A CARDIOLOGICAL GROUP RETARD
Active material: Metoprolol
When ATH: C07AB02
CCF: Beta1-adrenoblokator
ICD-10 codes (testimony): G43, I10, i20, I21, I47.1, I47.2, I50.0
When CSF: 01.01.01.02
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)
Pharmaceutical form, composition and packaging
Sustained-release tablets, Film-coated white or nearly white, oblong, lenticular, with Valium on both sides.
| 1 tab. | |
| metoprolol tartrate | 50 mg |
| -“- | 100 mg |
Excipients: sugar nibs (sucrose, starch stream), macrogol 6000, talc, ethyl cellulose, triэtiltsitrat, giproloza, magnesium stearate, microcrystalline cellulose, Colloidal anhydrous silica, gipromelloza, Titanium dioxide (E171).
10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
Pharmacological action
Kardioselektivnyj β-adrenoceptor Blocker, does not possess internal sympathomimetic and membrane-stabilizing activity. Provides antihypertensive, antianginalnoe and antiaritmicescoe action.
Metoprolol suppresses the effect of increased sympathetic activity on the heart, and also causes a rapid decrease in heart rate and cardiac output.
With arterial hypertension, metoprolol lowers blood pressure in patients standing and lying. Long-term antihypertensive effect of the drug is associated with a gradual decrease in TPR.
With a single and short-term repeated administration, metoprolol reduces plasma renin activity, which is explained by the suppression of renal β1-adrenoreceptorov, which leads to a decrease in renin production and, accordingly, a decrease in vasoconstriction, angiotensin-mediated.
In hypertension, long-term use of metoprolol leads to a statistically significant decrease in left ventricular mass.
Like other beta-blockers, metoprolol reduces myocardial oxygen demand by reducing systemic blood pressure, Heart rate and contractility. By reducing heart rate and corresponding lengthening of diastole, metoprolol improves blood supply and oxygenation of myocardial areas with impaired blood flow. Therefore, the drug reduces the frequency of angina attacks and increases physical performance..
When taken after myocardial infarction, metoprolol reduces the risk of recurrent myocardial infarction.
At therapeutic doses, the peripheral vasoconstrictor and bronchoconstrictor effects of metoprolol are less pronounced, than the same effects of non-selective beta-blockers.
Compared with non-selective beta-blockers, metoprolol has less effect on insulin production and carbohydrate metabolism. It does not significantly alter cardiovascular responses to hypoglycemia and does not increase the duration of hypoglycemic attacks.
Pharmacokinetics
Absorption
After oral administration, metoprolol is almost completely (about 95%) absorbed from the gastrointestinal tract. However, after absorption, metoprolol is largely metabolized when “first pass” through the liver. Bioavailability is approximately 35%. With repeated administration, the AUC increases by about 20%.
The curve of dependence of concentration in blood plasma from time has features, typical for sustained-release preparations.
The pharmacokinetics of metoprolol are linear up to dose 800 mg.
Distribution
Binding to plasma proteins is 10%.
Metoprolol is well distributed in tissues and has a large Vd – 5.5 l / kg.
For 4-6 hours after ingestion, the slow absorption phase passes into an approximately 6-hour plateau (Cmax = 37.4 ng / ml after a single dose, Cssmax is 54.7 ng / ml), this is followed by a phase of slow elimination.
Metabolism
Metoprolol is metabolized in the liver with the participation of cytochrome P450 isoenzymes. Metaʙolitы (O-desmethylmetoprolol and α-hydroxymetoprolol) do not have beta-adrenergic blocking activity. Since the metabolism of the drug is carried out by polymorphic enzymes, its level in blood plasma has significant (up to 17 times) differences in different patients.
Deduction
T1/2 metoprolol in the form of a retard tablet is 6-12 no, which is much more, than T1/2 metoprolol in conventional dosage form (about 3 no). Longer elimination half-life can be attributed to slower absorption.
Metoprolol is excreted primarily by the kidneys. (about 95%). About 10% the administered dose of metoprolol is excreted unchanged. Metabolites are excreted in the bile.
Pharmacokinetics in special clinical situations
Metoprolol is not removed from the body by hemodialysis. Treatment of patients with reduced renal function does not require dose adjustment.
Liver dysfunction slows down the metabolism of metoprolol, and in cases of liver failure, the dose of the drug should be reduced.
Testimony
- Arterial hypertension (in monotherapy or, if necessary, in combination with other antihypertensive drugs);
- chronic heart failure in the stage of compensation (in combination with standard diuretic therapy, ACE inhibitors, cardiac glycosides);
- CHD (secondary prevention of myocardial infarction – in the complex therapy; prevention of angina attacks);
- prevention of heart rhythm disturbances, especially supraventricular tachycardia and ventricular tachycardia, caused by adrenergic-dependent lengthening of the QT interval;
- hyperkinetic cardiac syndrome;
- Hyperthyroidism (in the complex therapy);
-Prevention of migraine attacks.
Dosage regimen
The drug is taken 1 time / day, morning, regardless of the meal.
In order to prevent bradycardia, the dose should be selected individually and increased gradually..
When hypertension The recommended starting dose is 50 mg 1 time / day. If the therapeutic effect is insufficient, the daily dose can be increased to 100 mg or 200 mg, or additionally prescribe another antihypertensive agent. The maximum daily dose is 200 mg.
Angina The recommended starting dose is 50 mg 1 time / day. If the therapeutic effect is insufficient, the daily dose can be increased to 100 mg or 200 mg, or additionally prescribe another antihypertensive agent.
To secondary prevention of myocardial infarction the usual maintenance dose is 200 mg 1 time / day.
At heart failure in compensation The recommended starting dose – 25 mg 1 time / day. Through 2 week, the daily dose can be increased to 50 mg, then two weeks before 100 mg and finally, later 2 of the week – to 200 mg.
At violations heart rhythm appoint 50-200 mg 1 time / day.
At gipertireoze the usual dose is 50-200 mg 1 time / day.
At hyperkinetic cardiac syndrome the drug is prescribed in a dose 50-200 mg 1 time / day.
To Prevention of migraines the drug is prescribed in a dose 100-200 mg 1 time / day.
In elderly patients and patients with renal insufficiency, and y patients, hemodialysis, dose adjustment is required.
At severe hepatic insufficiency the dose of the drug should be reduced in accordance with the clinical condition of the patient.
Tablets should be taken as a whole, without chewing, with some liquid. The tablets can be broken in half.
Side effect
Determination of the frequency of adverse reactions: Often (>1/10); often (>1/100, <1/10); sometimes (>1/1000, <1/100); rarely (>1/10 000, <1/1000); rarely (<1/10 000), including isolated reports.
From the central and peripheral nervous system: Often (especially at the beginning of treatment) – fatigue, weakness, dizziness and headache; sometimes – poor concentration, slowing of mental and motor responses, sleep disorders, drowsiness, insomnia, nightmares, depression, tremor, convulsions, anxiety; rarely – excitability, alarm, paresthesias in extremities (in patients with intermittent claudication and Raynaud's syndrome); rarely – short-term memory loss, confusion and hallucinations, muscular weakness, asthenia, myasthenia.
From the senses: rarely – reduced vision, reduced secreta slezna fluid, dryness and soreness of eyes, conjunctivitis, noise in ears, hearing loss.
Cardio-vascular system: often – excessive reduction of blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness), palpitation, sinusovaya bradycardia; rarely – reducing sokratimosti attack, development (aggravation) Heart Failure (swelling, swelling of the feet and / or lower legs, breathlessness), heart rhythm disturbances, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), conduction disturbances infarction, kardialgija; rarely – aggravation of pre-existing AV conduction disorders.
From the digestive system: nausea, vomiting, abdominal pain, dry mouth, constipation or diarrhea; rarely – increase in liver enzymes, giperʙiliruʙinemija; in some cases – abnormal liver function (dark urine, yellow skin or sclera, cholestasis), changes in taste.
Dermatological reactions: increased sweating; rarely – skin rash (exacerbation of psoriasis), dermahemia, rash, obratimaya alopecia; rarely – photodermatoses, psoriasiform skin reactions.
Allergic reactions: hives, itching, rash.
The respiratory system: nasal congestion, bronchospasm when administered in high doses (loss of selectivity and / or in predisposed patients), breathlessness.
From the hematopoietic system: rarely – thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.
Metabolism: lowering HDL cholesterol and increasing triglyceride levels (along with normal total cholesterol levels), weight gain.
On the part of the endocrine system: giperglikemiâ (in patients with non-insulin dependent diabetes mellitus), gipoglikemiâ (patients, receiving insulin), hypothyroid state.
Effect on the fetus: intrauterine growth, gipoglikemiâ, bradycardia.
Other: back pain or joint pain, decreased libido and / or potency, with abrupt termination of treatment – syndrome “cancel” (increasing angina attacks, increased blood pressure).
Contraindications
- Cardiogenic shock;
— AV-blockade II and III degrees;
- Sinoatrialynaya blockade;
- SSS;
- Heart failure decompensation;
- Angiospastic angina (Prinzmetal angina);
- Vыrazhennaya bradycardia (Heart Rate<50 u. / min);
- Hypotension;
— expressed by human peripheral blood circulation;
- Lactation;
- Simultaneous MAO inhibitors;
-simultaneous in/with the introduction of Verapamil;
- Up to 18 years (efficacy and safety have not been established);
-hypersensitivity to metoprololu and other ingredients of the drug.
Due to the limited clinical data, the use of the drug is contraindicated in myocardial infarction in the following conditions: HR less 45 u. / min, PQ interval exceeds 0.24 sec, systolic blood pressure less than 100 mmHg., severe heart failure and AV block II or III degree.
FROM caution should be prescribed for patients with diabetes, metabolic acidosis, asthma, chronic obstructive pulmonary disease (emphysema, chronic obstructive bronchitis), Obliterative diseases of peripheral vessels (intermittent claudication, Raynaud's syndrome), chronic renal and / or hepatic failure, myasthenia, pheochromocytoma, AV-blockade I degree, thyrotoxicosis, depression (incl. history), psoriaze, pregnancy, elderly patients, with fructose intolerance, malabsorption of glucose-galactose, sucrase / isomaltase deficiency.
Pregnancy and lactation
Application of the drug Egilok® Retard during pregnancy is possible only on strict indications in that case, when the intended benefits to the mother outweighs the potential risk to the fetus. If it is necessary to prescribe the drug during pregnancy, careful monitoring is necessary., especially for the condition of the fetus, since bradycardia is possible, hypotension, fetal hypoglycemia. Treatment must be interrupted for 48-72 hours before delivery. Where, when it's impossible, it is necessary to ensure the observation of the newborn during 48-72 hours after childbirth.
Influence of metoprolol on newborn baby during breast-feeding is not known, Therefore, women, host a cardiological group® Retard, should stop breastfeeding.
Cautions
Control of patients, taking beta-blockers, includes regular monitoring of heart rate and blood pressure, glucose content in diabetic patients. The patient should be taught the method of calculating the heart rate and instructed on the need for medical consultation with a heart rate of less than 50 u. / min. When taking the drug in a dose of more 200 mg / day decreases cardioselectivity of metoprolol.
Chronic heart failure should be compensated before starting treatment, and the state of compensation must be maintained throughout the treatment process.
Possible increased severity of hypersensitivity reactions (with aggravated allergic history) and the lack of effect from the introduction of medium doses of epinephrine (adrenaline). Patients, taking the drug, anaphylactic shock can be especially difficult.
The drug may exacerbate existing bradycardia. Patients, receiving beta- adrenoblokatorы, epinephrine (adrenaline) can increase blood pressure and cause (reflex) ʙradikardiju; this reaction is less likely in the case of the use of selective beta-blockers.
The drug may worsen the symptoms of peripheral circulatory disorders.
If necessary, the appointment of the drug to patients with bronchial asthma may require the simultaneous use of beta2-adrenostimuljatorov (changing the dose of previously used beta2-adrenostimuljatorov).
If it is necessary to prescribe the drug to patients with pheochromocytoma, alpha-blockers should be used.
Taking the drug may mask some of the clinical manifestations of hyperthyroidism (eg, taxikardiju). Sudden removal in patients with thyrotoxicosis is contraindicated, since this may increase his symptoms.
When strokes voltage selected dose should provide heart rate at rest within 55-60 u. / min, under load – no more 110 u. / min. In smokers, the effectiveness of the drug may be lower.
When prescribing the drug to patients with diabetes mellitus, it is necessary to more often monitor the parameters of carbohydrate metabolism and, if necessary, adjust the dose of insulin and oral hypoglycemic agents. In diabetes mellitus, the drug can mask tachycardia, induced hypoglycemia. In contrast, non-selective beta blockers hardly increase insulin-induced hypoglycemia or delay recovery of the concentration of glucose in the blood to normal levels.
Preparations, reducing stocks catecholamines (eg, reserpine), can enhance the effect of the drug Egilok Retard, so patients, accepting such combination drugs, should be constantly monitored by a physician to detect excessive lowering of blood pressure and bradycardia.
Patients with severe renal impairment are advised to monitor renal function (1 once every 4-5 months).
Bioavailability of metoprolol may increase in liver cirrhosis.
In elderly patients, it is recommended to regularly monitor liver function. Correction of the dosage regimen is required only if an increasing bradycardia appears in elderly patients (less 50 u. / min), significant decrease in blood pressure (systolic BP below 100 mmHg.), OF – Blockade, bronchospasm, ventricular arrhythmias, severe violations of the liver, sometimes you may need to stop treatment.
Should conduct special monitoring of patients with depressive disorders in anamnesis. In case of depression, Egilok® The retard should be canceled.
Before any surgery, the anesthesiologist must be warned, that the patient is taking Egilok® Retard. Cancellation of the drug should be carried out at least 48 h before surgery, except in special cases, eg, thyrotoxicosis or pheochromocytoma. In cases, when drug withdrawal before surgery is not possible, should choose a general anesthetic agent with minimal negative inotropic effect.
With the simultaneous use of the drug Egilok® Retard with clonidine in case of cancellation of Egilok® Retard clonidine should be canceled after a few days to avoid the development of a hypertensive crisis.
In a dramatic treatment may arise syndrome (increasing angina attacks, increase blood pressure), therefore, drug withdrawal is carried out gradually, reducing the dose during 10 days. Special attention should be paid to patients with angina pectoris when discontinuing the drug..
Patients, use contact lenses, We should take into account, that treatment with beta-adrenoblokatorami may reduce slezna fluid.
Taking into account, that the drug contains sucrose, it is not recommended for patients with fructose intolerance, impaired glucose / galactose absorption, as well as the lack of sucrase/izomal′tazy.
Effects on ability to drive vehicles and management mechanisms
During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.
Overdose
Symptoms: marked reduction in blood pressure, severe severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, arrhythmia, ventricular premature beats, bronchospasm, fainting; in acute overdose – cardiogenic shock, loss of consciousness, coma, AV блокада (until the development of a full cross-blockade and heart failure), kardialgija.
The first symptoms of an overdose appear after 20 min-2 h after administration of the drug.
Symptoms listed above may worsen while drinking alcohol, antihypertensive drugs, quinidine and barbiturates.
Treatment: intensive care and close monitoring of the patient (blood circulation and respiration parameters, kidney function, blood glucose level, serum electrolytes). If the drug has been recently taken, its further absorption can be reduced by gastric lavage, stimulation of vomiting and the introduction of activated carbon.
In marked decrease in blood pressure: the patient must be in the position of Trendelenburg; in case of an excessive decrease in blood pressure, bradycardia and the threat of heart failure, beta-adrenostimulants should be administered intravenously at intervals of 2-5 m, until the desired effect is achieved or intravenously enter 0.5-2 mg of atropine sulfate.
In the absence of a sufficient effect, dopamine should be used, dobutamine or norepinephrine (noradrenaline).
As a follow-up, it is possible to prescribe glucagon in a dose 1-10 mg of glucagon, setting an artificial pacemaker.
Bronchospasm can be controlled by IV injection of stimulants β2-adrenoreceptorov (eg, terbutaline).
Metoprolol bad displays using hemodialysis
Drug Interactions
If you are applying to Jegiloka® Retard with MAO inhibitors a significant increase in the hypotensive effect is possible. The interval between receiving MAO inhibitors and Jegiloka® The retard must be at least 14 days.
Simultaneous in/with the introduction of Verapamil can trigger cardiac arrest, the simultaneous appointment nifedipina leads to significant reduction of HELL.
When combined with antihypertensive drugs, Diuretics, with nitroglycerin or slow calcium channel blockers, a sharp decrease in blood pressure may develop (special care is needed when combined with prazosin); with Verapamil, diltiazemom, antiarrhythmics (amiodarone), reserpine, methyldopa, clonidine, guanfacinom, agents for general anesthesia and cardiac glycosides – an increase in the severity of a decrease in heart rate and inhibition of AV conduction.
Means for inhalation anesthesia (hydrocarbon derivatives) increase the risk of suppression of myocardial function and the development of arterial hypotension.
Beta-adrenostimulants, theophylline, cocaine, Estrogens (sodium retention), indomethacin and other NSAIDs (causing sodium retention and blocking the synthesis of prostaglandins by the kidneys) weaken the hypotensive effect of the drug.
When used simultaneously with Egilok® Retard three- and tetracyclic antidepressants, antipsychotics (neuroleptics), sedatives and hypnotics increase the depressing effect on the central nervous system.
When taken together with hypoglycemic agents for oral administration, their effect may be reduced; with insulin – increasing the risk of hypoglycemia, strengthening of its severity and duration, masking some symptoms of hypoglycemia (tachycardia, Sweating, increased blood pressure).
Inductors of microsomal liver enzymes (rifampicin, barbiturates) accelerate the metabolism of metoprolol, resulting in lower concentration metoprolola plasma and Jegiloka effect reduction® Retard.
Liver microsomal enzymes inhibitors (cimetidine, oral contraceptives, fenotiazinы) increase concentration metoprolola plasma.
Allergens, used for immunotherapy or allergen extracts for skin tests when used together with metoprolol, the risk of systemic allergic reactions or anaphylaxis; iodine-containing X-ray contrast agents for intravenous administration increase the risk of developing anaphylactic reactions.
Metoprolol reduces the clearance of xanthine derivatives, especially with an initially increased clearance of theophylline under the influence of smoking.
Metoprolol decreases the clearance of lidocaine, increases the concentration of lidocaine in blood plasma.
Boosts and prolongs the effect of muscle relaxants antidepolyarizuyuschih; lengthens the anticoagulant effect of coumarins.
When combined with ethanol, the risk of a pronounced decrease in blood pressure increases and there is an increase in the inhibitory effect on the central nervous system.
When combined with ergot alkaloids, the risk of developing peripheral circulatory disorders increases.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.
