Metoprolol retarde Acrichine pills 50mg, 30pcs

Composition

One tablet contains:  

Active ingredient:  

metoprolol succinate in terms of 100% substance 23,83 mg,47,66 mg and 95,32 mg, equivalent to 25 mg,50 mg and 100 mg of metoprolol tartrate, respectively;

excipients :

hypromellose 155,96 mg,161,92 mg or 184,84 mg;

ludipress of LA [lactose monohydrate 94,7-98,3%, povidone 3-4%] 117,21 mg,87,42 mg or 412,84 mg;

silicon dioxide colloidal 1.5 mg,1.5 mg or 3.5 mg;

magnesium stearate 1.5 mg,1.5 mg or 3.5 mg, respectively.

Shell composition:

For tablets with dosages of 25 mg and 100 mg – ready mix “Opadray II” orange (polyvinyl alcohol 6 mg or 14 mg, talc 2.22 mg or 5.18 mg, macrogol 3.03 mg or 7.07 mg, titanium dioxide 3.36 mg or 7.84 mg, iron oxide dye red 0.009 mg or 0.021 mg, iron oxide dye yellow 0.378 mg or 0.882 mg, iron oxide dye black 0.003 mg or 0.007 mg) 15 mg or 35 mg, respectively.

For tablets with a dosage of 50 mg – ready mix “Opadry II” green (polyvinyl alcohol 6 mg, talc of 2.22 mg, macrogol of 3.03 mg, titanium dioxide 2,925 mg, dye quinoline yellow (aluminum paint) 0,268 mg, dye iron oxide black 0,015 mg, dye Indigo Carmine (aluminum paint) 0,542 mg) 15 mg.

Pharmacological effects

of beta 1-selective blocker.

KodATH:  C 07 AB 02

Pharmacological properties

Pharmacodynamics

Cardioselective beta-1-adrenoblocker. It does not have a membrane-stabilizing effect and does not have internal sympathomimetic activity. It has antihypertensive, antianginal and antiarrhythmic effects.

Blocking the beta-1-adrenergic receptors of the heart in low doses, it reduces the formation of cyclic adenosine monophosphate (cAMP) stimulated by catecholamines from adenosine triphosphate (ATP), reduces the intracellular flow of calcium ions, has a negative chrono -, dromo -, batmo – and inotropic effect (reduces heart rate (HR), inhibits conduction and excitability, reduces myocardial contractility).

Total peripheral vascular resistance (OPSS) at the beginning of beta-blockers use (in the first 24 hours after oral use) increases (as a result of a reciprocal increase in alpha-adrenergic activity and elimination of beta-2-adrenergic stimulation), which returns to its original value after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is due to a decrease in the minute volume of blood flow and renin synthesis, inhibition of the activity of the renin-angiotensin-aldosterone system (it is more important in patients with initial hypersecretion of renin) and the central nervous system, restoration of sensitivity of the aortic arch baroreceptors (there is no increase in their activity in response to a decrease in blood pressure (BP) and, as a result, a decrease in peripheral sympathetic influences. Reduces elevated blood pressure at rest, during physical exertion and stress. The antihypertensive effect lasts more than 24 hours.

The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance. By increasing the final diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles, it can increase the need for oxygen, especially in patients with chronic heart failure (CHF).

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 the retrograde directions through the AV node) and along additional pathways.

With supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart diseases and thyrotoxicosis, it reduces the heart rate or can even lead to the restoration of the sinus rhythm.

Prevents the development of migraines.

Unlike non-selective beta-blockers, when administered in medium therapeutic doses, it has a less pronounced effect on organs containing beta-2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism; the severity of the atherogenic effect does not differ from that of propranolol. When taken for many years, it reduces the concentration of cholesterol in the blood. When used in large doses (more than 100 mg / day), it has a blocking effect on both subtypes of beta-adrenergic receptors.

Pharmacokinetics

Oral absorption is complete (95%). Solubility in fats is moderate. Undergoes intensive presystemic metabolism, bioavailability – 50% at the first dose and increases to 70% with repeated use. Binding to plasma proteins is 10%. The time to reach the maximum concentration in blood plasma is 6-12 hours after taking the drug. During the course of treatment, bioavailability increases. Food intake increases bioavailability by 20-40%.

It is rapidly distributed in tissues, penetrates through the blood-brain barrier, placental barrier. Penetrates into breast milk.

It is metabolized in the liver,2 metabolites have beta-adrenoblocking activity. The isoenzyme CYP2D6 is involved in the metabolism of the drug. The half-life is from 3.5 to 7 hours when taken orally. It is not removed during hemodialysis.

Significant accumulation of metabolites is observed in patients with a creatinine clearance of 5 ml / min, while the beta-blocking activity of the drug does not increase.

Bioavailability increases in cirrhosis of the liver, while reducing its total clearance.

Indications

Arterial hypertension.

Chronic heart failure of functional class II-IV according to NYHA classification in the compensation stage (as part of complex therapy).

Ischemic heart disease: prevention of stable angina attacks, reduction of mortality and frequency of recurrent myocardial infarction after the 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.

Contraindications

Hypersensitivity to metoprolol and other beta-blockers, cardiogenic shock, grade II-III AV block, sinoatrial block, sinus node weakness syndrome, severe bradycardia (heart rate less than 50 beats/min), acute heart failure or decompensated CHF, hypotension (systolic blood pressure less than 100 mm Hg), acute myocardial infarction (heart rate less than 45 beats/min, PQ interval more than 0.24 s, systolic blood pressure less than 100 mm Hg), lactation period, simultaneous use of monoamine oxidase inhibitors (MAO) or simultaneous intravenous use of verapamil, pheochromocytoma (without simultaneous use of alpha-blockers), age up to 18 years (efficacy and safety have not been established), lactase deficiency, lactose intolerance, glucose-galactose malabsorption, severe bronchial asthma, severe peripheral vision disorders blood circulation.

With caution

Diabetes mellitus, atrioventricular block I degree, Prinzmetal angina pectoris, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease, renal and/or severe liver failure, myasthenia gravis, pheochromocytoma (with simultaneous use of alpha-blockers), thyrotoxicosis, depression (including in the anamnesis), psoriasis, peripheral circulatory disorders (“intermittent” lameness, Raynaud’s syndrome), pregnancy, old age.

Side effects

Frequency of side effects: very often-more than 1/10, often-more than 1/100 and less than 1/10, infrequently-more than 1/1000 and less than 1/100, rarely-more than 1/10000 and less than 1/1000, very rarely-less than 1/10000, including individual reports.

From the cardiovascular system:  often-bradycardia, orthostatic hypotension (including syncope), cold of the lower extremities, palpitation sensation; infrequently-temporary increase in symptoms of heart failure, cardiogenic shock in patients with myocardial infarction, AV block of the first degree; rarely-myocardial conduction disorders, arrhythmia; very rarely-gangrene (in patients with peripheral circulatory disorders).

From the central nervous system:  very often-increased fatigue, decreased speed of mental and motor reactions; often-dizziness, headache; infrequently-paresthesia, convulsions, depression, decreased concentration, drowsiness, insomnia, “nightmarish” dreams; rarely – asthenia, tremor, increased nervous excitability, anxiety; very rarely – amnesia/memory impairment, depression, hallucinations, myasthenia gravis.

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

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

From the side of the skin:  infrequently-urticaria, increased sweating; rarely-alopecia; very rarely-photosensitization, exacerbation of psoriasis, psoriasis-like skin reactions.

Respiratory system disorders: often-shortness of breath; infrequently-bronchospasm in patients with bronchial asthma; rarely-rhinitis.

Laboratory parameters: very rarely – thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of “liver” enzymes, hyperbilirubinemia.

From the endocrine system: often-hypoglycemia (in patients with type I diabetes mellitus), rarely-hyperglycemia (in patients with type II diabetes mellitus), hypothyroidism.

Other services: infrequently-weight gain; rarely-impotence/sexual dysfunction; very rarely-arthralgia, thrombocytopenia.

Interaction

Drugs that reduce catecholamine stores (for example, reserpine, MAO inhibitors) when used simultaneously with metoprolol may increase the hypotensive effect or cause severe bradycardia. The treatment interval between taking MAO inhibitors and metoprolol should be at least 14 days.

Metoprolol is a substrate of the CYP2D6 isoenzyme. Drugs that inhibit or induce the activity of the CYP2D6 isoenzyme may affect the plasma concentration of metoprolol.

Inhibitors of the CYP2D6 isoenzyme: some antidepressants and neuroleptics, quinidine, terbinafine, celecoxib, propafenone, diphehydramine, hydroxychlorine, cimetidine-increase the concentration of metoprolol in blood plasma.

Inducers of the CYP2D6 isoenzyme: barbituric acid derivatives, rifampicin-reduce the concentration of metoprolol in blood plasma.

Concomitant use with cardiac glycosides, clonidine, slow calcium channel blockers (verapamil, diltiazem), amiodarone, class I antiarrhythmics, general anesthesia, methyldopa, guanfacine may lead to a decrease in blood pressure and severe bradycardia.

Inhaled anaesthetic agents (hydrocarbon derivatives) increase the risk of myocardial function depression and hypotension.

Simultaneous intravenous use of verapamil may cause cardiac arrest.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-adrenomimetics weaken the antihypertensive effect of beta-blockers.

Ergot alkaloids increase the risk of peripheral circulatory disorders.

When taken together with oral hypoglycemic drugs, their effect may decrease; with insulin – it may increase the risk of hypoglycemia, prolong and increase its severity, and mask some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).

Reduces the clearance of xanthines (except diphylline), 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.

Enhances and prolongs the action of non-depolarizing muscle relaxants; prolongs the anticoagulant effect of coumarins.

When taking epinephrine (epinephrine) with beta-blockers at the same time, blood pressure may increase and bradycardia may occur.

Phenylpropanolamine (norephedrine) may increase diastolic blood pressure.

Allergens used for immunotherapy, or allergen extracts for skin tests when combined with metoprolol, increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing radiopaque agents for intravenous use increase the risk of anaphylactic reactions.

When combined with ethanol, the risk of a pronounced decrease in blood pressure increases.

How to take, course of use and dosage

Metoprolol retard-Akrikhin is intended for oral use 1 time a day, it is recommended to take it in the morning, without chewing, with water. Metoprolol retard-Akrikhin can be taken regardless of food intake. In order to prevent bradycardia, the dose is selected individually and increased gradually.

With arterial hypertension and angina pectoris, the initial dose is 50 mg once a day, with insufficient therapeutic effect, the daily dose can be increased to 100-200 mg per day. In arterial hypertension, if the drug is ineffective at a dose of 100-200 mg per day, you can add another antihypertensive agent.

In patients with NYHA functional Class II chronic heart failure (no exacerbations in the last 6 weeks and no changes in complex therapy in the last 2 weeks), the recommended initial dose is 25 mg once a day. After two weeks, the daily dose can be increased to 50 mg, then after two weeks to 100 mg, and after another two weeks to 200 mg.

In patients with NYHA functional class III-IV chronic heart failure, the recommended initial dose for the first 2 weeks is 12.5 mg of the drug once a day. It is possible to use metoprolol in another dosage form, for example, tablets of 25 mg with a risk. 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 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 the drug is reached once a day.

Secondary prevention of myocardial infarction and cardiac arrhythmias – an initial dose of 100 mg once a day.

In case of functional cardiac disorders accompanied by tachycardia-50 mg per day, if necessary, the dose can be increased to 200 mg per day.

Prevention of migraine attacks: 100-200 mg once a day.

Elderly patients, patients with renal insufficiency, or patients undergoing hemodialysis do not need to adjust the dose.

Impaired liver function affects the elimination of metoprolol, so it may be necessary to adjust the dose depending on the clinical condition.

Overdose

Symptoms:

bradycardia, AV blockade (up to the full development of cross-blockade and cardiac arrest), marked reduction in blood pressure, impaired peripheral circulation, increased symptoms of heart failure, cardiogenic shock, respiratory depression, apnea, cyanosis, fatigue, dizziness, loss of consciousness, coma, tremors, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting may develop esophagospasm, hypoglycemia or hyperglycemia, hyperkalemia, transient myasthenia gravis. The first signs of overdose appear in 20 minutes-2 hours after taking the drug.

Treatment:

If the drug is taken recently – gastric lavage and intake of adsorbents; in case of violation of atrioventricular conduction and/or bradycardia – intravenous use of 1-2 mg of atropine, epinephrine (epinephrine) or setting a temporary pacemaker; with a decrease in blood pressure – the patient should be in the Trendelenburg position. If there are no signs of pulmonary edema-iv plasma-substituting solutions, if ineffective-use of epinephrine, dopamine, dobutamine; in acute heart failure-cardiac glycosides, diuretics; in convulsions-iv diazepam; in bronchospasm-inhalation or parenteral beta-2-adrenomimetics.

Special instructions

Monitoring of patients taking beta-blockers includes regular monitoring of their heart rate and blood pressure. The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

It is possible to increase the severity of allergic reactions (against the background of a burdened allergic history) and the lack of effect from the introduction of conventional doses of epinephrine (epinephrine).

In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months). It may increase the symptoms of peripheral arterial circulation disorders.

In case of stress angina, the selected dose of the drug should provide a resting heart rate of 55-60 beats / min, with a load of no more than 110 beats / min.

In “smokers”, the effectiveness of beta-blockers is lower.

Metoprolol retard-Akrikhin may mask some clinical manifestations of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, since it can increase symptoms.

With diabetes, it can mask tachycardia caused by hypoglycemia.

If necessary, beta-2-adrenomimetics are used as concomitant therapy for patients with bronchial asthma; alpha – blockers are used for pheochromocytoma.

If surgical intervention is necessary, it is necessary to warn the anesthesiologist about taking the drug Metoprolol retard-Akrikhin (it is necessary to choose a means for general anesthesia with minimal negative inotropic effect), drug cancellation is not recommended.

Reciprocal activation of the vagus nerve can be eliminated by intravenous use of atropine (1-2 mg).

In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe liver and kidney function disorders, the dose should be reduced or treatment should be discontinued.

It is recommended to stop therapy if skin rashes appear and depression develops due to taking beta-blockers.

Metoprolol may increase the symptoms of peripheral circulatory disorders.

When clonidine is abruptly discontinued, blood pressure may rise sharply, while taking beta-blockers at the same time. If clonidine is discontinued, discontinuation of beta-blockers should begin several days before clonidine is discontinued.

Drugs that reduce the supply of catecholamines (for example, reserpine) can increase the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision for excessive lowering of blood pressure or bradycardia.

If treatment is abruptly discontinued, a “withdrawal” syndrome may occur (increased angina attacks, increased blood pressure). Special attention should be paid to patients with angina pectoris, CHF, after a previous myocardial infarction when discontinuing the drug. Withdrawal of Metoprolol retard-Akrikhin is carried out gradually, reducing the dose over 10 days.

Patients who use contact lenses should take into account that against the background of treatment with beta-blockers, tear fluid production may decrease.

During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Film-coated tablets, round, biconvex. Tablets with dosages of 25 mg and 100 mg are yellowish-brown in color.

Tablets with a dosage of 50 mg are light green to green in color. On the fracture, the tablet is white with a grayish or creamy tint.

Active ingredient

Metoprolol

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

For adults as prescribed by a doctor, for pregnant women as prescribed by a doctor

Indications

Hypertension, Myocardial Infarction, Arrhythmia, Migraine, Angina