rare: tinnitus, taste disturbances. Metabolism Uncommon: weight gain. Musculoskeletal system Very rare: arthralgia. Blood Very rare: thrombocytopenia. Other Rare: impotence/sexual dysfunction. Overdose Symptoms Symptoms of overdose may include marked decrease in blood pressure, acute heart failure, bradycardia, bradyarrhythmia, impaired intra-cardiac conduction, and bronchospasm. Treatment Treatment should be carried out in a medical facility equipped with the necessary apparatus and conditions for maintaining vital functions and monitoring the patient's condition. For bradycardia and conduction disturbances, atropine and adreno-mimetics are used; artificial pacing of the heart rhythm is used if necessary. In case of marked decrease in blood pressure, acute heart failure, and shock, therapy aimed at maintaining circulating plasma volume should be carried out; administration of glucagon (followed by intravenous infusion of glucagon if necessary); intravenous administration of adreno-mimetics (such as dobutamine) with alpha-1 adreno-mimetics in case of vasodilation symptoms. Intravenous administration of preparations containing calcium ions is also possible. Bronchodilators should be used to relieve bronchospasm. Interactions with other drugs and other forms of interaction Betaloc should be avoided in combination with the following drugs: Barbituric acid derivatives: Barbiturates (studies were conducted with phenobarbital) slightly increase the metabolism of metoprolol due to enzyme induction. Propafenone: In 4 patients treated with metoprolol, propafenone administration resulted in a 2-5-fold increase in its plasma concentration, with metoprolol-specific side effects observed in two patients. This interaction was confirmed in studies with 8 volunteers. The interaction is likely due to propafenone inhibiting metoprolol metabolism (similar to quinidine) via the cytochrome P4502D6 system. Given that propafenone has beta-adreno-blocking properties, the simultaneous administration of metoprolol and propafenone is not recommended. Verapamil: Interaction between beta-adreno-blockers (atenolol, propranolol, and pindolol) and verapamil can cause bradycardia and hypotension. Verapamil and beta-adreno-blockers have mutually additive inhibitory effects on atrioventricular conduction and sinus node function. Dose adjustment may be necessary when combining Betaloc with the following drugs: Class I antiarrhythmic drugs: Class I antiarrhythmic drugs and beta-blockers can cause summation of negative inotropic effects, which can lead to serious hemodynamic effects in patients with impaired left ventricular function. Such a combination should also be avoided in patients with sick sinus syndrome and atrioventricular conduction disorders. The interaction is described using the example of dopexamine. Amiodarone: The combined use of amiodarone and metoprolol can cause pronounced sinus bradycardia. Due to the extremely long half-life of amiodarone (50 days), the possibility of interaction should be considered long after amiodarone withdrawal. Diltiazem: Diltiazem and beta-adreno-blockers enhance the inhibitory effect on atrioventricular conduction and sinus node function. Pronounced bradycardia has been observed when metoprolol is used in combination with diltiazem. Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs weaken the antihypertensive effect of beta-adreno-blockers. This interaction is most described for indomethacin. No interaction was observed with sulindac. Reactions described in studies with diclofenac were not observed. Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to alpha-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed. Epinephrine (adrenaline): 10 cases of marked arterial hypertension and bradycardia were observed in patients taking non-selective beta-adreno-blockers (including pindolol and propranolol) and epinephrine (adrenaline). The interaction has also been described in a group of healthy volunteers. It is likely that these reactions may occur when epinephrine is used with local anesthetics and enters the bloodstream. It is likely that this risk is much lower when using cardioselective beta-adreno-blockers. Phenylpropanolamine: In healthy volunteers, phenylpropanolamine (norepinephrine) - a single dose of 50 mg can cause a pathological increase in diastolic blood pressure. Propranolol primarily prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-adreno-blockers can cause paradoxical hypertensive reactions in patients taking phenylpropanolamine doses. Several cases of hypertensive crisis have been described with the use of phenylpropanolamine. Quinidine: In a specific group of patients, quinidine inhibits the metabolism of metoprolol by rapid hydroxylation (approximately 90% of the population in Switzerland), mainly causing an increase in metoprolol plasma concentration and enhancement of beta-blockade. It is assumed that this interaction is characteristic of other beta-adreno-blockers whose metabolism involves cytochrome P4502D6. Clonidine: Hypertensive reactions that occur upon abrupt withdrawal of clonidine may be enhanced by the use of beta-adreno-blockers. When used simultaneously, beta-adreno-blockers may be started a few days before clonidine withdrawal. Rifampicin: Rifampicin can enhance the metabolism of metoprolol, reducing its plasma concentration. The plasma concentration of metoprolol may increase when used with cimetidine, hydralazine, selective serotonin reuptake inhibitors such as paroxetine, fluoxetine, and sertraline. Patients taking metoprolol and other beta-adreno-blockers (eye drops) or monoamine oxidase (MAO) inhibitors simultaneously should be under close observation. Inhalational anesthetics enhance the cardiodepressive effect when beta-adreno-blockers are used. In patients taking beta-adreno-blockers, dose adjustment of oral hypoglycemic agents may be necessary. Cardiac glycosides, when used with beta-adreno-blockers, can enhance atrioventricular conduction and cause bradycardia. Special instructions Patients taking beta-adreno-blockers should not be administered intravenous "slow" calcium channel blockers of the verapamil type. In patients with bronchial asthma or chronic obstructive pulmonary disease, concomitant treatment with beta-2 adreno-mimetics should be prescribed. If necessary, the dose of the beta-2 adreno-mimetic should be increased. When using beta-1 adreno-blockers, the risk of their effect on carbohydrate metabolism or the possibility of masking hypoglycemia symptoms is lower than with non-selective beta-adreno-blockers. In patients with chronic heart failure in the decompensation stage, compensation must be achieved both before and during treatment. In patients with Prinzmetal's angina, the administration of non-selective beta-adreno-blockers is not recommended. Very rarely, the condition of patients with atrioventricular conduction disturbances may worsen (possible outcome - atrioventricular block). If bradycardia develops during treatment, the dose of Betaloc should be reduced. Metoprolol can enhance peripheral arterial circulation, mainly due to a decrease in blood pressure. Caution should be exercised when prescribing the drug to patients with severe hepatic insufficiency, metabolic acidosis, and when used with cardiac glycosides. Anaphylactic shock may be more severe in patients taking beta-adreno-blockers. In patients with pheochromocytoma, alpha-adreno-blockers should be prescribed along with Betaloc. In case of surgical intervention, the surgeon/anesthesiologist should be informed that the patient is taking a beta-adreno-blocker. Withdrawal of beta-adreno-blocker therapy before surgery is not recommended. In patients at risk of developing cardiovascular diseases during surgery, high doses of metoprolol without dose titration (except for cardiac surgery) should be avoided, as there is a risk of developing bradycardia, hypotension, and stroke, including fatal outcomes. If systolic blood pressure is less than 100 mm Hg, Betaloc should be administered intravenously only with special safety precautions due to the risk of further decrease (e.g., in patients with arrhythmias). When treating patients with myocardial infarction or suspected myocardial infarction, the main hemodynamic parameters should be assessed after each 5 mg dose of the drug (see section "Method of administration and dosage"). A repeated second or third dose should not be administered if the heart rate is less than 40 beats/min, the PQ interval is greater than 0.26 seconds, and systolic blood pressure is less than 90 mm Hg, or if there is increased shortness of breath or cold sweats. Effect on ability to drive and operate machinery The effect of Betaloc for intravenous administration on the ability to drive and operate machinery has not been studied. Dosage form 1 mg/ml solution for injection for intravenous administration. 5 ml in a colorless borosilicate glass ampoule with a score mark. 5 ampoules in a plastic holder, placed in a cardboard box with the instructions for use. Storage conditions Store in a protected place from light at a temperature not exceeding 25°C. Keep out of reach of children. Shelf life 5 years. Do not use after the expiry date. Dispensing conditions: Pharmaceutical product group II, dispensed by prescription form №3.
