Equator tablets 10mg/5mg №10×3

Name:
Equator tab 10mg/5mg in bl. in pack. No. 10×3 Main active ingredient Amlodipine + lisinopril Release form Tablets Composition 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: magnesium stearate; sodium starch glycolate (type A); cellulose microcrystalline, type 12; microcrystalline cellulose, type 101. 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); cellulose microcrystalline, 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 besilate 13.88 mg); Excipients: magnesium stearate; sodium starch glycolate (type A); cellulose microcrystalline, type 12; microcrystalline cellulose, type 101.
Description:
Tablets 10 mg/5 mg White or off-white round flat tablets with a bevel, scored on one side and debossed “A+L” on the other side. Diameter: 8mm±0.1mm. The score line is intended solely to facilitate breaking the tablet and making it easier to swallow, and not to divide the tablet into equal doses. Tablets 20 mg/5 mg White or almost white, round, biconvex tablets debossed with “CF2” on one side, the other side without engraving. Tablets 20 mg/10 mg White or almost white, round, biconvex (R: 13 mm) tablets, debossed with “CF3” on one side, the other side unengraved. Diameter: 11±0.1mm. Dosages 10 mg/5 mg and 20 mg/5 mg and 20 mg/10 mg Pharmacological properties Pharmacodynamics Equator® tablets 10 mg/5 mg, Equator® tablets 20 mg/5 mg and Equator® tablets 20 mg/10 mg are fixed dose combinations 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 (OPSS), blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and an increase in myocardial exercise tolerance in patients with chronic heart failure (CHF). Expands arteries more than veins. Some effects are explained by the effect on the tissue renin-angiotensin-aldosterone system (RAAS). With prolonged use, hypertrophy of the myocardium and walls of resistive arteries decreases. Improves blood supply to ischemic myocardium. ACE inhibitors prolong life expectancy in patients with CHF, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. The onset of action is 1 hour after ingestion. 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 a sharp withdrawal of the drug, there was no marked increase in blood pressure. Despite the primary effect, manifested in the impact 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 mellitus and does not lead to an increase in cases of hypoglycemia. Amlodipine is a derivative of dihydropyridine, a blocker of “slow” calcium channels (BCCC), has an antianginal and antihypertensive effect. Blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes). The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: in angina pectoris, it reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces peripheral vascular resistance, reduces afterload on the heart, 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 down the development of angina pectoris and “ischemic” ST segment depression, 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. With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure for 24 hours (in the patient’s position “lying” and “standing”). Orthostatic hypotension with the appointment of amlodipine is quite rare. Does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of hypertrophy of the myocardium of the left ventricle. It does not affect myocardial contractility and conduction, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate (GFR), has a weak natriuretic effect. In diabetic nephropathy does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and plasma lipid concentration 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. Equator® fixed-dose combined preparation 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 expanding arterioles, can lead to sodium and fluid retention in the body and, therefore, can activate the RAAS. The ACE inhibitor blocks this process. Pharmacokinetics Lisinopril Absorption After oral administration, lisinopril is absorbed from the gastrointestinal tract (GIT), the average degree of absorption is approximately 25%, the variability in different patients is from 6 to 60% in the studied dose range (from 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. Distribution and binding to plasma proteins 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 reached after 6-7 hours. The permeability through the blood-brain and placental barrier is low. Metabolism Lisinopril is not biotransformed in the body. Withdrawal Excreted by the kidneys unchanged. The half-life (T1 / 2) is 12.6 hours. Pharmacokinetics in selected groups of patients Impaired renal function Impaired renal function reduces the excretion of lisinopril, but this decrease becomes clinically significant only when GFR < 30 ml / min. With mild and moderate renal insufficiency (creatinine clearance (CC) 30-80 ml / min), the average value of the area under the concentration-time curve (AUC) increases by 13%, with severe renal insufficiency (CC 5-30 ml / min) there is an increase in the average value of AUC by 4.5 times. Lisinopril is excreted 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. Impaired liver function In patients with cirrhosis of the liver, absorption and clearance of lisinopril are reduced. Chronic heart failure In patients with CHF, absorption and clearance of lisinopril are reduced. There is an increase in AUC by an average of 125%. Elderly patients In elderly patients, plasma concentrations of lisinopril and AUC values are approximately 60% higher than in young patients. Amlodipine Absorption After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64% -80%. Eating does not affect the absorption of amlodipine. Distribution and binding to plasma proteins Most of the amlodipine in the blood (95% -98%) binds to plasma proteins. Cmax in blood serum is observed after 6-12 hours. Steady-state concentrations (Css) are reached after 7-8 days of therapy. The mean volume of distribution is 20 l/kg of body weight, indicating that most of the amlodipine is in the tissues, and less in the blood. Amlodipine crosses the blood-brain barrier. Metabolism Amlodipine undergoes slow but active hepatic metabolism with no significant first pass effect. Metabolites do not have significant pharmacological activity. Withdrawal Excretion consists of two phases, T1 / 2 of the final phase of 35-50 hours. About 60% of the ingested dose 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 groups of patients Impaired renal function Renal failure does not significantly affect the kinetics of amlodipine. It is not removed by hemodialysis. Impaired liver function In patients with hepatic insufficiency, there is a decrease in the clearance of amlodipine and an increase in AUC and T1 / 2 by approximately 40-60%. Chronic heart failure In patients with congestive heart failure, there is an increase in the AUC value and the half-life of amlodipine. Elderly patients The time to reach the maximum concentration of the drug in blood plasma in elderly and younger patients is almost the same. In elderly patients, there was a tendency to reduce the clearance of amlodipine, which leads to an increase in AUC and half-life (T1 / 2 - 65 hours). Fixed-dose combination drug Equator® No pharmacokinetic interactions between the active ingredients of the drug have been described. Pharmacokinetic parameters (AUC, time to reach and values of the maximum concentration, T1 / 2) did not differ from those after the use of 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: 10mg / 5mg, 20mg / 5mg and 20mg / 10mg is indicated as an alternative to the simultaneous administration of lisinopril and amlodipine at the indicated doses, which provide adequate control of blood pressure in adult patients. Contraindications Associated with lisinopril: Hypersensitivity to lisinopril or any other ACE inhibitor. Angioedema in history, 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 during breastfeeding"). Simultaneous use of ACE inhibitors or angiotensin II receptor blockers (ARB II) with aliskiren in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2). Associated with amlodipine: Hypersensitivity to amlodipine or other dihydropyridine derivatives. Severe arterial hypotension (systolic blood pressure less than 90 mm Hg). Shock (including cardiogenic shock). Obstruction of the outflow tract of the left ventricle (severe degree of aortic stenosis). Hemo dynamically unstable heart failure after acute myocardial infarction. Equator®-related 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 preparation 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"). With caution Severe renal dysfunction, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, abnormal liver function, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), coronary heart disease, coronary insufficiency, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology III-IV functional class 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), depression of bone marrow hematopoiesis, diabetes mellitus, salt-restricted diet, hypovolemic conditions (including as a result of diarrhea, vomiting), old age, hemodiasis dialysis using high flow dialysis membranes with high permeability (AN69®). Application during pregnancy and lactation Pregnancy The use of the drug Ekvator® is not recommended during the first trimester of pregnancy and is contraindicated during the II and III trimester of pregnancy (see section "Contraindications"). There are no data on the use of Equator® in pregnant women in adequate controlled clinical trials. Therefore, the use of both active substances during pregnancy is not recommended or contraindicated. If pregnancy is confirmed, Ekvator® should be discontinued immediately and, if necessary, alternative treatment should be started (see section "Precautions for Use"). Ekvator should not be started during pregnancy. If continued treatment with Equator® is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive drugs 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 the use of ACE inhibitors during the first trimester of pregnancy are not convincing, however, a small increase in risk cannot be ruled out. If continued treatment with an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive drugs with a known safety profile for use during pregnancy. If pregnancy is confirmed, treatment with an ACE inhibitor should be discontinued immediately and, if necessary, alternative treatment instituted. It is known that the use of ACE inhibitors in women during the II and III trimesters of pregnancy induces fetotoxicity (decrease in kidney function, oligohydramnios, slowing of the 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 the function of the kidneys and skull is recommended. For newborns and infants whose mothers took ACE inhibitors, it is recommended to conduct careful monitoring for the timely 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. Breastfeeding The use of Equator® during breastfeeding is not recommended (data not 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 babies). Fertility Data from adequate controlled clinical studies on the effect of Equator® on fertility are not available. Reversible biochemical changes in the heads of spermatozoa have been reported in some patients with the use of BMCC. Dosage and administration Inside, regardless of the meal. The recommended dose is one tablet of Equator® daily. The maximum daily dose is one tablet of Equator®. As a general rule, a fixed-dose combination should not be used for initial therapy. The drug Equator® at dosages of 10 mg/5 mg, 20 mg/5 mg and 20 mg/10 mg is indicated only for those patients in whom the optimal maintenance doses of lisinopril and amlodipine are titrated to 10 mg and 5 mg in the case of the drug Equator® tablets 10 mg / 5 mg, up to 20 mg and 5 mg in the case of the drug Equator® tablets 20 mg / 5 mg and up to 20 mg and 10 mg in the case of the drug Equator® tablets 20 mg / 10 mg, respectively. If a 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 insufficiency, it is necessary to titrate doses using lisinopril and amlodipine separately. During treatment with Ekvator®, it is necessary to monitor kidney function, the content of potassium and sodium in the blood serum. In case of deterioration of renal function, the drug should be discontinued and replaced with lisinopril and amlodipine in adequate doses. Patients with hepatic impairment Excretion of amlodipine may be delayed in patients with hepatic impairment. Clear recommendations on the dosing regimen in such cases have not been established, so Equator® should be prescribed from the lowest recommended dose. To determine the optimal initial and maintenance dose in patients with hepatic insufficiency, it is necessary to titrate doses separately for lisinopril and amlodipine. Elderly patients (over 65 years of age) Elderly patients should use the drug 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 dosing regimen on an individual basis, using lisinopril and amlodipine separately. Side effects The frequency of adverse reactions in patients receiving the combined drug was not higher than in patients receiving one of the active substances. Adverse reactions were consistent with previously reported data for amlodipine and/or lisinopril. Adverse reactions were mild, transient and rarely required discontinuation of treatment. The most commonly reported 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 system organ class according to the MedDRA classification and with the following frequency: very often (> 1/10); often (> 1/100 to < 1/10); infrequently (from > 1/1,000 to < 1/100); rarely (> 1/10,000 to < 1/1,000); very rarely (< 1/10,000); the frequency is unknown (cannot be established based on the available data). Organ system class Frequency Adverse reactions of lisinopril Adverse reactions of amlodipine Blood and lymphatic system disorders Very rare Bone marrow hematopoiesis, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, anemia, lymphadenopathy Thrombocytopenia, leukopenia Immune system disorders Very rare Autoimmune disorders Allergic reactions Endocrine disorders Rare Syndrome of inappropriate antidiuretic hormone secretion (SIAH) Metabolic and nutritional disorders Very rare Hypoglycemia Hyperglycemia Psychiatric disorders Uncommon Mood changes, sleep disturbances Insomnia, mood changes (including anxiety), depression Rare Psychiatric disorders Confusion of consciousness Frequency unknown Depression Nervous system disorders Common Dizziness, headache Drowsiness, dizziness, headache (especially during the initial period of treatment) Uncommon Vertigo, paresthesia , dysgeusia Syncope, tremor, dysgeusia, hypesthesia, paresthesia Very rare Muscle hypertonicity, peripheral neuropathy Unknown Syncope Visual disturbances Uncommon Visual disturbances (including diplopia) Hearing and labyrinth disturbances Uncommon Tinnitus Disorders from the side Heart palpitations Uncommon Myocardial infarction, possibly due to a pronounced decrease in blood pressure in high-risk patients, tachycardia, palpitations Very rare Myocardial infarction, arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation) Vascular disorders Common Orthostatic hypotension Hyperemia Skin disorders Uncommon Cerebrovascular accident, possibly caused by a pronounced decrease in blood pressure in high-risk patients, Raynaud's syndrome BP decrease Very rare Vasculitis Respiratory, chest and mediastinal disorders Common Cough Uncommon Rhinitis Dyspnoea, rhinitis Very rare Bronchitis ospasm, allergic alveolitis/eosinophilic pneumonia, sinusitis Cough Gastrointestinal disorders Common Diarrhea, vomiting Abdominal pain, nausea Uncommon Abdominal pain, nausea, indigestion Vomiting, dyspepsia, diarrhea or constipation, dryness of the oral mucosa Rare Dryness oral mucosa Very rare Pancreatitis, intestinal angioedema Pancreatitis, gastritis, gingival hyperplasia Liver and biliary tract disorders Very rare Liver failure, hepatitis, cholestatic jaundice Hepatitis, jaundice Skin and subcutaneous tissue disorders Uncommon Rash, pruritus Alopecia, purpura , discoloration of the skin, increased sweating, pruritus, rash, exanthema Rare Psoriasis, urticaria, alopecia, hypersensitivity/angioedema of the face, extremities, lips, tongue, glottis and/or larynx Very rare Toxic epidermal necrolysis, Stevens-Johnson syndrome, multiforme erythema, pemphigus vulgaris, sweating, skin pseudolymphoma* Angioedema, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, angioedema, photosensitivity, urticaria Musculoskeletal and connective tissue disorders Common Ankle edema Uncommon Arthralgia, myalgia, muscle cramps, back pain Renal and urinary tract disorders Common Renal dysfunction Uncommon Urination disorder, nocturia, increased frequency of urination Rare Acute renal failure, uremia Very rare Oliguria/anuria Genital and breast disorders Uncommon Impotence Impotence, gynecomastia Rare Gynecomastia General disorders and disorders at the injection site 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 serum blood tissue, hyperkalemia, elevated liver enzymes Weight gain, weight loss Rare Decreased hemoglobin, decreased hematocrit, elevated serum bilirubin, hyponatremia Very rare Increased liver enzymes** * Syndrome may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, increased antinuclear antibody (ANA) titer, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity, or other skin changes. ** 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 an overdose of Equator® in humans. Lisinopril Symptoms: arterial hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough. Treatment: gastric lavage, activated charcoal, giving the patient a horizontal position with raised legs, replenishment of circulating blood volume (VCC) - intravenous administration of plasma-substituting solutions, symptomatic therapy, the advisability of infusion administration of angiotensin II and / or intravenous administration of catecholamines can also be considered, function control cardiovascular and respiratory systems, bcc, urea concentration, creatinine and electrolytes in blood serum, as well as diuresis. With the development of bradycardia, resistant to drug therapy, the setting of an artificial pacemaker is indicated. Lisinopril can be removed from the systemic circulation by hemodialysis. Amlodipine Symptoms: a pronounced 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, maintenance of the function of the cardiovascular system, control of the functions of the cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, control of circulating blood volume (BCC) and diuresis. To restore vascular tone - the use of vasoconstrictor agents (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. Fixed-dose combination drug Equator® Symptoms: An overdose of Equator® can lead to excessive peripheral vasodilation with severe arterial hypotension, acute vascular insufficiency, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough. Treatment: it is recommended to carry out symptomatic treatment (put the patient in the supine position, monitor and, if necessary, maintain the functions of the cardiovascular and respiratory systems, control blood pressure, replenish bcc and restore electrolyte balance, monitor serum creatinine concentration). In case of severe arterial hypotension, the lower limbs should be raised above the head; if intravenous administration of blood substitutes has not led to a sufficient result, maintenance therapy may be required due to the introduction of peripheral vasopressors, provided that there are no contraindications to their use. Infusion administration 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 carry out hemodialysis to remove lisinopril from the systemic circulation. The use of high-flow polyacrylonitrile membranes during dialysis is not recommended. Interactions with other drugs Lisinopril Potassium-containing nutritional supplements, potassium-sparing diuretics, potassium-containing salt substitutes: potassium-sparing diuretics (for example, spironolactone, amiloride and triamterene), potassium-containing nutritional supplements, potassium-containing salt substitutes, and any other drugs that increase serum potassium (for example, heparin) can lead to the development of hyperkalemia when administered concomitantly with ACE inhibitors, especially in patients with renal insufficiency and other kidney diseases in history. When prescribing a drug that affects the content of potassium, simultaneously with lisinopril, the content of potassium in the blood serum should be monitored. Simultaneous administration should be carried out with extreme caution and regular monitoring of the state of kidney function and the content of potassium in the blood serum. Potassium-sparing diuretics can be used concomitantly 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 possibility of symptomatic hypotension while taking lisinopril can be minimized by discontinuing the diuretic before starting treatment with lisinopril. Simultaneous use should be carried out with caution. Lisinopril softens the kaliuretic effect of diuretics. Other antihypertensive drugs: the simultaneous use of these drugs may enhance the antihypertensive effect of the drug Ekvator®. Simultaneous reception with nitroglycerin, other nitrates or vasodilators can lead to a pronounced decrease in blood pressure. Dual blockade of the renin-angiotensin-aldosterone system: According to available data, dual blockade of the RAAS with 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 insufficiency (GFR < 60 ml/min/1.73 m2), concomitant use of aliskiren with ACE inhibitors or ARB II is contraindicated. In some cases, when the combined use of ACE inhibitors and ARB II is absolutely indicated, careful observation by a specialist and mandatory monitoring of renal function, water and electrolyte balance, and blood pressure are necessary. Tricyclic antidepressants / antipsychotics / general anesthetics / narcotic analgesics: Concomitant use with ACE inhibitors may lead to a pronounced 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 concomitantly with ACE inhibitors. Antacids and cholestyramine, when taken together 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: Concomitant use of ACE inhibitors and hypoglycemic drugs (insulin and oral hypoglycemic agents) may increase the risk of hypoglycemia. Most often, such conditions are observed during the first week of combined treatment and in patients with renal insufficiency. Non-steroidal 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 the use of NSAIDs and ACE inhibitors is manifested in an increase in the content of potassium in the blood serum and may lead to a deterioration in kidney function. These effects are usually reversible. Very rarely, acute renal failure may develop, especially in elderly and dehydrated patients. Lithium preparations: the excretion of lithium may be slowed down when used simultaneously with ACE inhibitors and therefore, in this case, the concentration of lithium in the blood serum should be monitored. When combined 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. The combined use of thiazide diuretics with ACE inhibitors may lead to an increased risk of lithium toxicity and further increase lithium intoxication. Gold preparations: with the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex is described, including facial flushing, nausea, vomiting, dizziness and arterial hypotension. Acetylsalicylic acid, thrombolytics, beta-blockers, nitrates: Lisinopril can be used simultaneously with acetylsalicylic acid (in cardiac doses), thrombolytics, beta-blockers and / or nitrates. Amlodipine Effects of other medicinal products on amlodipine CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolide antibiotics (such as erythromycin or clarithromycin), verapamil or diltiazem) may result in a significant increase in effects of amlodipine, which are more pronounced in elderly patients. Recommended medical supervision and, if necessary, dose adjustment of amlodipine. CYP3A4 isoenzyme inducers: simultaneous use with CYP3A4 isoenzyme inducers (for example, rifampicin, preparations containing St. The simultaneous use of amlodipine and inducers of the CYP3A4 isoenzyme should be carried out with caution. Taking amlodipine with grapefruit or grapefruit juice is not recommended because in some patients it may increase the bioavailability of amlodipine, resulting in an increase in its antihypertensive effect. Dantrolene (infusion): In animal stu