Equapress modified-release capsules 5mg+1.5mg+10mg, 28pcs

Composition

Active ingredients:  

amlodipine bezylate – 6.934 mg (equivalent to amlodipine 5 mg),

indapamide-1.5 mg,

lisinopril dihydrate-10.888 mg (equivalent to lisinopril 10 mg).

Auxiliary substances:  lactose monohydrate, hypromellose, calcium hydrophosphate dihydrate, mannitol, corn starch, microcrystalline cellulose, croscarmellose sodium, talc, magnesium stearate, colloidal silicon dioxide, Opadray II white (contains: polyvinyl alcohol, titanium dioxide, macrogol-3350, talc), solid gelatin capsule (contains: yellow iron oxide dye, titanium dioxide carbon dioxide, water, and gelatin).

Pharmacological action

Equapress is a fixed combination of antihypertensive components amlodipine, indapamide and lisinopril, which have complementary mechanisms of action that allow controlling blood pressure (BP), and also have a synergistic cardioprotective effect.

The combination of amlodipine, indapamide and lisinopril prevents the possible development of side effects that occur when prescribing individual components of the drug. For example, by dilating the arterioles, slow calcium channel blockers (BCCs) can cause sodium and fluid retention in the body, which leads to activation of the renin-angiotensin-aldosterone system (RAAS). An angiotensin-converting enzyme (ACE) inhibitor blocks this process and normalizes the body’s response to salt loading.

ACE inhibitors significantly reduce diuretic-induced hypokalemia.

Amlodipine

Dihydropyridine derivative is a slow calcium channel blocker that has antihypertensive and antianginal effects. Blocks “slow” calcium channels, reduces the transmembrane transfer of calcium ions into the cell (more to vascular smooth muscle cells than to cardiomyocytes). The antianginal effect is caused by dilation of the coronary and peripheral arteries and arterioles:

when angina reduces the severity of myocardial ischemia; dilating peripheral arterioles, reduces the total peripheral vascular resistance, reduces afterload on the heart, reduces the need for myocardium in oxygen;

– expanding coronary arteries and arterioles in the unaltered and in ischemic areas of the myocardium, increases the supply of oxygen to the myocardium (especially when vasospastic angina); prevents spasm of the coronary arteries (including caused by Smoking).

In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina attacks and ST-segment depression by 1 mm, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to the direct vasodilating effect on vascular smooth muscles. In patients with arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the “lying” and “standing” positions).

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 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, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on the metabolism and concentration of plasma lipids 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.

In patients with diseases of the cardiovascular system (including coronary atherosclerosis with damage to one vessel and before stenosis of 3 or more arteries, carotid artery atherosclerosis), who have suffered a myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or in patients with angina pectoris, the use of amlodipine prevents the development of thickening of the intima-media of the carotid arteries, reduces mortality from myocardial infarction, stroke, PTCA, aorto-coronary bypass surgery; reduces the number of hospitalizations for unstable angina and the progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

It does not increase the risk of death or development of complications and deaths in patients with CHF (functional class III-IV according to the classification of the New York Heart Association (NYHA)) against the background of therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (NYHA functional class III-IV) of non-ischemic etiology, amlodipine is likely to cause pulmonary edema.

Indapamide

Indapamide belongs to the derivatives of sulfonamide with an indole ring and is similar in pharmacological properties to thiazide diuretics, which inhibit the absorption of sodium ions in the cortical segment of the nephron loop. At the same time, the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys increases, which is accompanied by an increase in diuresis and an antihypertensive effect.

A 24 – hour antihypertensive effect was demonstrated in clinical studies when indapamide was used as monotherapy in doses that did not have a pronounced diuretic effect.

The antihypertensive activity of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in arteriolar and total peripheral vascular resistance.

Indapamide reduces left ventricular hypertrophy.

Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the frequency of side effects continues to increase with further increase in the dose of the drug. Therefore, do not increase the dose of the drug if the recommended dose does not achieve a therapeutic effect.

In short -, medium-and long-term studies involving patients with arterial hypertension, indapamide has been shown to:

– does not affect the parameters of lipid metabolism, including the concentration of triglycerides, cholesterol, low-and high-density lipoproteins;

– does not affect carbohydrate metabolism, including in patients with diabetes mellitus.

Lisinopril

Lisinopril is an ACE inhibitor that inhibits the conversion of angiotensin I to angiotensin II. A decrease in the concentration of angiotensin II leads to a direct decrease in the secretion of aldosterone. Lisinopril inhibits bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance, blood pressure, preload and pressure in the pulmonary capillaries. In patients with CHF, it increases the minute volume of blood and increases the resistance of the myocardium to stress. Dilates the arteries to a greater extent than the veins. Some of the effects are explained by its effect on the tissue renin-angiotensin system. With prolonged use, hypertrophy of the myocardium and arterial walls of the resistive type decreases.

Lisinopril improves blood supply to the ischemic myocardium.

In patients with CHF, ACE inhibitors increase life expectancy; in patients with a history of myocardial infarction in the absence of clinical manifestations of heart failure, lisinopril slows the progression of left ventricular dysfunction. In patients with CHF, lisinopril begins to act within 1 hour after oral use. The maximum effect is achieved within 6-7 hours; the duration of the effect is 24 hours. In patients with arterial hypertension, the effect appears within the first days after the start of treatment; stabilization of the effect occurs within 1-2 months of treatment. No cases of a marked increase in blood pressure after abrupt discontinuation of the drug have been reported. Lisinopril provides both a reduction in blood pressure and a reduction in albuminuria. In patients with hyperglycemia, the drug helps restore the function of damaged glomerular endothelium. In patients with diabetes mellitus, lisinopril does not affect the concentration of glucose in blood plasma; taking the drug does not lead to an increase in cases of hypoglycemia.

Indications

Arterial hypertension (patients who require combination therapy).

Contraindications

: Hypersensitivity to amlodipine or other dihydropyridine derivatives.

– Hypersensitivity to lisinopril or other ACE inhibitors.

– Hypersensitivity to indapamide or other sulfonamide derivatives.

– Hypersensitivity to excipients of the drug.

– Severe arterial hypotension (systolic blood pressure below 90 mm Hg).

– Past angioedema, including those associated with the use of ACE inhibitors.

– Hereditary or idiopathic angioedema.

– Severe renal insufficiency (creatinine clearance

– Hepatic encephalopathy or severe liver dysfunction.

– Hypokalemia.

– Hemodynamically significant obstruction of the outflow tract of the left ventricle (for example, in severe aortic stenosis, hypertrophic obstructive cardiomyopathy), hemodynamically significant mitral stenosis.

– Hemodynamically unstable heart failure after myocardial infarction.

– Shock (including cardiogenic shock).

– Unstable angina (with the exception of Prinzmetal angina).

– Concomitant use of Equapress and drugs containing aliskiren in patients with diabetes mellitus and / or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 of body surface area).

– Concomitant use with anThere are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Concomitant use of inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John’s wort) and amlodipine may lead to a decrease in the plasma concentration of amlodipine. Caution should be exercised when using Equapress concomitantly with inducers of the CYP3A4 isoenzyme.

Inhibitors of the CYP3A4 isoenzyme

Concomitant use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors, for example, ritonavir, azole antifungal drugs, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. The 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 Equapress.

Drug combinations that require caution when used

Simvastatin

Repeated use of 10 mg amlodipine in combination with 80 mg simvastatin resulted in a 77% increase in simvastatin exposure compared to simvastatin monotherapy. Therefore, patients receiving amlodipine should take simvastatin at a daily dose of no more than 20 mg.

Calcium supplements

They can reduce the effect of BMCC.

Lithium preparations

When BMCC is co-administered with lithium preparations (no data available for amlodipine), their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor or tinnitus).

Baclofen

Increased antihypertensive effect. Blood pressure and renal function should be monitored, and the dose of amlodipine should be adjusted if necessary.

Amifostin

It is possible to increase the antihypertensive effect of amlodipine.

Glucocorticosteroids

Reduced antihypertensive effect (fluid retention and sodium ions as a result of corticosteroids).

Tricyclic antidepressants neuroleptics, isoflurane

There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).

Tacrolimus

When used concomitantly with amlodipine, there is a risk of increasing the concentration of tacrolimus in blood plasma. In order to avoid toxicity of tacrolimus when used concomitantly 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 concomitantly, amlodipine may increase the systemic exposure of tasonermine in blood plasma. In such cases, regular monitoring of tasonermin in the blood is necessary and dose adjustment if necessary.

Other interactions with amlodipine

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, concomitant use of amlodipine with other antianginal drugs, such as long-and short-acting nitrates, beta-blockers, is possible.

It is likely to increase the antianginal and antihypertensive effects of BMCC when used simultaneously with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as their increased antihypertensive effect when prescribed with alpha-1-blockers and neuroleptics.

Amlodipine does not cause a negative inotropic effect. However, some BMCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (for example, amiodarone and quinidine). Unlike other BMCs, there was no significant interaction between amlodipine (3rd generation BMCs) and NSAIDs, including Indometacin. It is safe to administer amlodipine with oral hypoglycemic medications. A single 100 mg dose of sildenafil in patients with essential hypertension did not affect the pharmacokinetics of amlodipine. Co-use of multiple doses of amlodipine 10 mg and atorvastatin 80 mg resulted in insignificant changes in the pharmacokinetic parameters of atorvastatin at steady state. Ethanol (beverages containing alcohol): amlodipine has no significant effect on the pharmacokinetics of ethanol with a single and repeated use at a dose of 10 mg. Studies of the interaction of 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 either not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees up to 40%. Cyclosporine concentrations should be monitored in patients after kidney transplantation.

When amlodipine and digoxin are co-administered, renal clearance and serum digoxin concentrations do not change.

When warfarin is co-administered with amlodipine, the prothrombin time does not change.

When co-administered with cimetidine, the pharmacokinetics of amlodipine do not change.

Amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin and Indometacin to 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.

Indapamide

Contraindicated drug combinations

Lithium preparations

With the simultaneous use of indapamide and lithium preparations, as well as with a salt-free diet, an increase in the concentration of lithium in the blood plasma may occur due to a decrease in its excretion, accompanied by the appearance of signs of overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while carefully monitoring the lithium content in the blood plasma and selecting the dose of the drug accordingly.

Drug combinations that require extreme caution when used

Drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type

– Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide). – Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide). – Some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol). – Others: bepridil, cisapride, difemanil, erythromycin (intravenous), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (intravenous).

Increased risk of ventricular arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type (risk factor – hypokalemia).

It is necessary to determine the concentration of potassium in the blood plasma and, if necessary, adjust it before starting combination therapy with indapamide and the above drugs. It is necessary to monitor the patient’s clinical condition, monitor the level of blood plasma electrolytes, and ECG indicators.

In patients with hypokalemia, it is necessary to use drugs that do not cause polymorphic ventricular tachycardia of the “pirouette”type.

Nonsteroidal anti-inflammatory drugs (with systemic use), including selective COX-2 inhibitors, high doses of salicylic acid (≥3 g / day)

It is possible to reduce the antihypertensive effect of indapamide.

There is a risk of developing acute renal failure due to reduced glomerular filtration. Patients should be compensated for fluid loss and renal function should be carefully monitored at the beginning of treatment.

ACE inhibitors

The use of ACE inhibitors in patients with initially low blood sodium concentrations (especially in patients with renal artery stenosis) is associated with the risk of sudden hypotension and/or acute renal failure. Patients with arterial hypertension and possibly reduced due to taking diuretics, the content of sodium ions in the blood plasma should:

– stop taking the diuretic 3 days before starting treatment with an ACE inhibitor. In the future, if necessary, the use of a non-potassium-sparing diuretic can be resumed;

– or start therapy with an ACE inhibitor at low doses, followed by a gradual increase in the dose if necessary.

In patients with chronic heart failure, treatment with ACE inhibitors should be started at the lowest possible dose, with a possible preliminary reduction in diuretic doses. In all cases, renal function (plasma creatinine) should be monitored during the first weeks of taking ACE inhibitors in patients.

Other drugs that may cause hypokalemia: amphotericin B (with intravenous use), glucocorticosteroids (with systemic use), tetracosactide, laxatives that stimulate intestinal motility

Increased risk of hypokalemia (additive effect).

It is necessary to constantly monitor the concentration of potassium in the blood plasma, if necessary – its correction. Special attention should be paid to patients receiving concomitant cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.

Baclofen

There is an increase in the antihypertensive effect.

Patients should be compensated for fluid loss and renal function should be carefully monitored at the beginning of treatment.

Cardiac Glycosides

Hypokalemia increases the toxic effect of cardiac glycosides.

When indapamide and cardiac glycosides are used concomitantly, the potassium content in the blood plasma, ECG parameters should be monitored and, if necessary, therapy should be adjusted.

Drug combinations that require caution when used

Potassium-sparing diuretics (amiloride, spironolactone, triamterene, eplerenone) Combination therapy with indapamide and potassium-sparing diuretics is advisable in some patients, but the possibility of hypokalemia or hyperkalemia is not excluded (especially in patients with diabetes mellitus or in patients with renal insufficiency).

It is necessary to monitor the concentration of potassium in the blood plasma, ECG indicators and, if necessary, adjust therapy.

Metformin

Functional renal failure, which may occur with diuretics, especially loop diuretics, and concomitant use of metformin increases the risk of lactic acidosis.

Metformin should not be used if the plasma creatinine level exceeds 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

Iodine-containing contrast agents

Dehydration caused by diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

Before using iodine-containing contrast agents, patients need to compensate for fluid loss.

Tricyclic antidepressants, antipsychotic drugs (neuroleptics)

Drugs of these classes enhance the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Calcium Salts

When used concomitantly, the risk of hypercalcemia increases due to a decrease in the excretion of calcium ions by the kidneys.

Cyclosporine, tacrolimus

It is possible to increase the level of creatinine in blood plasma without changing the concentration of circulating cyclosporine, even with a normal volume of circulating blood and the content of sodium in blood plasma.

Glucocorticosteroid drugs, tetracosactide (for systemic use)

Reduced antihypertensive effect (fluid and sodium ion retention caused by corticosteroids).

Lisinopril

Contraindicated drug combinations

Aliskiren

Concomitant use of ACE inhibitors with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and / or moderate to severe renal impairment (GFR less than 60 ml / min/1.73 m2 of body surface area) contraindicated.

The use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy.

Not recommended drug combinations

Angiotensin II receptor antagonists (ARA II)

In the literature, it has been reported that in patients with established atherosclerotic disease, chronic heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and ARA II is associated with a higher incidence of hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared to using 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 content and blood pressure.

Potassium supplements, potassium-sparing diuretics (spironolactone, triamterene, amiloride. eplerenone) or potassium-containing salt substitutes

Hyperkalemia may occur (with a possible fatal outcome), especially if renal function is impaired (additional effects associated with hyperkalemia). ACE inhibitors should not be used simultaneously with substances that increase the potassium content in blood plasma, except in cases of hypokalemia. The combination of lisinopril and the above drugs is not recommended. If, however, concomitant use is indicated, they should be used with caution and regular monitoring of serum potassium levels.

Lithium preparations

With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in the blood serum and associated toxic effects may occur. Concomitant use of lisinopril and lithium preparations is not recommended. If such therapy is necessary, regular monitoring of the lithium concentration in the blood serum should be carried out.

Drug combinations that require extreme caution when used

Insulin and oral hypoglycemic agents

Epidemiological studies have shown that the combined use of ACE inhibitors and hypoglycemic agents (insulins, hypoglycemic agents for oral use) can increase their hypoglycemic effect up to the development of hypoglycemia. This effect is most likely observed during the first weeks of concomitant therapy, as well as in patients with impaired renal function. Baclofen

Increases the antihypertensive effect of ACE inhibitors. Blood pressure levels should be carefully monitored and, if necessary, the dose of antihypertensive drugs should be adjusted.

Diuretics

Patients taking diuretics, especially those that remove fluids and/or salts, may experience a significant decrease in blood pressure at the beginning of ACE inhibitor therapy. The risk of developing antihypertensive effects can be reduced by discontinuing the diuretic, replacing the loss of fluid or salts before starting therapy with ACE inhibitors. In hypertensive patients with previous diuretic therapy, which may have resulted in excessive fluid and/or salt excretion, diuretics should be discontinued prior to the use of Equapress.

Renal function (creatinine concentration) should be monitored during the first weeks of use of Equapress.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ≥3 g / day

Concomitant use of ACE inhibitors with NSAIDs (acetylsalicylic acid at a dose that has an anti-inflammatory effect, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of ACE inhibitors. Concomitant use of ACE inhibitors and NSAIDs can 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 kidney function both at the beginning of treatment and during treatment. Estramustine, mTOR inhibitors (sirolimus, everolimus, temsirolimus), neutral endopeptidase inhibitors (omapatrilate, ilepatril, daglutril, sacubitril) Concomitant use of estramustine with ACE inhibitors is associated with an increased risk of angioedema.

DPP-4 inhibitors (gliptins)

Linagliptin, saxagliptin, sitagliptin, vildagliptin – when combined with ACE inhibitors, the risk of angioedema increases due to the suppression of dipeptidyl peptidase-4 (DPP-4 ) activity by gliptin.

Racecadotril (an enkephalinase inhibitor used to treat acute diarrhea)

When used concomitantly with ACE inhibitors, the risk of angioedema may increase.

Drug combinations that require caution when used

Other antihypertensive agents (e. g. beta-blockers, slow calcium channel blockers, diuretics) and vasodilators

It is possible to increase the antihypertensive effect of the drug. Caution should be exercised when prescribing concomitantly with nitroglycerin, other nitrates or other vasodilators, as this may lead to an additional decrease in blood pressure.

Antacids and cholestyramine

Concomitant use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.

Tricyclic antidepressants, antipsychotics, general anaesthetics, barbiturates, phenothiazine, ethanol

When taken together, it is possible to increase the effect of lisinopril.

Sympathomimetics

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.

Muscle relaxants

Concomitant use of muscle relaxants with ACE inhibitors can lead to a marked decrease in blood pressure.

Gold preparations

When using ACE inhibitors, including lisinopril, patients receiving intravenous gold preparation (sodium aurothiomalate), rare cases of nitritoid reactions (a symptom complex that includes facial skin hyperemia, nausea, vomiting, and hypotension) have been described.

Co-trimoxazole (sulfamethoxazole and trimethoprim)

Increased risk of hyperkalemia.

Selective serotonin reuptake inhibitors (SSRIs: escitalopram, paroxetine, fluoxetine, sertraline)

When used concomitantly with SSRIs, severe hyponatremia may develop.

Allopurinol, procainamide, cytostatics (5-fluorouracil, vincristine, docetaxel)

Possible development of leukopenia.

Tissue plasminogen activators (alteplase, reteplase, tenecteplase)

Increased risk of angioedema when used concomitantly with ACE inhibitors.

How to take it, course of use and dosage

Method of application

The drug Equapress is taken orally, regardless of food intake.

Doses

Fixed-dose combination medications are not recommended for initial therapy. Equapress is prescribed to adult patients who have achieved adequate blood pressure control while taking lisinopril, amlodipine and indapamide, which the patient takes simultaneously in the same doses as in the combined drug: amlodipine 5 mg, indapamide 1.5 mg, lisinopril 10 mg (Equapress 5 mg + 1.5 mg + 10 mg), amlodipine 10 mg, indapamide 1.5 mg, lisinopril 20 mg (Equapress 10 mg + 1.5 mg + 20 mg), amlodipine 5 mg, indapamide 1.5 mg, lisinopril 20 mg (Equapress 5 mg + 1.5 mg + 20 mg).

The recommended dose is 1 capsule per day, preferably in the morning, at the same time every day. The maximum daily dose is 1 capsule.

If symptomatic hypotension develops at the beginning of treatment with Equapress, 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 for dose reduction should be evaluated.

If it is necessary to adjust the dose, the drugs amlodipine, indapamide and lisinopril should be used separately.

Skipping medication

If you forget to take a capsule of Equapress, then take the next dose at the usual time. Do not take two capsules at the same time to make up for a missed dose.

Special patient groups

Patients with renal insufficiency

During therapy with Equapress, it is necessary to monitor kidney function, as well as the content of potassium and sodium in the blood serum. If renal function worsens, Equapress should be discontinued and replaced with an individually selected therapy consisting of individual components.

Patients with hepatic insufficiency

Amlodipine elimination may be delayed in patients with impaired liver function. There are no specific recommendations for such cases, so Equapress should be used with caution in these patients.

Children and teenagers (

The safety and efficacy of Equapress in children and adolescents has not been established.

Elderly patients (>65 years)

This drug should be used with caution in elderly patients.

It is necessary to monitor the concentration of creatinine in blood plasma in accordance with age, body weight and gender.

No age-related changes in the efficacy and safety profiles of amlodipine or lisinopril were found in clinical trials.

Overdose

Amlodipine overdose

Symptoms: a significant decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (there is a risk of significant and persistent hypotension, with the development of shock and death).

Treatment: gastric lavage, use of activated charcoal (especially during the first 2 hours after overdose), giving the patient a horizontal position with raised lower limbs, active support of the cardiovascular system, monitoring of heart and lung function indicators, monitoring of circulating blood volume and diuresis. In the absence of contraindications to restore vascular tone and blood pressure, it may be advisable to prescribe vasoconstrictors. Intravenous injections of calcium gluconate can help stop the effects of calcium channel blockage. Since amlodipine is largely bound to serum proteins, hemodialysis is ineffective in treating amlodipine overdose.

Overdose of indapamide

No toxic effects of indapamide were observed in overdose, even in very high doses (up to 40 mg, i. e. 27 times higher than the therapeutic dose).

Signs of acute indapamide poisoning are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). Clinical symptoms of overdose may include nausea, vomiting, decreased blood pressure, seizures, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia).

Emergency measures include removing the drug from the body, gastric lavage, and / or taking activated carbon to restore the water-electrolyte balance.

Lisinopril overdose

Symptoms: significant decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, intravenous use of 0.9% sodium chloride solution and, if possible, vasopressors, blood pressure control, water-electrolyte balance control. Hemodialysis is possible.

Special instructions

If you are hospitalized, tell your doctor that you are taking Equapress.

When using the drug Equapress, special instructions regarding individual components of the drug should be taken into account.

Related to Amlodipine

It is necessary to maintain dental hygiene and follow-up by a dentist (to prevent soreness, bleeding and gum hyperplasia).

In elderly patients, T 1/2 may increase and clearance of amlodipine 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.

In vitro studies have shown that amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin or Indometacin to human plasma proteins.

Despite the absence of “withdrawal” syndrome in BMCC, it is advisable to stop treatment with amlodipine by gradually reducing the dose of the drug.

When amlodipine was used in patients with non-ischemic NYHA class III and IV CHF, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

Impact on fertility

In some patients treated with calcium channel blockers, reversible biochemical changes in the sperm head were found, which may be clinically significant during in vitro fertilization (IVF).

However, there are currently insufficient clinical data regarding the potential effect of amlodipine on fertility. A preclinical study identified undesirable effects on male fertility.

Related to Indapamide

Impaired liver function

When prescribing thiazide and thiazide-like diuretics to patients with impaired liver function, hepatic encephalopathy may develop, especially in the presence of an electrolyte imbalance. In this case, it is necessary to stop using diuretics.

Photosensitization

When using thiazide and thiazide-like diuretics, there have been cases of photosensitization. With the development of photosensitization, the withdrawal of these drugs is indicated. If it is necessary to continue treatment, it is recommended to protect the skin from sunlight or artificial UV radiation.

Water-electrolyte balance

Blood plasma sodium content

Before starting treatment, you should determine the sodium content in the blood plasma and regularly monitor this indicator. All diuretics can cause hyponatremia, which can lead to extremely serious consequences. Constant monitoring of the sodium content in the blood plasma is necessary, since at first its decrease may not have clinical manifestations. Especially careful monitoring of the sodium content should be carried out in patients with cirrhosis of the liver and in the elderly.

All diuretic drugs can cause hyponatremia, sometimes leading to extremely severe consequences. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. Concomitant reduction of chlorine ions can lead to secondary compensatory metabolic alkalosis: the frequency and severity of this effect are insignificant.

Potassium content in blood plasma

Against the background of therapy with thiazide and thiazide-like diuretics, a sharp decrease in the content of potassium in blood plasma is possible, as well as the development of hypokalemia. It is necessary to prevent the risk of hypokalemia (/k) in the following groups of patients: elderly, debilitated patients and / or receiving concomitant drug therapy, patients with cirrhosis of the liver, peripheral edema and ascites, coronary heart disease, heart failure.

In such patients, hypokalemia increases the toxic effects of cardiac glycosides and increases the risk of arrhythmias. In addition, the high-risk group includes patients with an extended QT interval, and it does not matter whether this increase is caused by congenital causes or the action of medications.

Hypokalemia, like bradycardia, contributes to the development of severe arrhythmias, especially cardiac arrhythmias that can lead to death. The first measurement of the potassium content in the blood plasma should be carried out within the first week after the start of treatment. If hypokalemia is detected, appropriate therapy is indicated.

Blood plasma calcium content

Thiazide and thiazide-like diuretics reduce the excretion of calcium in the urine, which leads to a slight temporary increase in the content of calcium in the blood plasma. Hypercalcemia with clinical manifestations may be the result of previously undiagnosed hyperparathyroidism.

You should stop taking diuretics before examining the function of the parathyroid glands.

Blood plasma glucose

Glucose control is indicated in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

Patients suffering from gout may have an increased frequency of gout attacks or exacerbation of its course.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are most effective in patients with normal or slightly reduced renal function (adult plasma creatinine The concentration of creatinine in blood plasma in elderly patients is estimated depending on age, body weight and gender.

At the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which may be associated with loss of water and sodium due to the action of diuretics. This may be due to an increase in the concentration of uric acid and creatinine in the blood plasma. With preserved renal function, such transient functional renal failure usually passes without complications. However, in the presence of renal failure, the general condition of patients may worsen.

Athletes

Indapamide can give a positive result of doping control in athletes.

Related to Lisinopril

Symptomatic hypotension

Most often, a marked decrease in blood pressure is associated with hypovolemia caused by the use of diuretics, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting. Patients with CHF, regardless of whether it is associated with renal failure, may develop hypotension. Patients with severe heart failure have been found to develop this condition more frequently due to high-dose diuretics, hyponatremia, or impaired renal function. In such patients, careful medical monitoring is required (it is necessary to carefully select the dose of lisinopril and diuretics). The same guidelines apply to patients with coronary heart disease and cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to a myocardial infarction or stroke.

With a significant decrease in blood pressure, it is recommended to place the patient in a supine position, if necessary, intravenously inject 0.9% sodium chloride solution.

A transient hypotensive reaction is not a contraindication for taking the next dose of lisinopril.

In patients with CHF, but with normal or reduced blood pressure, the use of lisinopril can lead to a decrease in blood pressure; this usually does not serve as a reason for discontinuing the drug. If arterial hypotension becomes symptomatic, it is necessary to reduce the dose of the drug or discontinue treatment with the drug. In patients at risk of developing symptomatic hypotension (with a low-salt or salt-free diet), regardless of the presence of hyponatremia, as well as in patients receiving high-dose diuretics, it is necessary to compensate for hypovolemia or lack of sodium before starting treatment.

Blood pressure should be monitored when taking the first dose of lisinopril.

Acute myocardial infarction

Standard treatment (thrombolytics, acetylsalicylic acid, beta – blockers) is recommended. Lisinopril can be used simultaneously with intravenous nitroglycerin or transdermal nitroglycerin.

In patients with acute myocardial infarction and risk of further deterioration of hemodynamics, worsening of symptoms after the appointment of vasodilators, lisinopril therapy should not be initiated. These are patients with systolic blood pressure <100 mm Hg and patients with cardiogenic shock. In patients with systolic blood pressure In patients with systolic blood pressure < 100 mm Hg, the maintenance dose should be reduced to 5 mg (or temporarily to 2.5 mg). In patients with persistent arterial hypotension (systolic blood pressure

Impaired renal function

In patients with CHF, a significant decrease in blood pressure during the use of ACE inhibitors may lead to increased renal dysfunction. Cases of acute renal failure have been reported.

Patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney during the use of ACE inhibitors showed an increase in the concentration of urea and serum creatinine; usually these disorders were transient and stopped after discontinuation of therapy. They were more common in patients with renal insufficiency.

In patients with acute myocardial infarction and severe renal impairment (serum creatinine > 177 mmol / l and / or proteinuria >500 mg / day) lisinopril should not be prescribed. If renal dysfunction develops during treatment (serum creatinine concentration >265 mmol/l or doubling compared to baseline), lisinopril should be discontinued.

Hypersensitivity, angioedema

In rare cases, angioedema of the face, extremities, lips, tongue, epiglottis, and/or larynx has been reported with the use of ACE inhibitors, including lisinopril. In such cases, immediate withdrawal of lisinopril is required; monitoring of the patient’s condition is indicated until the symptoms are fully resolved. Usually, angioedema of the face and lips is temporary and does not require treatment; however, antihistamines may be prescribed. Angioedema of the larynx can lead to death. Swelling of the tongue, epiglottis, or larynx can lead to secondary airway obstruction. In this case, it is necessary to immediately inject 0.3-0.5 ml of 1:1000 epinephrine solution subcutaneously, and also ensure patency of the respiratory tract.

In rare cases, angioedema of the intestine developed during therapy with ACE inhibitors. At the same time, patients experienced abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases without previous angioedema of the face and with normal levels of C1 – esterase.

The diagnosis was established by computed tomography of the abdominal organs, ultrasound examination, or during surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain treated with ACE inhibitors, the possibility of developing angioedema of the intestine should be taken into account during differential diagnosis.

Patients with a history of angioedema that is not associated with ACE inhibitors have a higher risk of developing angioedema when using ACE inhibitors.

Anaphylactic reactions associated with desensitization to hymenopteran insects

In very rare cases, patients taking ACE inhibitors may develop life-threatening anaphylactic reactions during desensitization to hymenopteran insects, so it is necessary to temporarily cancel ACE inhibitors before desensitization.

Patients undergoing hemodialysis

Anaphylactic reactions also occurred in patients undergoing hemodialysis using high-permeability dialysis membranes (for example, AN69) while receiving ACE inhibitors. In such patients, the use of other dialysis membranes or other antihypertensive drugs is indicated.

Cough

ACE inhibitor therapy can cause coughing, which should be taken into account when making a differential diagnosis. Prolonged dry cough usually stops after ACE inhibitors are discontinued.

Surgical interventions/general anesthesia

The use of antihypertensive drugs during volumetric surgery or during general anesthesia may lead to inhibition of angiotensin II formation due to compensatory renin secretion.

A significant decrease in blood pressure associated with this effect can be prevented by increasing the volume of circulating blood.

Patients taking ACE inhibitors should inform the surgeon / anaesthetist before performing surgery (including dental procedures).

Blood serum potassium

Cases of hyperkalemia have been reported.

Risk factors for hyperkalemia include renal failure, diabetes mellitus, therapy with potassium-sparing diuretics (spironolactone, triamterene and amiloride), the use of potassium preparations and potassium-based salt substitutes, especially in patients with impaired renal function.

If the combined use of lisinopril and these drugs is necessary, regular monitoring of the concentration of potassium in the blood serum is indicated.

Double blockade of the RAAS

Concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren has been shown to increase the risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure). Therefore, combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren for dual RAAS blockade is not recommended.

If there are absolute indications for double blockade of the RAAS, it should be carried out under the careful supervision of a specialist with frequent monitoring of renal function, electrolyte content and blood pressure.

Concomitant use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and / or moderate or severe renal insufficiency (GFR less than 60 ml / min/1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant 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

Neutropenia/agranulocytosis, thrombocytopenia, and anemia may occur while taking ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other aggravating factors.Ekvapress should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or when these risk factors are combined, especially in patients with impaired renal function.

Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Equapress to such patients, it is recommended to periodically monitor the number of white blood cells in the blood plasma. Patients should inform the doctor about any signs of infectious diseases (for example, sore throat, fever).

Mitral stenosis/ aortic stenosis/Hypertrophic cardiomyopathy

ACE inhibitors should be used with caution in patients with mitral stenosis, as well as in patients with obstruction of the left ventricular exit tract (aortic stenosis, hypertrophic cardiomyopathy).

Liver failure

Very rarely, cholestatic jaundice occurs while taking ACE inhibitors. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of “liver” enzymes occurs while taking ACE inhibitors, Equapress should be discontinued and the patient should be carefully monitored.

Ethnic differences

Patients of the black race are more likely than those of other races to develop angioedema while taking ACE inhibitors. ACE inhibitors may have a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the black race are more likely to have low renin activity.

Lactose

The drug contains lactose monohydrate, so it should not be taken in patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Influence on the ability to drive vehicles and mechanisms:

There are no data on the effect of Equapress on the ability to drive vehicles and manage mechanisms. Taking into account the possibility of lowering blood pressure, the risk of dizziness, drowsiness and similar side effects, patients should exercise caution when performing potentially dangerous activities that require special attention and quick response (driving vehicles, working with moving mechanisms, working as a dispatcher and operator, etc. ).

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use after the expiration date indicated on the package.

Active ingredient

Amlodipine, Indapamide, Lisinopril

Conditions of release from pharmacies

By prescription

Dosage form

Capsules