Egilok

The Hungarian pharmaceutical plant EGIS produces the innovative drug Egilok – a highly effective cardioselective beta ₁ -adrenoblocker designed to solve many problems associated with pathological changes in the functioning of the cardiovascular system.

Indications Egilok

The drug was initially developed to relieve cardiac pathologies. Hence the indications for the use of Egilok:

• Monotherapy in the treatment of arterial hypertension, as well as tandem work with other antihypertensive agents, antihypertensive drugs to relieve the same problem.
• Abnormal heartbeat in the supraventricular region.
• Ischemic heart pathologies, such as myocardial infarction, are included in the treatment protocol of complex therapy.
• Ventricular extrasystole is a disturbance of the heart rhythm, which is a premature contraction of the ventricles that occurs out of sequence.
• Prevention of angina attacks.
• Hyperthyroidism is an endocrinological syndrome caused by hyperfunction of the thyroid gland.
• Preventive measures to prevent migraine attacks.
• Functional disturbances in the work of 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 included in Egilok: MCC (microscopic crystalline cellulose), sodium carboxymethyl starch (type A), silicon dioxide (belonging to anhydrous colloids), povidone (K90), magnesium stearate.

Tablet form of release, one unit of the drug contains metoprolol tartrate - tablets of different dosages of the active substance are distinguished: a drug with 0.025 mg of the active substance, tablets containing 0.050 mg of metoprolol, as well as a drug with a concentration of 0.1 mg of the active chemical compound. The calculation of the dosage is carried out on the weight of dry matter.

The appearance of the medicinal unit is a white tablet, of a classic round shape, with two-sided truncation of the corners. On one of the planes, the embossing "E435" (at an active component concentration of 0.025 mg), "E434" (at an active component concentration of 50 mg) and "E432" (at an active component concentration of 0.1 mg) is visible.

Packaging material:

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

Pharmacodynamics

Cardioselective β-blockers of receptors of adrenergic substances (proteins of the outer cell membrane that recognize and bind adrenaline) have no effect on the increase of the refractory period, and do not block abnormal ectopic activity. They also do not have the ability to suppress beta-receptors from the action of hormones that “excite” them, but under certain conditions they are able, on the contrary, to stimulate them, showing the absence of sympathomimetic activity. Due to such characteristics, the pharmacodynamics of Egilok shows good antihypertensive, antiarrhythmic and antianginal properties.

By slightly inhibiting β ₁ -adrenoreceptors of the heart, metoprolol tartrate reduces irritation with the help of catecholamines, which stimulates the formation of the enzymatic component of cAMP from adenosine triphosphate (ATP). The pharmacodynamics of Egilok is aimed at reducing the rate of intracellular flow of calcium ions (Ca ²⁺ ). Metoprolol produces an antagonistic effect of chronotropic, inotropic, bathmotropic, dromotropic nature. Such properties allow it to reduce the rate of heart rate (HR), reduce 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 one to three days, this level returns to its original value, and continued use of the drug leads to a further decrease in this indicator.

The antihypertensive effect of the drug is due to a decrease in the renin binding capacity, a decrease in the heart's pumping function, and the likelihood of venous blood return to the heart. This characteristic of the drug allows at least partially blocking 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 barium receptors, making them amorphous when blood pressure decreases, which ultimately leads to the suppression of peripheral systemic effects. Egilok reduces high blood pressure, whether the patient's body is under physical exertion, stress, or at rest.

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

The antianginal properties of the drug are characterized by prolongation of diastole and correction of the throughput of vessels and myocardial cells, which normalizes the supply of oxygen to tissues, stabilizes the heart rate and the level of contractility. The antianginal characteristics of Egilok are also manifested by a decrease in the susceptibility of the myocardium to the stress of the connection of organs and tissues with the central nervous system using nerve receptors (sympathetic innervation). This indicator makes it possible to more easily tolerate physical and emotional stress, reducing the frequency and severity of sudden angina.

Antiarrhythmic efficacy is demonstrated by ridding the patient's body of arrhythmogenic symptoms, such as increased cAMP levels, increased heart rate, high intensity of the sympathetic nervous system, and symptoms of arterial hypertension.

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

Pharmacokinetics

The drug in question shows high (up to 95%) absorption characteristics, being almost completely absorbed by the gastrointestinal mucosa. The maximum amount of the active component in the plasma (C _max ) can be found already after one and a half to two hours after the drug is administered to the patient. Egilok has good pharmacokinetics, which determines 50% bioavailability of chemical compounds. During therapy and 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.

Quite high index and volume of distribution (V _d ) - 5.6 l/kg. The active substance Egilok shows considerable ease in penetrating the placental and blood-brain barriers, but in the breast milk of a nursing mother it is observed in small quantities. Metoprolol binds very weakly to any protein enzyme in the blood. The efficiency of the passed compounds is only about 12%.

The main elements of the drug are metabolized by biotransformation in the cellular structure of the liver. The substances - the result of metabolism - no longer have the same pharmacological activity as their original source.

The half-life (T _1/2 ) of substances and metabolites is approximately three and a half to seven hours. Complete excretion of metoprolol in the urine can be observed after 72 hours. Approximately five percent of the drug is excreted unchanged.

If the patient has a history of severe liver dysfunction, the half-life is prolonged and bioavailability increases, which requires adjustment of the amount of drug administered.

If the patient has a history of renal dysfunction, the systemic clearance of metoprolol and the half-life remain virtually unchanged and no dose adjustment is required.

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Dosing and administration

If it is necessary to introduce metoprolol into the course of therapy, the method of administration and dosage of the drug are prescribed by the doctor depending on the diagnosed disease and concomitant diseases present in the patient's medical history. For maximum effectiveness, it is recommended to administer a unit of the drug orally immediately after a meal or directly with it. The tablet can be bitten if it is difficult to swallow whole, but it should not be chewed.

Secondary maintenance therapy for myocardial infarction involves the administration of 200 mg of Egilok throughout the day, divided into two doses.

For preventive measures to prevent migraine attacks, as well as in the case of diagnosing heart rhythm disturbances in the supraventricular region and angina pectoris, for adult patients the drug is prescribed in an amount of 0.1 to 0.2 mg, divided into two daily doses.

In case of arterial hypertension diagnosis, the daily dose of the drug for adult patients is prescribed in the amount of 0.05 to 0.1 mg, divided into one or two approaches during the day. If medically necessary, the starting dosage can be gradually doubled and brought to 0.1 - 0.2 mg.

If the patient suffers from pathological disturbances in the functioning of the heart, accompanied by increased heart rate (tachycardia), metoprolol is prescribed in a dosage of 100 mg, taken twice a day (in the morning and before bedtime).

In elderly patients with kidney problems, even in the case of necessary hemodialysis, the dose of Egilok administered does not require adjustment.

If the patient has liver problems, 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, it is necessary to monitor the blood pressure and heart rate. If the heart rate drops below 50 beats per minute, you must immediately notify your doctor.
2. In case of long-term cardiac dysfunction, Egilok administration is possible only after the heart has reached the compensation level.
3. The drug is withdrawn slowly (over ten days) with a gradual reduction in dosage. If the drug is stopped abruptly, an increase in angina attacks and an increase in blood pressure (manifestation of withdrawal syndrome) may occur. During this period, blood pressure monitoring is necessary.
4. In diabetes mellitus, it is necessary to control the amount of glucose in the plasma. If necessary, it is necessary to adjust hypoglycemic drugs and/or insulin.
5. Elderly patients will benefit from constant monitoring of liver function. In case of failure or occurrence of bradycardia, bronchial spasm, ventricular arrhythmia, or a drop in blood pressure, the doctor may decide to discontinue Egilok.
6. In case of pheochromocytoma, one of the alpha-blockers must be administered in parallel with Egilok.
7. In case of bronchial asthma, in parallel with Egilok it is necessary to administer one of the beta ₂ -adrenergic agonists.
8. If the professional activity of a person who requires Egilok therapy is associated with the need for increased attention (working with dangerous moving mechanisms, driving a vehicle), the drug should be prescribed only after the patient’s individual reaction to the components of the drug has been established.
9. People who use contact lenses should remember that taking Egilok may reduce the production of sufficient amounts of fluid by the lacrimal glands.
10. Metoprolol can mask the symptoms of tachycardia, and in diabetes mellitus, the symptoms of hypoglycemia.
11. In case of a history of depressive disorders, constant monitoring of the patient's psychological state is recommended; if psychological problems worsen, metoprolol should be discontinued.
12. If the patient is preparing for surgery, the surgeon must be informed about metoprolol therapy. It is not worth stopping the intake. This will only affect the choice of the anesthesiologist in selecting general anesthesia, which must have minimal negative inotropic characteristics.
13. When using the drug in question together with clonidine, after stopping the administration of the first, the second drug should be discontinued no earlier than a few days after the withdrawal of metoprolol, in order to avoid withdrawal syndrome.

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Use Egilok during pregnancy

Due to the fact that the drug in question easily penetrates the blood-brain and placental membranes, the use of Egilok during pregnancy is not advisable. The prescription of metoprolol is justified only if the real medical effectiveness of the drug for the mother is significantly higher than the probable negative effect that threatens the embryo.

If the attending physician has nevertheless decided to use Egilok during pregnancy, it is necessary to monitor the fetus's heart condition throughout the entire 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: arrhythmia, a drop in blood pressure, a decreased heart rate, breathing problems, hypoglycemia.

Even though the clinical evidence of minor penetration of Egilok components into mother's milk has been confirmed, regular monitoring of the newborn's condition is necessary during therapeutic treatment during lactation, as arrhythmia with a decreased heart rate may occur. Therefore, it is advisable to refrain from taking metoprolol during breastfeeding, or, if therapy is necessary, stop breastfeeding the baby.

Contraindications

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

• Hypersensitivity to metoprolol, other components of the drug or beta-blockers.
• Failure of the sinus impulse to pass through the sinoatrial junction (sinoatrial block).
• Decreased intensity or complete cessation of the passage of electrical impulses between the ventricle and the atrium (atrioventricular block grade II or III).
• Sinus bradycardia is caused by a very low heart rate, the quantitative indicators of which show less than 50 rhythmic contractions per minute.
• Severe stage of bronchial asthma.
• Insufficiency of the heart muscle, which is at the level of failure of normal functioning.
• Decreased function of the sinus node.
• Acute left ventricular failure of extreme severity, developing during myocardial infarction, is a cardiological process that threatens the patient’s life.
• Severe pathology of peripheral circulation.
• Intravenous administration of verapamil, in parallel with the drug in question.
• For patients under 18 years of age, due to the lack of the necessary volume of sufficiently reliable clinical results.
• The presence of a benign or malignant tumor in the adrenal tissue (pheochromocytoma), if one of the alpha-blockers is not administered in tandem.
• Acute period of myocardial infarction, accompanied by arterial hypertension, in which the numbers on the tonometer show values below 100 mm Hg, heart rate less than 45 rhythmic contractions per minute and intervals of combination of ECG signs with paroxysmal supraventricular tachycardia greater than 240 ms.

Increased caution should be exercised when prescribing Egilok if there is a history of:

• Diabetes mellitus.
• Renal and/or hepatic dysfunction.
• Chronic obstructive pulmonary disease.
• Metabolic acidosis - a decrease in blood pH due to loss of bicarbonate or accumulation of acids.
• Thyrotoxicosis is a condition associated with excess thyroid hormones in the body.
• In case of allergic predisposition.
• Myasthenia is a neuromuscular disease with a characteristic chronically relapsing or chronically progressive course.
• Psoriasis is a dermatological disease that primarily affects the skin.
• Obliterating disease of peripheral vessels.
• During pregnancy or lactation.
• For elderly people.

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Side effects Egilok

Mostly, the introduction of the drug in question is well tolerated by the body, but there is still a possibility of a response. Side effects of Egilok are characterized by mild symptoms and can be stopped on their own when the drug is discontinued. The manifestations voiced below are confirmed by clinical data during therapy using metoprolol. There are precedents when a direct relationship between the introduction of the drug and the appearance of side symptoms could not be determined. The listed symptoms are divided into three groups by the probability of occurrence: often - more than ten percent of cases, moderately - from one to ten percent, rarely - up to one percent, including isolated cases.

• Cardiovascular response:
  • Common: cardiac arrhythmia with decreased heart rate, problems with thermoregulation of the lower extremities, increased intensity of contractions of the heart muscles, orthostatic hypotension.
  • Moderate: short-term attack of cardiac dysfunction, acute left ventricular failure of extreme severity (developing during myocardial infarction), Lenegre's disease stage I.
  • Rare: tissue necrosis, conduction pathology, cardiac arrhythmia.
• CNS response:
  • Moderate: dizziness, decreased overall tone, pain in the head, muscle weakness, inhibition of mental and motor reactions, high degree of fatigue.
  • Rare: increased excitability, confusion, depression, sleep disturbance, sexual dysfunction, seizures, problems with concentration and memory, nightmares and hallucinations, paresthesia and others.
• Respiratory system response:
  • Moderate: bronchospasm, shortness of breath, inflammation of the nasal mucosa.
• Dermal reaction:
  • Rare: urticaria, hair loss, rash, itching, excessive sweating, manifestation of increased sensitivity to ultraviolet rays, exacerbation of psoriasis, hyperemia of the skin, exanthema.
• Gastrointestinal reaction:
  • Common: nausea, pain in the epigastrium, hard stool, diarrhea.
  • Rare: vomiting reflex, liver dysfunction, change in taste preferences, decreased salivation - dry oral mucosa, hyperbilirubinemia.
• Other reactions of the body:
  • Rare: conjunctivitis, thrombocytopenia, decreased clarity of vision, decreased moisture in the eye membrane, which leads to irritation of its surface, constant background noise in the hearing organs, arthralgia, leukopenia, weight gain, pain symptoms in the joints and spine may appear.

If the side effects of Egilok manifest themselves in one or more symptoms and the intensity increases, the administration of metoprolol should be stopped and your doctor should be informed.

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Overdose

If the patient is careful and follows all the requirements for taking and dosage prescribed in the instructions or adjusted by the attending physician, then the probability of receiving high doses of the drug is reduced to a minimum. But if an overdose, for whatever reason, occurs, then its first signs, depending on the individual characteristics of the patient's body, can occur from the moment of taking it after twenty minutes to two hours.

An overdose may manifest itself with the following symptoms:

• Intense sinus bradycardia.
• Nausea, which, if severe, may lead to vomiting.
• Dizziness.
• Bluish discoloration of the skin in the triangle nose – left edge of the upper lip – right edge of the upper lip (cyanosis).
• Heart rhythm disturbance.
• Aching, burning and sharp painful sensations in the heart area (cardialgia).
• Arterial hypotension.
• Spasm of the bronchial muscle tissue.
• Brief loss of consciousness.
• Ventricular extrasystole.
• Cardiogenic shock.
• Coma.
• AV block, up to complete cardiac arrest.

If such symptoms appear, it is necessary to call an ambulance, and before it arrives, the stomach must be washed. Therapy for an overdose of Egilok is symptomatic.

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Interactions with other drugs

Quite often, one can observe an increase or, conversely, suppression of the characteristics of a particular drug during complex treatment, the protocol of which consists of two or more drugs. To achieve the maximum required efficiency, one must know the consequences of Egilok interaction with other drugs.

If, against the background of metoprolol therapy, surgical intervention is prescribed using inhalation anesthesia, the basic component of which is a hydrocarbon derivative, the risk of getting a blockade of the contractile capabilities of the myocardium is very high, and the likelihood of arterial hypotension also increases.

When Egilok is administered orally and verapamil is administered intravenously, this combination of drugs can cause AV block and lead to complete cardiac arrest. A sharp drop in blood pressure can be provoked by a combination of the drug in question with a drug such as nifedipine.

When MAO inhibitors are administered together with metoprolol, a significant increase in hypotensive characteristics may be observed. To avoid this, it is necessary to separate the administration of the drug with an interval of at least two weeks.

In case of combined administration of metoprolol with ethanol, an increase in blocking of receptor perception by the central nervous system is noted, the risk of a sharp drop in arterial pressure is high. When introducing ergot alkaloids into the treatment protocol with the drug in question, the likelihood of disruptions in the blood flow of the peripheral system increases.

When Egilok is administered in tandem with one of the following drugs: estrogens, indomethacin, beta-adrenaline stimulants, theophylline, cocaine, as well as other non-steroidal anti-inflammatory drugs, a decrease in the hypotensive characteristics of the former is observed.

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

Use in combination with diltiazem, reserpine, clonidine, antiarrhythmic drugs (amiodarone), guanfacine, methyldopa provokes an intense decrease in heart rate and blocks AV conduction.

Such drugs as barbiturates or rifampicin, which are stimulators of microsomal liver 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 "inhibitors" of these same enzymes, 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 as contrast agents in X-ray imaging, containing iodine ions, increase the risk of developing anaphylaxis and the appearance of systemic allergy symptoms.

Lidocaine clearance decreases, while its quantitative component in the blood increases. Such a clinical picture can be observed in the case of its tandem administration with Egilok. The prolonging properties of indirect anticoagulants are enhanced.

Allergy testing with irritating allergens should not be performed during metoprolol therapy. There is a high risk of anaphylaxis or systemic allergy.

The intensity of the characteristics and duration of their action of non-depolarizing muscle relaxants increases (their prolongation increases).

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Storage conditions

The duration of the effective operation of the drug and the maintenance of its pharmacodynamic characteristics at the required therapeutic level directly depend on how carefully the storage conditions of Egilok are observed.

The storage conditions for Egilok are standard and can be applied 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 kept within the reach of children.
3. The medicine should not be placed in a damp room or exposed to direct sunlight.

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Shelf life

If all storage conditions of the medicinal product Egilok are met, the shelf life and effective use is extended to five years. If the storage conditions are not met, the period of therapeutic characteristics necessary for treatment is significantly reduced. After the expiration of the final shelf life, use of the drug is not recommended.