Eclamise tablets 5mg + 10mg, No. 30

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

The tablets of the drug are taken orally once a day, regardless of the time of the meal, with a sufficient amount of liquid.
The recommended initial dose of Eclamiz is 5 mg of amlodipine + 10 mg of lisinopril 1 time per day.
If an additional decrease in blood pressure is required, the dose of Eclamiz can be increased to a maximum daily dose of 10 mg amlodipine + 20 mg lisinopril 1 time per day.
At the beginning of drug therapy, symptomatic arterial hypotension may develop, which often occurs in patients with impaired water and electrolyte balance due to previous diuretic therapy. Diuretics should be discontinued 2-3 days before starting therapy with Eclamise.
In cases where the withdrawal of diuretics is not possible, the initial dose of the drug Eclamiz is? tablets (5 mg amlodipine + 10 mg lisinopril) 1 time per day, after taking which, for several hours, the patient should be monitored due to the possible development of symptomatic arterial hypotension.
Renal dysfunction
In patients with renal dysfunction, it is recommended to use? tablets (5 mg amlodipine + 10 mg lisinopril) of the drug (increased half-life of lisinopril).
The maintenance dose is selected depending on the tolerability of the therapy, monitoring of renal function, potassium and sodium content in blood plasma is required.
Liver dysfunction
In patients with impaired liver function, it is recommended to use? tablets (5 mg amlodipine + 10 mg lisinopril) of the drug (increased half-life of amlodipine).
Use in elderly patients (over 65 years of age)
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 dosage regimen individually, using lisinopril and amlodipine separately.

Active substances: amlodipine besylate - 6.94 mg in terms of amlodipine - 5.00 mg, lisinopril dihydrate - 10.88 mg, in terms of lisinopril - 10.00 mg.
Excipients: microcrystalline cellulose - 173.00 mg, sodium carboxymethyl starch - 6.18 mg, colloidal silicon dioxide - 1.00 mg, magnesium stearate - 2.00 mg.

• Hypersensitivity to lisinopril or other ACE inhibitors, amlodipine, other dihydropyridine derivatives and other components of the drug;

• history of angioedema, incl. against the background of the use of ACE inhibitors,

• hereditary angioedema or idiopathic angioedema,

• hemodynamically significant aortic stenosis or mitral stenosis,

• hypertrophic obstructive cardiomyopathy,

• severe arterial hypotension (systolic blood pressure less than 90 mm Hg),

• unstable angina (with the exception of Prinzmetal's angina),

• cardiogenic shock,

• heart failure after acute myocardial infarction (within the first 28 days), simultaneous administration with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus or renal failure (glomerular filtration rate less than 60 ml / min / 1.73 m2);
  pregnancy and the period of breastfeeding, age up to 18 years (efficacy and safety have not been established).

Carefully

Severe renal dysfunction, bilateral renal artery stenosis or stenosis of a solitary kidney artery with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease , autoimmune systemic diseases of the connective tissue (including scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; diet with restriction of table salt; hypovolemic conditions (including as a result of diarrhea, vomiting); use in elderly patients, hemodialysis using high-flow, high-permeability dialysis membranes (eg AN69Ѓ); liver dysfunction,sick sinus syndrome (severe bradycardia, tachycardia), CHF of non-ischemic etiology of III-IV functional class according to NYHA classification, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction).

Trade name of the drug:

Eclamise

International non-proprietary or group name:

amlodipine + lisinopril

Dosage form:

pills

Composition for one tablet:

Tablet 5 mg + 10 mg:
Active substances: amlodipine besylate - 6.94 mg in terms of amlodipine - 5.00 mg, lisinopril dihydrate - 10.88 mg, in terms of lisinopril - 10.00 mg.
Excipients: microcrystalline cellulose - 173.00 mg, sodium carboxymethyl starch - 6.18 mg, colloidal silicon dioxide - 1.00 mg, magnesium stearate - 2.00 mg.

Tablet 10 mg + 20 mg:
Active substances: amlodipine besylate - 13.88 mg in terms of amlodipine - 10.00 mg, lisinopril dihydrate - 21.76 mg, in terms of lisinopril - 20.00 mg.
Excipients: microcrystalline cellulose - 346.00 mg, sodium carboxymethyl starch - 12.36 mg, colloidal silicon dioxide - 2.00 mg, magnesium stearate - 4.00 mg.

Description:

tablets are white or almost white in color, round, flat-cylindrical in shape with a bevel on both sides and a line on one side.

Pharmacotherapeutic group:

combined antihypertensive agent (blocker of 'slow' calcium channels + angiotensin-converting enzyme (ACE) inhibitor)

ATX code:

—09¬¬03

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 the minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure (CHF). Expands arteries more than veins. Some of the effects are attributed to the effect on the tissue renin-angiotensin-aldosterone system (RAAS). With prolonged use, the hypertrophy of the myocardium and the walls of the resistive arteries decreases. Improves blood supply to the ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with CHF, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure.
The onset of action is 1 hour after oral administration. The maximum antihypertensive effect is determined after 6-7 hours and lasts for 24 hours. In arterial hypertension, the antihypertensive effect is observed in the first days after the start of treatment, a stable effect develops after 1-2 months. With an abrupt withdrawal of the drug, a pronounced increase in blood pressure was not noted.
In addition to lowering blood pressure, lisinopril reduces albuminuria. Lisinopril does not affect the blood glucose concentration in patients with diabetes mellitus and does not lead to an increased incidence of hypoglycemia.
Amlodipine
Derivative of dihydropyridine - a blocker of 'slow' calcium channels, has antianginal and antihypertensive effects. Blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).
The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: with angina pectoris, it reduces the severity of myocardial ischemia; expanding the peripheral arterioles, reduces the systemic vascular resistance, reduces the afterload on the heart, and reduces myocardial oxygen demand. Expanding the coronary arteries and arterioles in the unchanged and ischemic zones of the myocardium, increases the supply of oxygen to the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina pectoris, a single daily dose increases exercise tolerance, slows down the development of angina pectoris and 'ischemic' depression of the ST segment, reduces the frequency of angina attacks and the consumption of nitroglycerin and other nitrates.
It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscle. In arterial hypertension, a single dose provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's 'lying' and 'standing' position). 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. Does not affect the contractility and conductivity 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, it 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.
Lisinopril + amlodipine
The combination of lisinopril with amlodipine in one drug allows you to achieve comparable blood pressure control and prevent the development of possible undesirable effects caused by one of the active substances. Thus, BMCC, by directly expanding the arterioles, can lead to sodium and fluid retention in the body, and, therefore, can activate the RAAS. An ACE inhibitor blocks this process.

Pharmacokinetics
Lisinopril
Absorption. After oral administration, lisinopril is absorbed from the gastrointestinal tract (GIT) by an average of 25%, but absorption can vary from 6 to 60%. Bioavailability is 25%. Food intake does not affect the absorption of lisinopril.
Distribution. Almost does not bind to blood plasma proteins. The maximum concentration in blood plasma (Cmax) of 90 ng / ml is achieved in 6-7 hours. Permeability through the blood-brain and placental barriers is low.
Metabolism. Lisinopril is not biotransformed in the body.
Excretion. It is excreted by the kidneys unchanged. The half-life (T1 / 2) is 12 hours.
Pharmacokinetics in certain groups of patients
In elderly patients, the concentration of lisinopril in the blood plasma and the area under the concentration-time curve (AUC) are twice as large as in young patients.
In patients with CHF, absorption and clearance of lisinopril are reduced, bioavailability is 16%.
In patients with renal insufficiency, the concentration of lisinopril is several times higher than the concentration in the blood plasma in healthy volunteers, and there is an increase in the time to reach Cmax 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. Bioavailability is 64-80%. Food intake does not affect the absorption of amlodipine.
Distribution. Most of the amlodipine in the blood (95%) binds to blood plasma proteins. Cmax is observed after 6-10 hours. Equilibrium concentrations are reached after 7-8 days of therapy. The average volume of distribution is 20 L / kg body weight, which indicates that most of the amlodipine is in the tissues, and a smaller part in the blood.
Metabolism. Amlodipine undergoes a slow but active metabolism in the liver with no significant Уprimary passageФ effect. Metabolites have no significant pharmacological activity.
Excretion. After a single dose, T1 / 2 - varies from 31 to 48 hours, with repeated use, T1 / 2 is approximately 45 hours.About 60% of the ingested 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).
Pharmacokinetics in selected patient groups
In elderly patients (over 65 years old), the excretion of amlodipine is slowed down (T1 / 2 - 65 hours) compared with young patients, but this difference has no clinical significance. Elongation of T1 / 2 in patients with hepatic insufficiency suggests that with prolonged use, the accumulation of the drug in the body will be higher (T1 / 2 - up to 60 hours). Renal failure does not significantly affect the kinetics of amlodipine. Amlodipine crosses the blood-brain barrier. It is not removed during hemodialysis.
Lisinopril + Amlodipine
Interaction between the active substances that make up the drug is unlikely.
AUC, the time to reach and the values ??of Cmax, T1 / 2 do not undergo changes in comparison with the indicators of each individual active substance. Food intake does not affect the absorption of active substances. Long-term circulation in the body of both active substances makes it possible to take the drug once a day.

Indications for use

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

Contraindications

• Hypersensitivity to lisinopril or other ACE inhibitors, amlodipine, other dihydropyridine derivatives and other components of the drug;

• history of angioedema, incl. against the background of the use of ACE inhibitors,

• hereditary angioedema or idiopathic angioedema,

• hemodynamically significant aortic stenosis or mitral stenosis,

• hypertrophic obstructive cardiomyopathy,

• severe arterial hypotension (systolic blood pressure less than 90 mm Hg),

• unstable angina (with the exception of Prinzmetal's angina),

• cardiogenic shock,

• heart failure after acute myocardial infarction (within the first 28 days), simultaneous administration with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus or renal failure (glomerular filtration rate less than 60 ml / min / 1.73 m2);
  pregnancy and the period of breastfeeding, age up to 18 years (efficacy and safety have not been established).

Carefully

Severe renal dysfunction, bilateral renal artery stenosis or stenosis of a solitary kidney artery with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, arterial hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease , autoimmune systemic diseases of the connective tissue (including scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; diet with restriction of table salt; hypovolemic conditions (including as a result of diarrhea, vomiting); use in elderly patients, hemodialysis using high-flow, high-permeability dialysis membranes (eg AN69Ѓ); liver dysfunction,sick sinus syndrome (severe bradycardia, tachycardia), CHF of non-ischemic etiology of III-IV functional class according to NYHA classification, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction).

Application during pregnancy and during breastfeeding

The use of the drug Eclamiz is not recommended during pregnancy.
When diagnosing pregnancy, the drug should be stopped as early as possible.
Taking ACE inhibitors in the II and III trimester of pregnancy led to the development of fetotoxic effects (impaired renal function, slowing of ossification of the fetal skull bones, oligohydramnios) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia) and death of the developing fetus. According to a retrospective analysis, the use of ACE inhibitors during the first trimester of pregnancy was accompanied by the development of fetal and newborn pathology. For newborns and infants who have been exposed to intrauterine exposure to ACE inhibitors, it is recommended to closely monitor for the timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia.
The safety of using amlodipine during pregnancy has not been established. In some patients treated with blockers of 'slow' calcium channels, there was a reversible decrease in sperm motility.
Lisinopril crosses the placenta. There is no data on the excretion of lisinopril in breast milk.
There is no evidence of the excretion of amlodipine in breast milk. However, it is known that other BMCCs, dihydropyridine derivatives, are excreted in breast milk.
The use of the drug Eclamise during breastfeeding is not recommended.
If the use of the drug is necessary during lactation, then breastfeeding should be discontinued.

Method of administration and dosage

The tablets of the drug are taken orally once a day, regardless of the time of the meal, with a sufficient amount of liquid.
The recommended initial dose of Eclamiz is 5 mg of amlodipine + 10 mg of lisinopril 1 time per day.
If an additional decrease in blood pressure is required, the dose of Eclamiz can be increased to a maximum daily dose of 10 mg amlodipine + 20 mg lisinopril 1 time per day.
At the beginning of drug therapy, symptomatic arterial hypotension may develop, which often occurs in patients with impaired water and electrolyte balance due to previous diuretic therapy. Diuretics should be discontinued 2-3 days before starting therapy with Eclamise.
In cases where the withdrawal of diuretics is not possible, the initial dose of the drug Eclamiz is? tablets (5 mg amlodipine + 10 mg lisinopril) 1 time per day, after taking which, for several hours, the patient should be monitored due to the possible development of symptomatic arterial hypotension.
Renal dysfunction
In patients with renal dysfunction, it is recommended to use? tablets (5 mg amlodipine + 10 mg lisinopril) of the drug (increased half-life of lisinopril).
The maintenance dose is selected depending on the tolerability of the therapy, monitoring of renal function, potassium and sodium content in blood plasma is required.
Liver dysfunction
In patients with impaired liver function, it is recommended to use? tablets (5 mg amlodipine + 10 mg lisinopril) of the drug (increased half-life of amlodipine).
Use in elderly patients (over 65 years of age)
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 dosage regimen individually, using lisinopril and amlodipine separately.