Metoprolol retard-Akrihin
Drugs that reduce catecholamine reserves (for example, reserpine, MAO inhibitors), when used simultaneously with metoprolol, can enhance the hypotensive effect or cause severe bradycardia. The treatment break between taking MAO inhibitors and metoprolol should be at least 14 days.
Metoprolol is a substrate of the CYP2D6 isoenzyme. Medicines that inhibit or induce the activity of the CYP2D6 isoenzyme may affect the plasma concentrations of metoprolol.
Inhibitors of the CYP2D6 isoenzyme: some antidepressants and antipsychotics, quinidine, terbinafine, celecoxib, propafenone, difehydramine, hydroxychlorine, cimetidine - increase the concentration of metoprolol in the blood plasma.
Inducers of the CYP2D6 isoenzyme: barbituric acid derivatives, rifampicin - reduce the concentration of metoprolol in the blood plasma.
The combined use of Metoprolol retard-Akrikhin with the following drugs should be avoided:
Barbituric acid derivatives: barbiturates (study conducted with pentobarbital) increase the metabolism of metoprolol due to enzyme induction.
Propafenone: When propafenone was prescribed to four patients treated with metoprolol, an increase in plasma concentrations of metoprolol was observed by 2-5 times, while two patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprololol via the CYP2D6 isoenzyme. Taking into account the fact that propafenone has beta-blocker properties, the co-administration of metoprolol and propafenone does not seem appropriate.
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 atrioventricular conduction and sinus node function.
The combination of Metoprolol retard-Akrikhin with the following drugs may require dose adjustment:
Amiodarone: Concomitant use of amiodarone and metoprolol may result in severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.
Class I Antiarrhythmics: Class I antiarrhythmics and beta-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and impaired AV conduction. The interaction is described using disopyramide as an example.
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs reduce the antihypertensive effect of beta-blockers. This interaction has been documented for indomethacin. It is likely that the described interaction will not be observed with sulindac. Negative interactions have been noted in studies with diclofenac.
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.
Diltiazem: Diltiazem and beta-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.
Epinephrine (adrenaline): Ten cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.
Phenylpropanolamine: Phenylpropanolamine (norephedrine) in a single dose of 50 mg can cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers may 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 the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and an increase in beta-blockers metabolized by the CYP2D6 isoenzyme.
Clonidine: Hypertensive reactions following abrupt discontinuation of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, if clonidine is discontinued, discontinuation of beta-blockers should begin several days before discontinuation of clonidine.
Rifampicin: Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.
Patients concomitantly taking metoprolol and other beta-blockers (eye drops) or monoamine oxidase inhibitors (MAOIs) should be closely monitored. While taking beta-blockers, inhalational anesthetics enhance the cardiodepressive effect. While taking beta-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.
Plasma concentrations of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Ergot alkaloids increase the risk of peripheral circulatory disorders.
When taken together with insulin, it increases the risk of developing hypoglycemia, prolongs and intensifies its severity, masks some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).
Reduces the clearance of xanthines (except diaphylline), especially in patients with initially increased clearance of theophylline under the influence of smoking. Reduces the clearance of lidocaine, increases the concentration of lidocaine in plasma.
Strengthens and prolongs the effect of non-depolarizing muscle relaxants: prolongs the anticoagulant effect of coumarins.
Allergens used for immunotherapy or allergen extracts for skin testing when used in combination with metoprolol increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiocontrast agents for intravenous administration increase the risk of developing anaphylactic reactions.
When used together with ethanol, the risk of a pronounced decrease in blood pressure increases.
Metoprolol retard-Akrikhin tab.prolonged.d.p.p/o 25mg N30 ext.
Indications: arterial hypertension; — chronic heart failure of functional class II-IV according to the NYHA classification in the compensation stage (as part of complex therapy); — IHD: prevention of attacks of stable angina, reduction in mortality and the incidence of recurrent myocardial infarction after the acute phase of myocardial infarction; - heart rhythm disturbances, including supraventricular tachycardia, decreased ventricular contraction frequency during atrial fibrillation and ventricular extrasystoles; - functional disorders of cardiac activity, accompanied by tachycardia; - prevention of migraine attacks. Contraindications for use: cardiogenic shock;
— AV blockade II-III degree;
- sinoatrial block;
— SSSU;
- severe bradycardia (HR
— acute heart failure or chronic heart failure in the stage of decompensation;
- arterial hypotension (systolic blood pressure
- acute myocardial infarction (HR
- severe bronchial asthma;
- severe peripheral circulatory disorders;
- simultaneous use of MAO inhibitors or simultaneous intravenous administration of verapamil;
- pheochromocytoma (without simultaneous use of alpha-blockers);
- age under 18 years (efficacy and safety have not been established);
- lactation period;
- lactase deficiency, lactose intolerance, glucose/galactose malabsorption syndrome;
- increased sensitivity to metoprolol and other beta-blockers.
The drug should be prescribed with caution in case of diabetes mellitus, AV blockade of the first degree, Prinzmetal's angina, metabolic acidosis, bronchial asthma, COPD, severe renal and/or liver failure, myasthenia gravis, pheochromocytoma (while taking alpha-blockers), thyrotoxicosis, depression (including a history), psoriasis, peripheral circulatory disorders (intermittent claudication, Raynaud's syndrome), pregnancy, and elderly patients.
Use during pregnancy and breastfeeding During pregnancy, Metoprolol retard-Akrikhin should be used only according to strict indications, when the expected benefit to the mother outweighs the potential risk to the fetus/child (due to the possible development of bradycardia, decreased blood pressure, hypoglycemia and respiratory paralysis in the newborn) . At the same time, careful monitoring is carried out especially over the development of the fetus. Treatment is stopped 48-72 hours before birth. If this is not possible, the newborn should be monitored especially closely for 48-72 hours after birth.
The use of Metoprolol retard-Akrikhin is contraindicated during lactation. If it is necessary to use the drug during lactation, breastfeeding should be stopped.
Use for impaired liver function Impaired liver function affects the elimination of metoprolol, so dose adjustment may be required depending on the clinical condition.
Use for impaired renal function: Patients with renal failure or patients on hemodialysis do not require dose adjustment.
Use in children Contraindicated in children and adolescents under 18 years of age.
Use in elderly patients Elderly patients do not require dose adjustment. In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).
Metoprolol retard-akrikhin extended-release film-coated tablets 25 mg No. 30
Pharmacokinetics
Metoprolol is a cardioselective beta-adrenergic receptor blocker that does not have intrinsic sympathomimetic activity and membrane-stabilizing properties.
It has hypotensive, antianginal and antiarrhythmic effects. By blocking beta1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect (reduces the heart rate (HR), inhibits conductivity and excitability, reduces myocardial contractility). The total peripheral resistance at the beginning of the use of beta-blockers (in the first 24 hours after oral administration) increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which after 1-3 days returns to the original one, and with prolonged application - decreases. The hypotensive effect is due to a reflex decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin-aldosterone system (of greater importance in patients with initial hypersecretion of renin) and the central nervous system, restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease blood pressure) and, ultimately, a decrease in peripheral sympathetic influences. Reduces high blood pressure (BP) at rest, during physical exertion and stress.
The hypotensive effect develops quickly (systolic blood pressure decreases after 15 minutes, maximum after 2 hours) and lasts for 6 hours, diastolic blood pressure changes more slowly: a stable decrease is observed after several weeks of regular use.
The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (lengthening diastole and improving myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance.
The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in atrioventricular (AV) conduction (mainly in the antegrade and, to a lesser extent, in retrograde directions) through the AV node and along additional pathways.
With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and hyperthyroidism, it reduces heart rate, or can even lead to the restoration of sinus rhythm.
Prevents the development of migraine. When used in average therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism. When used in large doses (more than 100 mg/day), it has a blocking effect on both subtypes of beta-adrenergic receptors.
Metoprolol
When used simultaneously with antihypertensive drugs, diuretics, antiarrhythmic drugs, nitrates, there is a risk of developing severe arterial hypotension, bradycardia, and AV block.
When used simultaneously with barbiturates, the metabolism of metoprolol is accelerated, which leads to a decrease in its effectiveness.
When used simultaneously with hypoglycemic agents, the effect of hypoglycemic agents may be enhanced.
When used simultaneously with NSAIDs, the hypotensive effect of metoprolol may be reduced.
When used simultaneously with opioid analgesics, the cardiodepressive effect is mutually enhanced.
When used simultaneously with peripheral muscle relaxants, neuromuscular blockade may be enhanced.
When used simultaneously with drugs for inhalation anesthesia, the risk of suppression of myocardial function and the development of arterial hypotension increases.
When used simultaneously with oral contraceptives, hydralazine, ranitidine, cimetidine, the concentration of metoprolol in the blood plasma increases.
When used simultaneously with amiodarone, arterial hypotension, bradycardia, ventricular fibrillation, and asystole are possible.
When used simultaneously with verapamil, the plasma Cmax and AUC of metoprolol increases. The minute and stroke volume of the heart, pulse rate, and arterial hypotension decrease. Possible development of heart failure, dyspnea and sinus node block.
With intravenous administration of verapamil while taking metoprolol, there is a risk of cardiac arrest.
With simultaneous use, bradycardia caused by digitalis glycosides may increase.
When used simultaneously with dextropropoxyphene, the bioavailability of metoprolol increases.
When used concomitantly with diazepam, a decrease in clearance and an increase in the AUC of diazepam is possible, which can lead to an increase in its effects and a decrease in the speed of psychomotor reactions.
When used simultaneously with diltiazem, the concentration of metoprolol in the blood plasma increases due to inhibition of its metabolism under the influence of diltiazem. The effect on cardiac activity is additively inhibited due to the slowing of impulse transmission through the AV node caused by diltiazem. There is a risk of developing severe bradycardia, a significant decrease in stroke and minute volume.
When used simultaneously with lidocaine, the elimination of lidocaine may be impaired.
When used simultaneously with mibefradil in patients with low activity of the CYP2D6 isoenzyme, it is possible to increase the concentration of metoprolol in the blood plasma and increase the risk of developing toxic effects.
When used simultaneously with norepinephrine, epinephrine, other adrenergic and sympathomimetics (including in the form of eye drops or as part of antitussives), a slight increase in blood pressure is possible.
When used simultaneously with propafenone, the concentration of metoprolol in the blood plasma increases and a toxic effect develops. It is believed that propafenone inhibits the metabolism of metoprolol in the liver, reducing its clearance and increasing serum concentrations.
When used simultaneously with reserpine, guanfacine, methyldopa, clonidine, severe bradycardia may develop.
When used simultaneously with rifampicin, the concentration of metoprolol in the blood plasma decreases.
Metoprolol may cause a slight decrease in the clearance of theophylline in patients who smoke.
Fluoxetine inhibits the CYP2D6 isoenzyme, which leads to inhibition of metoprolol metabolism and its accumulation, which can enhance the cardiodepressive effect and cause bradycardia. A case of the development of lethargy is described.
Fluoxetine and mainly its metabolites are characterized by a long T1/2, so the likelihood of drug interactions remains even several days after fluoxetine is discontinued.
There are reports of a decrease in the clearance of metoprolol from the body when used simultaneously with ciprofloxacin.
When used simultaneously with ergotamine, peripheral circulatory disorders may increase.
When used simultaneously with estrogens, the antihypertensive effect of metoprolol is reduced.
With simultaneous use, metoprolol increases the concentration of ethanol in the blood and prolongs its elimination.
