Metoprolol Retard-Acrichin, 100 mg 30 pcs

A cardioselective beta1-adrenoblocker. It has no membrane stabilizing effect and has no intrinsic SMA. It has hypotensive, anti-anginal and antiarrhythmic effects. By blocking in low doses beta1-adrenoceptors of heart, it reduces catecholamine-stimulated cAMP formation from ATP, decreases intracellular Ca2+ flow, has negative chrono-, dromo-, batmo- and inotropic effect (decreases heart rate, inhibits conduction and excitability, reduces myocardial contractility).

The HRP at the beginning of beta-adreno-blockers use (in the first 24 hours after oral administration) increases (as a result of reciprocal increase of alpha-adrenoreceptors activity and elimination of beta2-adrenoreceptors stimulation) which returns to baseline in 1-3 days and decreases with prolonged administration. Its hypotensive action is caused by decrease of IOC and renin synthesis, inhibition of renin-angiotensin system activity (it is more important in patients with initial renin hypersecretion) and CNS, restoration of aortic arch baroreceptors sensitivity (there is no increase of their activity in response to pressure decrease) and as a result – by decrease of peripheral sympathetic effects.

Limits elevated BP at rest, during physical exertion and stress. Hypotensive effect develops quickly (systolic BP decreases after 15 min, maximum – after 2 h) and lasts for 6 h, diastolic BP changes slower: stable decrease is observed after several weeks of regular use. Antianginal effect is determined by decrease of myocardial oxygen demand as a result of HR decrease (prolongation of diastole and improvement of myocardial perfusion) and contractility and decrease of myocardial sensitivity to sympathetic innervation.

Limits the number and severity of angina attacks and increases exercise tolerance. By increasing LV end-diastolic pressure and increasing ventricular muscle fiber stretch may increase oxygen demand, especially in patients with CHF.

. The antiarrhythmic effect is caused by the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of CAMF, arterial hypertension), the decrease of spontaneous excitation rate of sinus and ectopic pacemakers and delay of AV conduction (mainly in antegrade and less so in retrograde direction through the AV node) and through additional pathways. In supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart disease and thyrotoxicosis it reduces HR or may even lead to restoration of sinus rhythm.

Prevent the development of migraine. Compared with non-selective beta-adrenoblockers when administered in medium therapeutic doses, it has less pronounced effect on the organs containing beta2-adrenoreceptors (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism; intensity of atherogenic action does not differ from action of propranololol.

In long-term use it reduces the concentration of cholesterol in the blood. When used in high doses (more than 100 mg/day) it has a blocking effect on both beta-adrenoreceptor subtypes. When metoprolol tartrate is infused intravenously for 10 min or more the maximal effect occurs after 20 min, the heart rate slowing down by doses of 5 and 10 mg is 10 and 15% respectively.

Indications

Active ingredient

Composition

1 tablet:
– metoprolol 100 mg

Excipients:

lactose,

potato starch,

colloidal silica,

magnesium stearate,

povidone,

sodium starch glycolate.

How to take, the dosage

Tablets are taken orally during or immediately after a meal, do not chew, wash with a small amount of liquid.

Arterial hypertension:
The initial daily dose is 50-100 mg in 1-2 doses (morning and evening). In case of insufficient therapeutic effect, the daily dose may be gradually increased to 100-200 mg and/or additional prescription of other antihypertensive agents. The maximum daily dose is 200 mg.

Angina pectoris, arrhythmias, prevention of migraine attacks:
100-200 mg daily in two doses (morning and evening).

Secondary prevention of myocardial infarction:
200 mg per day in two doses (morning and evening).
Hyperthyroidism:
50 mg 2 times a day (morning and evening).

In elderly patients, with impaired renal function, as well as with the need for hemodialysis the dose is not changed. In patients with impaired liver function the dose of Metoprolol-Acri should be reduced depending on the clinical condition.

Interaction

Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving metoprolol.

Iodine-containing radiopaque drugs for IV administration increase the risk of anaphylactic reactions. Phenytoin when administered by IV, drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of cardiodepressive effects and the likelihood of BP reduction. Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased BP).

Decreases clearance of lidocaine and xanthines (except diphylline) and increases their plasma concentrations, especially in patients with initially increased clearance of theophylline under the influence of smoking. The hypotensive effect is weakened by NSAIDs (Na+ retention and blockade of Pg synthesis by kidneys), GCS and estrogens (Na+ retention).

The cardiac glycosides, methyldopa, reserpine and guanfacine, BMCC (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and CH. Nifedipine can lead to a significant decrease in BP. Diuretics, clonidine, sympatholytics, hydralazine, and other hypotensive drugs can lead to excessive BP reduction.

Longens the effect of nondepolarizing myorelaxants and the anticoagulant effect of coumarins. Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics increase CNS depression. Concomitant use with MAO inhibitors is not recommended due to significant increase in hypotensive effect, a treatment break between MAO inhibitors and metoprolol should be at least 14 days. Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

Special Instructions

Monitoring of patients taking beta-adrenoblockers includes monitoring heart rate and BP (daily at the beginning of therapy, then once every 3-4 months), blood glucose concentration in diabetic patients (once every 4-5 months).

The patient should be trained in the method of HR counting and instructed to consult a physician if the HR is less than 50/min. Allergic reactions may become more pronounced (with a strong allergic history) and have no effect from the usual doses of epinephrine. In elderly patients it is recommended to monitor renal function (once every 4-5 months). It may aggravate the symptoms of peripheral arterial circulatory disorders.

Patients with cardiac rhythm disorders whose systolic BP is below 100 mmHg should be administered by IV only with special precautions (there is a risk of further BP reduction). The drug should be withdrawn gradually, reducing the dose over 10 days. For arterial hypertension, the effect occurs within 2-5 days, and a stable effect is noted after 1-2 months. With angina pectoris, a dose of the drug should provide an HR at rest within 55-60 bpm, while the load – not more than 110 bpm. In “smokers” the effectiveness of beta-adrenoblockers is lower.

In combined therapy with clonidine, the latter should be discontinued several days after withdrawal of metoprolol, to avoid a hypertensive crisis. At a dose above 200 mg/day, cardio-selectivity decreases. Metoprolol may mask some clinical manifestations of thyrotoxicosis (e.g. tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it may exacerbate the symptoms.

In diabetic patients may mask tachycardia caused by hypoglycemia. Unlike non-selective beta-adrenoblockers, it practically does not increase insulin-induced hypoglycemia and does not delay the recovery of blood glucose concentration to normal levels. If it is necessary to prescribe to patients with bronchial asthma, beta2-adrenergic stimulants are used as concomitant therapy; in pheochromocytoma – alpha-adrenoblockers.

If it is necessary to perform surgical intervention it is necessary to warn the anesthesiologist about the therapy (choice of drugs for general anesthesia with minimal negative inotropic effect), cancellation of the drug is not recommended. Reciprocal activation of n.vagus can be eliminated by IV administration of atropine (1-2 mg). Drugs that reduce catecholamine stores (e.g., reserpine) may potentiate the effects of beta-adrenoblockers, so patients taking such combinations of drugs should be under constant medical supervision for excessive BP reduction or bradycardia.

In elderly patients with increasing bradycardia (less than 50/min), arterial hypotension (systolic BP below 100 mmHg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and renal dysfunction the dose should be reduced or treatment should be stopped.

It is recommended to discontinue therapy if there are skin rashes and development of depression caused by taking beta-adrenoblockers. Discontinuation of the drug is done gradually, reducing the dose over 10 days. If treatment is stopped abruptly, a “withdrawal” syndrome may occur (increased angina pectoris attacks, increased BP).

Particular attention should be given to patients with angina pectoris when withdrawing the drug. Patients who use contact lenses should take into account that against the background of treatment with beta-adrenoblockers tear fluid production may decrease. During pregnancy, the drug is prescribed only on strict indications (due to possible development of bradycardia, hypotension, hypoglycemia and respiratory paralysis in a newborn). The treatment should be interrupted 48-72 hours before delivery.

In cases where this is not possible, close monitoring of the newborn for 48-72 h after delivery should be ensured. During treatment, caution must be exercised when driving motor vehicles and engaging in other potentially hazardous activities that require increased concentration and quick psychomotor reactions.

Contraindications

Side effects

Cardiovascular system: sinus bradycardia, palpitations, decreased blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness). Rarely – reduction of myocardial contractility, temporary aggravation of symptoms of chronic heart failure (edema, swelling of feet and/or lower leg, dyspnea), arrhythmias, manifestation of angiospasm (increase of peripheral circulation disorders, coldness of the lower extremities, Raynaud’s syndrome), myocardial conduction disorders.

Sensory system disorders: rare – decreased vision, decreased tear fluid secretion, dry and sore eyes, conjunctivitis, tinnitus.

As to the central nervous system: increased fatigue, weakness, headache, slowing of mental and motor reactions. Rarely – paraesthesia in extremities (in patients with “intermittent” claudication and Raynaud’s syndrome), depression, anxiety, reduced attention, drowsiness, insomnia, “nightmares” dreams, confusion or short-term memory loss, muscle weakness.

Digestive system disorders: nausea, vomiting, abdominal pain, dry mouth, diarrhea, constipation, change in taste.

Skin disorders: urticaria, skin itching, rash, exacerbation of psoriasis, psoriasis-like skin reactions, skin hyperemia, exanthema, photodermatosis, increased sweating, reversible alopecia.

Respiratory system: nasal congestion, difficulty in exhalation (bronchospasm when administered in high doses-tract selectivity and/or in predisposed patients), dyspnea.

Endocrine system: hypoglycemia (in patients receiving insulin), rarely – hyperglycemia (in patients with insulin-dependent diabetes).

Laboratory parameters: rare – thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of “liver” enzymes, extremely rare – Hyperbilirubinemia.

Fetal effects: possible intrauterine growth retardation, hypoglycemia, bradycardia.

Others: back or joint pain, like all beta-adrenoblockers in single cases may cause a slight increase in body weight, decreased libido and/or potency.

Overdose

Symptoms:

.Severe severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked decrease in blood pressure, arrhythmia, ventricular extrasystole, bronchospasm, syncope, in acute overdose – cardiogenic shock, loss of consciousness, coma, atrioventricular block (up to development of complete transverse block and cardiac arrest), cardialgia. The first signs of overdose appear 20 minutes to 2 hours after taking the drug.

Treatment:

Gastric lavage and administration of adsorptive agents; symptomatic therapy: with a marked decrease in blood pressure – the patient should be in the Trendelenburg position; in case of excessive reduction of blood pressure, bradycardia and heart failure – IV, with intervals of 2-5 minutes, beta-adrenomimetics – until the desired effect or IV 0.5-2 mg of atropine sulfate. In the absence of a positive effect – dopamine, dobutamine or norepinephrine (noradrenaline).

As a follow-up, it is possible to administer 1-10 mg of glucagon, installation of transvenous intracardiac pacemaker. For bronchospasm, IV beta2-adrenomimetics should be administered. Metoprolol is poorly excreted by hemodialysis.

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