2010/06/23

Egilok

Composition, structure and packing

Tablets are white or nearly white, round, biconvex, with a dividing line-cross and double-bevel on one side and engraved "E435" - on the other side, and odorless. 1 tab. metoprolol tartrate 25 mg. Excipients: microcrystalline cellulose, sodium karboksimetilkrahmal, silicon dioxide, colloidal anhydrous, povidone, magnesium stearate.

Tablet is white or nearly white, round, biconvex, with the risk to one side and engraved "E434" - on the other side, and odorless. 1 tab. metoprolol tartrate 50 mg. Excipients: microcrystalline cellulose, sodium karboksimetilkrahmal, silicon dioxide, colloidal anhydrous, povidone, magnesium stearate.

Tablets are white or nearly white, round, biconvex, with risks on the one side and engraved "E432" - on the other side, and odorless. 1 tab. metoprolol tartrate 100 mg. Excipients: microcrystalline cellulose, sodium karboksimetilkrahmal, silicon dioxide, colloidal anhydrous, povidone, magnesium stearate.

Clinico-pharmacological group: beta1-blocker.

Pharmacological action

Cardioselective β-adrenoceptor blocker, not having internal membranes and sympathomimetic activity. Has antihypertensive, antianginal and antiarrhythmic action. Blocking in low doses, β1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces the intracellular current is Ca2 +, has a negative chrono-, Drome, BATM-and inotropic effects (slows heart rate, depresses conduction and excitability, reduces myocardial contractility). TPVR at the beginning of the drug (in the first 24 h after oral administration) increases after 1-3 days of returning to its original level, while continuing to use - is reduced.

Antihypertensive effects were due to a decrease in cardiac output and renin synthesis, inhibition of renin-angiotensin system and central nervous system, restoring the sensitivity of baroreceptors of the aortic arch (not going to enhance their activity in response to BP decrease), and eventually decrease peripheral sympathetic influences.

Lowers high blood pressure at rest, on exertion and stress. BP reduced within 15 min, maximum - 2 hours; effect persists for 6 h. The steady decline is observed after several weeks of regular use. Antianginal effect is determined by the decrease in myocardial oxygen demand by decreasing heart rate (lengthening of diastole and improved myocardial perfusion) and contractility, and decreased sensitivity to the effects of myocardial sympathetic innervation.

Reduces frequency and severity of angina attacks and improves exercise tolerance. Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, elevated levels of cAMP, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing AV-conduction (mainly in the antegrade and to a lesser extent in the retrograde direction through the AV-node) and on additional routes.
In supraventricular tachycardia, atrial fibrillation, sinus tachycardia with functional diseases of the heart and hyperthyroidism heart rate slows and may even lead to the restoration of sinus rhythm. Prevents the development of migraine.
With many years of taking reduces cholesterol.
When used in the medium therapeutic doses has a less pronounced effect on the organs that contain the β2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi, uterus) and carbohydrate metabolism.
When used in high doses (100 mg / day) has a blocking effect on both β-adrenoceptor subtype.

Pharmacokinetics

Absorption

Quickly and completely (95%) absorbed from the gastrointestinal tract. Cmax in plasma achieved by 1.5-2 h after ingestion. Bioavailability is 50%. In the course of treatment increases bioavailability of up to 70%. Eating increases the bioavailability by 20-40%.

Distribution

Vd is 5.6 L / kg. Linking to plasma proteins - 12%. Penetrates through the BBB and placental barrier. Excreted in breast milk in small amounts.

Metabolism

Metoprolol biotransformiruetsya in the liver. The metabolites have no pharmacological activity.

Withdrawal

T1 / 2 on average 3.5-7 hours Metoprolol almost completely excreted in urine over 72 h. About 5% of the dose was excreted unchanged.

Pharmacokinetics in special clinical situations
When expressed violations of liver function bioavailability and T1 / 2 of metoprolol increases, which may require correction dose.
In case of violation of renal function T1 / 2 and systemic clearance of metoprolol did not significantly change.

Statement
hypertension (as monotherapy or in combination with other antihypertensive drugs), including hyperkinetic type;
CHD (secondary prevention of myocardial infarction, prevention of angina attacks);
cardiac arrhythmias (Supraventricular arrhythmia, ventricular extrasystoles);
hyperthyroidism (in the complex therapy);
prevention of migraine.

Dosage regimen
When hypertension is prescribed in a daily dose 50-100 mg / day in 1 or 2 divided doses (morning and evening).
In case of insufficient therapeutic effect may be a gradual increase in daily dose to 100-200 mg.
In angina pectoris, supraventricular arrhythmias, for the prevention of migraine attacks is prescribed in doses of 100-200 mg / day in 2 divided doses (morning and evening). For secondary prevention of myocardial infarction in the prescribed average daily dose of 200 mg in 2 divided doses (morning and evening).

In functional disorders of cardiac activity, accompanied by tachycardia, prescribe a daily dose of 100 mg in 2 divided doses (morning and evening). In elderly patients, patients with impaired renal function, as well as the need for dialysis dosing regime change is not required.

In patients with severe disturbances of liver function should use the drug in smaller doses, due to slowing metabolism of metoprolol. Tablets, taken orally during or immediately after meals. The tablets can be divided in half, but do not chew.

Side effect
From the side of the central nervous system and peripheral nervous system: fatigue, weakness, headache, slow down the rate of mental and motor responses; rare - paresthesias in the extremities, depression, anxiety, reduced ability to concentrate, drowsiness, insomnia, nightmares, confusion, or transient memory impairment, asthenic syndrome, muscular weakness.
From the sense organs: rarely - reduced vision, reduced secretion of the lacrimal fluid, xerophthalmia, conjunctivitis, tinnitus.
Since the cardiovascular system: sinus bradycardia, palpitation, reduction in blood pressure, orthostatic hypotension, rarely - reduction of myocardial contractility, a temporary worsening of symptoms of chronic heart failure, arrhythmias, increased violations of the peripheral circulation (cooling of the lower extremities, Raynaud syndrome), conduction disorders infarction; in rare cases - AV-blockade cardiodynia.
On the part of the digestive system: nausea, vomiting, abdominal pain, diarrhea, constipation, xerostomia, changes in taste, increase in liver transaminases; rarely - hyperbilirubinemia. Dermatological reactions: urticaria, pruritus, rash, exacerbation of psoriasis, psoriazopodobnye changes in the skin, skin hyperemia, rash, photodermatosis, sweating, reversible alopecia.
On the part of the respiratory system: nasal congestion, difficulty exhaling (bronchospasm when administered high doses or in predisposed patients), shortness of breath.
From the Endocrine: hypoglycemia (in patients receiving insulin), rarely - hyperglycemia.
The part of the hemopoietic system: thrombocytopenia, agranulocytosis, leukopenia. Other: pain in the back or joints, slight weight gain, decreased libido and / or potency.

Contraindications
cardiogenic shock;
AV-block II and III degree;
sinoatrial block;
SSS;
pronounced bradycardia (HR <50 bpm);
heart failure in the stage of decompensation;
angiospastic angina (Prinzmetal angina);
marked hypotension (systolic BP <100 mm Hg);
lactation;
simultaneous reception of MAO inhibitors;
simultaneous in / introduction of verapamil;
Hypersensitivity to metoprolol and other ingredients.

Precautions should be prescribed medication for diabetes, metabolic disorders, bronchial asthma, chronic obstructive pulmonary disease (emphysema, chronic obstructive bronchitis), obliterating peripheral vascular disease (intermittent claudication, Raynaud syndrome), chronic liver disease, chronic renal insufficiency, myasthenia gravis, pheochromocytoma, AV-blockade of I degree, thyrotoxicosis, depression (including history), psoriasis, pregnancy, as well as children and adolescents under the age of 18 years, elderly patients.

Pregnancy and lactation

Application Egiloka during pregnancy is possible only when the intended benefits to the mother outweighs the potential risk to the fetus. If necessary, the appointment of the drug in this period should be careful monitoring of the fetus and the newborn within 48-72 hours after birth, as intrauterine growth retardation, bradycardia, hypotension, respiratory depression, hypoglycemia.

Effect of metoprolol in the newborn during breast feeding has not been studied, and women receiving Egilok should stop breastfeeding.

Application for violations of liver function

In patients with severe disturbances of liver function should use the drug in smaller doses, due to slowing metabolism of metoprolol. Precautions should be prescribed the drug for chronic pechenochenoy failure.

Application for violations of renal function

Patients with impaired renal function, as well as the need for dialysis change the dosage required. Precautions should be prescribed the drug in patients with chronic renal failure.

Cautions
In appointing the drug Egilok should regularly monitor heart rate and blood pressure.

Patients should be warned that if HR <50 bpm is necessary to consult a doctor. Patients with diabetes should regularly monitor blood glucose levels and if necessary correction of insulin or oral hypoglycemic agents. Appointment Egiloka patients with chronic heart failure is possible only after reaching the stage of compensation.

Patients receiving Egilok may gain expression of hypersensitivity reactions (on the background of aggravated allergic history), and the lack of effect of the introduction of conventional doses of epinephrine (adrenaline). Against the background of Egiloka possible aggravation of symptoms of peripheral circulation. Egilok should be lifted gradually, consistently reducing the dose within 10 days.
With a sharp cessation of treatment may be withdrawal symptoms (increased angina attacks, increased blood pressure). During the withdrawal of the drug to patients with angina should be under close medical supervision.
When angina selected dose should provide heart rate at rest within 55-60 bpm, with a load - no more than 110 bpm.

Patients who use contact lenses should be aware that patients receiving beta-blockers may decrease production lacrimal fluid. Metoprolol may mask certain clinical signs of hyperthyroidism (tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since the symptoms can increase.
In diabetes reception Egiloka may mask symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure).
In the appointment of metoprolol for patients with asthma should be the simultaneous use of beta 2-sympathomimetics.

In patients with pheochromocytoma Egilok should be used in combination with alpha-blockers. Prior to any surgical intervention is necessary to inform the anesthesiologist about the therapy Egilokom (drug choice for general anesthesia with minimal negative inotropic action); drug withdrawal is not required.
Administration of these drugs to elderly patients should regularly monitor liver function. Correction of dosage regimen is required only in case of elderly patients increasing bradycardia, BP decrease, AV-blockade, bronchospasm, ventricular arrhythmias, severe disturbances of liver function.

Sometimes it is necessary to stop treatment. There should be a special condition monitoring of patients with depressive disorders in history. In the case of depression Egilok should be abolished.
With simultaneous application of Egiloka with Clonidine in case of cancellation Egiloka Clonidine should be lifted in a few days (due to risk of cancellation syndrome).

Drugs that reduce the supply of catecholamines (eg reserpine) may enhance the action of beta-blockers, so patients taking these combinations of drugs should be under constant medical supervision in order to identify an excessive reduction of blood pressure or bradycardia.

Use in pediatrics

Efficacy and safety of Egiloka in children and adolescents under the age of 18 are not defined.

Effects on ability to drive vehicles and management mechanisms

Patients whose work requires more attention, the appointment of an outpatient drug should be resolved only after the evaluation of individual patient response.

Overdose

Symptoms: pronounced sinus bradycardia, dizziness, nausea, vomiting, cyanosis, hypotension, arrhythmia, ventricular extrasystoles, bronchospasm, syncope, acute overdose - cardiogenic shock, unconsciousness, coma, AV-block until the full development of cross-blockade and heart failure , cardiodynia.

First signs of overdose appear within 20 min-2 h after administration. Treatment: gastric lavage, the appointment of adsorbents, symptomatic therapy: marked reduction in blood pressure - Trendelenburg position, in the case of severe hypotension, bradycardia, and threatening heart failure - in / in (with an interval of 2-5 minutes) introduction of beta-adrenostimulyatorov or in / introduction of 0.5-2 mg of atropine sulfate, in the absence of a positive effect - dopamine, dobutamine, or norepinephrine.

As a follow up appointment may be 1-10 mg of glucagon, staging transvenous intracardial electrostimulator. If bronchospasm - to / at the introduction of beta2-adrenostimulyatorov, in convulsions - slow to / in the introduction of diazepam. Metoprolol poorly displayed with hemodialysis.

Drug Interactions
With simultaneous application Egiloka with MAO inhibitors may significantly increased the hypotensive actions. The interval between admission and MAO inhibitors Egiloka must be at least 14 days. At the same time / in the introduction of verapamil can trigger heart failure, co-administration of nifedipine leads to a significant decrease in BP. Means for inhalation anesthesia (derivatives of hydrocarbons), while applying to Egilokom increase the risk of myocardial depression and arterial hypotension.
With simultaneous use of beta-adrenostimulyatorov, theophylline, cocaine, estrogens, indomethacin and other NSAIDs reduce the hypotensive effect Egiloka.
With simultaneous application Egiloka and ethanol has increased, inhibitory action on the CNS. With simultaneous application Egiloka with ergot alkaloids increases the risk of peripheral circulatory disorders.
With simultaneous application Egilok increases the effect of oral hypoglycemic agents and insulin and increases the risk of hypoglycemia.
With simultaneous application Egiloka with antihypertensive diuretics, nitrates, calcium channel blockers increased risk of arterial hypotension.
With simultaneous application of Egiloka with verapamil, diltiazem, antiarrhythmics (amiodarone), reserpine, methyldopa, clonidine, guanfatsinom, means for general anesthesia and cardiac glycosides may be a manifestation of shortening increased heart rate and inhibition of AV-conduction.

Inductors microsomal liver enzymes (rifampicin, barbiturates) accelerate the metabolism of metoprolol, which reduces the concentration of metoprolol in plasma and reduce the effect Egiloka.

Inhibitors of microsomal liver enzymes (cimetidine, oral contraceptives, phenothiazines) increase the concentration of metoprolol in plasma. The allergens used for immunotherapy, or allergen extracts for skin tests or combined with Egilokom, increase the risk of systemic allergic reactions or anaphylaxis.

Iodine radiopaque substances for in / in the introduction, while the use of Egilokom increase the risk of anaphylactic reactions. Egilok while applying reduced clearance of xanthine, especially in patients with initially increased clearance of theophylline under the influence of smoking.
At simultaneous application with Egilokom reduced clearance of lidocaine and increases the concentration of lidocaine in plasma.
With simultaneous application Egilok strengthens and extends the effect of nondepolarizing muscle relaxants, prolongs the action of indirect anticoagulants.
When combined with the use of ethanol increases the risk of significant decrease of BP.

Terms and Conditions of storage

List B. The drug should be stored out of reach of small children at a temperature of 15 ° to 25 ° C. Shelf life - 5 years.