Two-component drug for hypertension "Equator". Antihypertensive tablets for blood pressure Equator: reviews, price, analogues and recommendations for use Release form and composition of the product

Essential hypertension (patients for whom combination therapy is indicated).

Contraindications Equator tablets 5mg+10mg

Hypersensitivity to any of the components of the drug or to other ACE inhibitors and dihydropyridine derivatives; history of angioedema, including those caused by the use of other ACE inhibitors, hereditary or idiopathic angioedema; hemodynamically significant aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy; severe arterial hypotension; cardiogenic shock; heart failure after acute myocardial infarction (within the first 28 days); unstable angina (with the exception of Prinzmetal angina); pregnancy; lactation period; age under 18 years (due to the lack of data on the effectiveness and safety of the drug in this age group) bilateral renal artery stenosis, stenosis of the artery of a single kidney. With caution: cerebrovascular diseases (including cerebrovascular insufficiency), coronary heart disease, severe bradycardia, tachycardia, chronic heart failure in the stage of decompensation, mild or moderate arterial hypotension, severe autoimmune diseases (including scleroderma, systemic lupus erythematosus), suppression of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, condition after kidney transplantation, sodium-restricted diet, old age, renal and/or liver failure, sick sinus syndrome (SSNS), arterial hypotension. Use during pregnancy and lactation: the drug is not recommended for use during the entire period of pregnancy, since the risk of teratogenesis and fetotoxicity (reduced renal function, oligohydramnios, delayed ossification of the skull) and neonatal toxicity (renal failure, hypotension, hyperkalemia) cannot be excluded. . There are no data from well-controlled clinical studies on the use of the drug in pregnant women. Once pregnancy is detected, the drug should be stopped immediately. Patients planning a pregnancy should consult a doctor so that he or she can recommend medications with proven safety during pregnancy. Equator is not recommended for use during lactation, since lisinopril can be excreted in breast milk. There is no information about the penetration of amlodipine into breast milk.

Directions for use and dosage Equator tablets 5mg+10mg

Inside, regardless of food intake. The recommended dose is one Equator tablet daily. The maximum daily dose is one tablet. Patients with renal insufficiency: To determine the optimal starting and maintenance dose for patients with renal insufficiency, doses must be titrated and determined on an individual basis using lisinopril and amlodipine separately. Equator is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 10 mg, respectively. During treatment with the drug, it is necessary to monitor renal function, potassium and sodium levels in the blood serum. If renal function deteriorates, the drug should be discontinued and replaced with single medications in adequate doses. Patients with hepatic impairment: The elimination of amlodipine may be delayed in patients with impaired liver function. Clear recommendations on the dosage regimen in such cases have not been established, so the drug should be prescribed with caution in patients with liver failure. Elderly patients (over 65 years of age): in clinical studies on the effectiveness and safety of amlodipine or lisinopril in elderly patients, no changes were detected. To determine the optimal maintenance dose, it is necessary to determine the dosage regimen on an individual basis, using lisinopril and amlodipine separately. Equator is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 10 mg, respectively.

Equator tablets are a combination drug for the treatment of arterial hypertension. Medicines containing two components act much more effectively: they quickly cope with hypertension, maintaining blood pressure levels at the proper level. Below are instructions for using Equator blood pressure tablets, reviews of the drug, its price and analogues.

"Equator" is available in the form of round, flat tablets of almost white color. The edge of each dragee is marked with a chamfer, on one side there is a mark, and on the other there is an engraving in the form of the letters A and L. One tablet contains lisinopril dihydrate 10.88 mg and amlodipine besylate 6.94 mg. In addition, the composition includes additional components: microcrystalline cellulose, magnesium stearate and carboxymethyl starch type A. Equator tablets are placed in blisters of 10 pieces and in cardboard packaging. The box may contain 1-3 blisters.

You can also purchase the medicine in a larger dosage. One tablet contains lisinopril dihydrate 21.76 mg, amlodipine besylate 13.88 mg. The drug in this dosage is marked with the engraving CF3.

Pharmacological action, pharmacodynamics

The combined blood pressure remedy contains two active ingredients – amlodipine and lisinopril. Since the medicinal substances act in combination, the effect of therapy is achieved much faster and lasts longer.

Lisinopril

This active ingredient is an ACE inhibitor. It helps reduce the levels of aldosterone and angiotensin II, while at the same time increasing the levels of bradykinin, one of the vasodilatory mediators. Lisinopril reduces the overall resistance of the cardiovascular system and lowers blood pressure. At the same time, the pressure in the pulmonary capillaries becomes significantly lower, and the blood flow in the kidneys increases.

The drug also helps to dilate arteries and improves blood flow into the myocardium. With long-term course use, cardiac output increases, blood flow in the kidneys increases, and the volume of hypertrophied myocardium decreases. The body's tolerance to physical activity in patients with heart failure, as well as life expectancy, significantly increases. Lisinopril helps reduce albuminuria and does not affect blood glucose levels in patients with diabetes mellitus.

A decrease in blood pressure is observed an hour after the first dose of the drug. The maximum effect is achieved after 6 hours and lasts up to a day. The effectiveness of the drug does not decrease with long-term therapy, and if the drug is abruptly stopped, “withdrawal syndrome” does not occur.

Amlodipine

One of the third generation slow calcium channel blockers. It reduces the likelihood of developing angina pectoris and has a powerful hypotensive effect. As a result of taking the drug, the entry of calcium into the cells of myocardial tissue, as well as into the smooth muscle of the vascular wall, is excluded. There is a decrease in the tone of smooth muscles of arterioles, vascular resistance, and, as a result, a decrease in blood pressure.

The active substance, among other things, has an antianginal effect by reducing the load of arteries and arterioles, as well as reducing afterload. As a result, the patient’s body tolerates physical activity much easier, the number of angina attacks decreases, and the need for nitroglycerin is significantly reduced. Healthy and ischemic areas of the myocardium are well supplied with oxygen due to the expansion of coronary arterioles and arteries. The conductivity and contractility of the myocardium remains unchanged.

Amlodipine also has other properties:

• has a long-term hypotensive effect;
• helps reduce left ventricular hypertrophy;
• reduces sclerotic changes in blood vessels;
• has a cardioprotective effect in case of coronary artery disease.

Long-lasting action is ensured due to slow absorption and excretion, wide distribution in the body. Therefore, you can take the medicine only once in 24 hours. The effect of the drug is not accompanied by a sharp decrease in blood pressure.

In addition, amlodipine has a mild natriuretic effect, increases glomerular filtration, and reduces platelet aggregation. It can be prescribed to patients with bronchial asthma, gout, and diabetes mellitus, since the drug does not have a negative effect on metabolic processes in the body.

When amlodipine is taken simultaneously with lisinopril, it becomes possible to prevent the development of negative reactions provoked by any active substance. For example, a calcium channel blocker may cause fluid and sodium retention in the body by dilating the arteries. This promotes activation of the renin-angiotensin-aldosterone system, and the ACE inhibitor lisinopril blocks the development of this process and normalizes the body’s response to salt load.

Pharmacokinetics

After a single oral dose, the maximum amount of lisinopril in the blood is reached after approximately 6 hours. Absorption is 60%, bioavailability is not higher than 29%. Metabolism does not occur; the drug is excreted unchanged in the urine. After more than half of lisinopril is eliminated, its fraction associated with ACE is released - this is what ensures a long-term therapeutic effect. Seeps through the placental and blood-brain barriers. For patients with renal failure, the drug is prescribed in reduced doses due to impaired excretory functionality of the kidneys.

Amlodipine after a single oral dose is absorbed from the gastrointestinal tract quite slowly and almost completely (about 90%). Its maximum amount in the blood is observed after 6-10 hours. Normal concentration is achieved after a week of regular daily use. Bioavailability – 65-80%. The binding rate to plasma proteins is about 96%. Amlodipine is metabolized in the liver, most of it becomes an inactive metabolite. In unchanged form, the drug is excreted in the urine (10%), in the form of metabolites - 60%. About 25% of metabolites are excreted in bile through the intestines. May pass into breast milk.

The time to reach the maximum amount of Amlodipine in the blood in elderly and young patients is approximately the same, therefore, when prescribing, dose adjustment is not required for elderly patients. Negative reactions as a result of interaction between the active substances of “Equator” included in the drug are unlikely. Eating does not affect their absorption. Due to the long-term circulation of amlodipine and lisinopril in the body, a single dose of the drug per day is possible.

Indications for use

Equator tablets are used for arterial hypertension (high blood pressure) in patients for whom combination therapy is indicated. Used to treat hypertension in both young and old people. It is possible to prescribe the drug to patients with diabetes mellitus and other metabolic disorders.

Contraindications

Equator tablets are used with extreme caution in patients with bilateral stenosis of the renal arteries or stenosis of the vessels of a single kidney and other disorders of this organ. Caution is also required when prescribing this drug to patients with the following diseases or conditions:

• tachycardia;
• bradycardia;
• cerebrovascular accidents;
• other cerebrovascular disorders;
• cardiac ischemia;
• heart and coronary failure;
• autoimmune systemic pathologies of connective tissue;
• diabetes;
• acute myocardial infarction;
• hypovolemia (decreased blood volume).

Instructions for use

The drug "Equator" for blood pressure should be taken orally, at any time of the day, regardless of meals, with water or other liquid. The recommended dose is no more than 1 tablet per day, the maximum is 1 tablet per day.

The initiation of therapy may be associated with the development of arterial hypotension, which usually appears in patients with fluid and electrolyte imbalances. Typically, such abnormalities occur as a result of previous treatment with diuretics, so such medications should be discontinued several days before starting therapy. If discontinuation of diuretics is not possible, you should start taking Equator tablets with ½ tablet. once a day and always under the supervision of a doctor to prevent the occurrence of persistent arterial hypotension.

To determine the optimal daily dose for patients with renal failure, an individual approach is required. Using amlodipine and lisinopril separately, treatment tactics are built, starting with low doses. During treatment with Equator tablets, kidney function and sodium and potassium levels in the blood serum should be monitored. If deterioration in kidney function is observed, the drug must be discontinued or replaced with other drugs.

If the patient has impaired liver function, the elimination of amlodipine from the body may be slowed down. There are no clear dosage recommendations, so Equator is prescribed to such patients with caution and under medical supervision.

Side effects

The incidence of adverse reactions in patients taking Equator tablets is almost the same as in those who took one of the active ingredients. Mostly mild transient (quickly passing) cases were observed and did not require discontinuation of the drug. The most common negative phenomena are headache (about 8%), cough (not more than 5%), dizziness (3%).

Lisinopril

Side effects from the hematopoietic and immune systems occur very rarely. The main observed disorders were bone marrow hematopoiesis, leukopenia, thrombocytopenia, agranulocytosis, lymphadenopathy, and anemia. The appearance of positive indicators for antinuclear antibodies and the development of vasculitis are possible. Very rarely, metabolic disorders develop - hypoglycemia.

Among disorders of the nervous and mental systems, headaches, dizziness, and paresthesia are noted in one out of ten cases. Much less often - sleep disturbances, confusion, pathological mental states.

From the digestive system, liver and biliary tract, the following may occur: often - vomiting, diarrhea; rarely - abdominal pain, dry mouth, severe thirst; very rarely - pancreatitis, jaundice, liver failure.

Allergic reactions: infrequently, angioedema, skin rash, itching, less often - psoriasis, alopecia, urticarial rash. In isolated cases, the occurrence of erythema multiforme, epidermal necrolysis, and pemphigus vulgaris was noted.

In addition to the listed negative phenomena, in rare and very rare situations the following pathologies may develop:

Amlodipine

The nervous system often develops drowsiness, headaches, and systemic dizziness. In more rare cases, paresthesia has been observed, hand tremors have been noted, and migraine pain has occurred. Also, when taking Equator tablets, visual disturbances were noticed: conjunctivitis, diplopia, pain in the eyeballs.

The cardiovascular system also does not always respond positively to taking the drug. Quite often, increased heartbeat and skin hyperemia were noted. A sharp decrease in blood pressure and the development of orthostatic hypotension are possible. In rare cases, the following were recorded: ventricular tachycardia, myocardial infarction, arrhythmia, atrial fibrillation.

When taking Equator tablets, problems with the digestive system may occur. Abdominal pain occurs quite often, less often - diarrhea, vomiting, dyspepsia, constant thirst, increased appetite. In isolated cases - pancreatitis, cholestasis, gastritis, jaundice, hepatitis.

In addition, you may develop:

Overdose

In case of accidental ingestion of high doses of the drug "Equator", a strong decrease in arterial systolic pressure is possible, with the development of tachycardia and shock. In some cases, death is possible as a result of persistent arterial hypotension.

Treatment includes:

In this case, monitoring of blood and urine tests is necessary, and intravenous administration of calcium gluconate is possible. Hemodialysis with excessive use of amlodipine is ineffective, but lisinopril can be removed from the body in this way.

Interaction with other drugs

Simultaneous use of Equator tablets and potassium-sparing tablets can lead to hyperkalemia. In this case, mandatory monitoring of potassium in the blood serum is necessary.

The combination of the drug with diuretics can enhance the hypotensive effect. When taking Equator simultaneously with non-steroidal anti-inflammatory drugs, the antihypertensive effect of lisinopril is reduced. Antiepileptic drugs, rifampicin, and drugs containing St. John's wort can reduce the amount of amlodipine in the blood.

Interaction with alcohol

Ethanol increases the hypotensive effect of amlodipine and lisinopril.

Taking the drug during pregnancy and lactation

Carrying a child and breastfeeding are periods when taking Equator is contraindicated. If pregnancy is detected, the drug should be stopped immediately. Taking lisinopril in later stages may contribute to the development of hypotension, hyperkalemia, and renal failure in the fetus. The drug also helps reduce the amount of amniotic fluid, which leads to bone deformations in the fetus.

One of the features of amlodipine can be considered its ability to pass into breast milk, which is why, if there is an urgent need to use the drug "Equator", breastfeeding should be completely abandoned. Data on the penetration of lisinopril and its derivatives into breast milk have not been recorded.

Childhood

In children (under 18 years of age), Equator is not prescribed, since there is no sufficient experimental data, and the effectiveness and safety of the drug has not been proven.

special instructions

A sharp decrease in systolic blood pressure is often observed in patients with reduced blood volume or sodium as a result of taking diuretics. To avoid the development of unpleasant symptoms, restoration of sodium or fluid loss should be carried out before starting treatment with Equator. After taking the first carefully selected dose, blood pressure monitoring is necessary.

In patients with kidney problems taking this drug, an increase in the concentration of urea and creatinine in the blood is often recorded. If your kidney condition worsens, you should stop taking Equator.

In case of angioedema, as well as other anaphylactic reactions, discontinuation of the drug is also necessary. For patients with liver failure, the drug is prescribed with extreme caution, carefully selecting the dose, assessing the possible risks and benefits expected from its use.

Caution is also required when prescribing the drug if the patient is diagnosed with:

• left ventricular obstruction;
• mitral valve stenosis;
• vascular collagenosis;
• unproductive, exhausting cough;
• metabolic acidosis;
• heart failure.

During Equator therapy, constant weight monitoring is required, as well as regular monitoring by a dentist. This is necessary to prevent hyperplasia and bleeding gums.

When operating machinery and vehicles while taking Equator tablets, caution should be exercised, especially at the beginning of therapy. There is a high risk of developing hypotension and dizziness.

Analogs

Two drugs are completely synonymous with the drug “Equator”: “Equacard”, “Eclamise”. They contain the same active substances, only differences in dosage are possible. If it is impossible to use Equator tablets, it is possible to prescribe analogues, also used to normalize blood pressure. The most common are:

Compound

Each tablet contains:

Tablets 10 mg/5 mg

Active ingredients: lisinopril - 10.00 mg (in the form of lisinopril dihydrate 10.88 mg), amlodipine - 5.00 mg (in the form of amlodipine besylate 6.94 mg);

Excipients:

Tablets 20 mg/5 mg

Active ingredients: lisinopril - 20.00 mg (in the form of lisinopril dihydrate 21.76 mg), amlodipine - 5.00 mg (in the form of amlodipine besylate 6.94 mg);

Excipients: magnesium stearate; sodium starch glycolate (type A); microcrystalline cellulose, type 12; microcrystalline cellulose, type 101.

Tablets 20 mg/10 mg

Active ingredients: lisinopril - 20.00 mg (in the form of lisinopril dihydrate 21.76 mg), amlodipine - 10.00 mg (in the form of amlodipine besylate 13.88 mg);

Excipients: magnesium stearate; sodium starch glycolate (type A); microcrystalline cellulose, type 12; microcrystalline cellulose, type 101.

Description

Tablets 10 mg/5 mg

White or almost white round flat tablets with a bevel, with a score on one side and with an engraving “A+L” on the other. Diameter: 8mm ± 0.1mm.

The score is intended solely to make the tablet easier to break and swallow and not to divide the tablet into equal doses.

Tablets 20 mg/5 mg

White or off-white, round, biconvex tablets engraved “CF2” on one side and unengraved on the other side.

Tablets 20 mg/10 mg

White or off-white, round, biconvex (R: 13 mm) tablets, engraved “CF3” on one side, unengraved on the other side. Diameter: 11 ± 0.1 mm.

Pharmacotherapeutic group

ACE inhibitors and blockers of “slow” calcium channels. ATX code: С09ВВ03 .

Pharmacological properties

Pharmacodynamics

Equator® tablets 10 mg/5 mg, Equator® tablets 20 mg/5 mg and Equator® tablets 20 mg/10 mg are combination drugs with fixed doses of the active ingredients: lisinopril and amlodipine.

Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces total peripheral vascular resistance (TPVR), blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure (CHF). Dilates arteries more than veins. Some effects are explained by effects on the tissue renin-angiotensin-aldosterone system (RAAS).

With long-term use, hypertrophy of the myocardium and the walls of resistive arteries decreases. Improves blood supply to ischemic myocardium.

ACE inhibitors extend life expectancy in patients with CHF and slow the progression of left ventricular dysfunction in patients who have suffered a myocardial infarction without clinical manifestations of heart failure.

The onset of action is 1 hour after oral administration. The maximum antihypertensive effect is determined after 6 hours and persists for 24 hours. In arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1-2 months. With abrupt discontinuation of the drug, no pronounced increase in blood pressure was observed.

Despite the primary effect, which manifests itself in the effect on the RAAS, it is also effective in arterial hypertension with low renin activity. In addition to lowering blood pressure, lisinopril reduces albuminuria. Lisinopril does not affect blood glucose concentrations in patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.

Amlodipine is a dihydropyridine derivative, a blocker of “slow” calcium channels (SCCC), has an antianginal and antihypertensive effect. Blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent into vascular smooth muscle cells than into cardiomyocytes).

The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: in case of angina pectoris, it reduces the severity of myocardial ischemia; by expanding peripheral arterioles, it reduces peripheral vascular resistance, reduces afterload on the heart, and reduces myocardial oxygen demand. By expanding the coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases the supply of oxygen to the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina and “ischemic” depression of the ST segment, reduces the frequency of angina attacks and the consumption of nitroglycerin and other nitrates.

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscle. For arterial hypertension, a single dose provides a clinically significant reduction in blood pressure over 24 hours (in the patient’s “lying” and “standing” position). Orthostatic hypotension when prescribing amlodipine is quite rare. Does not cause a decrease in exercise tolerance or left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate (GFR), and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and plasma lipid concentrations and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

The combination of amlodipine with lisinopril in one drug helps prevent the development of possible undesirable effects caused by one of the active substances. Thus, BMCC, directly dilating the arterioles, can lead to sodium and fluid retention in the body and, therefore, can activate the RAAS. An ACE inhibitor blocks this process.

Pharmacokinetics

Lisinopril

Suction

After oral administration, lisinopril is absorbed from the gastrointestinal (GIT) tract, the average extent of absorption is approximately 25%, with inter-patient variability ranging from 6 to 60% over the dose range studied (5 to 80 mg). In patients with CHF, the absolute bioavailability of lisinopril is reduced to approximately 16%. Eating does not affect the absorption of lisinopril.

Lisinopril does not bind to plasma proteins, with the exception of circulating angiotensin-converting enzyme (ACE). The maximum concentration (Cmax) in blood plasma of 90 ng/ml is achieved after 6-7 hours. Permeability through the blood-brain and placental barrier is low.

Metabolism

Lisinopril does not undergo biotransformation in the body.

Removal

It is excreted unchanged by the kidneys. The half-life (T1/2) is 12.6 hours.

Renal dysfunction

Impaired renal function reduces the elimination of lisinopril, but this reduction only becomes clinically significant when the GFR

For mild to moderate renal failure (creatinine clearance (CC)

30-80 ml/min) the average value of the area under the concentration-time curve (AUC) increases by 13%; in severe renal failure (creatinine clearance 5-30 ml/min) an increase in the average AUC value by 4.5 times is observed.

Lisinopril is eliminated from the body by hemodialysis. After 4 hours of hemodialysis, plasma concentrations of lisinopril are reduced by an average of 60%.

Dialysis clearance ranges from 40 to 55 ml/min.

Liver dysfunction

In patients with liver cirrhosis, the absorption and clearance of lisinopril is reduced.

In patients with CHF, the absorption and clearance of lisinopril is reduced. An average increase in AUC of 125% was observed.

Elderly patients

In elderly patients, lisinopril plasma concentrations and AUC values ​​are approximately 60% higher than in young patients.

Amlodipine

Suction

After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64%-80%. Food intake does not affect the absorption of amlodipine.

Distribution and binding to plasma proteins

Most of the amlodipine found in the blood (95%-98%) is bound to plasma proteins. Cmax in the blood serum is observed after 6-12 hours. Equilibrium concentrations (Css) are achieved after 7-8 days of therapy. The mean volume of distribution is 20 l/kg body weight, indicating that most amlodipine is located in tissues and less in the blood. Amlodipine penetrates the blood-brain barrier.

Metabolism

Amlodipine undergoes slow but active metabolism in the liver with no significant first-pass effect. Metabolites do not have significant pharmacological activity.

Removal

Excretion consists of two phases, T1/2 of the final phase is 35-50 hours. About 60% of the dose taken orally is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - in the form of metabolites through the intestines with bile. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).

Pharmacokinetics in selected patient groups

Renal dysfunction

Renal failure does not significantly affect the kinetics of amlodipine. It is not removed by hemodialysis.

Liver dysfunction

In patients with liver failure, there is a decrease in amlodipine clearance and an increase in AUC and T1/2 values ​​by approximately 40-60%.

Chronic heart failure

In patients with congestive heart failure, an increase in the AUC value and half-life of amlodipine is observed.

Elderly patients

The time to reach the maximum concentration of the drug in the blood plasma in elderly and younger patients is almost the same. In elderly patients, there was a tendency to decrease the clearance of amlodipine, which leads to an increase in AUC and half-life (T1/2 - 65 hours).

Combination drug Equator® with fixed doses

Pharmacokinetic interactions between the active ingredients of the drug have not been described. Pharmacokinetic parameters (AUC, time to reach and maximum concentration values, T1/2) did not differ from those after using the active substances separately.

Eating does not affect the absorption of active substances in the gastrointestinal tract.

Indications for use

Treatment of hypertension in adults.

The drug Equator® tablets in dosages: 10 mg/5 mg, 20 mg/5 mg and 20 mg/10 mg is indicated as an alternative to the simultaneous use of lisinopril and amlodipine in the indicated doses, providing adequate control of blood pressure in adult patients.

Contraindications

Related to lisinopril:

Hypersensitivity to lisinopril or any other ACE inhibitor. History of angioedema, incl. against the background of the use of ACE inhibitors. Hereditary or idiopathic angioedema. Children under 18 years of age (efficacy and safety have not been established). II and III trimesters of pregnancy (see sections “Precautions for use” and “Use during pregnancy and breastfeeding”). Concomitant use of ACE inhibitors or angiotensin II receptor blockers (ARBs) with aliskiren in patients with diabetes mellitus or moderate/severe renal failure (GFR Amlodipine-related: Hypersensitivity to amlodipine or other dihydropyridine derivatives. Severe hypotension (systolic blood pressure less than 90 mm Hg).Shock (including cardiogenic shock).Obstruction of the left ventricular outflow tract (severe aortic stenosis).Hemodynamically unstable heart failure after acute myocardial infarction.

Related to Equator® tablets 10 mg/5 mg. Equator® tablets 20 mg/5 mg and Equator® tablets 20 mg/10 mg:

All of the above contraindications associated with the use of individual components also apply to the combined drug Equator® tablets 10 mg/5 mg, Equator® tablets 20 mg/5 mg and Equator® tablets 20 mg/10 mg.

Hypersensitivity to any of the excipients (see section "Composition").

Carefully

Severe renal dysfunction, bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, liver dysfunction, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic disease heart, coronary insufficiency, sick sinus syndrome (severe bradycardia, tachycardia), CHF of non-ischemic etiology of functional class III-IV according to the NYHA classification, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction), autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), suppression of bone marrow hematopoiesis, diabetes mellitus, salt-restricted diet, hypovolemic conditions (including as a result of diarrhea, vomiting), old age, hemodialysis using high-flow dialysis high permeability membranes (AN69®).

Use during pregnancy and breastfeeding

Pregnancy

There are no data on the use of Equator® in pregnant women in adequate controlled clinical studies. Therefore, the use of both active ingredients during pregnancy is not recommended or contraindicated. If pregnancy is confirmed, you should immediately stop taking Equator® and, if necessary, begin alternative treatment (see section "Precautions for Use").

Taking Equator® should not be started during pregnancy. If continued treatment with Equator® is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive agents with a known safety profile for use during pregnancy.

Lisinopril

The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section "Precautions for use") and is contraindicated during the second and third trimester of pregnancy (see sections "Contraindications" and "Precautions for use").

Epidemiological data on the risk of teratogenicity associated with taking ACE inhibitors during the first trimester of pregnancy are not convincing, however, a small increase in risk cannot be excluded. If continued treatment with an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive agents with a known safety profile for use during pregnancy. If pregnancy is confirmed, treatment with an ACE inhibitor should be stopped immediately and, if necessary, alternative treatment should be prescribed.

It is known that the use of ACE inhibitors in women during the second and third trimesters of pregnancy induces fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia). If an ACE inhibitor has been used since the second trimester of pregnancy, an ultrasound examination of kidney and skull function is recommended. It is recommended that newborns and infants whose mothers took ACE inhibitors be closely monitored for early detection of arterial hypotension (see sections “Contraindications” and “Precautions for Use”).

Amlodipine

The safety of amlodipine during pregnancy has not been established, therefore the use of amlodipine is not recommended during pregnancy.

Breast-feeding

The use of Equator® during breastfeeding is not recommended (no data available). If the use of the drug is necessary during lactation, alternative antihypertensive drugs with a known safety profile should be prescribed (especially during breastfeeding of newborns and premature infants).

Fertility

There are no data from adequate controlled clinical studies on the effect of Equator® on fertility. Reversible biochemical changes in the sperm heads have been reported in some patients when using BMCC.

Directions for use and doses

Inside, regardless of food intake.

The maximum daily dose is one tablet of the drug Equator®.

In general, fixed-dose combinations should not be used for initial therapy.

Equator® in dosages of 10 mg/5 mg, 20 mg/5 mg and 20 mg/10 mg is indicated only for those patients whose optimal maintenance doses of lisinopril and amlodipine are titrated to 10 mg and 5 mg in the case of Equator® tablets 10 mg/5 mg, up to 20 mg and 5 mg in the case of Equator® tablets 20 mg/5 mg and up to 20 mg and 10 mg in the case of Equator® tablets 20 mg/10 mg, respectively. If dose adjustment is necessary, dose titration of the individual components of the drug should be considered.

Patients with impaired renal function

To determine the optimal initial and maintenance dose for patients with renal failure, dose titration is necessary using lisinopril and amlodipine separately. During treatment with Equator®, it is necessary to monitor renal function, potassium and sodium levels in the blood serum. If renal function deteriorates, the drug should be discontinued and replaced with lisinopril and amlodipine in adequate doses.

Patients with liver dysfunction

The elimination of amlodipine may be slowed in patients with impaired liver function. Clear recommendations on the dosage regimen in such cases have not been established, therefore Equator® should be prescribed at the lowest recommended dose. To determine the optimal initial and maintenance dose in patients with hepatic impairment, it is necessary to titrate doses separately for lisinopril and amlodipine.

Elderly patients (over 65 years old)

In elderly patients, the drug should be used with caution. In clinical studies, there were no age-related changes in the efficacy or safety profile of amlodipine and lisinopril. To determine the optimal maintenance dose, it is necessary to determine the dosage regimen on an individual basis, using lisinopril and amlodipine separately.

Side effect

The incidence of adverse reactions in patients receiving the combination drug was no higher than in patients receiving one of the active ingredients. Adverse reactions were consistent with previously obtained data on amlodipine and/or lisinopril. Adverse reactions were mild, transient and rarely required discontinuation of treatment. The most common adverse reactions when taking the combination of drugs were: headache (8%), cough (5%), dizziness (3%).

The frequency of adverse reactions is given separately for lisinopril and amlodipine.

Data are presented by organ system class according to the MedDRA classification and with the following frequency: very common (> 1/10); often (from > 1/100 to 1/1,000 to 1/10,000 to

Organ system class	Frequency	Adverse reactions of lisinopril	Adverse reactions of amlodipine
Blood and lymphatic system disorders	Very rarely	Suppression of bone marrow hematopoiesis, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, anemia, lymphadenopathy	Thrombocytopenia, leukopenia
Immune system disorders	Very rarely	Autoimmune disorders	Allergic reactions
Endocrine system disorder	Rarely	Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Metabolic and nutritional disorders	Very rarely	Hypoglycemia	Hyperglycemia
Mental disorders	Infrequently	Mood changes, sleep disturbances	Insomnia, mood changes (including anxiety), depression
	Rarely	Mental disorders	Confusion
	Frequency unknown	Depression
Nervous system disorders	Often	Dizziness, headache	Drowsiness, dizziness, headache (especially during the initial period of treatment)
	Infrequently	Vertigo, paresthesia, dysgeusia	Fainting, tremor, dysgeusia, hypoesthesia, paresthesia
	Very rarely		Muscle hypertonicity, peripheral neuropathy
	Frequency unknown	Fainting
Visual disorders	Infrequently		Visual disturbances (including diplopia)
Hearing and labyrinth disorders	Infrequently		Noise in ears
Heart disorders	Often		Cardiopalmus
	Infrequently	Myocardial infarction, possibly caused by a pronounced decrease in blood pressure in high-risk patients, tachycardia, palpitations
	Very rarely		Myocardial infarction, arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation)
Vascular disorders	Often	Orthostatic hypotension	Skin hyperemia
	Infrequently	Cerebrovascular accident, possibly caused by a marked decrease in blood pressure in high-risk patients, Raynaud's syndrome	Decreased blood pressure
	Very rarely		Vasculitis
Respiratory, thoracic and mediastinal disorders	Often	Cough
	Infrequently	Rhinitis	Shortness of breath, rhinitis
	Very rarely	Bronchospasm, allergic alveolitis/eosinophilic pneumonia, sinusitis	Cough
Gastrointestinal disorders	Often	Diarrhea, vomiting	Abdominal pain, nausea
	Infrequently	Abdominal pain, nausea, indigestion	Vomiting, dyspepsia, diarrhea or constipation, dry mouth
	Rarely	Dryness of the oral mucosa
	Very rarely	Pancreatitis, intestinal angioedema	Pancreatitis, gastritis, gum hyperplasia
Disorders of the liver and biliary tract	Very rarely	Liver failure, hepatitis, cholestatic jaundice	Hepatitis, jaundice
Skin and subcutaneous tissue disorders	Infrequently	Rash, itching	Alopecia, purpura, skin discoloration, increased sweating, itching, rash, exanthema
	Rarely	Psoriasis, urticaria, alopecia, hypersensitivity/angioedema of the face, extremities, lips, tongue, glottis and/or larynx
	Very rarely	Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus vulgaris, increased sweating, cutaneous pseudolymphoma*	Angioedema, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, Quincke's edema, photosensitivity, urticaria
Musculoskeletal and connective tissue disorders	Often		Swelling of the ankles
	Infrequently		Arthralgia, myalgia, muscle cramps, back pain
Renal and urinary tract disorders	Often	Renal dysfunction
	Infrequently		Urinary dysfunction, nocturia, increased frequency of urination
	Rarely	Acute renal failure, uremia
	Very rarely	Oliguria/anuria
Disorders of the genital organs and breast	Infrequently	Impotence	Impotence, gynecomastia
	Rarely	Gynecomastia
General and administration site disorders	Often		Peripheral edema, increased fatigue
	Infrequently	Increased fatigue, asthenia	Chest pain, pain, malaise, asthenia
Influence on the results of laboratory and instrumental studies	Infrequently	Increased concentration of urea in the blood, creatinine in the blood serum, hyperkalemia, increased activity of liver enzymes	Weight gain, weight loss
	Rarely	Decreased hemoglobin, decreased hematocrit, increased serum bilirubin concentration, hyponatremia
	Very rarely		Increased activity of liver enzymes**

* The syndrome may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, increased antinuclear antibodies (ANA), increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity or other changes in the skin.

** Most often corresponds to cholestasis.

Isolated cases of extrapyramidal syndrome have also been reported with the use of amlodipine.

Overdose

There is no evidence of overdose of Equator® in humans.

Lisinopril

Symptoms: hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

Treatment: gastric lavage, taking activated charcoal, placing the patient in a horizontal position with raised legs, replenishing circulating blood volume (CBV) - intravenous administration of plasma-substituting solutions, symptomatic therapy, you can also consider the advisability of infusion of angiotensin II and/or intravenous administration of catecholamines, monitoring of cardiovascular functions vascular and respiratory systems, bcc, urea concentration, creatinine and electrolyte content in blood serum, as well as diuresis. With the development of bradycardia that is resistant to drug therapy, placement of an artificial pacemaker is indicated. Lisinopril can be removed from the systemic circulation using hemodialysis.

Amlodipine

Symptoms: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of developing severe and persistent arterial hypotension, including the development of shock and death).

Treatment: gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring the functions of the cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, monitoring circulating blood volume (CBV) and diuresis. To restore vascular tone - use vasoconstrictors (in the absence of contraindications to their use); in order to eliminate the consequences of blockade of calcium channels - intravenous administration of calcium gluconate. Hemodialysis is ineffective.

Combination drug Equator® with fixed doses

Symptoms:

An overdose of Equator® can lead to excessive peripheral vasodilation with severe arterial hypotension, acute vascular insufficiency, electrolyte imbalance, renal failure, hyperventilation, tachycardia, rapid heartbeat, bradycardia, dizziness, anxiety and cough.

Treatment: It is recommended to carry out symptomatic treatment (put the patient in a supine position, observe and, if necessary, maintain the functions of the cardiovascular and respiratory systems, control blood pressure, replenish blood volume and restore electrolyte balance, monitor the concentration of creatinine in the blood serum). In case of severe arterial hypotension, the lower limbs should be raised above the head; if intravenous administration of blood substitutes does not lead to a sufficient result, maintenance therapy may be required through the administration of peripheral vasopressors, provided there are no contraindications to their use. Infusion of angiotensin II is advisable. Intravenous administration of calcium gluconate may have a positive effect on reversing the effects caused by calcium channel blockade.

Since amlodipine is absorbed slowly, gastric lavage may be effective in some cases. It is advisable to perform hemodialysis to remove lisinopril from the systemic circulation. The use of high-flow polyacrylonitrile membranes during dialysis is not recommended.

Interaction with other drugs

Lisinopril

Potassium-containing food supplements, potassium-sparing diuretics, potassium-containing salt substitutes: Potassium-sparing diuretics (for example, spironolactone, amiloride and triamterene), potassium-containing dietary supplements, potassium-containing salt substitutes and any other drugs that increase serum potassium levels (for example, heparin) may cause hyperkalemia when administered concomitantly with ACE inhibitors , especially in patients with a history of renal failure and other kidney diseases. When prescribing a drug that affects potassium levels concomitantly with lisinopril, serum potassium levels should be monitored. Co-administration should be carried out with extreme caution and regular monitoring of renal function and serum potassium levels. Potassium-sparing diuretics can be used simultaneously with Equator® only under close medical supervision.

Diuretics: The antihypertensive effect is usually enhanced when a diuretic is prescribed to a patient receiving lisinopril. The potential for symptomatic hypotension when taking lisinopril can be minimized by discontinuing the diuretic before starting treatment with lisinopril. Concomitant use should be done with caution. Lisinopril mitigates the kaliuretic effect of diuretics.

Other antihypertensive drugs: simultaneous use of these drugs may enhance the antihypertensive effect of Equator®. Concomitant use with nitroglycerin, other nitrates or vasodilators can lead to a significant decrease in blood pressure.

Double blockade of the renin-angiotensin-aldosterone system: According to available data, dual blockade of the RAAS using ACE inhibitors, ARB II or aliskiren cannot be recommended for any patient, especially patients with diabetic nephropathy.

In patients with diabetes mellitus or moderate/severe renal impairment (GFR

In some cases, when the combined use of ACE inhibitors and ARB II is absolutely indicated, careful supervision by a specialist and mandatory monitoring of renal function, water and electrolyte balance, and blood pressure are necessary.

Tricyclic antidepressants/antipsychotics/general anesthesia/narcotic analgesics: Concomitant use with ACE inhibitors can lead to a significant decrease in blood pressure.

Ethanol enhances the antihypertensive effect.

Allopurinol, procainamide, cytostatics or immunosuppressants (systemic glucocorticosteroids) may lead to an increased risk of developing leukopenia when used simultaneously with ACE inhibitors.

Antacids and cholestyramine when taken together with ACE inhibitors, they reduce the bioavailability of the latter.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors; it is necessary to carefully monitor the achievement of the desired effect.

Hypoglycemic drugs: with simultaneous use of ACE inhibitors and hypoglycemic drugs (insulin and oral hypoglycemic agents), the risk of hypoglycemia may increase. Most often, such conditions are observed during the first week of combination treatment and in patients with renal failure.

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors): long-term use of NSAIDs, including high doses of acetylsalicylic acid more than 3 g/day, may reduce the antihypertensive effect of ACE inhibitors. The additive effect of NSAIDs and ACE inhibitors is an increase in serum potassium and may lead to deterioration of renal function. These effects are usually reversible. Very rarely, acute renal failure may develop, especially in elderly and dehydrated patients.

Lithium preparations: Lithium excretion may be slowed down when used concomitantly with ACE inhibitors and therefore in this case the concentration of lithium in the blood serum should be monitored. When used together with lithium preparations, it is possible to increase the manifestation of their neurotoxic effect (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). The combined use of lisinopril and lithium preparations is not recommended. Concomitant use of thiazide diuretics with ACE inhibitors may lead to an increased risk of lithium toxicity and further increase lithium toxicity.

Gold preparations: with the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex has been described, including facial flushing, nausea, vomiting, dizziness and arterial hypotension.

Acetylsalicylic acid, thrombolytics,beta blockers, n expenses: Lisinopril can be used simultaneously with acetylsalicylic acid (in cardiac doses), thrombolytics, beta-blockers and/or nitrates.

Amlodipine

Effect of other drugs on amlodipine

Isoenzyme inhibitorsCYP3 A4: simultaneous use of amlodipine with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungals, macrolide antibiotics (such as erythromycin or clarithromycin), verapamil or diltiazem) may lead to a significant increase in the effects of amlodipine, which are more pronounced in elderly patients. Medical supervision and, if necessary, dose adjustment of amlodipine are recommended.

Isoenzyme inducersCYP3 A4: simultaneous use with inducers of the CYP3A4 isoenzyme (for example, rifampicin, drugs containing St. John's wort) may lead to a decrease in the concentration of amlodipine in the blood plasma. The simultaneous use of amlodipine and inducers of the CYP3A4 isoenzyme should be carried out with caution.

Taking amlodipine with grapefruit or grapefruit juice not recommended as this may increase the bioavailability of amlodipine in some patients, thereby increasing its antihypertensive effect.

Dantrolene (infusion): In animal studies, the development of ventricular fibrillation and cardiovascular failure with concomitant hyperkalemia and death was observed after administration of verapamil and intravenous administration of dantrolene. Due to the risk of developing hyperkalemia, it is recommended to avoid the simultaneous use of calcium channel blockers such as amlodipine in patients predisposed to malignant hyperthermia, as well as for the treatment of malignant hyperthermia.

Effect of amlodipine on other drugs

The antihypertensive effect of amlodipine is enhanced by drugs that have antihypertensive properties.

In clinical studies examining interactions with other drugs, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine.

Simvastatin", simultaneous administration of repeated doses of 10 mg amlodipine and 80 mg simvastatin resulted in an increase in simvastatin concentrations by 77% compared with those with simvastatin monotherapy. The dose of simvastatin in patients taking amlodipine should be limited to 20 mg per day.

Precautions for use

All warnings below related to the use of individual components also apply to the combination drug Equator®.

Related to lisinopril:

Arterial hypotension

A marked decrease in blood pressure with the development of clinical symptoms may occur in patients with a decrease in circulating blood volume and/or sodium content due to diuretics, fluid loss, or other reasons, such as increased sweating, prolonged vomiting and/or diarrhea, or severe renin-dependent hypertension . It is necessary that restoration of fluid and/or sodium loss be carried out before starting therapy with Equator®. It is necessary to monitor blood pressure after taking the initial dose. Such conditions apply to patients with coronary heart disease or cerebrovascular diseases, in whom a pronounced decrease in blood pressure can lead to myocardial infarction or stroke.

A transient hypotensive reaction is not a contraindication to subsequent use of lisinopril, which can usually be used immediately after an increase in blood pressure following an increase in blood volume.

Some patients with heart failure with normal or low blood pressure may experience an additional decrease in systemic blood pressure when taking lisinopril. This effect is expected and does not usually require discontinuation of treatment. If hypotension becomes symptomatic, dose reduction or discontinuation of lisinopril may be necessary.

Double blockade of the RAAS

Dual blockade of the RAAS is associated with an increased risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Dual blockade of the RAAS using ACE inhibitors, ARB II or aliskiren cannot be recommended in any patient, especially in patients with diabetic nephropathy.

In some cases, when the combined use of ACE inhibitors and ARB II is absolutely indicated, careful supervision by a specialist and mandatory monitoring of renal function, water and electrolyte balance, and blood pressure are necessary. This applies to the use of candesartan or valsartan as adjunctive therapy to ACE inhibitors in patients with chronic heart failure. Carrying out double blockade of the RAAS under the careful supervision of a specialist and mandatory monitoring of renal function, water-electrolyte balance and blood pressure is possible in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistence of symptoms of chronic heart failure, despite other adequate therapy .

Arterial hypotension in acute myocardial infarction

Treatment with lisinopril should not be initiated in patients with acute myocardial infarction who are at risk of further serious hemodynamic deterioration after treatment with vasodilators. These are patients with a systolic blood pressure (SBP) of 100 mmHg. Art. or lower, as well as with cardiogenic shock. During the first 3 days after myocardial infarction, the dose of lisinopril should be reduced if SBP is 120 mmHg. Art. or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if SBP is 100 mmHg. Art. or lower. If arterial hypotension persists (SBP less than 90 mm Hg persists for more than 1 hour), lisinopril should be discontinued.

Aortic and mitral valve stenosis/hypertrophiccardiomyopathy

As with other ACE inhibitors, lisinopril should be administered with caution to patients with mitral valve stenosis and left ventricular outflow tract obstruction (aortic stenosis or hypertrophic cardiomyopathy).

Kidney failure

In case of renal failure (KR

In patients with heart failure, hypotension after initiation of treatment with ACE inhibitors may lead to further deterioration of renal function. Acute renal failure has been reported in such cases, but is usually reversible.

In some patients with bilateral renal artery stenosis or with arterial stenosis of a solitary kidney who received ACE inhibitors, increases in serum urea and creatinine concentrations were observed, usually reversible when treatment was discontinued. This is especially likely in patients with kidney failure. In the case of concomitant renovascular hypertension, there is an increased risk of developing severe arterial hypotension and renal failure. In such patients, treatment should be initiated under close medical supervision at low doses and the dose titrated carefully. Since treatment with diuretics may contribute to the development of the above conditions, their use should be discontinued and renal function monitored during the first weeks of lisinopril therapy.

In some patients with arterial hypertension without significant preexisting renovascular hypertension, an increase in serum urea and creatinine concentrations was observed, usually slight and transient, especially in cases where lisinopril was used concomitantly with a diuretic. This is especially likely in patients with pre-existing renal failure. A dose reduction and/or discontinuation of the diuretic and/or lisinopril may be required.

In acute myocardial infarction, treatment with lisinopril should not be initiated in patients with signs of renal failure, which was defined as a serum creatinine concentration exceeding 177 micromol/l and/or proteinuria exceeding 500 mg/24 hours. In case of impaired renal function during treatment with lisinopril (serum creatinine concentration exceeding 265 micromol/l or 2 times higher than the corresponding value before treatment), the doctor should consider the advisability of discontinuing lisinopril.

Angioedema

Angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx has been reported in patients taking ACE inhibitors, including lisinopril. In these cases, taking Equator® should be stopped immediately and the patient should be closely monitored until symptoms disappear completely.

Swelling of the face, lips and limbs usually goes away on its own, however, antihistamines should be used to reduce the severity of symptoms. Angioedema, accompanied by swelling of the larynx or swelling of the tongue, can be fatal. If swelling of the tongue, pharynx or larynx is detected, which may be the cause of airway obstruction, emergency measures must be started immediately. Appropriate measures include: the use of a 0.1% solution of epinephrine (adrenaline) subcutaneously at a dose of 0.3 - 0.5 mg or 0.1 mg intravenously slowly, followed by the use of glucocorticosteroids (intravenously) and antihistamines and simultaneous monitoring of vital signs. important functions.

Intestinal angioedema has rarely been observed in patients taking ACE inhibitors. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, no previous facial angioedema was observed and C-1 esterase activity was within normal limits. Intestinal angioedema was diagnosed by computed tomography of the gastrointestinal tract or ultrasound, or by surgery; symptoms disappeared after discontinuation of the ACE inhibitor. When conducting a differential diagnosis of abdominal pain in patients taking ACE inhibitors, the development of intestinal angioedema should be taken into account.

In patients with a history of angioedema not associated with ACE inhibitor use, use of ACE inhibitors may be associated with a higher risk of developing angioedema.

Anaphylactic reactions in patients on hemodialysis

Cases of anaphylactic shock have been reported in patients undergoing hemodialysis using polyacrylonitrile membranes (eg, AN69®) and concomitantly receiving ACE inhibitors, and this combination should be avoided. Patients are recommended to use either a different type of dialysis membrane or an antihypertensive drug of a different pharmacotherapeutic group.

Anaphylactic reactions in patients during low-density lipoprotein (LDL) apheresis procedures

Rarely, life-threatening anaphylactic reactions have developed in patients receiving ACE inhibitors during LDL apheresis with dextran sulfate. Such reactions can be prevented by stopping the ACE inhibitor before each apheresis procedure.

Poison desensitizationHymenoptera

Sometimes patients taking ACE inhibitors developed anaphylactic reactions when desensitized by hymenoptera venom (for example, wasps or bees). Such life-threatening situations can be avoided by discontinuing the ACE inhibitor before the desensitization procedure.

Effects on the liver

In rare cases, the use of ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and developed into fulminant liver necrosis and, in some cases, led to death. The mechanism of this syndrome is unclear. Patients receiving Equator® who experience jaundice or increased liver enzyme activity should discontinue the drug and carefully monitor their condition.

Neutropenia/agranulocytosis

Rare cases of neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor. Equator® should be used with extreme caution in patients with systemic connective tissue diseases, during immunosuppressive therapy, during treatment with allopurinol or procainamide, or a combination of these aggravating factors, especially in the presence of pre-existing renal impairment. Some of these patients developed serious infections, which in some cases did not respond to antibiotic treatment. In such patients, during treatment with Equator®, it is necessary to periodically monitor the number of leukocytes (blood test with leukocyte count). Patients should be warned about the need to inform the doctor about the appearance of the first signs of an infectious disease.

Race

Representatives of the Black race who used ACE inhibitors were more likely to experience angioedema compared to patients of other races.

Like other ACE inhibitors, lisinopril is less effective as an antihypertensive agent in black patients compared to patients of other races. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Cough

Cough was frequently observed during the use of ACE inhibitors. As a rule, the cough is non-productive, constant and stopped after discontinuation of the drug. In the differential diagnosis of cough, cough associated with the use of ACE inhibitors must be taken into account.

Surgery/general anesthesia

During surgery or general anesthesia with the use of drugs that cause arterial hypotension, lisinopril can block the formation of angiotensin II associated with the compensatory release of renin.

If arterial hypotension develops as a result of the above mechanism, correction can be made by increasing the volume of blood volume.

Hyperkalemia

In some patients receiving ACE inhibitors, an increase in serum potassium levels was observed. Patients at risk for the development of hyperkalemia are patients with renal failure, type 2 diabetes mellitus, acute heart failure, dehydration, metabolic acidosis, or concomitant use of potassium-sparing diuretics, potassium-containing dietary supplements, potassium-containing salt substitutes, or any other drugs that increase potassium levels in the blood. serum (for example, heparin). If simultaneous use with the above drugs is necessary, it is recommended to monitor the potassium content in the blood serum.

Patients with diabetes mellitus

In patients with diabetes mellitus taking oral hypoglycemic drugs or receiving insulin, blood sugar levels should be monitored during the first month of treatment with an ACE inhibitor (see section “Interaction with other drugs”).

Related to amlodipine:

The safety and effectiveness of amlodipine in hypertensive crisis has not been established.

Patients with heart failure

Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure as they may increase the risk of cardiovascular complications and mortality.

Use in patients with liver failure

In patients with hepatic impairment, a prolonged half-life of amlodipine and an increased AUC are observed, but appropriate dosing recommendations have not been developed. Therefore, amlodipine should be started at the lowest dose in the dosing range; Treatment should be initiated and dose increased with caution. In patients with severe hepatic impairment, slow dose titration and close medical monitoring may be required.

Elderly patients

Elderly patients with impaired renal function should undergo dose adjustment using lisinopril and amlodipine separately.

During treatment, body weight control and dental supervision are necessary (to prevent pain, bleeding and gum hyperplasia).

Impact on the ability to drive vehicles and operate machinery

Related to lisinopril:

When operating vehicles or machinery, the possibility of dizziness or fatigue should be taken into account.

Related to amlodipine:

Amlodipine may have a slight or moderate effect on the ability to drive vehicles and machines. Due to the possible development of dizziness, headache, fatigue and nausea, the speed of psychomotor reactions may be impaired. Caution is recommended, especially at the beginning of treatment.

On prescription.

Manufacturer

JSC "Gedeon Richter"

1103 Budapest, st. Dymroyi, 19-21, Hungary.

Company representing the interests of the manufacturer and applicant

name of the drug

Registration number: LP 001645-200314

Trade name: EQUATOR®

International nonproprietary or generic name: amlodipine + lisinopril&

Dosage form: tablets

Composition per 1 tablet:
active ingredients: amlodipine besylate 6.94 mg (equivalent to 5.00 mg amlodipine), lisinopril dihydrate 21.76 mg (equivalent to 20.00 mg lisinopril);
Excipients: microcrystalline cellulose (type 101) - 181.08 mg, microcrystalline cellulose (type 12) - 173.28 mg, sodium carboxymethyl starch (type A) - 8.00 mg, magnesium stearate - 2.00 mg.

Description
White or off-white, round, biconvex tablets debossed with "CF2" on one side.

Pharmacotherapeutic group: combined antihypertensive agent (angiotensin-converting enzyme inhibitor and slow calcium channel blocker)

ATX code: S09ВВ03

pharmachologic effect
Pharmacodynamics
A combination drug containing the active ingredients: lisinopril and amlodipine.
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces total peripheral vascular resistance (TPVR), blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure. Dilates arteries more than veins. Some effects are explained by effects on the tissue renin-angiotensin-aldosterone system (RAAS).
With long-term use, hypertrophy of the myocardium and the walls of resistive arteries decreases. Improves blood supply to ischemic myocardium.
ACE inhibitors extend life expectancy in patients with chronic heart failure and slow the progression of left ventricular dysfunction in patients who have suffered a myocardial infarction without clinical manifestations of heart failure.
The onset of action is 1 hour after oral administration. The maximum antihypertensive effect is determined after 6 hours and persists for 24 hours. In arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1-2 months. With abrupt discontinuation of the drug, no pronounced increase in blood pressure was observed.
Despite the primary effect, which manifests itself in the effect on the RAAS, it is also effective in arterial hypertension with low renin activity. In addition to lowering blood pressure, lisinopril reduces albuminuria. Lisinopril does not affect blood glucose concentrations in patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.
Amlodipine is a dihydropyridine derivative, a blocker of “slow” calcium channels (SCCC), has an antianginal and antihypertensive effect. Blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent into vascular smooth muscle cells than into cardiomyocytes).
The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: in case of angina pectoris, it reduces the severity of myocardial ischemia; by expanding peripheral arterioles, it reduces peripheral vascular resistance, reduces afterload on the heart, and reduces myocardial oxygen demand. By expanding the coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases the supply of oxygen to the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina and “ischemic” depression of the ST segment, reduces the frequency of angina attacks and the consumption of nitroglycerin and other nitrates.
It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscle. For arterial hypertension, a single dose provides a clinically significant reduction in blood pressure over 24 hours (in the patient’s “lying” and “standing” position). Orthostatic hypotension when prescribing amlodipine is quite rare. Does not cause a decrease in exercise tolerance or left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. Doesn't provide any
adverse effects on metabolism and plasma lipid concentrations and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.
Amlodipine + lisinopril
The combination of lisinopril with amlodipine in one drug helps prevent the development of possible undesirable effects caused by one of the active substances. Thus, BMCC, directly dilating the arterioles, can lead to sodium and fluid retention in the body, and, therefore, can activate the RAAS. An ACE inhibitor blocks this process.
Pharmacokinetics
Lisinopril
Suction
After oral administration, lisinopril is absorbed from the gastrointestinal tract (GIT), its absorption can vary from 6 to 60%. Bioavailability is 29%. Eating does not affect the absorption of lisinopril.
Distribution
Almost does not bind to blood plasma proteins. The maximum concentration (Cmax) in blood plasma of 90 ng/ml is achieved after 6-7 hours. Permeability through the blood-brain and placental barrier is low.
Metabolism
Lisinopril is not biotransformed in the body.
Removal
It is excreted unchanged by the kidneys. The half-life (T1/2) is 12.6 hours.

In elderly patients, the plasma concentration of lisinopril and the area under the concentration-time curve (AUC) are 2 times greater than in young patients.
In patients with chronic heart failure, the absorption and clearance of lisinopril is reduced.
In patients with renal failure, the concentration of lisinopril is several times higher than the concentration in the blood plasma of healthy volunteers, and there is an increase in the time to reach the maximum concentration in the blood plasma and an increase in the half-life.
Lisinopril is eliminated from the body by hemodialysis.
Amlodipine
Suction
After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64%-80%. Food intake does not affect the absorption of amlodipine.
Distribution
Most of the amlodipine found in the blood (95%-98%) is bound to plasma proteins. Cmax in serum is observed after 6-10 hours. Equilibrium concentrations (Css) are achieved after 7-8 days of therapy. The mean volume of distribution is 20 l/kg body weight, indicating that most amlodipine is located in tissues and less in the blood.
Metabolism
Amlodipine undergoes slow but active metabolism in the liver with no significant first-pass effect. Metabolites do not have significant pharmacological activity.
Removal
Excretion consists of two phases, T1/2 of the final phase is 30-50 hours. About 60% of the dose taken orally is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - in the form of metabolites through the intestines with bile. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).
Pharmacokinetics in selected patient groups
In elderly patients (over 65 years of age), the elimination of amlodipine is slower (T1\2 - 65 hours) compared to young patients, but this difference is not clinically significant.
In patients with liver failure, prolongation of T1/2 suggests that with long-term use, the accumulation of amlodipine in the body will be higher (T1/2 - up to 60 hours).
Renal failure does not significantly affect the kinetics of amlodipine. Amlodipine penetrates the blood-brain barrier. It is not removed by hemodialysis.
Amlodipine + lisinopril
Interaction between the active ingredients included in the drug Equator® is unlikely. AUC, time to reach maximum concentration and half-life do not change compared to the values ​​of each individual active substance. Eating does not affect the absorption of active substances.

Indications for use
Essential hypertension (patients for whom combination therapy is indicated).

Contraindications
- Hypersensitivity to lisinopril or other ACE inhibitors;
- Hypersensitivity to amlodipine or other dihydropyridine derivatives;
- Hypersensitivity to other components of the drug;
- History of angioedema, including during the use of ACE inhibitors;
- Hereditary or idiopathic angioedema;
- Hemodynamically significant stenosis of the aorta or mitral valve;
- Hypertrophic obstructive cardiomyopathy;
- Severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
- Cardiogenic shock;
- Unstable angina (with the exception of Prinzmetal's angina);
- Heart failure after acute myocardial infarction (within the first 28 days).
- Pregnancy and lactation;
- Age up to 18 years (efficacy and safety have not been established).

Carefully:
Severe renal dysfunction, bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, liver dysfunction, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic disease heart failure, coronary insufficiency, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure (CHF) of non-ischemic etiology of functional class III-IV according to the NYHA classification, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after a heart attack myocardium), autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), suppression of bone marrow hematopoiesis, diabetes mellitus, salt-restricted diet, hypovolemic conditions (including as a result of diarrhea, vomiting), old age, hemodialysis using high-flow, high-permeability dialysis membranes (AN69®).

Use during pregnancy and lactation
The use of Equator® is not recommended during pregnancy.
If pregnancy is diagnosed, taking Equator® should be stopped immediately.
Taking ACE inhibitors in the second and third trimester of pregnancy has an adverse effect on the fetus (a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, and intrauterine death are possible). There is no data on the negative effects of the drug on the fetus when used during the first trimester of pregnancy. For newborns and infants who have been exposed in utero to ACE inhibitors, it is recommended to conduct careful monitoring for timely detection of a pronounced decrease in blood pressure, oliguria, and hyperkalemia.
The safety of amlodipine during pregnancy has not been established, therefore the use of amlodipine is not recommended during pregnancy.
Lisinopril crosses the placenta and can be excreted in breast milk. There is no data indicating the excretion of amlodipine into breast milk. However, it is known that other BMCCs, dihydropyridine derivatives, are excreted in breast milk.
The use of Equator® during breastfeeding is not recommended.
If the use of the drug is necessary during lactation, then breastfeeding must be stopped.

Directions for use and doses
Inside, regardless of food intake. The recommended dose is one tablet of Equator® daily. The maximum daily dose is one tablet of the drug Equator®.
Patients with kidney failure
To determine the optimal initial and maintenance dose for patients with renal insufficiency, doses must be titrated and determined on an individual basis using lisinopril and amlodipine separately. Equator® is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg, respectively. During treatment with Equator®, it is necessary to monitor renal function, potassium and sodium levels in the blood serum. If renal function deteriorates, Equator® should be discontinued and replaced with lisinopril and amlodipine in adequate doses.
Patients with liver failure
The elimination of amlodipine may be slowed in patients with impaired liver function. Clear recommendations on the dosage regimen in such cases have not been established, so Equator® should be prescribed with caution in patients with liver failure.
Elderly patients (over 65 years old)
In clinical studies, no age-related changes in the efficacy or safety profile were found for amlodipine and lisinopril. To determine the optimal maintenance dose, it is necessary to determine the dosage regimen on an individual basis, using lisinopril and amlodipine separately. Equator® is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg, respectively.

Side effect
The incidence of adverse reactions in patients receiving the combination drug was no higher than in patients receiving one of the active ingredients. Adverse reactions were consistent with previously obtained data on amlodipine and/or lisinopril. Adverse reactions were mild, transient and rarely required discontinuation of treatment. The most common adverse reactions when taking the combination of drugs were: headache (8%), cough (5%), dizziness (3%).
The frequency of adverse reactions is given separately for lisinopril and amlodipine.
Data are presented by system-organ classes in accordance with the MedDRA classification and with the following frequency: very often (≥1/10); often (from ≥1/100 to

MedDRA Organ System Class Frequency Adverse effects of lisinopril Adverse effects of amlodipine
Disorders of the hematopoietic and lymphatic system
Very rare: Suppression of bone marrow hematopoiesis, Agranulocytosis, Leukopenia, neutropenia, Thrombocytopenia, Hemolytic anemia, Anemia, Lymphadenopathy. Thrombocytopenia
Immune system disorders Very rare Vasculitis, Positive antinuclear antibody test Hypersensitivity
Metabolic and nutritional disorders
Very rare Hypoglycemia Hyperglycemia
Mental disorders Uncommon Mood changes, sleep disturbances Insomnia, unusual dreams, mood changes, increased excitability, depression, anxiety.
Rarely Mental disorders Apathy, agitation.
Nervous system disorders Common: Dizziness, headache, drowsiness. Drowsiness, dizziness, headache.
Uncommon: Systemic dizziness, paresthesia, dysgeusia, convulsive twitching of the muscles of the limbs and lips. Syncope, tremor, dysgeusia, hypoesthesia, paresthesia.
Rare Confusion Migraine
Very rare: Peripheral neuropathy, ataxia, amnesia, parosmia.
Visual disturbances: Uncommon: Visual disturbances (diplopia, impaired accommodation), xerophthalmia, conjunctivitis, eye pain.
Hearing and labyrinth disorders Uncommon Tinnitus
Cardiac disorders Common: Palpitations
Uncommon: Myocardial infarction, atrioventricular conduction disturbance, bradycardia, tachycardia, rapid heartbeat, worsening CHF, chest pain.
Rarely, worsening of the course of CHF.
Very rare: Myocardial infarction, ventricular tachycardia, atrial fibrillation, arrhythmia.
Disorders of the vascular system Often Marked decrease in blood pressure, orthostatic hypotension Skin hyperemia
Uncommon: Cerebrovascular accident, Raynaud's syndrome. Marked decrease in blood pressure, orthostatic hypotension.
Very rare Vasculitis
Respiratory, thoracic and mediastinal disorders Common Dry cough
Uncommon Rhinitis Dyspnea, rhinitis, nosebleeds.
Rarely Dyspnea
Very rare Bronchospasm, allergic alveolitis/eosinophilic pneumonia, sinusitis Cough
Digestive system disorders Often Diarrhea, vomiting Abdominal pain, nausea.
Uncommon: Abdominal pain, nausea, indigestion. Vomiting, dyspepsia, constipation or diarrhea, dry mouth, anorexia, thirst.
Rarely Dry mouth Increased appetite.
Very rare Pancreatitis, intestinal angioedema Pancreatitis, gastritis, gingival hyperplasia.
Liver and biliary tract disorders Very rare Liver failure, hepatitis, cholestatic jaundice Hepatitis, jaundice, cholestasis
Skin and subcutaneous tissue disorders Uncommon Allergic reactions/angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx, skin rash, itching, photosensitivity. Skin rash, purpura, itching, xeroderma.
Rarely Psoriasis, urticarial rash, alopecia Dermatitis.
Very rare: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme. Pemphigus vulgaris, increased sweating, cutaneous pseudolymphoma* Erythema multiforme, angioedema, urticarial rash, increased sweating, cold sweat, alopecia, skin discoloration.
Musculoskeletal and connective tissue disorders Uncommon Arthralgia, myalgia, muscle cramps, back pain, arthrosis.
Rare: Arthralgia, myalgia, arthritis. Myasthenia.
Renal and urinary tract disorders Common Renal dysfunction.
Uncommon Urinary dysfunction, nocturia, increased frequency of urination
Rare: Acute renal failure, uremia.
Very rare: Oliguria/anuria.
Disorders of the reproductive system and mammary glands Uncommon Impotence Impotence, gynecomastia
Rarely Gynecomastia
General (systemic) and local reactions
Often Peripheral edema, increased fatigue
Uncommon Fatigue, asthenia Chest pain, pain, malaise, asthenia
Laboratory abnormalities: Uncommon: Increased concentrations of urea and creatinine in the blood serum, hyperkalemia, increased activity of liver enzymes. Weight gain, weight loss.
Rarely: Decreased hemoglobin and hematocrit, erythropenia, hyperbilirubinemia, hyponatremia.
Very rare Increased activity of liver enzymes

* A complex symptom complex has been reported that may include all or some of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, positive antinuclear antibody test, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity or others changes in the skin.

Overdose
Amlodipine
Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including the development of shock and death).
Treatment: gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring the functions of the cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, monitoring circulating blood volume (CBV) and diuresis. To restore vascular tone - use vasoconstrictors (in the absence of contraindications to their use); in order to eliminate the consequences of blockade of calcium channels - intravenous administration of calcium gluconate. Hemodialysis is ineffective.
Lisinopril
Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.
Treatment: gastric lavage, taking activated charcoal, placing the patient in a horizontal position with elevated legs, replenishing the bcc - intravenous administration of plasma-substituting solutions, symptomatic therapy, monitoring the functions of the cardiovascular and respiratory systems, bcc, urea, creatinine and electrolytes in the blood serum, as well as diuresis. Lisinopril can be removed from the body using hemodialysis.

Interaction with other drugs
Lisinopril
Substances that affect potassium levels: potassium-sparing diuretics (for example, spironolactone, amiloride and triamterene), potassium-containing dietary supplements, potassium-containing salt substitutes and any other drugs that increase serum potassium levels (for example, heparin) can lead to hyperkalemia when combination with ACE inhibitors, especially in patients with renal failure and other kidney diseases in history. When prescribing a drug that affects potassium levels concomitantly with lisinopril, serum potassium levels should be monitored. Therefore, simultaneous administration must be carefully justified and carried out with extreme caution and
regular monitoring of both serum potassium levels and renal function. Potassium-sparing diuretics can be taken together with Equator® only under close medical supervision.
Diuretics: if a diuretic is prescribed to a patient receiving Equator®, the antihypertensive effect is usually enhanced. Concomitant use should be done with caution. Lisinopril mitigates the kaliuretic effect of diuretics.
Other antihypertensive drugs: simultaneous use of these drugs may enhance the antihypertensive effect of Equator®. Concomitant use with nitroglycerin, other nitrates or vasodilators can lead to a significant decrease in blood pressure.
Tricyclic antidepressants / antipsychotics / general anesthesia / narcotic analysts: Concomitant use with ACE inhibitors can lead to a significant decrease in blood pressure.
Ethanol enhances the antihypertensive effect.
Allopurinol, procainamide, cytostatics or immunosuppressants (systemic glucocorticosteroids) may lead to an increased risk of leukopenia when used simultaneously with ACE inhibitors.
Antacids and cholestyramine, when taken simultaneously with ACE inhibitors, reduce the bioavailability of the latter.
Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors; it is necessary to carefully monitor the achievement of the desired effect.
Hypoglycemic drugs: When taking ACE inhibitors and hypoglycemic drugs (insulin and oral hypoglycemic agents) simultaneously, the likelihood of a decrease in blood glucose concentrations and the risk of hypoglycemia may increase. This phenomenon is most often observed during the first week of combination treatment and in patients with renal failure.
Nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors): Long-term use of NSAIDs, including high doses of acetylsalicylic acid greater than 3 g/day, may reduce the antihypertensive effect of ACE inhibitors. The additive effect of taking NSAIDs and ACE inhibitors is manifested by an increase in serum potassium and may lead to a deterioration in renal function. These effects are usually reversible. Very rarely, acute renal failure may develop, especially in elderly and dehydrated patients.
Lithium preparations: Lithium excretion may be slowed during concomitant use with ACE inhibitors and therefore serum lithium concentrations should be monitored during this period. When used together with lithium drugs, it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Gold preparations: with the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex has been described, including facial flushing, nausea, vomiting and arterial hypotension.
Amlodipine
Inhibitors of the CYP3A4 isoenzyme: studies in elderly patients have shown that diltiazem suppresses the metabolism of amlodipine, probably through the CYP3A4 isoenzyme (plasma/serum concentration increases by almost 50% and the effect of amlodipine is increased). The possibility cannot be excluded that more potent inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole, ritonavir) may increase the serum concentration of amlodipine to a greater extent than diltiazem. Concomitant use should be done with caution.
Inducers of the CYP3A4 isoenzyme: simultaneous use with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort can lead to a decrease in the concentration of amlodipine in the blood plasma. Monitoring with possible dose adjustment of amlodipine is indicated during treatment with inducers of the CYP3A4 isoenzyme and after their discontinuation. Concomitant use should be done with caution.
As monotherapy, amlodipine was well combined with thiazide and loop diuretics, general anesthesia, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide, magnesium hydroxide), simethicone, cimetidine, non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic agents.
It is possible to enhance the antianginal and antihypertensive effect of BMCC when used together with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as enhance their antihypertensive effect when used together with alpha-blockers, antipsychotics.
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Antiviral agents (ritonavir) increase plasma concentrations of BMCC, incl. amlodipine.
Neuroleptics and isoflurane - enhance the antihypertensive effect of dihydropyridine derivatives.
Amlodipine does not have a significant effect on the pharmacokinetics of ethanol.
Calcium supplements may reduce the effect of slow calcium channel blockers. When amlodipine is used together with lithium preparations, it is possible to increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.
Does not affect the serum concentration of digoxin and its renal clearance.
Does not have a significant effect on the effect of warfarin (prothrombin time).
Cimetidine does not affect the pharmacokinetics of amlodipine.
It is possible to reduce the antihypertensive effect of the drug Equator® when used simultaneously with estrogens and sympathomimetics.
Procainamide, quinidine, and other drugs that prolong the QT interval may cause significant prolongation of the QT interval.
In in vitro studies, amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to blood proteins.
Taking amlodipine with grapefruit juice is not recommended as this may increase the bioavailability of amlodipine in some patients, thereby increasing its antihypertensive effect.

special instructions
Arterial hypotension
A marked decrease in blood pressure with the development of clinical symptoms can be observed in patients with a decrease in circulating blood volume and/or sodium content due to diuretics, fluid loss, or for other reasons, such as increased sweating, prolonged vomiting and/or diarrhea. It is necessary that restoration of fluid and/or sodium loss be carried out before starting therapy with Equator®. It is necessary to monitor blood pressure after taking the initial dose. Such conditions apply to patients with coronary heart disease or cerebrovascular diseases, in whom a pronounced decrease in blood pressure can lead to myocardial infarction or stroke.
Aortic and mitral stenosis
Like all vasodilators, Equator® should be prescribed with caution to patients with left ventricular outflow tract obstruction and mitral valve stenosis.
Renal dysfunction
In some patients with arterial hypertension without significant manifestations of renovascular diseases, an increase in the concentration of creatinine and urea in the blood serum was observed, in most cases minimal or transient, more pronounced when taking an ACE inhibitor and a diuretic simultaneously. This is most common in patients with a history of kidney disease.
To determine the optimal maintenance dose, it is necessary to determine the dosage regimen on an individual basis, using lisinopril and amlodipine separately, while simultaneously monitoring renal function. Equator® is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg, respectively.
If renal function decreases, Equator® should be discontinued and replaced with monotherapy with drugs in adequate doses. In addition, dose reduction or discontinuation of diuretics may be required.
Angioedema
Angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx has been reported in patients taking ACE inhibitors, including lisinopril. In these cases, taking Equator® should be stopped immediately and the patient should be closely monitored until symptoms disappear completely.
Swelling of the face, lips and limbs usually goes away on its own, however, antihistamines should be used to reduce the severity of symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. If swelling of the tongue, pharynx or larynx is detected, which is the cause of airway obstruction, emergency measures must be immediately initiated. Appropriate measures include: the use of a 0.1% solution of epinephrine (adrenaline) subcutaneously at a dose of 0.3-0.5 mg or 0.1 mg intravenously slowly, followed by the use of glucocorticosteroids (intravenously) and antihistamines and simultaneous monitoring of vital signs. important functions.
Intestinal angioedema has rarely been observed in patients taking ACE inhibitors. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, no previous facial angioedema was observed, and C-1 esterase activity was within normal limits. Intestinal angioedema was diagnosed according to computed tomography of the gastrointestinal tract, or after ultrasound examination, or during surgery; the symptoms disappeared after stopping the ACE inhibitor. When carrying out the differential diagnosis of abdominal pain in patients taking ACE inhibitors, intestinal angioedema should also be taken into account.
Anaphylactic reactions in patients on hemodialysis
Anaphylactic shock has been reported in patients undergoing hemodialysis via polyacrylonitrile membranes (eg AN 69) and concomitantly receiving ACE inhibitors, and this combination should be avoided. Patients are recommended to use either a different type of dialysis membrane or an antihypertensive drug of a different pharmacotherapeutic group.
Anaphylactic reactions in patients undergoing low-density lipoprotein (LDL) apheresis
Rarely, life-threatening anaphylactic reactions have developed in patients receiving ACE inhibitors during LDL dextran sulfate apheresis. Such reactions were prevented by stopping the ACE inhibitor before each apheresis procedure.
Desensitization from wasp or bee venom
Sometimes patients taking ACE inhibitors developed anaphylactic reactions when desensitized by hymenoptera venom (for example, wasps or bees). Such life-threatening situations can be avoided by discontinuing the ACE inhibitor before the desensitization procedure.
Effects on the liver
In rare cases, the use of ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and developed into fulminant liver necrosis and, in several cases, led to death. The mechanism of this syndrome is unclear. Patients receiving Equator® who develop jaundice or experience increased liver enzyme activity should discontinue the drug and monitor their condition.
Liver failure
In patients with impaired liver function, the half-life of amlodipine is prolonged. At the moment, recommendations on the dosage regimen have not been developed, and therefore this drug should be prescribed with caution, having previously assessed the expected benefits and potential risks of treatment.
Neutropenia/agranulocytosis
In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor. Equator® should be used with extreme caution in patients with systemic connective tissue diseases, during immunosuppressive therapy, during treatment with allopurinol or procainamide, or a combination of these aggravating factors, especially in the presence of pre-existing renal impairment. Some of these patients developed serious infections, which in several cases did not respond to antibiotic treatment. During treatment with Equator®, periodic monitoring of leukocytes (blood test with leukocyte count) is necessary in such patients, as well as warning them of the need to report the first signs of an infectious disease.
Cough
Cough has been frequently reported during the use of ACE inhibitors. As a rule, the cough is non-productive, constant and stopped after discontinuation of the drug. When making a differential diagnosis of cough, cough caused by the use of ACE inhibitors must also be taken into account.
Surgery/general anesthesia
In patients undergoing major surgery or during general anesthesia with drugs that lead to hypotension, lisinopril may block the formation of angiotensin II after compensatory renin release. If arterial hypotension develops, probably as a result of the above mechanism, correction can be made by increasing the volume of circulating blood.
Elderly patients
Elderly patients with impaired renal function should undergo dose adjustment using lisinopril and amlodipine separately.
Hyperkalemia
In some patients receiving ACE inhibitors, an increase in serum potassium levels was observed. The risk group for the development of hyperkalemia includes patients with renal failure, diabetes mellitus, acute heart failure, dehydration, metabolic acidosis, or while taking potassium-sparing diuretics, potassium-containing food supplements, potassium-containing salt substitutes or any other drugs that lead to an increase in serum potassium levels (for example, heparin). If it is necessary to take it simultaneously with the above drugs, it is necessary to monitor the potassium content in the blood serum.
Patients with reduced body weight, patients of short stature and patients with severe liver dysfunction may require a dose reduction.
Equator® does not have any adverse effects on metabolism and blood plasma lipids and can be used to treat patients with bronchial asthma, diabetes mellitus and gout.
During treatment, body weight control and dental supervision are necessary (to prevent pain, bleeding and gum hyperplasia).

The effect of the drug on the ability to drive vehicles and machinery.
It is necessary to use the drug Equator® with caution (risk of developing a pronounced decrease in blood pressure and dizziness). Therefore, at the beginning of treatment, it is recommended to avoid driving vehicles, operating machinery and performing other work that requires increased concentration.

Catad_pgroup Combined antihypertensives

Equator - instructions for use

Registration number:

LS-002321

Trade name of the drug:

Ekvator ®

International nonproprietary name:

amlodipine + lisinopril& (amlodipine + lisinopril&)

Dosage form:

pills

Compound:

Each tablet contains
active ingredients: amlodipine besylate 13.88 mg, equivalent to 10.00 mg amlodipine and lisinopril dihydrate 21.76 mg, equivalent to 20.00 mg lisinopril;
Excipients: microcrystalline cellulose 101,181.08 mg, microcrystalline cellulose 12,173.28 mg, sodium carboxymethyl starch 8.00 mg, magnesium stearate 2.00 mg.

Description:

White or almost white round flat tablets with a bevel, with a score on one side and with an engraving “A+L” on the other.

Pharmacotherapeutic group:

combined antihypertensive drug (angiotensin-converting enzyme inhibitor and slow calcium channel blocker).

ATX code:

S09ВВ03.

Pharmacological properties

Pharmacodynamics
A combination drug containing the active ingredients: lisinopril and amlodipine.
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces total, peripheral vascular resistance (TPVR), blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure. Dilates arteries more than veins. Some effects are explained by effects on the tissue renin-angiotensin-aldosterone system (RAAS).
With long-term use, hypertrophy of the myocardium and the walls of resistive arteries decreases. Improves blood supply to ischemic myocardium.
ACE inhibitors extend life expectancy in patients with chronic heart failure and slow down the progression of left ventricular dysfunction in patients who have suffered a myocardial infarction without clinical manifestations of heart failure. / Onset of action - 1 hour after oral administration. The maximum antihypertensive effect is determined after 6 hours and persists for 24 hours. In arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months. With abrupt discontinuation of the drug, no pronounced increase in blood pressure was observed.
Despite the primary effect, which manifests itself in the effect on the RAAS, it is also effective in arterial hypertension with low renin activity. In addition to lowering blood pressure, lisinopril reduces albuminuria. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes and does not lead to an increase in cases of hypoglycemia.
Amlodipine is a dihydropyridine derivative, a blocker of “slow” calcium channels (SCCC), has an antianginal and antihypertensive effect. Blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent into vascular smooth muscle cells than into cardiomyocytes).
The antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles during angina pectoris and reduces the severity of myocardial ischemia; by expanding peripheral arterioles, it reduces peripheral vascular resistance, reduces afterload on the heart, and reduces myocardial oxygen demand. By expanding the coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases the supply of oxygen to the myocardium (especially with vasospastic angina) and prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows down the development of angina and "ischemic" depression - the ST segment, reduces the frequency of attacks, angina and consumption of nitroglycerin and other nitrates.
It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscle.
For arterial hypertension, a single dose provides a clinically significant reduction in blood pressure over 24 hours (in the patient’s “lying” and “standing” position). Orthostatic hypotension is quite rare when amlodipine is prescribed. Does not cause a decrease in exercise tolerance or left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and plasma lipid concentrations and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.
A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.
Amlodipine + lisinopril
The combination of lisinopril with amlodipine in one drug helps prevent the development of possible undesirable effects caused by one of the active substances. Thus, BMCC, directly dilating the arterioles, can lead to sodium and fluid retention in the body, and, therefore, can activate the RAAS. ACE inhibitor. blocks this process.

Pharmacokinetics
Lisinopril
Suction
After oral administration, lisinopril is absorbed from the gastrointestinal tract (GIT), its absorption can vary from 6 to 60%. Bioavailability is 29%. Eating does not affect the absorption of lisinopril.
Distribution
Almost does not bind to blood plasma proteins. The maximum concentration (Cmax) in blood plasma of 90 ng/ml is achieved after 6-7 hours. Permeability through the blood-brain and placental barrier is low.
Metabolism
Lisinopril is not biotransformed in the body.
Removal
It is excreted unchanged by the kidneys. The half-life (T½) is 12.6 hours.

In elderly patients, the plasma concentration of lisinopril and the area under the concentration-time curve (AUC) are 2 times greater than in young patients. In patients with chronic heart failure, the absorption and clearance of lisinopril is reduced.
In patients with renal failure, the concentration of lisinopril is several times higher than the concentration in the blood plasma of healthy volunteers, and there is an increase in the time to reach the maximum concentration in the blood plasma and an increase in the half-life.
Lisinopril is eliminated from the body by hemodialysis.
Amlodipine
Suction
After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64%-80%. Food intake does not affect the absorption of amlodipine.
Distribution
Most of the drug in the blood (95%-98%) binds to blood plasma proteins. Sss in the blood serum is observed after 6-10 hours. Equilibrium concentrations (C ss) are achieved after 7-8 days of therapy. The mean volume of distribution is 20 l/kg body weight, indicating that most of the drug is in the tissues and a smaller part is in the blood.
Metabolism
Amlodipine undergoes slow/but active metabolism in the liver with no significant first pass effect. Metabolites do not have significant pharmacological activity.
Removal
Excretion consists of two phases, T½ of the final phase is 30-50 hours. About 60% of the dose taken orally is excreted by the kidneys mainly in the form of metabolites, 10% unchanged, and 20-25% in the form of metabolites through the intestines with bile. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min./kg, 0.42 l/h/kg).
Pharmacokinetics in selected patient groups
In elderly patients (over 65 years of age), the elimination of amlodipine is slower (T½ - 65 hours) compared to young patients, but this difference is not clinically significant.
In patients with liver failure, the prolongation of T½ suggests that with long-term use, the accumulation of the drug in the body will be higher (T½ - up to 60 hours). Renal failure does not have a significant effect on the kinetics of amlodipine.
Amlodipine penetrates the blood-brain barrier. It is not removed by hemodialysis.
Amlodipine + lisinopril
Interaction between the active substances that make up the drug Equator ® is unlikely. AUC, time to reach and values ​​of maximum concentration, half-life do not undergo changes compared to the indicators of each individual active substance. Eating does not affect the absorption of active substances.

Indications for use

Essential hypertension (patients for whom combination therapy is indicated).

Contraindications

• Hypersensitivity to lisinopril or other ACE inhibitors;
• Hypersensitivity to amlodipine or other dihydropyridine derivatives;
• Hypersensitivity to other components of the drug;
• History of angioedema, including during the use of ACE inhibitors;
• Hereditary or idiopathic angioedema;
• Hemodynamically significant stenosis of the aorta or mitral valve;
• Hypertrophic obstructive cardiomyopathy;
• Severe arterial hypotension (systolic blood pressure less than 90 mmHg);
• Cardiogenic shock;
• Unstable angina (with the exception of Prinzmetal's angina);
• Heart failure after acute myocardial infarction (within the first 28 days).
• Pregnancy and lactation;
• Age up to 18 years (efficacy and safety have not been established).

Carefully
Severe renal dysfunction, bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary, hyperaldosteronism, liver dysfunction, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic - heart disease, coronary insufficiency/sick sinus syndrome (severe bradycardia, tachycardia), CHF of non-ischemic etiology of functional class III-IV according to the NYHA classification, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction) , autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), suppression of bone marrow hematopoiesis, diabetes mellitus, diet with limited salt, hypovolemic conditions (including as a result of diarrhea, vomiting), old age, - hemodialysis using high-flow, high-permeability dialysis membranes (AN69 ®).

Use during pregnancy and lactation

The use of Equator ® is not recommended during pregnancy.
At. If pregnancy is diagnosed, taking Equator ® should be stopped immediately.
Taking ACE inhibitors in the second and third trimester of pregnancy has an adverse effect on the fetus (a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, and intrauterine death are possible). There is no data on the negative effects of the drug on the fetus when used during the first trimester of pregnancy. Close monitoring is recommended for neonates and infants exposed in utero to ACE inhibitors. timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia.
The safety of amlodipine during pregnancy has not been established, therefore the use of amlodipine is not recommended during pregnancy.
Lisinopril crosses the placenta and can be excreted in breast milk. There is no data indicating the excretion of amlodipine into breast milk. However, it is known that other BMCA - dihydropyridine derivatives are excreted in breast milk.
The use of Equator ® during breastfeeding is not recommended.
If the use of the drug is necessary during lactation, then breastfeeding must be stopped.

Directions for use and doses

Equator ® tablets are taken orally, once a day, regardless of meal time, with a sufficient amount of liquid.
The recommended dose is 1 tablet of the drug Equator ® 1 time per day. The maximum daily dose is 1 tablet of Equator ®.
At the beginning of therapy with Equator ®, symptomatic arterial hypotension may develop, which more often occurs in patients with water and electrolyte imbalance due to previous diuretic therapy. Diuretics should be discontinued 2-3 days before starting therapy with Equator ® . In cases where discontinuation of diuretics is impossible, the initial dose of Equator ® is ½ tablet once a day, after taking which the patient should be monitored for several hours due to the possible development of symptomatic arterial hypotension.
Patients with kidney failure
To determine the optimal initial and maintenance dose for patients with renal insufficiency, doses must be titrated and determined on an individual basis using lisinopril and amlodipine separately. Equator ® is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively. During treatment with Equator ® it is necessary to monitor renal function, potassium and sodium levels in the blood serum. If kidney function deteriorates, taking Equator ® should be stopped and replaced with lisinopril and amlodipine in adequate doses.
Patients with liver failure
The elimination of amlodipine may be slowed down in patients with impaired liver function: Clear recommendations on the dosage regimen in such cases have not been established, therefore the drug Equator ® should be prescribed with caution in patients with hepatic impairment.
Elderly patients (over 65 years old)
In clinical studies, no age-related changes in the efficacy or safety profile were found for amlodipine and lisinopril. To determine the optimal maintenance dose, it is necessary to determine 1 dosing regimen on an individual basis, using lisinopril and amlodipine separately. Equator ® is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively.

Side effect

The incidence of adverse reactions in patients receiving the combination drug was no higher than in patients receiving one of the active ingredients. Adverse reactions were consistent with previously obtained data on amlodipine and/or lisinopril. Adverse reactions were mild, transient and rarely required discontinuation of treatment. The most common adverse reactions when taking a combination of drugs were: headache (8%), cough (5%), dizziness (3%).
The frequency of adverse reactions is given separately for lisinopril and amlodipine.
Data are presented by organ system class according to the MedDRA classification and with the following frequency: very common (> 1/10); often (from > 1/100 to<1/10); нечасто (от >1/1 000 to<1/100); редко (от >1/10,000 to<1/1 000); очень редко (<1/10 000); частота неизвестна (не может быть установлена на основании имеющихся данных).

Overdose

Symptoms: Overdose can lead to excessive peripheral vasodilation with severe arterial hypotension, collapse, water and electrolyte imbalance, renal failure, shortness of breath, tachycardia, bradycardia, dizziness, anxiety, cough.
Treatment: symptomatic therapy, monitoring of cardiac activity, blood pressure, diuresis and water-electrolyte balance, if necessary, its correction. With a pronounced decrease in blood pressure, the patient is given a horizontal position with raised legs; if necessary, intravenous infusion of 0.9% sodium chloride solution; if these measures do not achieve sufficient results, the use of a peripheral vasopressor (dopamine) may be required to maintain circulation. Intravenous administration of calcium gluconate may have a positive effect on reversing the effects caused by calcium channel blockade. If necessary, intravenous administration of angiotensin II.
Due to the slow absorption of amlodipine, in some cases activated charcoal is used to wash the stomach.
Lisinopril is eliminated by hemodialysis. Due to the strong binding of amlodipine to blood proteins, amlodipine hemodialysis is ineffective. .

Interaction with other drugs

Lisinopril
Substances affecting potassium content: Potassium-sparing diuretics (eg, spironolactone, amiloride, and triamterene), potassium-containing dietary supplements, potassium-containing salt substitutes, and any other drugs that increase serum potassium (eg, heparin) may lead to hyperkalemia when combined with ACE inhibitors, especially in patients with point failure and a history of other kidney diseases. When prescribing a drug that affects potassium levels concomitantly with lisinopril, serum potassium levels should be monitored. Therefore, simultaneous administration should be carefully justified and carried out with extreme caution and regular monitoring of both serum potassium levels and renal function.
Potassium-sparing diuretics can be taken together with Equator ® only under close medical supervision.
Diuretics: if a diuretic is prescribed to a patient receiving Equator ® , the antihypertensive effect is usually enhanced. Concomitant use should be done with caution. Lisinopril mitigates the kaliuretic effect of diuretics.
Other antihypertensive drugs: simultaneous use of these drugs may enhance the antihypertensive effect of the drug Equator ® . Concomitant use with nitroglycerin, other nitrates or vasodilators can lead to a pronounced decrease in blood pressure.
Tricyclic antidepressants/antipsychotics/general anesthesia/narcotic analgesics: Concomitant use with ACE inhibitors can lead to a significant decrease in blood pressure.
Ethanol enhances the antihypertensive effect.
Allopurinol, procainamide, cytostatics or immunosuppressants. (systemic glucocorticosteroids) may lead to an increased risk of developing leukopenia when used simultaneously with ACE inhibitors.
Antacids and cholestyramine, when taken simultaneously with ACE inhibitors, reduce the bioavailability of the latter.
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors; it is necessary to carefully monitor the achievement of the desired effect.
Hypoglycemic drugs: When taking ACE inhibitors and hypoglycemic drugs (insulins and oral hypoglycemic agents) simultaneously, the likelihood of a decrease in blood glucose concentrations and the risk of hypoglycemia may increase. This phenomenon is most often observed during the first week of combination treatment in patients with renal failure.
Nonsteroidal anti-inflammatory drugs (NSAIDs): Long-term use of NSAIDs, including high doses of acetylsalicylic acid more than 3 g/day, may reduce the antihypertensive effect of ACE inhibitors. The additive effect of taking NSAIDs and ACE inhibitors is manifested by an increase in serum potassium and may lead to a deterioration in renal function. These effects are usually reversible. Very rarely, acute renal failure may develop, especially in elderly and dehydrated patients.
Lithium preparations: Lithium excretion may be slowed during concomitant use with ACE inhibitors and therefore serum lithium concentrations should be monitored during this period. When used together with lithium preparations, it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia; tremor, tinnitus).
Gold preparations: with the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex has been described, including facial flushing, nausea, vomiting and arterial hypotension.
Amlodipine
CYP3A4 isoenzyme inhibitors: Studies in elderly patients have shown that diltiazem inhibits the metabolism of amlodipine, probably through CYP3A4 (plasma concentration increases by almost 50% and the effect of amlodipine is increased). The possibility that stronger CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir) may increase serum concentrations of amlodipine to a greater extent than diltiazem cannot be excluded. Concomitant use should be done with caution.
Inducers of the CYP3A4 isoenzyme: simultaneous use with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort ( Hypericum perforatum), may lead to a decrease in amlodipine plasma concentrations. Clinical monitoring with possible dose adjustment of amlodipine is indicated during treatment with inducers of the CYP3A4 isoenzyme and after their discontinuation.
Concomitant use should be done with caution.
As monotherapy, amlodipine was well combined with thiazide and loop diuretics, general anesthesia, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide, magnesium hydroxide), simethicone, - cimetidine, non-steroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral administration.
Amlodipine does not have a significant effect on the pharmacokinetics of ethanol.
Calcium supplements may reduce the effect of slow calcium channel blockers.
Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.
It is possible to reduce the antihypertensive effect of the drug Equator ® when taken simultaneously with estrogen drugs and adrenergic stimulants.
Procainamide, quinidine, and other drugs that prolong the QT interval may cause significant prolongation of the QT interval.

special instructions

Arterial hypotension
A marked decrease in blood pressure with the development of clinical symptoms can be observed in patients with a decrease in circulating blood volume and/or sodium content due to the use of diuretics, fluid loss, or for other reasons, for example, increased sweating, prolonged vomiting and/or diarrhea. It is preferable that recovery, loss of fluid and/or sodium be carried out before starting therapy with Equator ®.
It is necessary to monitor blood pressure after taking the initial dose. Such conditions apply to patients with ischemic, heart disease or cerebrovascular diseases, in whom a pronounced decrease in blood pressure can lead to myocardial infarction or stroke.
Aortic and mitral stenosis.
Like all vasodilators, Equator ® should be prescribed with caution to patients with left ventricular outflow tract obstruction and mitral valve stenosis.
Renal dysfunction
In some patients with arterial hypertension without significant manifestations of renovascular diseases, an increase in the concentration of creatinine and urea in the blood serum was observed, in most cases minimal or transient, more pronounced when taking an ACE inhibitor and a diuretic simultaneously. This is most common in patients with a history of kidney disease.
To determine the optimal; maintenance dose, the dosage regimen must be determined individually, using lisinopril and amlodipine separately, with simultaneous monitoring of renal function: Equator ® is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 and 5 mg, respectively.
If renal function decreases, taking Equator ® should be discontinued and replaced with monotherapy with drugs in adequate doses. In addition, dose reduction or discontinuation of diuretics may be required.
Angioedema
Angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx has been reported in patients taking ACE inhibitors, including lisinopril. In these cases, taking the drug Equator should be stopped immediately and the patient should be closely monitored until the symptoms disappear completely.
Swelling of the face, lips and limbs usually goes away on its own, however, antihistamines should be used to reduce the severity of symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. If swelling of the tongue, pharynx or larynx is detected, which is the cause of airway obstruction, emergency measures must be immediately initiated. Appropriate measures include: the use of a 0.1% solution of epinephrine (adrenaline) subcutaneously at a dose of 0.3 - 0.5 mg or 0.1 mg intravenously slowly, followed by the use of glucocorticosteroids (intravenously) and antihistamines and simultaneous monitoring of vital signs. important functions.
Angioedema of the intestine has rarely been observed in patients taking ACE inhibitors. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, no previous facial angioedema was observed, and C-1 esterase activity was within normal limits. Angioedema of the intestine was diagnosed by computed tomography of the gastrointestinal tract or after ultrasound examination, or with surgical intervention, the symptoms disappeared after stopping the ACE inhibitor. When conducting a differential diagnosis of abdominal pain in patients taking ACE inhibitors, angioedema of the intestine should also be taken into account.
Anaphylactic reactions in patients on hemodialysis
Cases of anaphylactic shock have been reported in patients undergoing polyacrylonitrile membrane hemodialysis (eg, AN-69) and concomitantly receiving ACE inhibitors, and this combination should be avoided.
Patients are advised; use either another type of dialysis membrane or an antihypertensive drug of a different pharmacotherapeutic group.
Anaphylactic reactions in patients undergoing low-density lipoprotein (LDL) apheresis
Rare in patients receiving ACE inhibitors during apheresis. LDL dextran sulfate, life-threatening anaphylactic reactions developed. Such reactions were prevented by discontinuation of ACE inhibitors before each apheresis procedure.
Desensitization from wasp or bee venom
Sometimes patients taking ACE inhibitors developed anaphylactic reactions when desensitized by hymenoptera venom (for example, wasps or bees). Such life-threatening situations can be avoided with timely discontinuation of ACE inhibitors.
Effects on the liver
In rare cases, taking ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and developed into fulminant liver necrosis and, in several cases, led to death. The mechanism of this syndrome is unclear.
Patients receiving Equator ® who develop jaundice or experience increased liver enzyme activity should discontinue the drug and monitor their condition.
Liver failure
In patients with impaired liver function, the half-life of amlodipine is prolonged. At the moment, recommendations on the dosage regimen have not been developed, and therefore this drug should be prescribed with caution, having previously determined the expected benefits and potential risks of treatment.
Neutropenia/agrayulocytosis
In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor. Equator ® should be used with extreme caution in patients with systemic connective tissue diseases, during immunosuppressive therapy, during treatment with allopurinol or procainamide, or a combination of these aggravating factors, especially in the presence of pre-existing renal impairment. Some of these patients developed serious infections, which in several cases did not respond to antibiotic treatment.
Periodically, in such patients during treatment with Equator ®, it is recommended to conduct laboratory tests (blood test with leukocyte count), and also warn them of the need to report the appearance of the first signs of an infectious disease.
Cough
Cough has been frequently reported during the use of ACE inhibitors. As a rule, the cough is non-productive, constant and stopped after discontinuation of the drug. When making a differential diagnosis of cough, cough caused by the use of ACE inhibitors must also be taken into account.
Surgery/general anesthesia
In patients undergoing major surgery or during general anesthesia with drugs that lead to arterial hypotension, lisinopril can block the formation of angiotensin II after a compensatory release of renin. If arterial hypotension develops, probably as a result of the above mechanism, correction can be made by increasing the volume of circulating blood.
Elderly patients
Elderly patients with impaired renal function should undergo a dose adjustment of the drug Equator ® .
Hyperkalemia:
In some patients receiving ACE inhibitors, an increase in serum potassium was observed. The risk group for the development of hyperkalemia includes patients with renal failure, diabetes mellitus, acute heart failure, dehydration, metabolic acidosis, or while taking potassium-sparing diuretics, potassium-containing food additives, potassium-containing salt substitutes or any other drugs that lead to an increase in potassium levels, in blood serum (for example, heparin). If necessary, simultaneous use with the above drugs should monitor the potassium content in the blood serum.
Patients with low body weight, short patients, and patients with severe liver dysfunction may require a dose reduction.
Equator ® does not have any adverse effect on metabolism and blood plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.
During treatment, weight control and observation by a dentist is necessary (to prevent pain, bleeding and gum hyperplasia).

The effect of the drug on the ability to drive vehicles and work with mechanisms with an increased risk of injury

The use of the drug Equator ® may affect the ability to drive vehicles and complex machinery. Transient hypotension and dizziness may occur mainly at the beginning of treatment. Therefore, at the beginning of treatment, it is recommended to avoid driving vehicles, operating machinery, and performing other work that requires increased concentration.

Release form

Tablets, 5 mg + 10 mg.
10 tablets in a blister of white PVC foil/polyethylene/PVDC and varnished hard aluminum foil. 1, 2, 3 or 6 blisters in a cardboard box with attached instructions for use.

Storage conditions

Store in a place protected from light at a temperature not exceeding 25 °C.
Keep out of the reach of children!

Best before date

3 years.
Do not take after the expiration date stated on the package.

Vacation conditions

Dispensed by prescription.

Manufacturer

1. JSC "Gedeon Richter"
   1103 Budapest, st. Dymroyi 19-21, Hungary
2. CJSC "GEDEON RICHTER - RUS"
   140342 Russia, Moscow region, Egoryevsky district, Shuvoe village, st. Lesnaya, 40.

Consumer complaints should be sent to:
Moscow Representative Office of JSC Gedeon Richter
119049 Moscow, 4th Dobryninsky lane, building 8