Egilok

Hungarian Pharmaceutical Plant EGIS produces an innovative drug Egilok (Egilok) - a highly effective cardioselective beta- _1- adrenoblocker, designed to solve many problems associated with pathological changes in the work of the cardiovascular region.

Indications Egilok

The drug was originally developed for the relief of cardiac pathologies. Hence the following are the indications for the use of Egilok:

• Monotherapy in the treatment of hypertension, as well as tandem work with other antihypertensive drugs, antihypertensive drugs to stop the same problem.
• Heart palpitations in the supraventricular region.
• Ischemic heart diseases, for example, such as myocardial infarction - in the protocol of treatment of complex therapy.
• Ventricular extrasystole - failure of the heart rhythm, which is premature, arisen out of turn, ventricular contractions.
• Preventing attacks of angina pectoris.
• Hyperthyroidism is an endocrinological syndrome caused by hyperfunction of the thyroid gland.
• Preventive measures to prevent migraine attacks .
• Functional malfunctions in the heart, accompanied by tachycardia.

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Release form

The active substance of the drug in question is metoprolol (metoprololum), or as it is also called metoprolol tartrate. Additional chemical compounds that form part of the Egilok: MCC (microscopic crystalline cellulose), sodium carboxy-methyl-starch (type A), silicon dioxide (belonging to anhydrous colloids), povidone (K90), magnesium stearate. 

Tablet form of release, the composition of one unit of the drug includes tartrate metoprolol - the tablets vary in the dosage of the active substance: the drug with 0.025 mg of active ingredient, tablets that include 0.050 mg of metoprolol, as well as a drug with a concentration of 0.1 mg active chemical compound. The calculation of the disinfection is carried out by the weight of the dry matter.  

Appearance of the unit is a tablet of white hue, classical round shape, with two-sided truncation of corners. On one of the planes, the embossing "E435" (at the concentration of the active component of 0.025 mg), "E434" (at the active component concentration of 50 mg) and "E432" (at the concentration of the active component of 0.1 mg) is seen on one of the planes.

Packing material:

• "E435": three blisters with 20 tablets each, or a bottle of darkened glass, which contains 60 tablets, packed in a cardboard box and equipped with instructions for use.
• "E434": four blisters of 15 tablets each, or a bottle of darkened glass, which contains 60 tablets, packed in a cardboard box and equipped with instructions for use.
• "E432": a vial of darkened glass, which contains 30 or 60 tablets packed in a cardboard box and equipped with instructions for use.

Pharmacodynamics

Cardioselective β-blockers of the receptors of adrenergic substances (outer cell membrane proteins that recognize and bind adrenaline) have no effect on the increase in the refractory period, and do not block abnormal ectopic activity. They also do not possess depressing abilities of beta-receptors from the action of "exciting" their hormones, but under certain conditions they can, on the contrary, stimulate them, showing the absence of sympathomimetic activity. Thanks to such characteristics, the pharmacodynamics of Egilok shows good antihypertensive, antiarrhythmic and antianginal properties.

Slightly inhibiting β ₁ -adrenoceptors of the heart, metoprolol tartrate with the help of catecholamines reduces irritation, which stimulates the formation of adenosine triphosphate (ATP) from the enzymatic component of cAMP. Pharmacodynamics Egilok directed to reduce the rate of intracellular calcium ions (Ca ²⁺ ). Metoprolol produces an antagonistic effect of chronotropic, inotropic, butmotropic, dromotropic character. Such its properties allow to reduce the rate of heart rate (HR), to reduce the increased excitability of the heart muscles and their level of conductivity. Egilok effectively inhibits the intensity of myocardial contractility.

In the first day after oral administration of the drug, a slight increase in OPSS (total peripheral vascular resistance) is observed, then, after a day, three, this level returns to its original value, and continued use of the drug leads to a further decrease in this indicator.

Antihypertensive drug is caused by a decrease in the connective ability of renin, a decrease in the pumping function of the heart, as well as the probability of a venous return of blood to the heart. This characteristic of the drug allows at least partially block the intensity of the central nervous and renin-angiotensin systems. The active substance of the drug Egilok makes it possible to restore the susceptibility of the aortic baroid artery receptors, making them amorphous with a decrease in blood pressure, which ultimately leads to suppression of peripheral systemic influences. Egilok reduces the indicators of high blood pressure, whether the patient's body under the influence of physical exertion, stress or at rest.

The reaction to reduce blood pressure can be observed after a quarter of an hour after the administration of the drug. The maximum amount of active substance in the serum can be observed after two hours. The therapeutic effect of the drug remains for the next six hours. Normalization and stabilization of blood pressure can be observed after at least a month of therapy.

Antianginal properties of the drug are characterized by diastole lengthening and correcting the capacity of blood vessels and myocardium cells, which normalizes the flow of oxygen into tissues, stabilizes heart rate and the level of contractility. Antianginal characteristics of Egiloks are also manifested by a decrease in the susceptibility of the myocardium to the tension of the connection of organs and tissues with the central nervous system by means of nerve receptors (sympathetic innervation). This indicator makes it easier to carry loads of both physical and emotional nature, reducing the frequency and severity of sudden angina.

Anti-arrhythmic effectiveness is manifested by delivering the patient's body from arrhythmogenic symptoms, for example, such as increased cAMP content, increased palpitation, high intensity of the sympathetic nervous system, and symptoms of hypertension.

If the drug is used regularly and for more than one year, there is a decrease in the level of cholesterol in the blood plasma.

Pharmacokinetics

This drug shows high (up to 95%) absorbing characteristics, almost completely absorbed by the gastrointestinal mucosa. The maximum amount of the active component in the plasma (C _max ) can be found after one and a half to two hours after the drug is injected into the patient's body. A good pharmacokinetics of Egilok, stipulating 50% bioavailability of chemical compounds, was established. In the process of therapy and the regular intake of metoprolol, this parameter can reach 70%. Food products make it possible to increase the bioavailability of the drug by twenty to forty percent.

A fairly high index and volume distribution (V _d ) - 5.6 l / kg. Active active agent Egilok shows considerable ease in penetration through the placental and blood-brain barrier, but in breast milk of the nursing mother is observed in small amounts. Metoprolol very weakly binds to any protein enzyme of the blood. The efficiency of passable compounds is only about 12%.

The main elements of the drug are metabolized by biotransformation in the cell structure of the liver. Substances - the result of metabolism - do not already have the same pharmacological activity as their primary source.

The half-life (T _1/2 ) of substances and metabolites approximates between three and a half to seven hours. The complete withdrawal of metoprolol together with urine can be observed after 72 hours. In an unchanged state, approximately five percent of the drug is excreted.

If a history of the patient is diagnosed with a serious disruption in the functioning of the liver, the half-life is prolonged, and the bioavailability is increased, which requires an adjustment of the amount of the drug administered.

If a history of the patient is experiencing a failure in the functioning of the renal system, the systemic clearance of metoprolol and the half-life period remains virtually unchanged and dose adjustment is not required.

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Dosing and administration

If it is necessary to introduce metoprolol in the course of therapy, the method of administration and dose of the medicine is prescribed by the doctor depending on the diagnosed disease and the concomitant diseases present in the patient's anamnesis. For maximum effectiveness, a unit of the drug is recommended to be administered orally immediately after ingestion or directly with it. A tablet can be figured out if you swallow a whole is difficult, but you should not chew.

Secondary maintenance therapy of myocardial infarction involves the introduction during the day 200 mg of Egiloka, divided into two doses.

In case of preventive measures to prevent migraine attacks, as well as in case of diagnosis of cardiac rhythm failures in the supraventricular and angina pectoris, for adults, the drug is prescribed in the amount of 0.1 to 0.2 mg divided into two daily doses.

In the case of diagnosing arterial hypertension, the daily amount of the drug for adult patients is prescribed in an amount from 0.05 to 0.1 mg, divided into one or two approaches throughout the day. With medical necessity, the starting dosage can be gradually increased two-fold and brought to 0.1-0.2 mg.

If the patient suffers from pathological malfunctions in the heart, accompanied by an increased palpitation (tachycardia), metoprolol is attributed in a dosage of 100 mg taken twice a day (during the morning and before bedtime).

Older patients with kidney problems, even in the case of the necessary passage of hemodialysis, do not adjust the dose of Egiloca administered.

If the patient has problems with the liver, the amount of medication used is reduced - this is due to the inhibition of metoprolol metabolism.

Additional recommendations:

1. During the entire period of taking Egilok, the pressure and heart rate must be monitored. In the event that the number of heartbeats becomes below 50 beats per minute, you must immediately notify your doctor about this.
2. With prolonged cardiac dysfunction, Egiloc's entry is possible only after the heart reaches the compensation level.
3. The drug is withdrawn slowly (for ten days) with a gradual decrease in dosage. With a sharp termination of the input, there may be an increase in angina attacks, a rise in blood pressure (manifestation of withdrawal syndrome). In this period, it is necessary to control blood pressure.
4. When diabetes is required to control the amount of glucose in the plasma. If necessary, an adjustment of hypoglycemic drugs or / and insulin is necessary.
5. Elderly patients will not be superfluous will be a permanent control of the hepatic function. In the event of a malfunction or bradycardia, spasm of bronchial tubes, ventricular arrhythmia, falling BP, the doctor may decide to abolish Egiloc.
6. When pheochromocytoma, in parallel with Egilokom, one of the alpha-blockers must be administered.
7. In bronchial asthma, in parallel with Egilokom it is necessary to introduce one of the beta ₂ -adrenomimetics.
8. If the professional activity of a person who needs Egiloc's therapy is associated with the need for increased attention (working with dangerous moving mechanisms, driving vehicles), the drug should be administered only after the patient's individual response to the components of the drug has been established.
9. People who use contact lenses should not forget that taking Egiloka can lead to a decrease in the production of tear glands, a sufficient amount of fluid.
10. Metoprolol is able to mask the symptoms of tachycardia, and in diabetes mellitus the symptoms of hypoglycemia.
11. In case of anamnesis with depressive disorders, continuous monitoring of the patient's psychological state is recommended, if psychological problems are aggravated, metoprolol should be canceled.
12. If the patient is preparing for surgery, the surgeon must be informed about metoprolol therapy. Stop taking is not necessary. This will only affect the choice of an anesthesiologist in the selection of general anesthesia, which must be with minimal negative inotropic characteristics.
13. When the drug in question is combined with clonidine, after stopping the first, the second drug should be discontinued no earlier than a few days after metoprolol withdrawal in order to avoid withdrawal syndrome.

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Use Egilok during pregnancy

Due to the fact that the drug under consideration does not easily leak through the blood-brain and placental membrane, the use of Egilok during pregnancy is not desirable. The appointment of metoprolol is justified only if the real medical effectiveness of the drug for the mother is much higher than the likely negative that threatens the embryo.

If the attending physician still decided to use Egiloc during pregnancy, it is necessary to monitor the fetal heart condition throughout the course of treatment, and not to reduce control during the next two to three days after delivery. This is necessary in order not to miss the appearance of unpleasant and dangerous symptoms: arrhythmias, a drop in blood pressure, a lower heart rate, breathing problems, hypoglycemia.

Even though it is clinically confirmed that the components of Egiloc are not clinically confirmed in the mother's milk, during its therapeutic treatment during lactation, regular monitoring of the newborn's condition is necessary, since arrhythmia with a reduced heart rate is possible. Therefore, it is advisable in the period of breastfeeding to refrain from taking metoprolol, or, if therapy is necessary, to stop feeding the baby.

Contraindications

Any pharmacological agent is, first of all, a mixture of chemical compounds, which invariably affect not only the problem area of interest, but also the whole organism as a whole. Therefore, each drug has its own limitations to use. There are also
Contraindications to the use of Egilok.

• Increased susceptibility to metoprolol, other components of the drug or beta-blockers.
• Failure of the sinus pulse to pass through the sinoatrial connection (sinoatrial blocking).
• Decrease in intensity or complete cessation of electrical impulses between the ventricle and atrium (atrioventricular blocking of II or III severity).
• Sinus bradycardia due to a very low heart rate, whose quantitative indices show less than 50 rhythmic cuts per minute.
• Severe stage of bronchial asthma.
• Inadequacy of the cardiac muscle, which is at the level of failure of normal functioning.
• Reduction of the functions of the sinus node.
• Acute left ventricular failure of extreme severity, developing with myocardial infarction is a cardiological process that threatens the patient's life.
• Pathology of peripheral blood circulation in the severe stage.
• Intravenous administration of verapamil, in parallel with the drug in question.
• Patients who have not reached the age of 18 years, in the absence of the required amount of sufficiently reliable clinical results.
• The presence of a benign or malignant tumor in adrenal tissue (pheochromocytoma), if one of the alpha-blockers is not administered tandem.
• An acute period of myocardial infarction, accompanied by hypertension, in which the figures on the tonometer give indicators below 100 mm Hg. The heart rate is less than 45 rhythmic contractions for a minute and the intervals of combining ECG-signs with paroxysmal supraventricular tachycardia are more than 240 ms.

Increased caution in the appointment of Egilok should be shown in the presence of an anamnesis:

• Diabetes mellitus.
• Renal and / or hepatic dysfunction.
• Chronic obstructive pulmonary disease.
• Metabolic acidosis - lowering the pH of the blood due to loss of bicarbonate or the accumulation of acids.
• Thyrotoxicosis - a condition associated with an excess of thyroid hormones in the body.
• With allergic predisposition.
• Myasthenia gravis - a neuromuscular disease with a characteristic chronic-recurring or chronically-progressive course.
• Psoriasis is a dermatological disease affecting mainly the skin.
• Obliterating disease of peripheral vessels.
• In pregnancy or lactation.
• The elderly.

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Side effects Egilok

Preferably, the administration of the drug in question is well tolerated by the body, but there is still a chance of a response. Side effects of Egilok, are characterized by a mild symptomatology and can be cured independently when the drug is withdrawn. The manifestations shown below are confirmed by clinical data with metoprolol therapy. There are precedents, when the direct dependence of the injection and the emergence of secondary symptoms could not be determined. The listed symptoms are divided into three groups according to the likelihood of manifestation: often - more than ten percent of cases, moderately from one to ten percent, rarely - up to one percent, including single cases.

• Reaction of the cardiovascular system:
  • Often: failure of cardiac rhythm with a decreased heart rate, the problem of thermoregulation of the lower limbs, increased intensity of contractions of the heart muscles, orthostatic hypotension.
  • Moderately: short-term attack of cardiac dysfunction, acute left ventricular failure of extreme severity (developing with myocardial infarction), Lenegra's disease of the 1st degree.
  • Rare: tissue necrosis, conduction pathology, cardiac rhythm disturbance.
• CNS response:
  • Moderate: dizziness, decreased overall tone, pain in the head, muscle weakness, inhibition of mental and motor reactions, high fatigue.
  • Rarely: increased excitability, confusion, depressed state, sleep disturbance, sexual dysfunction, convulsions, problems with concentration and memory, nightmares and hallucinations, paresthesia and others.
• Reaction of the respiratory system:
  • Moderate: spasm of bronchi, shortness of breath, inflammation of mucous nasal passages.
• Reaction of the dermis:
  • Rarely: urticaria, hair loss, rash, itching, high sweating, a manifestation of hypersensitivity to ultraviolet rays, exacerbation of psoriasis, hyperemia of the skin, exanthema.
• The reaction of the gastrointestinal tract:
  • Often: nausea, pain symptoms in epigastrium, tight stools, diarrhea.
  • Rarely: gag reflex, liver dysfunction, change in taste preferences, decreased salivation - dryness of oral mucosa, hyperbilirubinemia.
• Other body reactions:
  • Rarely: conjunctivitis, thrombocytopenia, decreased clarity of the perception of the picture by the organ of vision, a decrease in the moisture of the skin of the eye, which leads to irritation of its surface, there may be a constant noise background in the organs of hearing, arthralgia, leukopenia, weight gain, pain symptoms in the joints and spine.

If side effects of Egiloc are manifested by one or more symptoms and intensity is gaining momentum, the introduction of metoprolol should be discontinued and notified to your doctor.

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Overdose

If the patient is accurate and fulfills all the requirements for intake and dosages prescribed in the instructions or adjusted by the attending doctor, the probability of obtaining high doses of the drug is minimized. But if the overdose, for whatever reason, has occurred, then its first signs, depending on the individual characteristics of the patient's body, can come from the moment of admission after twenty minutes - two hours.

Overdose can manifest itself with such symptoms:

• Intensive sinus bradycardia.
• Nausea, with severe manifestation, which may cause vomiting.
• Dizziness.
• Cyanosis of the skin in the triangle of the nose - the left edge of the upper lip - the right edge of the upper lip (cyanosis).
• Heart rate failure.
• Aching, burning and sharp pain in the heart (cardialgia).
• Arterial hypotension.
• Spasmodic muscle tissue bronchus.
• Short-term loss of consciousness.
• Ventricular extrasystole.
• Cardiogenic shock.
• Coma.
• AV-blockade, until the cardiac arrest.

If you have this symptom, you need to call an ambulance, and before she arrives you need to rinse your stomach. Therapy of an overdose of Egilok is symptomatic. 

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Interactions with other drugs

It is often enough to see an increase or, vice versa, oppression of the characteristics of a particular drug in a complex treatment, the protocol of which consists of two or more drugs. To achieve the maximum necessary efficiency, you need to know the consequences of the interaction of Egilok with other drugs.

If metoprolol therapy is prescribed with the use of inhalation anesthesia, the basic component of which is a hydrocarbon derivative, there is a very high risk of getting blocked myocardial contractility, and the likelihood of arterial hypotension increases.

With the simultaneous administration of oral Egiloc and intravenous verapamil, this combination of drugs can cause AV blockage and lead to complete cardiac arrest. Provoke a sharp drop in blood pressure can be a combination of the drug in question with a drug such as nifedipine.

With the introduction of MAO inhibitors, together with metoprolol, there may be a significant increase in hypotensive characteristics. To avoid this, you need to spread the medication with an interval of at least two weeks.

In the case of co-administration of metoprolol with ethanol, an increase in the blocking of receptor perception by the central nervous system is noted, the risk of a sharp drop in blood pressure is high. When ergot alkaloids are added to the protocol of treatment with the drug in question, the probability of malfunctions in the circulation of the peripheral system increases.

When tandem introduction of Egilok with one of such drugs as estrogens, indomethacin, stimulants of adrenaline beta group, theophylline, cocaine, as well as other non - steroidal anti - inflammatory drugs, the hypotensive characteristics of the former decrease.

Tandem hypoglycemic drugs, including insulin, and Egiloca increases the likelihood of hypoglycemia. Metoprolol with calcium channel blockers, diuretics, with antihypertensive drugs, nitrate-containing drugs can provoke arterial hypotension.

Application together with diltiazem, reserpine, clonidine, antiarrhythmic drugs (amiodarone), guanfacin, methyldopom provokes the intensity of reduction in the heart rate and blocks AV-conduction.

Such drugs as barbiturates or rifampicin, which are the causative agents of microsomal hepatic enzyme derivatives, activate the metabolism of the active substance Egilok. This fact reduces the amount of metoprolol entering the serum, which significantly reduces the therapeutic effectiveness of the drug in question. Inhibitors or "oppressors" of these same enzymes, for example, such as oral contraceptives, cimetidine, phenothiazine, on the contrary provoke an increase in the concentration of the active component of the drug Egilok.

Chemical compounds used in the role of contrasts during X-ray diffraction, containing iodine ions , increase the risk of anaphylaxis and the onset of systemic allergy symptoms.

The clearance of lidocaine decreases , while its quantitative component increases in blood. Such a clinical picture can be observed in the case of its tandem entry with Egilokom. Prolonging properties of indirect anticoagulants are enhanced.

It is not necessary to conduct test samples for allergic reactions with the use of irritating allergens during metoprolol therapy. The risk of getting anaphylaxis or a systemic allergy is great.

The intensity of the characteristics and the duration of their action of nondepolarizing muscle relaxants increases (their prolongation is enhanced).

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Storage conditions

Depending on how carefully the conditions of storage of Egilok are strictly observed, the duration of the effective work of the drug directly depends on maintaining its pharmacodynamic characteristics at the required therapeutic level.

 The conditions of storing Egilok are standard, and they can be attributed to many other medicinal products.

1. The temperature in the room where the medicine is stored should be between 15 ° and 25 ° C.
2. The drug should not be within reach of children.
3. The medicine should not be located in a damp room and be exposed to direct sunlight.

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Shelf life

If all the conditions for storing the medicinal product of Egilok are fulfilled, the expiry date and effective use are extended by five years. If the storage conditions are not observed, the period of the therapeutic characteristics necessary for treatment is significantly reduced. After the expiration date, the use of the drug is not recommended.