Metoprolol Retard-Acrichin, 25 mg 30 pcs

Metoprolol refers to the cardioselective beta-adrenoceptor blockers, which have no intrinsic sympathomimetic activity and membrane stabilizing properties. It has hypotensive, antianginal and antiarrhythmic effects. In low doses it blocks beta1-adrenoceptors of heart, decreases catecholamine-stimulated cAMP formation from ATP, decreases intracellular calcium ions flow, produces negative chrono-, dromo-, batmo- and inotropic effect (decreases heart rate, inhibits conduction and excitability and decreases myocardial contractility).

General peripheral resistance at the beginning of administration of beta-adrenoblockers (in the first 24 hours after oral administration) increases (as a result of reciprocal increase of activity of alpha-adrenoreceptors and elimination of stimulation of beta2-adrenoreceptors) which comes back to the basic one after 1-3 days and decreases with long-term use.

. Hypotensive effect is caused by reflex reduction of cardiac output and renin synthesis, inhibition of renin-angiotensin-apdosterone system activity (of greater importance in patients with initial renin hypersecretion) and central nervous system, restoration of aortic arch baroreceptors sensitivity (their activity in response to blood pressure decrease is not increased) and, eventually, reduction of peripheral sympathetic effects. Reduces elevated blood pressure (BP) at rest, during physical exertion and stress.

Hypotensive effect is rapid (systolic BP decreases in 15 min, maximum in 2 h) and lasts for 6 h. Diastolic BP changes slower: stable decrease is observed after several weeks of regular use.

The antianginal effect is determined by decreasing myocardial oxygen demand as a result of HR shortening (prolongation of diastole and improvement of myocardial perfusion) and contractility and decreasing myocardial sensitivity to sympathetic innervation. It reduces the number and severity of angina attacks and increases exercise tolerance.

Antiarrhythmic effect is caused by the removal 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 atrioventricular (AV) conduction (mainly in antegrade and, to a lesser degree, in retrograde direction) through the AV node and through additional pathways.

In supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart disease and hyperthyroidism, reduces HR, or may even lead to restoration of sinus rhythm.

Prevent the development of migraine. When used in medium therapeutic doses, unlike non-selective beta-adrenoblockers, 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. When used in high doses (more than 100 mg/day) it has a blocking effect on both beta-adrenoreceptor subtypes.

Pharmacokinetics

Absorption when ingested is complete (95%). Maximum plasma concentration is reached 1-2 hours after oral administration. Period of half-life is on average 3.5 hours (within 1 to 9 hours). It is subjected to intensive presystemic metabolism, bioavailability is 50% during the first use and increases to 70% during repeated use. Food intake increases bioavailability by 20-40 %.

Bioavailability of metoprolol increases in liver cirrhosis. Binding with blood plasma proteins is 10%. It penetrates through the blood-brain and placental barriers. Only a small amount penetrates into breast milk. The drug is metabolized in the liver; 2 metabolites have beta-adrenoblocking activity. CYP2D6 isoenzyme is involved in the metabolism of the drug.

About 5% is excreted unchanged by the kidneys. Treatment of patients with impaired renal function does not require adjustment of the drug dose. Impaired hepatic function slows down the metabolism of the drug and in cases of poor hepatic function the drug dose should be reduced. It is not eliminated by hemodialysis.

Indications

– arterial hypertension;

– CHD: prevention of stable angina attacks, reduction of mortality and the rate of recurrent myocardial infarction after the acute phase of myocardial infarction;

– cardiac rhythm disorders, including supraventricular tachycardia, reduced rate of ventricular contractions in atrial fibrillation and ventricular extrasystoles;

– functional cardiac disorders accompanied by tachycardia;

– prevention of migraine attacks.

Active ingredient

Composition

Excipients:

hypromellose – 155.96 mg,

ludipress LCE (lactose monohydrate – 94.7-98.3%, povidone – 3-4%) – 117.21 mg,

colloidal silicon dioxide – 1.5 mg,

magnesium stearate – 1.5 mg.

Coating composition:

Prepared Opadray II orange mixture (polyvinyl alcohol – 6 mg, talc – 2.22 mg, macrogol – 3.03 mg, titanium dioxide – 3.36 mg, iron oxide red dye – 0.009 mg, iron oxide yellow dye – 0.378 mg, iron oxide black dye – 0.003 mg) – 15 mg.

How to take, the dosage

The tablets are taken orally during or immediately after a meal, not chewed, with a small amount of liquid. Arterial hypertension. The initial daily dose is 50-100 mg in 1-2 doses (in the morning and in the 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 per day 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, in patients with renal dysfunction and if hemodialysis is necessary, the dose is not changed. In patients with liver dysfunction the dose of the drug should be reduced depending on the clinical condition.

Interaction

Special Instructions

Contraindications

– cardiogenic shock;

– degree II-III AV blockade;

– Sinoatrial block;

– SSRI;

– Severe bradycardia (HR < 50 bpm./min);

– Acute heart failure or decompensated chronic heart failure;

– Arterial hypotension (systolic BP < 100 mmHg.

– Acute myocardial infarction (HR < 45 bpm, PQ interval greater than 0.24 s, systolic BP < 100 mm Hg).);

– severe bronchial asthma;

– severe peripheral circulatory disorders;

– concomitant use of MAO inhibitors or concomitant intravenous administration of pheochromocytoma (without concomitant use of alpha-adrenoblockers);

– age less than 18 years (efficacy and safety not established);

– period of lactation;

– lactase deficiency, lactose intolerance, glucose/galactose malabsorption syndrome;

– hypersensitivity to metoprolol and other beta-adrenoblockers.

With cautiousness.the drug should be prescribed in diabetes mellitus, 1st degree AV blockade, Prinzmetal angina, metabolic acidosis, bronchial asthma, COPD, severe renal and/or hepatic failure, myasthenia gravis, pheochromocytoma (while taking alpha-adrenoblockers at the same time), thyrotoxicosis, depression (including depression in history).

Peripheral circulatory disorders (intermittent claudication, Raynaud’s syndrome), pregnancy, as well as elderly patients.

Side effects

Central nervous system: increased fatigue, weakness, headache, slowing of mental and motor reactions. Rarely – paresthesias in the 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.

Sensory organs: rarely – decreased vision, decreased tear fluid secretion, dry and sore eyes, conjunctivitis, tinnitus.

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.

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:

. pronounced 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 occur 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 an excessive decrease in blood pressure, bradycardia and heart failure – IV, at 2-5 min intervals, beta-adrenomimetics – until the desired effect or IV 0.5-2 mg of atropine sulfate. If there is no 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.

Similarities