Equator 5 what features in the standard package. Antihypertensive pills for pressure Equator: reviews, price, analogues and recommendations for use. Interaction with other drugs
Instructions for use
Active ingredients
Release form
Pills
Compound
Active ingredient: Amlodipine + Lisinopril (Amlodipine + Lisinopril) Active ingredient concentration (mg): Amlodipine besylate 6.94 mg, which corresponds to the content of amlodipine 5 mg, lisinopril dihydrate 10.88 mg, which corresponds to the content of lisinopril 10 mg
Pharmacological effect
A combined antihypertensive drug containing lisinopril and amlodipine. Lisinopril, an ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces peripheral vascular resistance, blood pressure, 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. Expands arteries more than veins. Some effects are explained by the effect on the tissue 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 chronic heart failure, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. 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. 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. Amlodipine is a blocker of slow calcium channels, a derivative of dihydropyridine. It has antianginal and antihypertensive effects. It 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). 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 coronary arteries(including those caused by smoking). In patients with stable angina pectoris, 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 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 (with the patient 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 left ventricular myocardial hypertrophy. It does not affect the contractility and conduction of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. Does not have any adverse influence 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. 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, a calcium channel blocker, by directly dilating 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, its absorption can vary from 6 to 60%. Bioavailability - 29%. Eating does not affect the absorption of lisinopril. Cmax in plasma is 90 ng / ml and is reached after 6 hours. Distribution Almost does not bind to plasma proteins. Permeability through the BBB and the placental barrier is low. Metabolism Lisinopril is not metabolized in the body. Excretion Excreted in the urine unchanged, T1 / 2 - 12.6 hours. Pharmacokinetics in special clinical situations In elderly patients, the concentration of lisinopril in plasma and AUC is 2 times higher than in patients of young age. In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced. In patients with renal insufficiency, the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, and there is an increase in the time to reach Cmax in blood plasma and an increase in T1 / 2. Lisinopril is excreted from the body by hemodialysis. Amlodipine Absorption After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64% -80%. Cmax in blood serum is observed after 6-10 hours. Food intake does not affect the absorption of amlodipine. Distribution Most of the amlodipine in the blood (95% -98%) binds to plasma proteins. Css are achieved after 7-8 days of therapy. The average Vd is 20 l/kg of body weight, which indicates that most of the amlodipine is in the tissues, and less in the blood. Amlodipine crosses the BBB. Metabolism Amlodipine undergoes slow but active metabolism in the liver with no significant first pass effect. Metabolites do not have significant pharmacological activity. Excretion 10% of amlodipine is excreted in the urine unchanged, 60% - in the form of metabolites; 20-25% - in the form of metabolites with bile through the intestines. The withdrawal is biphasic. T1 / 2 of the final phase is 30-50 hours. Pharmacokinetics in special clinical situations In elderly patients (over 65 years old), the elimination of amlodipine is slowed down (T1 / 2 - 65 hours) compared with young patients, but this difference has no clinical significance. In patients with hepatic insufficiency prolongation of T1 / 2 suggests that with prolonged 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. It is not removed during hemodialysis. Amlodipine and lisinopril Interaction between the active substances that make up the drug is unlikely. AUC, time to reach and Cmax in blood plasma, T1 / 2 do not change compared to the indicators of each individual active substance. Eating does not affect the absorption of active substances.
Indications
Essential arterial hypertension (patients who are indicated for combination therapy).
Contraindications
Quincke's edema in history, incl. against the background of 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 pectoris (with the exception of Prinzmetal's angina); - heart failure after acute myocardial infarction (during the first 28 days); - pregnancy; - lactation; - children and adolescence up to 18 years (efficacy and safety have not been established in this age group); - hypersensitivity to the components of the drug; - hypersensitivity to lisinopril and other ACE inhibitors; - hypersensitivity to other dihydropyridine derivatives.
Precautionary measures
Caution should be used in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia, with azotemia, primary hyperaldosteronism, with severe renal dysfunction, a condition after kidney transplantation, hyperkalemia, abnormal liver function, arterial hypotension, cerebrovascular diseases (in including cerebrovascular insufficiency), ischemic heart disease, coronary insufficiency, SSSU (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology III-IV FC according to the NYHA classification, with aortic stenosis, mitral stenosis, acute myocardial infarction (and in within 1 month after myocardial infarction), autoimmune systemic diseases connective tissue(including with scleroderma, systemic lupus erythematosus), with oppression of bone marrow hematopoiesis, diabetes mellitus, a diet with salt restriction, with hypovolemic conditions (including as a result of diarrhea, vomiting), in elderly patients, with hemodialysis using high-flow dialysis membranes with high permeability (AN69).
Use during pregnancy and lactation
The drug is contraindicated for use in pregnancy. When diagnosing pregnancy, taking Equator should be stopped immediately. Lisinopril crosses the placental barrier. Taking ACE inhibitors in the II and III trimesters of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, intrauterine fetal death are possible). Data about negative impact There is no drug for the fetus when used in the first trimester of pregnancy. For newborns and infants who have been exposed to ACE inhibitors in utero, it is recommended to carefully monitor for the timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia. The safety of amlodipine during pregnancy has not been established, therefore its use in this category of patients is contraindicated. milk. There are no data indicating the release of amlodipine with breast milk. However, other calcium channel blockers, dihydropyridine derivatives, are known to be excreted in breast milk. The use of the drug Equator during lactation is not recommended. If necessary, the use of the drug Equator during lactation, breastfeeding should be discontinued.
Dosage and administration
The drug is taken orally, regardless of food intake, with a sufficient amount of liquid. The recommended dose is 1 tab. 1 time / day The maximum daily dose is 1 tab. At the beginning of therapy with Equator, symptomatic arterial hypotension may develop, which occurs more often in patients with impaired water and electrolyte balance due to previous diuretic therapy. Reception of diuretics should be stopped 2-3 days before the start of therapy with Equator. In the case when the abolition of diuretics is not possible, the initial dose of the drug Equator is 1/2 tab. 1 time / day, after which the patient should be monitored for several hours due to the possible development of symptomatic arterial hypotension. Patients with renal insufficiency To determine the optimal initial and maintenance dose for patients with renal insufficiency, doses must be titrated and determined in individually using lisinopril and amlodipine separately. Equator 5 mg/10 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively. Equator 5 mg/20 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 mg and 5 mg, respectively. Equator 10 mg/20 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 mg and 10 mg, respectively. During treatment with Ekvator, it is necessary to monitor kidney function, the content of potassium and sodium in the blood serum. If renal function worsens, Ekvator should be discontinued and replaced with lisinopril and amlodipine in adequate doses. Patients with hepatic insufficiency The elimination of amlodipine may be slowed down in patients with impaired liver function. Clear recommendations on the dosing regimen in such cases have not been established, therefore, Equator should be administered with caution to patients with hepatic insufficiency. Elderly patients (over 65 years) In clinical studies, there were no age-related changes in the efficacy or safety profile for 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. Equator 5 mg/10 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively. Equator 5 mg/20 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 mg and 5 mg, respectively. Equator 10 mg/20 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 mg and 10 mg, respectively.
Side effects
The frequency of adverse reactions in patients receiving the combination 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 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 system organ classes in accordance with MedDRA classification and with the following frequency: very often (≥1/10); often (from ≥1/100 to
Overdose
Amlodipine Symptoms: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of developing severe and persistent arterial hypotension, including with the development of shock and death). Treatment: gastric lavage, prescription activated carbon, maintaining the function of cardio-vascular system, control of the functions of the cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, control of 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 - in / in the introduction of calcium gluconate. Hemodialysis is ineffective. Lisinopril Symptoms: pronounced decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability. solutions, symptomatic therapy, control of 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 by hemodialysis.
Interaction with other drugs
Lisinopril Potassium-sparing diuretics (eg, spironolactone, amiloride, and triamterene), potassium supplements, potassium-containing salt substitutes, and other medications that can increase serum potassium levels (eg, heparin) may cause hyperkalemia when combined with ACE inhibitors, especially in patients with renal insufficiency and other kidney diseases in history. When prescribing a drug that affects the concentration of potassium, simultaneously with lisinopril, the concentration of potassium in the blood serum should be monitored. Therefore, the simultaneous appointment should be carefully justified and made with extreme caution and regular monitoring of both the level of potassium in the blood serum and kidney function. Potassium-sparing diuretics can be taken together with Equator only under medical supervision. If a diuretic is prescribed to a patient receiving Equator, the hypotensive effect is usually enhanced. Therefore, it is necessary to take Equator with extreme caution in combination with diuretics. Lisinopril softens the kaliuretic effect of diuretics. With the simultaneous use of other antihypertensive drugs, the hypotensive effect of the drug Equator may be enhanced. When taken simultaneously with nitroglycerin, other nitrates or vasodilators, a more pronounced decrease in blood pressure is possible. for general anesthesia, opioid analgesics may have a more pronounced decrease in blood pressure. Ethanol enhances the hypotensive effect of the drug. Allopurinol, procainamide, cytostatics or immunosuppressants (systemic corticosteroids) may increase the 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 can reduce the hypotensive effect of ACE inhibitors; it is necessary to carefully monitor the achievement of the desired effect. With the simultaneous use of ACE inhibitors and hypoglycemic drugs (insulins and oral hypoglycemic agents), it is possible to increase the likelihood of a decrease in blood glucose concentration and the risk of hypoglycemia. Most often, this phenomenon is observed during the first week of combined treatment and in patients with renal insufficiency. With prolonged use of NSAIDs, including acetylsalicylic acid at high doses, the effectiveness of ACE inhibitors may decrease. The additive effect when taking NSAIDs and ACE inhibitors is manifested by an increase in the level of potassium in the blood serum and can lead to a deterioration in kidney function. These effects are usually reversible. Very rarely, acute renal failure may develop, especially in elderly patients and patients in a state of dehydration. Lithium excretion may be slowed down during concomitant use with ACE inhibitors and therefore the concentration of lithium in the blood serum should be monitored during this period. When combined with lithium drugs, it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). , vomiting and arterial hypotension. Amlodipine Studies in elderly patients have shown that diltiazem inhibits the metabolism of amlodipine, probably due to inhibition of the CYP3A4 isoenzyme (plasma concentration increases by almost 50% and the effect of amlodipine increases). It cannot be ruled out that stronger inhibitors of the CYP3A4 isoenzyme (i.e. ketoconazole, itraconazole, ritonavir) are able to increase the concentration of amlodipine in blood plasma to a greater extent than diltiazem. Simultaneous use should be carried out with caution. With simultaneous use with inducers of the CYP3A4 isoenzyme - with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort - a decrease in the concentration of amlodipine in blood plasma is possible. Clinical control is shown with a possible dose adjustment of amlodipine during treatment with inducers of the CYP3A4 isoenzyme and after their cancellation. Simultaneous use should be carried out with caution. As monotherapy, amlodipine was well combined with thiazide and loop diuretics, general anesthesia, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide, magnesium hydroxide), simethicone, cimetidine, NSAIDs, antibiotics and oral hypoglycemic drugs. It is possible to enhance the antianginal and antihypertensive effect of slow calcium channel blockers when used together with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as strengthening their antihypertensive action 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 slow calcium channel blockers , incl. amlodipine. Antipsychotics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives. Amlodipine does not significantly affect the pharmacokinetics of ethanol. Calcium preparations can reduce the effect of slow calcium channel blockers. tremor, tinnitus). Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine. It does not affect the serum concentration of digoxin and its renal clearance. It does not significantly affect the action of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine. It is possible to reduce the antihypertensive effect of the drug Equator with simultaneous use with estrogens, sympathomimetics. Procainamide, quinidine and others medicines prolonging the QT interval may contribute to its significant lengthening. 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, since in some patients this may lead to an increase in the bioavailability of amlodipine resulting in an increase in its antihypertensive effect.
special instructions
Arterial hypotension A pronounced decrease in blood pressure with the development of clinical symptoms can be observed in patients with reduced BCC and / or sodium content due to diuretics, fluid loss, or for other reasons, for example, with profuse sweating, prolonged vomiting and / or diarrhea. In the event of arterial hypotension, the patient should be laid down and fluid loss replenished (in / in infusion of 0.9% sodium chloride solution) if necessary. Preferably, fluid and/or sodium loss should be restored prior to initiation of therapy with Equator. It is necessary to monitor blood pressure after taking the initial dose. This is especially true for patients with coronary heart disease or cerebrovascular diseases, when 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 obstruction of the outflow tract of the left ventricle and mitral valve stenosis. Dysfunction kidneys In some patients with arterial hypertension without pronounced manifestations of renovascular diseases, an increase in serum creatinine and urea was observed, in most cases minimal or transient, more pronounced while taking ACE inhibitors and a diuretic. This is most typical for patients with a history of kidney disease. To determine the optimal maintenance dose, it is necessary to determine the dosing regimen on an individual basis, using lisinopril and amlodipine separately, while monitoring kidney function. In the event of a decrease in renal function, Ekvator should be discontinued and replaced with monotherapy with drugs in adequate doses. In addition, a reduction in the dose or withdrawal of diuretics may be required. Angioedema Angioedema of the face, extremities, lips, tongue, vocal cords and / or larynx has been reported in patients taking an ACE inhibitor, including lisinopril. In these cases, Equator should be stopped immediately and the patient should be closely monitored until the symptoms disappear completely. Edema of the face, lips and extremities usually resolves on its own, however, antihistamines should be used to reduce the severity of symptoms. Angioedema, accompanied by swelling of the larynx, may lead to death. If edema of the tongue, pharynx, or larynx is detected, which is the cause of airway obstruction, it is urgent to start emergency measures. Appropriate measures include: s / c injection of 0.3-0.5 mg or slow / in / in the introduction of 0.1 mg of a 0.1% solution of epinephrine (adrenaline), followed by / in the introduction of corticosteroids and antihistamines and simultaneous monitoring of vital functions. Patients taking ACE inhibitors rarely experienced intestinal angioedema. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, no previous facial edema was observed, and C-1 esterase activity was within the normal range. Intestinal angioedema of the intestine was diagnosed according to computed tomography of the gastrointestinal tract, or after ultrasound, or during surgery, the symptoms disappeared after discontinuation of the ACE inhibitor. In the differential diagnosis of abdominal pain in patients taking ACE inhibitors, intestinal angioedema should also be considered. Anaphylactic reactions in patients on hemodialysis In patients who underwent hemodialysis through polyacrylonitrile membranes (for example, AN69) and who simultaneously received ACE inhibitors, cases of anaphylactic shock have been reported, so this combination should be avoided. Patients are advised to use either another type of dialysis membrane or antihypertensive drug of another pharmacotherapeutic group. Anaphylactic reactions in patients during LDL apheresis Rarely, patients receiving ACE inhibitors during LDL apheresis with dextran sulfate developed life-threatening anaphylactic reactions. Such reactions were prevented by discontinuing ACE inhibitors before each apheresis procedure. Desensitization with wasp or bee venom Anaphylactic reactions have occasionally developed in patients treated with ACE inhibitors when desensitized by hymenoptera (eg, wasps or bees) venom. Such life-threatening situations can be avoided with the timely cancellation of ACE inhibitors. Hepatotoxicity 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. In patients receiving Equator, with the development of jaundice or increased activity of liver enzymes, Equator should be canceled with subsequent monitoring of their condition. Liver failure In patients with impaired liver function, T1 / 2 of amlodipine is extended. At the moment, recommendations on the dosing regimen have not been developed, so Equator should be prescribed with caution, after evaluating the expected benefits and potential risks of treatment. Hematological toxicity In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with 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 vascular collagenosis, during immunosuppressive therapy, during treatment with allopurinol or procainamide, or a combination of these aggravating factors, especially in the presence of previous renal dysfunction. Some of these patients developed serious infectious diseases, which in several cases were not corrected by antibiotic therapy. During treatment with Equator, it is recommended to periodically monitor the level of leukocytes in such patients, as well as warn them about the need to report the first signs of an infectious disease. Cough Cough has often been recorded during the use of ACE inhibitors. As a rule, the cough is unproductive, persistent and stopped after the drug was discontinued. In the differential diagnosis of cough, cough caused by the use of ACE inhibitors should also be taken into account. Surgery / General anesthesia In patients undergoing major surgery or during general anesthesia with drugs leading 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, an increase in BCC can be corrected. Elderly patients Elderly patients with impaired renal function should adjust the dose of Equator. Hyperkalemia In some patients treated with ACE inhibitors, an increase in serum potassium was observed. The risk group for the development of hyperkalemia are patients with renal insufficiency, diabetes mellitus, acute heart failure, dehydration, metabolic acidosis, or while taking potassium-sparing diuretics, food additives with potassium, potassium-containing salt substitutes, or any other medicinal products that lead to an increase in the level of potassium in the blood serum (for example, heparin). If necessary, simultaneous administration with the above drugs should monitor the concentration of potassium in the blood serum. Patients with reduced body weight, patients of short stature and patients with severe liver dysfunction may need to reduce the dose. Equator does not have any adverse effect on metabolism and plasma lipids blood and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. During treatment, body weight control and supervision by a dentist is necessary (to prevent soreness, bleeding and gum hyperplasia). caution (risk of developing a pronounced decrease in blood pressure and dizziness). Therefore, at the beginning of treatment, it is recommended to avoid administration vehicles, work with mechanisms and perform other work that requires increased concentration.
Active ingredients
Lisinopril (lisinopril)
- amlodipine (amlodipine)
Release form, composition and packaging
Pills white or almost white color, round, flat, chamfered, scored on one side and engraved "A+L" on the other.
Excipients: magnesium stearate, sodium carboxymethyl starch (type A), microcrystalline cellulose (type 101), microcrystalline cellulose (type 12).
10 pieces. - blisters (2) - packs of cardboard.
Pills white or almost white, round, biconvex, engraved with "CF2" on one side.
Excipients: magnesium stearate, sodium carboxymethyl starch (type A), microcrystalline cellulose (type 101), microcrystalline cellulose (type 12).
10 pieces. - blisters (3) - packs of cardboard.
Pills white or almost white, oblong, biconvex, with a risk on both sides and engraved "CF" to the left of the risk and the number "5" to the right of the risk on one side.
Excipients: magnesium stearate, sodium carboxymethyl starch, microcrystalline cellulose (type 12), microcrystalline cellulose (type 101).
10 pieces. - blisters (3) - packs of cardboard.
Pills white or almost white, round, biconvex, engraved with "CF3" on one side.
Excipients: microcrystalline cellulose 101, microcrystalline cellulose 12, sodium carboxymethyl starch, magnesium stearate.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
pharmachologic effect
Equator is a combination drug containing active ingredients - amlodipine and lisinopril.
Amlodipine
A derivative of dihydropyridine - a blocker of slow calcium channels (BMCC), reduces the transmembrane transition of calcium ions into the cell (to a greater extent into vascular smooth muscle cells than into cardiomyocytes).
It has a long-term dose-dependent hypotensive 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 use of amlodipine is quite rare.
Amlodipine 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, inhibits platelet aggregation, increases glomerular filtration rate, and 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 blood 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.
Does not increase the risk of death or the development of complications and deaths in patients with CHF (III-IV FC according to the NYHA classification) during therapy with diuretics and ACE inhibitors.
In patients with CHF (III-IV FC according to the NYHA classification) of non-ischemic etiology, when using amlodipine, there is a possibility of pulmonary edema.
Lisinopril
Lisinopril is an ACE inhibitor that prevents the conversion of angiotensin I to angiotensin II. A decrease in the content of angiotensin II leads to a direct decrease in the secretion of aldosterone. Lisinopril reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces OPSS, blood pressure, preload and pressure in the pulmonary capillaries. Lisinopril provides a more pronounced expansion of the arteries than veins. Some of the effects of lisinopril are mediated by its effect on the tissue renin-angiotensin system. Its long-term use leads to a decrease in myocardial hypertrophy and the walls of resistive arteries.
Lisinopril improves myocardial blood supply during ischemia.
The effect occurs within 1 hour after taking lisinopril orally. The maximum effect develops within 6-7 hours; the duration of the effect lasts 24 hours. In patients with arterial hypertension, the effect is observed during the first days after the start of treatment; a stable effect is achieved within 1-2 months of treatment. With the abrupt abolition of lisinopril, cases of a significant increase in blood pressure were not observed. Lisinopril provides both a decrease in blood pressure and a decrease in albuminuria. In patients with hyperglycemia, lisinopril helps to restore the function of the damaged glomerular endothelium. In patients with diabetes mellitus, lisinopril does not affect the concentration of glucose in the blood; the use of lisinopril does not lead to an increase in the incidence of hypoglycemia.
Equator
A combination drug containing amlodipine and lisinopril helps prevent the development of possible side effects caused by one of the active substances. For example, a slow calcium channel blocker, by causing dilation of arterioles, can lead to sodium and fluid retention in the body, which, in turn, can lead to activation of the renin-angiotensin-aldosterone system. The ACE inhibitor blocks this process and normalizes the response to salt loading.
Pharmacokinetics
Amlodipine
Suction
After oral administration, amlodipine is well absorbed from the gastrointestinal tract. The average absolute bioavailability of amlodipine is 64-80%. C max in blood serum is observed after 6-12 hours. Food intake does not affect the absorption of amlodipine.
Distribution
Most of the amlodipine in the blood (97.5%) binds to plasma proteins. C ss are achieved after 7-8 days of therapy. The average V d is 21 l / kg of body weight, which indicates that most of the amlodipine is in the tissues, and the smaller part is in the blood. Amlodipine crosses the BBB.
Metabolism and excretion
Amlodipine undergoes slow but active hepatic metabolism with no significant first pass effect. Metabolites do not have significant pharmacological activity.
T 1/2 from plasma varies from 35 to 50 hours, which allows you to take the drug 1 time / day. T1 / 2 with repeated use is approximately 45 hours. About 60% of the oral dose is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - 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).
Amlodipine is not removed from plasma during hemodialysis.
Elderly patients: in elderly patients (over 65 years of age), the excretion of amlodipine is slower (T 1 / 2 - 65 h) compared with young patients, but this difference has no clinical significance.
Patients with liver failure: prolongation of T 1/2 in patients with hepatic insufficiency suggests that with prolonged use, the accumulation of the drug in the body will be higher (T 1/2 - up to 60 hours).
Patients with renal insufficiency: renal failure does not significantly affect the kinetics of amlodipine.
Lisinopril
Suction
When taking lisinopril orally, 25% of the active substance is absorbed in the gastrointestinal tract. Absorption of lisinopril does not depend on food intake. The average level of absorption is 30%, bioavailability is 29%.
Distribution
Cmax in blood plasma is achieved within 6-8 hours after ingestion. Lisinopril binds poorly to plasma proteins, poorly penetrates the BBB.
Metabolism
Lisinopril is not biotransformed in the body.
breeding
T 1/2 is 12 hours.
Pharmacokinetics in selected groups of patients
At patients with CHF absorption and clearance of lisinopril are reduced. In this category of patients, the absolute bioavailability of lisinopril is reduced by approximately 16%, but AUC increases by an average of 125% compared with healthy volunteers.
Impaired renal function leads to an increase in AUC and T 1/2 lisinopril, but these changes become clinically significant only when the GFR falls below 30 ml / min / 1.73 m 2.
With mild to moderate renal insufficiency (CC from 30 to 80 ml / min), the average AUC value increases by 13%, while in severe renal failure (CC from 5 to 30 ml / min), an increase in the average AUC value by 4.5 times is observed. .
In patients with cirrhosis of the liver, the absorption of lisinopril is reduced (approximately 30%), but the effect of the drug is increased (approximately 50%) compared with healthy volunteers due to a decrease in clearance.
In elderly patients, the plasma concentration of lisinopril and AUC are 2 times higher than in young patients.
Equator
Interaction between the active ingredients of the drug Equator is unlikely. The values of AUC, C max , the time to reach C max , as well as T 1/2 do not change in comparison with the indicators of each individual active substance. Eating does not affect the absorption of active substances. Long-term circulation of both active substances in the body allows you to take the drug 1 time / day.
Indications
- arterial hypertension (in patients who are indicated for combination therapy).
Contraindications
- hypersensitivity to lisinopril or any other ACE inhibitor;
- hypersensitivity to amlodipine or any other derivative of dihydropyridine;
- hypersensitivity to any of the excipients;
- angioedema in history, incl. in connection with the use of ACE inhibitors;
- hereditary or idiopathic angioedema;
- shock (including cardiogenic);
- unstable angina (with the exception of Prinzmetal's angina);
- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
- hemodynamically significant obstruction of the outflow tract of the left ventricle (for example, with severe aortic stenosis, hypertrophic obstructive cardiomyopathy), hemodynamically significant mitral stenosis;
- unstable hemodynamic parameters in acute myocardial infarction (and within 1 month after it);
- simultaneous use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and / or moderate or severe renal impairment (GFR less than 60 ml / min / 1.73 m 2 body surface area);
- simultaneous use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy;
- simultaneous use with neutral endopeptidase inhibitors (such as sacubitril);
- pregnancy;
- period breastfeeding;
- age up to 18 years (efficacy and safety have not been established).
Carefully: aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, non-ischemic heart failure of FC III-IV, Prinzmetal's angina, SSSU (severe tachycardia or bradycardia), severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), taking potassium-sparing diuretics, potassium preparations and potassium-based salt substitutes, hyperkalemia, hyponatremia, myelosuppression, diabetes, bilateral renal artery stenosis, renal artery stenosis in patients with a solitary kidney, renovascular hypertension, condition after kidney transplantation, renal failure, azotemia, hemodialysis using high-permeability membranes, primary aldosteronism, salt-restricted diet, conditions associated with a decrease in circulating blood volume (including vomiting and diarrhea), elderly age, liver failure, simultaneous use with inhibitors or inducers of the CYP3A4 isoenzyme, simultaneous use with drugs containing aliskiren, or angiotensin II receptor antagonists (increased risk of arterial hypotension, hyperkalemia and renal failure with double blockade of the RAAS), immunosuppressive therapy, simultaneous use of allopurinol or procainamide, or a combination of these complicating factors (risk of developing neutropenia and agranulocytosis), simultaneous use with lithium preparations, aggravated allergic history, simultaneous desensitization with an allergen from hymenoptera venom, simultaneous LDL apheresis using dextran sulfate, gout, hyperuricemia, use in during major surgical interventions or during general anesthesia, in patients of the black race.
Dosage
The drug is taken orally, regardless of food intake, with a sufficient amount of liquid.
Equator, tablets, 5 mg + 10 mg is indicated only for those patients in whom the optimal maintenance dose of amlodipine and lisinopril is 5 mg and 10 mg, respectively.
Equator, tablets, 5 mg + 20 mg is indicated only for those patients in whom the optimal maintenance dose of amlodipine and lisinopril is 5 mg and 20 mg, respectively.
Equator, tablets, 10 mg + 10 mg is indicated only for those patients in whom the optimal maintenance dose of amlodipine and lisinopril is 10 mg and 10 mg, respectively.
Equator, tablets, 10 mg + 20 mg is indicated only for those patients in whom the optimal maintenance dose of amlodipine and lisinopril is 10 mg and 20 mg, respectively.
The maximum daily dose of the drug Equator - 1 tab.
The maximum daily doses of active substances in monotherapy: amlodipine - 10 mg, lisinopril - 40 mg.
With the development of arterial hypotension at the beginning of therapy with Equator: with the development of arterial hypotension, the patient should lie on his back, stop taking the drug and consult a doctor. Transient arterial hypotension usually does not require discontinuation of the drug, but the need to reduce the dose should be assessed. If dose adjustment is necessary, use medications amlodipine and lisinopril separately.
If the patient has forgotten to take a tablet of the drug Equator, then you should wait until the time of the next dose and take the drug at the usual dose. Do not take a double dose to make up for a missed dose.
Special patient groups
Patients with renal insufficiency. To determine the optimal initial and maintenance dose for patients with renal insufficiency, it is necessary to titrate doses and determine the dosing regimen on an individual basis, using lisinopril and amlodipine separately. During therapy with Equator, kidney function should be monitored, as well as the content of potassium and sodium in the blood serum. In case of deterioration of kidney function, Ekvator should be discontinued and therapy should be prescribed with correctly selected doses of individual components.
Patients with liver failure. Possible delay in the excretion of amlodipine in patients with impaired liver function. Clear recommendations regarding the dose of the drug Equator in such cases have not been established, therefore, patients with impaired liver function should be prescribed the drug with caution. To determine the optimal initial and maintenance dose for patients with hepatic insufficiency, it is necessary to titrate doses and determine the dosing regimen on an individual basis, using lisinopril and amlodipine separately. Treatment should be started at lower doses with caution.
Children and teenagers (under 18). The safety and efficacy of Equator in children and adolescents have not been established.
Elderly patients (over 65 years of age). Elderly patients should be treated 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 occurrence of adverse reactions in patients taking the combination drug did not exceed that in patients receiving one of the active substances. Adverse reactions were consistent with those previously reported for amlodipine and/or lisinopril. Adverse reactions were mild, transient and rarely required discontinuation of therapy. The most frequently reported adverse reactions with the combination drug were headache (8%), cough (5%) and dizziness (3%).
The frequency of adverse reactions is given separately for lisinopril and amlodipine. The following are the adverse drug reactions (ADRs) reported during the separate use of amlodipine and lisinopril.
Determining the frequency of adverse reactions: very often - 1/10 cases (≥10%), often - 1/100 cases (≥1% and<10%), нечасто - 1/1000 случаев (≥0.1% и <1%), редко - 1/10 000 случаев (≥0.01% и <0.1%), очень редко - менее 1/10 000 случаев (<0.01%), частота неизвестна - частота не могла быть установлена на основе имеющихся данных.
Within each group, adverse reactions are presented in descending order of severity.
| junkreaction | Amlodipine | Lisinopril |
| From the blood and lymphatic system | ||
| Decreased hemoglobin | - | Rarely |
| Decreased hematocrit | - | Rarely |
| Inhibition of bone marrow hematopoiesis | - | Very rarely |
| Leukopenia | Very rarely | Very rarely |
| Thrombocytopenia | Very rarely | Very rarely |
| Agranulocytosis | - | Very rarely |
| Hemolytic anemia | - | Very rarely |
| Neutropenia | - | Very rarely |
| Anemia | - | Very rarely |
| Lymphadenopathy | - | Very rarely |
| From the side of the immune system | ||
| allergic reactions | Very rarely | - |
| Autoimmune disorders | - | Very rarely |
| From the endocrine system | ||
| Syndrome of inappropriate secretion of antidiuretic hormone | - | Rarely |
| From the side of metabolism | ||
| hyperglycemia | Very rarely | - |
| hypoglycemia | - | Very rarely |
| Mental disorders | ||
| Mood lability | Infrequently | Infrequently |
| Sleep disorders | - | Infrequently |
| hallucinations | - | Infrequently |
| Insomnia | Infrequently | - |
| Anxiety | Infrequently | - |
| Depression | Infrequently | Frequency unknown |
| Confusion | Rarely | Rarely |
| From the side of the nervous system | ||
| Dizziness | Often | Often |
| Headache | Often | Often |
| Drowsiness | Often | - |
| Vertigo | - | Infrequently |
| paresthesia | Infrequently | Infrequently |
| Dysgeusia | Infrequently | Infrequently |
| Fainting | Infrequently | Frequency unknown |
| Tremor | Infrequently | - |
| hypoesthesia | Infrequently | - |
| Parosmia (impaired sense of smell) | - | Rarely |
| Muscle hypertonicity | Very rarely | - |
| Peripheral neuropathy | Very rarely | - |
| Extrapyramidal disorders | Frequency unknown | - |
| From the organ of vision | ||
| Visual impairment (including diplopia) | Often | - |
| On the part of the organ of hearing and labyrinth disorders | ||
| Noise in ears | Infrequently | - |
| From the side of the heart | ||
| Feeling the heartbeat | Often | Infrequently |
| myocardial infarction | Very rarely | Infrequently |
| Tachycardia | - | Infrequently |
| Ventricular tachycardia | Infrequently | - |
| Arrhythmia | Infrequently | - |
| Bradycardia | Infrequently | - |
| Atrial fibrillation | Infrequently | - |
| From the side of the vessels | ||
| Orthostatic hypotension and related symptoms | - | Often |
| "Tides" of blood to the skin of the face | Often | - |
| Acute cerebrovascular accident (due to a pronounced decrease in blood pressure in high-risk groups of patients) | - | Infrequently |
| Raynaud's syndrome | - | Infrequently |
| Vasculitis | Very rarely | - |
| Arterial hypotension | Infrequently | Often |
| From the respiratory system, chest organs and mediastinum | ||
| Dyspnea | Often | - |
| Cough | Infrequently | Often |
| Rhinitis | Infrequently | Infrequently |
| Bronchospasm | - | Very rarely |
| Allergic alveolitis | - | Very rarely |
| Eosinophilic pneumonia | - | Very rarely |
| Sinusitis | - | Very rarely |
| From the digestive system | ||
| Abdominal pain | Often | Infrequently |
| Nausea | Often | Infrequently |
| Dyspepsia | Often | Infrequently |
| Changing the rhythm of bowel movements | Often | - |
| Diarrhea | Often | Often |
| Constipation | Often | - |
| Vomit | Infrequently | Often |
| Dry mouth | Infrequently | Rarely |
| Pancreatitis | Very rarely | Very rarely |
| Gastritis | Very rarely | - |
| Intestinal angioedema | - | Very rarely |
| gum hyperplasia | Very rarely | - |
| From the side of the liver and biliary tract | ||
| Hepatitis | Very rarely | - |
| Hepatitis (including hepatocellular or cholestatic) | - | Very rarely |
| Jaundice | Very rarely | Very rarely |
| Liver failure | - | Very rarely |
| Increased activity of liver enzymes | Very rarely | Infrequently |
| From the skin and subcutaneous tissues | ||
| Alopecia | Infrequently | Rarely |
| Exanthema | Infrequently | - |
| Purpura | Infrequently | - |
| Skin depigmentation | Infrequently | - |
| Hyperhidrosis | Infrequently | Very rarely |
| Skin itching | Infrequently | Infrequently |
| Skin rash | Infrequently | Infrequently |
| Hives | Infrequently | Rarely |
| Psoriasis | - | Rarely |
| Erythema multiforme | Very rarely | Very rarely |
| Angioedema | Very rarely | Rarely |
| Exfoliative dermatitis | Very rarely | - |
| Toxic epidermal necrolysis | Frequency unknown | Very rarely |
| Stevens-Johnson Syndrome | Very rarely | Very rarely |
| Quincke's edema | Very rarely | - |
| photosensitivity | Very rarely | - |
| Pemphigus vulgaris | - | Very rarely |
| Benign skin lymphadenosis* | - | Very rarely |
| Hypersensitivity/angioedema of the face, arms and legs, lips, tongue, glottis and/or larynx | - | Rarely |
| From the musculoskeletal system | ||
| muscle cramps | Often | - |
| Swelling in the ankles | Often | - |
| Arthralgia | Infrequently | - |
| Myalgia | Infrequently | - |
| Backache | Infrequently | - |
| From the side of the kidneys and urinary tract | ||
| Impaired kidney function | - | Often |
| urinary disorder | Infrequently | - |
| nocturia | Infrequently | - |
| Frequent urination | Infrequently | - |
| Acute renal failure | - | Rarely |
| Uremia | - | Rarely |
| Oliguria | - | Very rarely |
| Anuria | - | Very rarely |
| From the genital organs and mammary gland | ||
| Gynecomastia | Infrequently | Rarely |
| Impotence | Infrequently | Infrequently |
| General disorders | ||
| Edema | Often | - |
| Fatigue | Often | Infrequently |
| Asthenia | Often | Infrequently |
| Chest pain | Infrequently | - |
| Pain | Infrequently | - |
| Malaise | Infrequently | - |
| Laboratory and instrumental data | ||
| Increasing the concentration of creatinine and urea | - | Infrequently |
| Hyperkalemia | - | Infrequently |
| Hyperbilirubinemia | - | Rarely |
| Hyponatremia | - | Rarely |
| Decrease or increase in body weight | Infrequently | - |
* A symptom complex has been reported that may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, antinuclear antibody (ANA) positive reaction, increased ESR, eosinophilia and leukocytosis, skin rash, photosensitivity or other changes from the side skin.
Overdose
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 with the development of shock and death).
Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose), maintaining the function of the cardiovascular system, the elevated position of the lower extremities, monitoring the performance of the heart and lungs, monitoring BCC and diuresis. To restore vascular tone - the use of vasoconstrictor agents (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - in / in the introduction. Hemodialysis is ineffective.
Lisinopril
Symptoms: pronounced decrease in blood pressure, dry mouth, drowsiness, urinary retention, anxiety, irritability.
Treatment: symptomatic therapy, infusion of a 0.9% solution and vasopressors (if possible), control of blood pressure, maintenance of water and electrolyte balance. Perhaps hemodialysis.
drug interaction
Amlodipine
Contraindicated drug combinations
Dantrolene (in / in the introduction)
In laboratory animals, there have been cases of ventricular fibrillation with a fatal outcome and collapse during the use of verapamil and intravenous administration of dantrolene, accompanied by hyperkalemia. Due to the risk of developing hyperkalemia, simultaneous administration of slow calcium channel blockers, incl. amlodipine, in patients susceptible to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.
Grapefruit juice
Taking amlodipine with grapefruit or grapefruit juice is not recommended, as in some patients the bioavailability of amlodipine may increase, leading to increased blood pressure lowering effects.
CYP3A4 isoenzyme inducers
With the simultaneous use of known inducers of CYP3A4, the concentration of amlodipine in the blood plasma may fluctuate. For this reason, it is necessary to both control blood pressure and adjust the dose of the drug during and after simultaneous use, especially with powerful inducers of CYP3A4 (for example, rifampicin, St. John's wort preparations).
CYP3A4 isoenzyme inhibitors
Co-administration of amlodipine and strong or moderate inhibitors of CYP3A4 (protease inhibitors, such as ritonavir, azole antifungals, macrolides, such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this regard, it may be necessary to monitor the clinical condition and adjust the dose of Equator.
Simvastatin
Multiple doses of amlodipine 10 mg in combination with simvastatin 80 mg resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. Thus, patients receiving amlodipine should take simvastatin at a daily dose not exceeding 20 mg.
Calcium preparations
May reduce the effect of BMCC.
Lithium preparations
With the combined use of BMCC with lithium preparations (data are not available for amlodipine), it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor or tinnitus).
Baclofen
Strengthening the antihypertensive effect. Blood pressure and renal function should be monitored, if necessary, the dose of amlodipine should be adjusted.
Amifostine
It is possible to enhance the antihypertensive effect of amlodipine.
Glucocorticoids
Reduced antihypertensive effect (fluid retention and sodium ions as a result of the action of corticosteroids).
Tricyclic antidepressants, neuroleptics
There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).
Tacrolimus
With simultaneous use with amlodipine, there is a risk of increasing the concentration of tacrolimus in the blood plasma. In order to avoid toxicity of tacrolimus when used simultaneously with amlodipine, the concentration of tacrolimus in the blood plasma of patients should be monitored and the dose of tacrolimus adjusted if necessary.
Tasonermin: when used simultaneously, amlodipine may increase systemic exposure tasonermina in blood plasma. In such cases, regular monitoring of tasonermin in the blood and dose adjustment, if necessary, is necessary.
Interaction of amlodipine with other drugs
For the treatment of hypertension, amlodipine can be safely used with thiazide diuretics, alpha-blockers, beta-blockers and ACE inhibitors. In patients with stable angina pectoris, amlodipine may be co-administered with other antianginal drugs such as nitrates long and short action beta blockers.
Probably, an increase in the antianginal and antihypertensive effect of BMCC with simultaneous use with thiazide and "loop" diuretics, ACE inhibitors, beta-blockers and nitrates, as well as an increase in their antihypertensive effect when administered with alpha 1-blockers and antipsychotics.
Amlodipine does not cause a negative inotropic effect. However, some BMCs may increase the negative inotropic effect of antiarrhythmic drugs that prolong the QT interval (eg, amiodarone and quinidine).
Unlike other BMCCs, there was no significant interaction between amlodipine (3rd generation BMCC) and NSAIDs including indomethacin.
Is it safe to prescribe amlodipine with oral hypoglycemic drugs.
Single dose sildenafil at a dose of 100 mg in patients with essential arterial hypertension had no effect on the pharmacokinetics of amlodipine.
Co-administration of multiple doses of amlodipine 10 mg and atorvastatin at a dose of 80 mg led to an insignificant change in the pharmacokinetic parameters of atorvastatin in a state of equilibrium concentration.
Ethanol (drinks containing alcohol): Amlodipine does not significantly affect the pharmacokinetics of ethanol with a single and multiple use at a dose of 10 mg.
Interaction studies cyclosporine and amlodipine in healthy volunteers and in special groups of patients have not been conducted, with the exception of patients after kidney transplantation. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees up to 40%. Cyclosporine levels should be monitored in patients after kidney transplantation.
With the simultaneous use of amlodipine and digoxin renal clearance and serum digoxin concentration do not change.
With the simultaneous use warfarin with amlodipine, prothrombin time does not change.
When used simultaneously with cimetidine the pharmacokinetics of amlodipine does not change.
Amlodipine does not affect the degree of binding digoxin, phenytoin, warfarin and indomethacin with plasma proteins in vitro.
Aluminum and magnesium-containing antacids: a single dose of such antacids together with amlodipine does not significantly affect the pharmacokinetics of amlodipine.
mTOR inhibitors (eg, temsirolimus, sirolimus, everolimus) are substrates of CYP3A4. Since amlodipine is a weak inhibitor of CYP3A4, exposure to mTOR inhibitors may increase when used together.
Lisinopril
Contraindicated drug combinations
Aliskiren
Concomitant use of ACE inhibitors with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and / or moderate or severe renal impairment (GFR less than 60 ml / min / 1.73 m 2 body surface area) is contraindicated.
The appointment of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy.
Angiotensin II receptor antagonists (ARA II)
It has been reported in the literature that in patients with established atherosclerotic disease, chronic heart failure, or diabetes mellitus with end organ damage, concomitant therapy with an ACE inhibitor and ARA II is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared with the use of only one drug that affects the RAAS. Double blockade (for example, when an ACE inhibitor is combined with ARA II) should be limited to individual cases with careful monitoring of renal function, potassium levels and blood pressure.
Potassium supplements, potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), or potassium-containing salt substitutes
Hyperkalemia may develop (with a possible fatal outcome), especially if kidney function is impaired (additional effects associated with hyperkalemia). ACE inhibitors should not be used simultaneously with substances that increase the content of potassium in the blood plasma, except in cases of hypokalemia. The combination of lisinopril and the above agents is not recommended. If, however, simultaneous use is indicated, they should be used with precautions and regularly monitoring the content of potassium in the blood serum.
Lithium preparations
With the simultaneous use of lithium preparations and ACE inhibitors, there may be a reversible increase in the concentration of lithium in the blood serum and associated toxic effects. The simultaneous use of lisinopril and lithium preparations is not recommended. If it is necessary to carry out such therapy, regular monitoring of the concentration of lithium in the blood serum should be carried out.
Combinations of drugs requiring special care when using
Insulin and oral hypoglycemic agents
Epidemiological studies have shown that the combined use of ACE inhibitors and hypoglycemic agents (insulins, oral hypoglycemic agents) can enhance their hypoglycemic effect up to the development of hypoglycemia. This effect is most likely to be observed during the first weeks of simultaneous therapy, as well as in patients with impaired renal function.
Baclofen
Enhances the antihypertensive effect of ACE inhibitors. The level of blood pressure should be carefully monitored and, if necessary, the dose of antihypertensive drugs should be adjusted.
Diuretics
In patients taking diuretics, especially those that remove fluid and / or salts, a significant decrease in blood pressure may be observed at the beginning of therapy with an ACE inhibitor. The risk of developing antihypertensive effects can be reduced by discontinuing the diuretic, replenishing the loss of fluid or salts before starting therapy with ACE inhibitors. In case of arterial hypertension in patients with previous diuretic therapy, which could lead to excessive excretion of fluid and / or salts, diuretics should be discontinued before starting the use of the drug Equator.
Kidney function (creatinine concentration) should be monitored in the first weeks of using Equator.
NSAIDs, including ≥3 g/day
The simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid at a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. The concomitant use of ACE inhibitors and NSAIDs may lead to deterioration of renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and carefully monitor renal function, both at the beginning of treatment and during treatment.
Estramustine, mTOR inhibitors (sirolimus, everolimus, temsirolimus), neutral endopeptidase inhibitors (omapatrilat, ilepatril, daglutril, sacubitril)
Simultaneous use with ACE inhibitors is accompanied by an increased risk of developing angioedema.
DPP-4 inhibitors (gliptins)
Linagliptin, saxagliptin, sitagliptin, vildagliptin: when used together with ACE inhibitors, the risk of angioedema increases due to the suppression of dipeptidyl peptidase-4 (DPP-IV) activity by gliptin.
Neutral endopeptidase inhibitors (NEPs)
An increased risk of angioedema has been reported with concomitant use of ACE inhibitors and racecadotril (an enkefalipase inhibitor).
With the simultaneous use of ACE inhibitors with drugs containing sacubitril (neprilysin inhibitor), the risk of developing angioedema increases, and therefore the simultaneous use of these drugs is contraindicated. ACE inhibitors should be prescribed no earlier than 36 hours after discontinuation of drugs containing sacubitril. The administration of drugs containing sacubitril is contraindicated in patients receiving ACE inhibitors, as well as within 36 hours after discontinuation of ACE inhibitors.
Combinations of drugs requiring caution when using
Other antihypertensive agents (eg, beta-blockers, calcium channel blockers, diuretics) and vasodilators
It is possible to enhance the antihypertensive effect of the drug. Caution should be exercised when co-administered with nitroglycerin, other nitrates or other vasodilators, as this may further reduce blood pressure.
Antacids and cholestyramine
Simultaneous use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.
Tricyclic antidepressants, antipsychotics, general anesthetics, barbiturates, phenothiazines, ethanol
When taken together, it is possible to enhance the action of lisinopril.
Sympathomimetics
Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors.
Muscle relaxants
Simultaneous use of muscle relaxants with ACE inhibitors can lead to a pronounced decrease in blood pressure.
Preparations of gold
When using ACE inhibitors, incl. lisinopril, patients receiving an intravenous gold preparation (sodium aurothiomalate) have described rare cases of nitritoid reactions (a symptom complex that includes flushing of the skin of the face, nausea, dizziness and arterial hypotension), which can be very severe.
Co-trimoxazole (sulfamethoxazole and trimethoprim)
Increased risk of developing hyperkalemia.
Selective serotonin reuptake inhibitors (escitalopram, paroxetine, fluoxetine, sertraline)
With simultaneous use with SSRIs, severe hyponatremia may develop.
Allopurinol, procainamide, cytostatics (5-fluorouracil, vincristine, docetaxel)
Perhaps the development of leukopenia.
Tissue plasminogen activators (alteplase, reteplase, tenecteplase)
Increased risk of angioedema with simultaneous use with ACE inhibitors. Observational studies have shown an increased incidence of angioedema in patients treated with ACE inhibitors following the use of alteplase for thrombolytic therapy in ischemic stroke.
special instructions
The equator should not be used to stop a hypertensive crisis.
Upon admission to the hospital, the patient must inform the doctor about taking the drug Equator.
When using the drug Equator, you should take into account the warnings regarding its individual components below.
Related to amlodipine
It is necessary to maintain dental hygiene and see a dentist (to prevent soreness, bleeding and gum hyperplasia.
In elderly patients, T 1/2 may increase and the clearance of the drug may decrease. Dose changes are not required, but more careful monitoring of patients in this category is necessary.
The efficacy and safety of amlodipine in hypertensive crisis have not been established.
withdrawal syndrome
Despite the absence of a withdrawal syndrome in BMCC, it is desirable to stop treatment with amlodipine by gradually reducing the dose of the drug. Amlodipine does not prevent the development of a withdrawal syndrome when beta-blockers are abruptly discontinued.
Cardiovascular diseases
In rare cases, in patients with coronary artery disease (especially with severe obstructive coronary artery disease), there was an increase in the frequency, duration and / or severity of angina attacks after starting the use of BMCC or after increasing their dose.
Against the background of the use of amlodipine in patients with chronic heart failure class III and IV according to NYHA of non-ischemic origin, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.
Peripheral edema
Mild to moderate peripheral edema was the most common adverse event with amlodipine in clinical trials. The incidence of peripheral edema increases with increasing dose of amlodipine. It is necessary to carefully differentiate peripheral edema associated with the use of amlodipine from symptoms of progression of left ventricular heart failure.
Impact on fertility
In some patients treated with slow calcium channel blockers, reversible biochemical changes in the head of spermatozoa were found, which may be clinically significant during IVF. However, there are currently insufficient clinical data regarding the potential effect of amlodipine on fertility. In a preclinical study, undesirable effects on fertility in males have been identified.
Related to lisinopril
Symptomatic arterial hypotension
Most often, a significant decrease in blood pressure occurs with a decrease in BCC caused by the use of diuretics, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting. In patients with chronic heart failure, in combination with renal failure or without it, symptomatic arterial hypotension may develop. It develops more often in patients with severe heart failure, which is associated with the use of high doses of diuretics, hyponatremia, or impaired renal function. Such patients need careful medical supervision (with careful selection of doses of lisinopril and diuretics). The same recommendations apply to patients with coronary artery disease and cerebrovascular insufficiency, when a rapid decrease in blood pressure can lead to the development of myocardial infarction or stroke.
Patients with a marked decrease in blood pressure should be given a horizontal position; if necessary, an infusion of 0.9% sodium chloride solution is performed. Transient arterial hypotension is not a contraindication to taking the next dose of lisinopril.
In patients with chronic heart failure with normal or low blood pressure, the use of lisinopril may lead to a decrease in blood pressure; as a rule, this does not require discontinuation of treatment. If arterial hypotension becomes symptomatic, the indications for reducing the dose of lisinopril or its withdrawal should be evaluated.
In patients at risk of developing symptomatic arterial hypotension (patients on a salt-free or low-salt diet) with or without hyponatremia, as well as in patients receiving high doses of diuretics, these deviations (loss of water and salts) must be compensated before starting treatment.
It is necessary to monitor the effect of the starting dose of lisinopril on blood pressure.
Acute myocardial infarction
The use of Equator in patients with acute myocardial infarction is not recommended due to insufficient clinical experience.
kidney failure
In patients with chronic heart failure, a significant decrease in blood pressure that occurs after the start of therapy with ACE inhibitors can lead to aggravation of impaired renal function. Cases of acute renal failure have been reported.
In patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney, there have been cases of increased serum urea and creatinine concentrations associated with the use of ACE inhibitors; as a rule, these disturbances were transient and stopped after the abolition of lisinopril. They are more common in patients with renal insufficiency.
kidney transplant
There is no experience with the use of lisinopril in patients who have recently undergone kidney transplantation.
Hypersensitivity, angioedema
In patients receiving ACE inhibitors, incl. lisinopril, rare cases of angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx have been reported, which could occur at any time during treatment. In such cases, it is necessary to immediately cancel lisinopril; observation of patients should be carried out until the complete disappearance of symptoms. Usually cases of angioedema of the face and lips are temporary and do not require any treatment; possible appointment of antihistamines.
Angioedema of the larynx can be fatal. Angioedema of the tongue, epiglottis, or larynx can lead to secondary airway obstruction, so promptly initiate appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) at a concentration of 1:1000 s / c) and / or take measures to ensure airway patency .
In rare cases, during therapy with ACE inhibitors, angioedema of the intestine developed. At the same time, patients had abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases, without previous angioedema of the face and with a normal level of C1-esterase. Diagnosis was established by abdominal CT, ultrasound, or at the time of surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with pain in the abdomen receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.
In patients with a history of angioedema unrelated to ACE inhibitors, the use of ACE inhibitors may be associated with a higher risk of developing angioedema.
Anaphylactic reactions associated with desensitization by hymenoptera venom
There are reports of very rare cases of life-threatening anaphylactic reactions that have developed in patients taking ACE inhibitors during desensitization with hymenoptera venom. To prevent such cases, ACE inhibitors should be temporarily discontinued before desensitization.
Hemodialysis
Anaphylactic reactions have also been reported in patients undergoing hemodialysis using high permeability membranes (eg AN69) who were concomitantly treated with ACE inhibitors. In this group of patients, the use of other dialysis membranes or other antihypertensive drugs should be considered.
Cough
The use of ACE inhibitors may be associated with cough. Dry cough that persists for a long time usually disappears after discontinuation of the ACE inhibitor. When conducting a differential diagnosis, the possibility of cough associated with the use of ACE inhibitors should be taken into account.
Surgery/general anesthesia
The use of drugs that lower blood pressure during major surgery or general anesthesia can lead to suppression of the formation of angiotensin II in response to compensatory renin secretion. A significant decrease in blood pressure, which is considered as the result of this effect, can be controlled by reducing the volume of blood.
Patients taking ACE inhibitors should inform their surgeon/anaesthetist before undergoing surgery (including dental procedures).
Cases of hyperkalemia have been reported. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, and concomitant use of potassium-sparing diuretics (spironolactone, triamterene, and amiloride), as well as potassium supplements and potassium-based salt substitutes, especially in patients with impaired renal function. If necessary, the simultaneous use of lisinopril and the above drugs should be careful and regularly monitor the content of potassium in the serum.
Double blockade of the RAAS
It has been proven that the simultaneous administration of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and impaired renal function (including acute renal failure). Thus, it is not recommended to prescribe ACE inhibitors, angiotensin II receptor blockers or aliskiren for dual blockade of the RAAS.
If there is an absolute indication for a double blockade of the RAAS, then it should be carried out under the close supervision of a specialist with frequent monitoring of blood pressure, renal function and electrolytes.
The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and / or with moderate or severe renal insufficiency (GFR less than 60 ml / min / 1.73 m 2 body surface area) and is not recommended in other patients.
The simultaneous use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Neutropenia/agranulocytosis/thrombocytopenia/anemia
While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor.
With extreme caution, Ekvator should be prescribed to patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially in patients with impaired renal function. Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Equator, such patients are advised to periodically monitor the number of leukocytes in the blood plasma. Patients should report any signs of an infectious disease (eg, sore throat, fever) to their doctor.
Mitral stenosis/aortic stenosis/hypertrophic cardiomyopathy
ACE inhibitors should be used with caution in patients with mitral stenosis, as well as in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy).
Liver failure
Very rarely, cholestatic jaundice occurs while taking ACE inhibitors. With the progression of this syndrome, fulminant necrosis of the liver develops, sometimes with a fatal outcome. The mechanism by which this syndrome develops is unclear. If jaundice or a significant increase in liver enzyme activity occurs while taking ACE inhibitors, Equator should be discontinued and the patient should be carefully monitored.
Diabetes
When using lisinopril in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood.
Elderly age
In elderly patients, the use of standard doses leads to a higher concentration of lisinopril in the blood, so special care is required when determining the dose, despite the fact that there are no differences in the antihypertensive effect of lisinopril in elderly and young patients.
ethnic differences
In patients of the Negroid race, more often than in representatives of other races, angioedema develops while taking ACE inhibitors. ACE inhibitors may have a less pronounced antihypertensive effect in patients of the black race compared with representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race often have low renin activity.
Influence on the ability to drive vehicles and mechanisms
There are no data on the effect on the ability to drive vehicles and mechanisms. Due to the possibility of an excessive decrease in blood pressure, the development of dizziness, drowsiness and other side effects at the beginning of treatment, patients should refrain from driving a car and driving other vehicles, working with mechanisms and performing other work that requires concentration.
Pregnancy and lactation
Pregnancy
The use of the drug Equator is contraindicated during pregnancy.
There are no data on the use of Equator in pregnant women in adequate controlled clinical trials. If pregnancy is detected, treatment with Equator should be discontinued immediately. Patients planning a pregnancy should consult a doctor for antihypertensive therapy with an established safety profile in pregnancy.
Amlodipine
The safety of amlodipine during pregnancy has not been established. In preclinical studies, the fetotoxic and embryotoxic effects of amlodipine have not been identified. In rats, amlodipine increased the duration of the gestational period and labor. Some other BMCs are teratogenic.
Lisinopril
The use of ACE inhibitors in the II-III trimesters of pregnancy can lead to the death of the fetus and newborn. It is recommended to carefully monitor newborns and infants exposed to ACE inhibitors in utero in order to timely detect a significant decrease in blood pressure, oliguria and hyperkalemia. Perhaps the occurrence of oligohydramnios, hypoplasia of the facial bones, deformities of the bones of the face and skull, hypoplasia of the lungs and anomalies in the development of the kidneys in a child.
Women of childbearing age must use effective contraceptive methods when treated with lisinopril.
Lisinopril can penetrate the hematoplacental barrier. Treatment with lisinopril should not be initiated during pregnancy. Patients planning a pregnancy should consult a doctor for antihypertensive therapy with an established safety profile in pregnancy.
breastfeeding period
The use of the drug Equator during breastfeeding is contraindicated.
Amlodipine
Experience with the drug shows that amlodipine is excreted in breast milk. The mean milk/plasma ratio for amlodipine concentration was 0.85 among 31 lactating women who suffered from pregnancy-induced hypertension and received amlodipine at an initial dosage of 5 mg/day. The dose of the drug was adjusted if necessary (depending on the average daily dose and weight: 6 mg and 98.7 mcg/kg, respectively). The estimated daily dose of amlodipine received by an infant through breast milk is 4.17 mcg / kg.
The use of amlodipine during breastfeeding is contraindicated. If necessary, the use of the drug during lactation should stop breastfeeding.
With caution, the drug should be prescribed for liver failure.
Equator, tablets, 5 mg + 20 mg: the shelf life of the drug is 3 years.
Equator, tablets, 10 mg + 20 mg: - 3 years.
Do not use after the expiry date stated on the packaging.
In this article, we will get acquainted with such a drug as Equator. With its biological effects on the body (impact at various stages of development, overdose, complications). With instructions for use. With reviews of tablets and their derivatives, which are widely distributed throughout the world. How to replace tablets Equator. What are the Russian analogues.
Pharmacological properties
- The main components in the Equator preparation, discussed above, acquire the maximum effect approximately 6 hours after application. From whom, what dose of the drug was involved, the duration of the result depends. 24 hours is considered optimal. The very same antihypertensive effect is seen within one hour.
- Lisinopril does not lose its properties with prolonged use. After the expiration date of the drug, sharp jumps in blood pressure are not noticed. The use of the substance lisinopril for people with diabetes mellitus did not cause side effects. The glucose level remained stable.
- under the influence of amlodipine decreased vascular tone. Due to the increase in arterioles, an antiangilic effect is exerted. When it is used, the level of air oxygen consumption by the myocardium decreases. Amlodipine improves the perfusion of the middle muscle layer in the heart.
- The substance is well absorbed inside after taking it. For a long time lies in the tissues of the body, which guarantees the duration of the effect. For this reason, it is enough to use it once a day. The duration of amlodipine is approximately the same as that of lisinopril (about 24 hours, with a maximum effect after 6 hours). It does not have various harmful metabolic effects, thereby contributing to blood lipid levels. With various diseases associated with the liver, the duration of storage of amlodipine in the body increases.
- At various meals it has been observed that there are no interactions between the main components of Equator. The degree of absorption also did not differ from pure use. All this has been proven by kinetic methods of pharmacy. The duration of stay inside the body during the day of both substances.
Contraindications to the use of the drug
- First of all, the drug is contraindicated in persons who have not reached the age of 18 years, since the results in this age group have not been unambiguously studied. Use with caution in people over 65 years of age.
- The presence in a person of hereditary or acquired stenosis of the aorta or valve.
- Severe arterial hypotension.
- Various cardiac shocks.
- During pregnancy (If pregnancy is detected, it is necessary to stop using the drug in a reactionary manner). Lisinopril can cause fetal death in later stages, as it strongly affects the kidneys. It can also lead to various pathological changes: deformation of the skull, changes in the limbs. No other secondary data were identified.
- During periods of breastfeeding (lactation).
- Hypersensitivity to the components of the drug.
- With caution, you need to use the drug for coronary insufficiency, angina pectoris, tachycardia, embolism, pericarditis, hypertension, arrhythmias, heart defects.
- With various chronic heart diseases.
- With liver failure.
- If various hypertrophic cardiomyopathies are present.
Instructions for use
Equator is used 1 time during the day at any time of the day, one tablet.
There are specific instructions for different dosages.
Release Equator 5mg + 10mg:
- This dose is recommended to be taken once a day, one tablet.
- During the first period of use symptomatic arterial hypotension may develop. This must be observed with caution. Most often this occurs in those if there are various disturbances in the water and electrolyte balance during periods of consumption of diuretic drugs.
Required condition- stop the course of diuretics a couple of days before the start of the use of the drug Equator. Otherwise, various imbalances in the accumulation of potassium in the blood may occur. If it is impossible to stop taking them in any way, then it is necessary to reduce the dose of Equator to half a tablet during the day, ensuring constant monitoring of the patient.
- For people who have kidney failure, you need to initially determine the dosage of the substances lisinopril and amlodipine. Each active component is considered separately. For this, a structural analysis is carried out using the titrimetric method.
Release Equator 5mg + 10mg indicated only in patients whose levels of lisinopril and amlodipine are in the range up to 10 and 5 mg. In the course of treatment, it is necessary to control the content of potassium and sodium in the kidneys. If there is any deterioration in the renal system, immediately stop using the medicine. Replace Equator with a lower dosage or completely abandon the drug and find a suitable analogue with a lower concentration. - Inhibition of output from the body of lisinopril is typical for people with liver failure. Due to the slow functioning of the body. Therefore, it is worth paying attention to the course of administration and dosage.
- No exact data no age limit has been found to date. It should only be noted that the drug Equator with the release of 5 + 10 mg should be used for people over 65 years of age with individual characteristics. To do this, you must consult with a specialist before use and make certain tests for the content of substances in the body.
- Persons under 18 years of age the drug is undesirable. If necessary, consult a doctor.
Release Equator 10mg + 20mg:
Precautionary measures
Equator Reception can cause a sharp drop in blood pressure in people who suffer from hyponatremia (the level of potassium in the blood plasma is below 130 mmol / l) or who have problems with blood circulation due to the use of diuretics.
If the patient is hypotensive, you need to urgently put it on a horizontal surface, after relaxing all the muscles. When it is necessary to enter a certain dosage of a physical solution of sodium chloride NaCl with a concentration of about 3% to restore the level of BCC (volume of blood circulation).
During the use of the drug Equator, it is constantly necessary to monitor the level of blood pressure in patients. Pay special attention to those patients who suffer from hyponatremia.
When patients develop pathologies that are associated with narrowing of the aorta or hypertrophy of the heart muscle, the use of the drug should be monitored. Also monitor your blood pressure.
When taking Equator there may be problems associated with impaired functioning of the kidneys, since it can affect their functioning due to the presence of lisinopril and amlodipine in it.
Since there is a possibility the appearance of agranulocytosis due to the content of superactive substances in the preparation that affect the function of hematopoiesis, it is necessary to constantly monitor all blood parameters. It is advisable to take tests every 6 months.
For people over 65 the dosage of the drug should be selected taking into account the individual characteristics of the body associated with the ability to remove lisinopril and amlodipine from the body.
Restrict in use Equator for people with impaired renal system.
Possibility of appearance various allergic reactions to excipients and active substances in Equator. In order to avoid various reactions, the course must be stopped with the first appearances and consult a specialist.
Possibility of appearance uncontrolled hypotension. For this reason, it is necessary to refrain from driving after using Equator.
To avoid various problems associated with bleeding and hyperplasia of the gums, you need to visit a dentist before using the drug.
Side effects
Equator can cause many side effects:
- the occurrence of orthostatic hypotension,
- arrhythmia,
- increased heartbeat,
- a sharp drop in blood pressure.
- There may be various headaches associated with a sharp drop in blood pressure.
- Psychological attacks: nervousness, depression, anxiety, increased drowsiness or insomnia.
- The appearance of convulsions, shortness of breath, apathy, new bleeding. Various diseases in the abdomen: pancreatitis, constipation, loss of appetite, vomiting.
- The appearance of pain in the eyes, in the back, in the abdomen, in the chest.
- With prolonged use of the drug, a decrease in the level of hemoglobin in the blood is possible.
- Various pathological phenomena associated with the appearance of antibodies.
- And various other side effects.
Interaction with other drugs
It is necessary to carefully use the drug Equator with other diuretics due to a sharp increase in the level of potassium in the blood. The hypotensive effect may increase with the use of various drugs that resemble Equator in structure. With nitroglycerin, blood pressure can drop sharply. The same effect will appear with the use of other antipsychotic drugs.
Overdose
The dosage of Equator tablets must be monitored daily, otherwise the following complications may occur:
With an overdose of amlodipine, the following symptoms may occur:
A sharp decrease in blood pressure, tachycardia, with the development of various shock strokes, which can be fatal.
In this case, you should immediately rinse the stomach, drink activated charcoal, which is perfect as an adsorbent. To restore the condition, it is necessary to drink vasoconstrictor substances.
With an overdose of lisinopril, the following symptoms may occur:
As with amlodipine, a sharp decrease in pressure. There will be drowsiness, dry mouth, various problems associated with the retention of unnecessary elements in the body, mental instability, irritability.
In such cases, it is necessary to take a horizontal position to wash the stomach.
Price and analogues
It is possible to purchase Equator's drug of any form of release only by prescription:
- Form 5 mg + 10 mg, 10 tablets. From 197 rubles;
- Form 5 mg + 10 mg, 30 tablets. From 531 rubles;
- Form 10 mg + 20 mg, 10 tablets. From 269 rubles.
Both components can also be found in Ekvakard. You can buy it already from 123 rubles.
Dosage is slightly different:
- Form 5 mg + 5 mg, 30 tablets. From 319 rubles;
- Form 5 mg + 10 mg, 10 tablets. From 144 rubles;
- Form 5 mg + 10 mg, 30 tablets. From 359 rubles.
The second analogue, by right, is considered Lisinopril. But it contains only lisinopril. This drug is much cheaper. You can buy it from 40 rubles.
- Form 5 mg, 30 tablets. From 40 rubles;
- Form 10 mg, 30 tablets. From 58 rubles;
- Form 20 mg, 30 tablets. From 73 rubles.
Catad_pgroup Combined antihypertensives
Equator - instructions for use
Registration number:
LS-002321Trade name of the drug:
Equator ® (Ekvator ®)International non-proprietary name:
amlodipine + lisinopril& (amlodipine + lisinopril&)Dosage form:
pillsCompound:
Each tablet contains
active substances: amlodipine besylate 13.88 mg, equivalent to 10.00 mg of amlodipine and lisinopril dihydrate 21.76 mg, equivalent to 20.00 mg of 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 off-white round flat tablets with a bevel, scored on one side and engraved "A+L" on the other.
Pharmacotherapeutic group:
combined antihypertensive agent (angiotensin-converting enzyme inhibitor and blocker of "slow" calcium channels).ATX code:
C09BB03.Pharmacological properties
Pharmacodynamics
Combined preparation containing 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 tolerance to stress in patients with chronic heart failure. 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 chronic heart failure, 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. With arterial hypertension, the effect is noted 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).
Antianginal action due to the expansion of the coronary and peripheral arteries and arterioles in angina pectoris 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) and prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina pectoris, a single daily dose increases exercise tolerance, slows down the development of angina pectoris and "ischemic" depression - ST segment, reduces the frequency of attacks, angina pectoris 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.
With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure for 24 hours (in the position of the patient "lying" and "standing"). Orthostatic hypotension, with the appointment of amlodipine, is quite rare. Does not cause a decrease in exercise tolerance, ejection fraction-left ventricle. Reduces the degree of hypertrophy of the myocardium of the left ventricle. It does not affect the contractility and conduction of the myocardium, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate, 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.
Amlodipine + lisinopril
The combination of lisinopril with amlodipine in one drug helps to 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. 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 plasma proteins. 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.
breeding
Excreted by the kidneys unchanged. 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 higher than in young patients. In patients with chronic heart failure, absorption and clearance of lisinopril are reduced.
In patients with renal insufficiency, the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, and there is an increase in the time to reach maximum plasma concentration and an increase in the half-life.
Lisinopril is excreted 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%. Eating does not affect the absorption of amlodipine.
Distribution
Most of the drug in the blood (95% -98%) binds to plasma proteins. Sshah in blood serum is observed after 6-10 hours. Steady-state concentrations (C ss) 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 drug is in the tissues and less in the blood.
Metabolism
Amlodipine undergoes slow/but active metabolism in the liver in the absence of a significant first-pass effect. Metabolites do not have significant pharmacological activity.
breeding
Excretion consists of two phases, T½ of the final phase is 30-50 hours. About 60% of the oral 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
In elderly patients (over 65 years of age), the elimination of amlodipine is slower (T½ - 65 hours) compared with young patients, but this difference is not of clinical significance.
In patients with hepatic insufficiency, the prolongation of T½ suggests that with prolonged 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 crosses the blood-brain barrier. It is not removed by hemodialysis.
Amlodipine + lisinopril
The interaction between the active substances that make up the drug Equator ® is unlikely. AUC, time to reach and maximum concentration values, half-lives do not change in comparison with the indicators of each individual active substance. Eating does not affect the absorption of active substances.
Indications for use
Essential hypertension (in patients who are indicated for combination therapy).
Contraindications
- Hypersensitivity to lisinopril or other ACE inhibitors;
- Hypersensitivity to amlodipine or other dihydropyridine derivatives;
- Hypersensitivity to other components of the drug;
- Quincke's edema in history, including against the background of 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 (during the first 28 days).
- Pregnancy and lactation;
- Age up to 18 years (efficacy and safety not established).
Carefully
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, liver dysfunction, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic - 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 diseases of the connective tissue (including scleroderma, systemic lupus erythematosus), depression of bone marrow hematopoiesis, diabetes mellitus, diet with salt restriction, hypovolemic conditions (including as a result of diarrhea, vomiting), old age, - hemodialysis using high-flow dialysis membranes with high permeability (AN69 ®).
Use during pregnancy and lactation
The use of the drug Equator ® is not recommended during pregnancy.
At. diagnosing pregnancy, taking the drug Equator ® should be stopped immediately.
Taking ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, intrauterine death are possible). There are no data on the negative effects of the drug on the fetus if used during the first trimester of pregnancy. Newborns and infants who have been exposed to ACE inhibitors in utero are recommended to be carefully monitored for. 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 may be excreted in breast milk. There are no data indicating the release of amlodipine into breast milk. However, it is known that other BMKK - derivatives of dihydropyridine are excreted in breast milk.
The use of the drug Equator ® during lactation is not recommended.
If the use of the drug is necessary during lactation, then breastfeeding should be discontinued.
Dosage and administration
Tablets of the drug Equator ® are taken orally, once a day, regardless of the time of the meal, with a sufficient amount of liquid.
The recommended dose is 1 tablet of Equator ® once a day. The maximum daily dose is 1 tablet of Equator ® .
At the beginning of therapy with Ekvator ®, symptomatic arterial hypotension may develop, which occurs more often in patients with impaired water and electrolyte balance, due to previous diuretic therapy. Reception of diuretics should be stopped 2-3 days before the start of therapy with Equator ®. In cases where the abolition of diuretics is not possible, the initial dose of the drug Equator ® is ½ tablet 1 time per day, after which the patient should be monitored for several hours due to the possible development of symptomatic arterial hypotension.
Patients with renal insufficiency
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 in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively. 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 kidney function, taking the drug Equator ® should be discontinued and replaced with lisinopril and amlodipine in adequate doses.
Patients with liver failure
Excretion of amlodipine may be slowed down in patients with impaired liver function: Clear recommendations on the dosing regimen in such cases have not been established, therefore the drug Equator ® should be administered with caution in patients with hepatic insufficiency.
Elderly patients (over 65 years old)
In clinical studies, no age-related changes in efficacy or safety profile were found for amlodipine and lisinopril. To determine the optimal maintenance dose, it is necessary to determine 1 regimen - dosing on an individual basis, using lisinopril and amlodipine separately. Equator® is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively.
Side effect
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 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 system organ class according to the MedDRA classification and with the following frequency: very often (> 1/10); often (from > 1/100 to<1/10); нечасто (от >1/1 000 to<1/100); редко (от >1/10 000 up 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, control of cardiac activity, blood pressure, diuresis and water and 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 are not successful, 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, gastric lavage and activated charcoal are used.
Lisinopril is eliminated by hemodialysis. Due to the strong binding of amlodipine to blood proteins, hemodialysis of amlodipine is ineffective. .
Interaction with other drugs
Lisinopril
Substances that affect the content of potassium: 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 cause hyperkalemia when combined with ACE inhibitors, especially in patients with point 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. Therefore, the simultaneous appointment should be carefully justified and made with extreme caution and regular monitoring of both the content of potassium in the blood serum and kidney function.
Potassium-sparing diuretics may only be taken with Ekvator under close medical supervision.
Diuretics: in the case of the appointment of a diuretic to a patient receiving Equator ® , the antihypertensive effect is usually enhanced. 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.
Tricyclic antidepressants/antipsychotics/general anesthetics/narcotic analgesics: Simultaneous administration with ACE inhibitors can 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 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: Concomitant use of ACE inhibitors and hypoglycemic drugs (insulins and oral hypoglycemic agents) may increase the likelihood of a decrease in blood glucose concentration and the risk of hypoglycemia. Most often this phenomenon is observed during the first week of combined treatment in patients with renal insufficiency.
Non-steroidal 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 in an increase in the content of potassium in the blood serum and can 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: lithium excretion may be slowed down during concomitant use with ACE inhibitors and therefore the concentration of lithium in the blood serum should be monitored during this period. When combined with lithium preparations, it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia; tremor, tinnitus).
Preparations of gold: with the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex is 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 increases). It cannot be ruled out that stronger CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir) may increase amlodipine serum concentrations to a greater extent than diltiazem. Simultaneous use should be carried out with caution.
CYP3A4 isoenzyme inducers: simultaneous use with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort ( Hypericum perforatum), can lead to a decrease in the concentration of amlodipine in the blood plasma. Clinical control is shown with a possible dose adjustment of amlodipine during treatment with inducers of the CYP3A4 isoenzyme and after their cancellation.
Simultaneous use should be carried out with caution.
As monotherapy, amlodipine was well combined with thiazide and "loop" diuretics, general anesthesia agents, 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.
Amlodipine does not significantly affect the pharmacokinetics of ethanol.
Calcium preparations can 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 Ekvator ® while taking it with estrogenic drugs, adrenostimulants.
Procainamide, quinidine, and other drugs that prolong the QT interval may contribute to its significant prolongation.
special instructions
Arterial hypotension
A pronounced 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 diuretic intake, fluid loss, or for other reasons, such as increased sweating, prolonged vomiting and / or diarrhea. Preferably, recovery, loss of fluid and / or sodium was carried out before the start of therapy with Equator ® .
It is necessary to monitor blood pressure after taking the initial dose. Similar conditions apply to patients with ischemic, cardiac or cerebrovascular disease, in whom a pronounced decrease in blood pressure can lead to myocardial infarction or stroke.
Aortic and mitral stenosis.
As with all vasodilators, Equator should be used with caution in patients with left ventricular outflow tract obstruction and mitral valve stenosis.
Impaired kidney function
In some patients with arterial hypertension without pronounced 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. This is most common in patients with a history of kidney disease.
To determine the optimal; maintenance dose, the dosing regimen must be determined on an individual basis, using lisinopril and amlodipine separately, while monitoring kidney 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.
In the event of a decrease in kidney function, taking the drug Equator ® should be discontinued and replaced with monotherapy with drugs in adequate doses. In addition, dose reduction or withdrawal of diuretics may be required.
Angioedema
Angioedema of the face, extremities, lips, tongue, vocal cords and/or larynx has been reported in patients treated with 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 extremities usually resolves on its own, however, antihistamines should be used to reduce 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 should be urgently 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 (intravenous) and antihistamines and simultaneous monitoring of vital signs. important functions.
In patients taking ACE inhibitors, angioedema of the intestine was rarely observed. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, no previous angioedema of the face was observed, and C-1 esterase activity was within the normal range. Angioedema of the intestine was diagnosed by computed tomography of the gastrointestinal tract or after ultrasound, or during surgery, the symptoms disappeared after discontinuation of 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
Anaphylactic shock has been reported in patients undergoing polyacrylonitrile membrane hemodialysis (e.g. AN-69) and concomitantly treated with ACE inhibitors, so this combination should be avoided.
Patients are advised; use either another type of dialysis membrane, or an antihypertensive drug of another pharmacotherapeutic group.
Anaphylactic reactions in patients during low-density lipoprotein (LDL) apheresis
Rare in patients treated with 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
Occasionally, patients treated with ACE inhibitors have developed anaphylactic reactions during desensitization with hymenoptera (eg, wasp or bee) venom. Such life-threatening situations can be avoided with the timely cancellation of ACE inhibitors.
Impact 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 hepatic necrosis and, in several cases, led to death. The mechanism of this syndrome is unclear.
Patients receiving Equator ® who develop jaundice or have an increase in the activity of "liver" enzymes should stop the drug with subsequent monitoring of their condition.
Liver failure
In patients with impaired liver function, the half-life of amlodipine is prolonged. At the moment, recommendations on the dosing regimen have not been developed, and therefore this drug should be prescribed with caution, having previously determined the expected benefit and potential risk of treatment.
Neutropenia/Agraiulocytosis
In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with 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 previous renal dysfunction. Some of these patients developed serious infectious diseases, in which 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), as well as warn them about the need to report the first signs of an infectious disease.
Cough
During the use of ACE inhibitors, cough was often recorded. As a rule, the cough is unproductive, persistent and stopped after the drug was discontinued. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of ACE inhibitors.
Surgery/general anesthesia
In patients undergoing major surgery or during general anesthesia with drugs that cause 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, a correction can be made by increasing the volume of circulating blood.
Elderly patients
Elderly patients with impaired renal function should adjust the dose of Equator ®.
Hyperkalemia:
In some patients treated with ACE inhibitors, an increase in the content of potassium in the blood serum was observed. The risk group for the development of hyperkalemia is patients with renal insufficiency, diabetes mellitus, acute heart failure, dehydration, metabolic acidosis, or while taking potassium-sparing diuretics, potassium-containing nutritional supplements, potassium-containing salt substitutes, or any other drugs that lead to an increase in potassium content, in serum (for example, heparin). If necessary, simultaneous administration with the above drugs, it is necessary to control the content of potassium in the blood serum.
Patients with low body weight, patients of short stature, 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, it is necessary to control body weight and see a dentist (to prevent soreness, 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 mechanisms. Predominantly at the beginning of treatment, transient arterial hypotension and dizziness may occur. Therefore, at the beginning of treatment, it is recommended to avoid driving, working with mechanisms and performing other work that requires increased concentration.
Release form
Tablets, 5 mg + 10 mg.
10 tablets in a white PVC/polyethylene/PVDC/lacquered hard aluminum foil blister. 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 use after the expiry date which is stated on the package.
Holiday conditions
Released by prescription.
Manufacturer
- OJSC "Gedeon Richter"
1103 Budapest, st. Dömröi, 19-21, Hungary - CJSC "GEDEON RICHTER - RUS"
140342 Russia, Moscow region, Egoryevsky district, Shuvoe settlement, st. Lesnaya, 40.
Consumer claims should be sent to:
Moscow Representative Office of JSC "Gedeon Richter"
119049 Moscow, 4th Dobryninsky lane, building 8
Essential hypertension (in patients who are indicated for combination therapy).
Contraindications Equator tablets 5mg+10mg
Hypersensitivity to any of the components of the drug or to other ACE inhibitors and dihydropyridine derivatives; angioedema in history, including those caused by the use of other ACE inhibitors, hereditary or idiopathic angioedema; hemodynamically significant stenosis of the aorta or mitral valve or hypertrophic obstructive cardiomyopathy; severe arterial hypotension; cardiogenic shock; heart failure after acute myocardial infarction (during the first 28 days); unstable angina (with the exception of Prinzmetal's angina); pregnancy; lactation period; age up to 18 years (due to lack of data on the efficacy and safety of the drug in this age group) bilateral stenosis of the renal arteries, 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), bone marrow suppression, diabetes mellitus, hyperkalemia, condition after kidney transplantation, sodium-restricted diet, advanced age, renal and / or liver failure, sick sinus syndrome (SSS), 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 kidney function, oligohydramnios, delayed ossification of the skull) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia) cannot be ruled out. . 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 discontinued immediately. Patients planning a pregnancy should consult a doctor so that he can recommend drugs with proven safety during pregnancy. Equator is not recommended for use during lactation, as lisinopril may be excreted in breast milk. There is no information on the penetration of amlodipine into breast milk.
Method of application and dosage Equator tablets 5mg + 10mg
Inside, regardless of the meal. The recommended dose is one tablet of Equator 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 in whom the 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 kidney function, the content of potassium and sodium in the blood serum. In case of deterioration of kidney function, the drug should be discontinued and replaced with monodrugs in adequate doses. Hepatic impairment: Elimination of amlodipine may be delayed in patients with hepatic impairment. Clear recommendations on the dosing regimen in such cases have not been established, so the drug should be administered with caution in patients with hepatic insufficiency. Elderly patients (over 65 years of age): in clinical studies on the efficacy and safety of amlodipine or lisinopril in elderly patients, no changes were found. To determine the optimal maintenance dose, it is necessary to determine the dosing regimen on an individual basis, using lisinopril and amlodipine separately. Equator is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 10 mg, respectively.
