Equapress, 10 mg+1.5 mg+20 mg 28 pcs.

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

The combination of amlodipine, indapamide, and lisinopril prevents possible side effects of the individual components of the drug. For example, by dilating the arterioles, slow calcium channel blockers (SCBs) can cause sodium and fluid retention in the body, resulting in activation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin-converting enzyme (ACE) inhibitor blocks this process and normalizes the body’s response to salt load.

The ACE inhibitors significantly reduce hypokalemia caused by diuretics.

Amlodipine

The dihydropyridine derivative is a “slow” calcium channel blocker that has antihypertensive and antianginal effects. It blocks “slow” calcium channels, decreases transmembrane transition of calcium ions into cells (more in vascular smooth muscle cells than in cardiomyocytes). Antianginal action is due to the dilation of coronary and peripheral arteries and arterioles:

In angina, it reduces the severity of myocardial ischemia; by dilating the peripheral arterioles, it reduces total peripheral vascular resistance, reduces the afterload on the heart, and reduces myocardial oxygen demand;

– expanding coronary arteries and arterioles in unchanged and in ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina); prevents spasm of coronary arteries (including those caused by smoking).Also caused by smoking.)

In patients with stable angina, a single daily dose increases exercise tolerance, delays the development of angina attacks and ST-segment depression by 1 mm, 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 vasodilatory effect on the vascular smooth muscles. In arterial hypertension a single dose provides clinically significant reduction of BP during 24 hours (in “lying” and “standing” positions).

Orthostatic hypotension when using amlodipine is quite rare. Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy. It does not affect myocardial contractility and conduction, does not cause reflex increase of heart rate, inhibits platelet aggregation, increases glomerular filtration rate, has weak natriuretic effect.

In diabetic nephropathy it does not increase microalbuminuria. It does not have any adverse effect on metabolism and blood plasma lipid concentration and can be used for therapy of patients with bronchial asthma, diabetes and gout. Significant decrease in BP is observed after 6-10 hours, the duration of effect – 24 hours.

In patients with diseases of the cardiovascular system (including coronary atherosclerosis with lesions of one vessel and up to stenosis of 3 or more arteries, atherosclerosis of the carotid arteries), who had myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or in patients with angina pectoris, the use of amlodipine prevents the development of carotid intima-media thickening, reduces mortality from myocardial infarction, stroke, PTCA, aortocoronary bypass; leads to fewer hospitalizations for unstable angina and progression of chronic heart failure (CHF); reduces the frequency of interventions to restore coronary blood flow.

Does not increase risk of death or complications and lethal outcomes in patients with CHF (New York Heart Association (NYHA) Class III-IV functional class) during therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (functional class III-IV according to NYHA classification) of non-ischemic etiology, there is a possibility of pulmonary edema when using amlodipine.

Indapamide

Indapamide refers to sulfonamide derivatives with an indole ring and has pharmacological properties similar to thiazide diuretics, which inhibit sodium ion absorption in the cortical segment of the nephron loop. The renal excretion of sodium and chlorine ions and, to a lesser extent, potassium and magnesium ions increases, which is accompanied by increased diuresis and antihypertensive effect.

In clinical studies, a 24-hour antihypertensive effect has been demonstrated with indapamide in monotherapy in doses that have no pronounced diuretic effect.

The antihypertensive activity of indapamide is associated with improvement of elastic properties of large arteries, reduction of arteriolar and total peripheral vascular resistance.

Indapamide reduces left ventricular hypertrophy.

The thiazide and thiazide-like diuretics reach a plateau of therapeutic effect at a certain dose, whereas the incidence of side effects continues to increase with further increasing of the drug dose. Therefore, do not increase the dose of the drug if the therapeutic effect is not achieved at the recommended dose.

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

– has no effect on lipid metabolism, including triglyceride, cholesterol, low and high density lipoprotein concentrations;

– has no effect on carbohydrate metabolism, including in patients with diabetes.

Lisinopril

Lisinopril is an ACE inhibitor and inhibits the transformation of angiotensin I into angiotensin II. Reducing the concentration of angiotensin II leads to a direct reduction of aldosterone secretion. Lisinopril inhibits bradykinin degradation and increases prostaglandin synthesis. It reduces total peripheral vascular resistance, BP, preload and pulmonary capillary pressure. In patients with CHF it increases minute blood volume and increases myocardial resistance to stress.

Dilates arteries more than veins. Some effects are explained by its effect on the tissue renin-angiotensin system. Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy.

Lisinopril improves the 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 starts working within 1 hour after oral administration. Maximum effect is achieved within 6-7 hours; the duration of effect is 24 hours. In patients with arterial hypertension the effect is seen during the first days after treatment start; stabilization of the effect occurs within 1-2 months of treatment. Cases of marked increase in BP after abrupt withdrawal of the drug have not been registered.

Lisinopril provides both BP reduction and albuminuria reduction. In patients with hyperglycemia the drug promotes restoration of function of damaged glomerular endothelium. In patients with diabetes, lisinopril has no effect on plasma glucose concentration; the drug does not lead to increased incidence of hypoglycemia.

Indications

Arterial hypertension (patients who require combination therapy).

Active ingredient

Amlodipine, Indapamide, Lisinopril

Composition

Active ingredients:

Amlodipine besylate – 13.868 mg (equivalent to amlodipine 10 mg),

indapamide – 1.5 mg,

lisinopril dihydrate – 21.776 mg (equivalent to lisinopril 20 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), hard gelatin capsule (contains: iron oxide yellow dye, titanium dioxide, water, gelatin)

How to take, the dosage

Instructions for Use

The drug Equapress is taken orally, regardless of meals.

Dosages

The fixed-dose combination medication is not recommended for initial therapy. Equapress is indicated in adult patients in whom adequate BP control has been achieved with lisinopril, amlodipine and indapamide, which the patient takes simultaneously in the same doses as in the combination 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 daily, preferably in the morning, at the same time each day. The maximum daily dose is 1 capsule.

If symptomatic arterial hypotension develops at the beginning of treatment with Equapress, the patient should lie on his back, suspend the drug and consult a physician. Transient arterial hypotension usually does not require withdrawal of the drug, but the need for dose reduction should be assessed.

If a dose adjustment is necessary, amlodipine, indapamide and lisinopril should be used separately.

Missing a dose

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

Patient special groups

Patients with renal impairment

With Equapress therapy, renal function and serum potassium and sodium should be monitored. If renal function is impaired, Equapress should be discontinued and replaced with an individually tailored single component therapy.

Patients with hepatic impairment

In patients with impaired hepatic function, amlodipine excretion may be delayed. There are no precise recommendations for these cases, so Equapress should be used with caution in these patients.

Children and adolescents (< 18 years)

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

Elderly patients (>65 years)

This drug should be used with caution in elderly patients.

Plasma creatinine concentrations should be monitored according to age, body weight, and sex.

There have been no age-related changes in the efficacy and safety profile of amlodipine or lisinopril in clinical studies.

Interaction

Amlodipine

Contraindicated drug combinations

Dantrolene (intravenous administration)

There have been cases of fatal ventricular fibrillation and collapse in laboratory animals when using verapamil and intravenous administration of dantrolene. accompanied by hyperkalemia. Due to the risk of hyperkalemia, concomitant use of Equapress containing amlodipine, a “slow” calcium channel blocker, in patients with malignant hyperthermia should be excluded, as well as during treatment of malignant hyperthermia.

Unrecommended drug combinations

Grapefruit juice

Taking amlodipine with grapefruit or grapefruit juice is not recommended because in some patients the bioavailability of amlodipine may increase, resulting in increased BP-lowering effects.

Combinations of drugs requiring particular caution when using

CYP3A4 isoenzyme inducers

There are no data on the effect of CYP3A4 isoenzyme inducers on amlodipine pharmacokinetics. Concomitant use of CYP3A4 isoenzyme inducers (e.g., rifampicin, St. John’s Wort preparations) and amlodipine may lead to decreased plasma concentration of amlodipine. Caution should be exercised when using Equipress concomitantly with CYP3A4 isoenzyme inducers.

CYP3A4 isoenzyme inhibitors

. Simultaneous use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors such as ritonavir, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in amlodipine concentration. 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 the drug Equipress.

Drug combinations requiring caution when using

Simvastatin

Multiple administration of amlodipine at a dose of 10 mg in combination with simvastatin at a dose of 80 mg resulted in an increase in simvastatin exposure of 77% compared to simvastatin monotherapy. Thus, patients receiving amlodipine should take simvastatin in a daily dose not exceeding 20 mg.

Calcium preparations

May decrease the effect of DMARDs.

Lithium preparations

The co-administration of BMCC with lithium preparations (no data for amlodipine) may increase their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor or tinnitus).

Baclofen

Augmentation of the antihypertensive effect. BP and renal function should be monitored; if necessary, the dose of amlodipine should be adjusted.

Amifostine

Amifostine may increase the antihypertensive effect of amlodipine.

Glucocorticosteroids

Decreased antihypertensive effect (fluid and sodium ion retention as a result of corticosteroid action).

Tricyclic antidepressants neuroleptics, isoflurane

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

Tacrolimus

In concomitant use with amlodipine there is a risk of increased plasma concentrations of tacrolimus. To avoid tacrolimus toxicity when used concomitantly with amlodipine, tacrolimus plasma concentrations in patients should be monitored and the tacrolimus dose should be adjusted if necessary.

Tasonermin

Concomitant use of amlodipine may increase the systemic plasma exposure of tasonermin. In such cases, regular monitoring of tasonermine in blood and dose adjustment if necessary are required.

Other interactions with amlodipine

Amlodipine may be safely used with thiazide diuretics, alpha-adrenoblockers, beta-adrenoblockers and ACE inhibitors for treatment of arterial hypertension. In patients with stable angina pectoris, concomitant use of amlodipine with other antianginal drugs, such as long- and short-acting nitrates, beta-adrenoblockers is possible.

The antianginal and antihypertensive effects of DMARDs are likely to be enhanced with thiazide and loop diuretics, ACE inhibitors, beta-adrenoblockers and nitrates and their antihypertensive effects are likely to be enhanced when prescribed with alpha 1-adrenoblockers and neuroleptics.

Amlodipine does not cause negative inotropic effects. However, some BMCCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (e.g., amiodarone and quinidine).

Unlike other PBMCs, no significant interaction between amlodipine (3rd generation PBMCs) and NSAIDs, including indomethacin, was found.

It is safe to prescribe amlodipine with oral hypoglycemic drugs. A single intake of sildenafil at a dose of 100 mg in patients with essential arterial hypertension had no effect on amlodipine pharmacokinetics. Co-administration of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg resulted in insignificant changes in pharmacokinetic parameters of atorvastatin at equilibrium concentration state.

Ethanol (beverages containing alcohol): amlodipine has no significant effect on the pharmacokinetics of ethanol with single and multiple doses of 10 mg. Studies of interaction between cyclosporine and amlodipine in healthy volunteers and in special patient groups have not been conducted, except for patients after kidney transplantation.

Various studies of interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may either lead to no 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 concomitant use of amlodipine and digoxin, renal clearance and serum concentrations of digoxin are not changed.

Concomitant use of warfarin with amlodipine does not change prothrombin time.

The pharmacokinetics of amlodipine is not changed when concomitant use with cimetidine.

Amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin and indomethacin to plasma proteins in vitro.

Aluminum and magnesium-containing antacids: single administration of these antacids together with amlodipine has no significant effect on the pharmacokinetics of amlodipine.

Indapamide

Controlled combinations of drugs

Lithium preparations

Concomitant use of indapamide and lithium preparations, as well as adherence to a salt-free diet, may result in increased plasma lithium concentrations due to reduced excretion, accompanied by signs of overdose. If necessary, diuretics may be used in combination with lithium preparations, and plasma lithium content should be carefully monitored and the dose of the drug should be adjusted accordingly.

Combinations of drugs requiring special caution during use

Drugs that can cause pirouette-type polymorphic ventricular tachycardia

– Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide).

– Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide).

– Certain neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenones (droperidol, haloperidol).

– Others: bepridil, cisapride, difemanil, erythromycin (intravenous), halofantrine, misolastin, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (intravenous).

Increased risk of ventricular arrhythmias, especially pirouette-type polymorphic ventricular tachycardia (hypokalemia is a risk factor).

In patients with hypokalemia, drugs that do not cause pirouette-type polymorphic ventricular tachycardia should be used.

Non-steroidal anti-inflammatory drugs (when used systemically), including selective COX-2 inhibitors, high doses of salicylic acid (≥3 g/day)

The antihypertensive effect of indapamide may decrease.

There is a risk of acute renal failure due to decreased glomerular filtration. Patients should compensate for fluid loss and carefully monitor renal function at the beginning of treatment.

ACE inhibitors

The administration of ACE inhibitors to patients with initially decreased concentration of sodium ions in blood (especially patients with renal artery stenosis) is accompanied by the risk of sudden arterial hypotension and/or acute renal failure. Patients with arterial hypertension and possibly decreased plasma sodium ion content due to diuretics should:

– 3 days before starting treatment with an ACE inhibitor, stop taking a diuretic. Subsequently, if necessary, the intake of noncaliberative diuretic may be resumed;

– or ACE inhibitor therapy may be started at low doses with subsequent gradual increase of the dose, if necessary.

In chronic heart failure, treatment with ACE inhibitors should be started at the lowest dose with possible prior reduction of diuretics. In all cases during the first weeks of taking ACE inhibitors in patients it is necessary to monitor renal function (creatinine content in plasma).

Other drugs that may cause hypokalemia: amphotericin B (when administered intravenously), gluco- and mineralocorticosteroids (when used systemically), tetracosactide, intestinal motility stimulating laxatives

Additive effect increases risk of hypokalemia.

Potassium concentration in plasma should be monitored constantly, and corrected if necessary. Particular attention should be paid to patients concomitantly receiving cardiac glycosides. The use of laxatives that do not stimulate intestinal motility is recommended.

Baclofen

Augmentation of the antihypertensive effect has been noted.

Patients should compensate for fluid loss and monitor renal function carefully at the beginning of treatment.

Cardiac glycosides

Hypokalemia increases the toxic effects of cardiac glycosides.

In concomitant use of indapamide and cardiac glycosides, plasma potassium and ECG parameters should be monitored and, if necessary, therapy should be adjusted.

Combinations of drugs requiring caution when using

Potassium-saving diuretics (amiloride, spironolactone, triamterene, eplerenone) Combination therapy with indapamide and potassium-saving diuretics is reasonable in some patients, but cannot exclude the possibility of hypokalemia or hyperkalemia (especially in diabetic patients or patients with renal impairment).

Potassium concentration in plasma and ECG parameters should be monitored and, if necessary, therapy should be adjusted.

Metformin

Functional renal insufficiency, which may occur with diuretics, especially loop diuretics, when metformin is concomitantly administered increases the risk of lactic acidosis.

Metformin should not be used if plasma creatinine levels exceed 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.

Iodine-containing contrast agents

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

Patients should compensate for fluid loss before using iodine-containing contrast agents.

Tricyclic antidepressants, antipsychotics (neuroleptics)

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

Calcium salts

Concomitant use increases the risk of hypercalcemia due to reduced renal excretion of calcium ions.

Cyclosporine, tacrolimus

Possible increase in plasma creatinine without change in circulating cyclosporine concentration, even with normal circulating blood volume and plasma sodium content.

Glucocorticosteroid drugs, tetracosactide (when used systemically)

Decrease 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 function impairment (GFR less than 60 ml/min/1.73 m2 body surface area) is contraindicated.

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

Unrecommended drug combinations

Angiotensin II receptor antagonists (ARA II)

. The literature has reported that in patients with established atherosclerotic disease, chronic heart failure, or diabetes mellitus with target organ damage, concurrent therapy with an ACE inhibitor and ARA II is associated with higher rates of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to use of the RAAS-acting drug alone. Dual blockade (e.g., when ACE inhibitor is combined with APA II) should be limited to individual cases with close monitoring of renal function, potassium and BP. Hyperkalemia (possibly fatal) may occur, especially with impaired renal function (additional effects associated with hyperkalemia). ACE inhibitors should not be used concomitantly with substances that increase plasma potassium content, except in cases of hypokalemia. Combination of lisinopril and the above mentioned agents is not recommended. Nevertheless, if concomitant use is indicated, they should be used with caution, and serum potassium levels should be monitored regularly.

Lithium preparations

Concomitant use of lithium preparations and ACE inhibitors may cause reversible increase in serum lithium concentration and associated toxic effects. Simultaneous use of lisinopril and lithium preparations is not recommended. Serum lithium concentration should be monitored regularly if such therapy is necessary.

Combinations of drugs requiring special caution when using

Insulin and oral hypoglycemic agents

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

Enhances the antihypertensive effect of ACE inhibitors. BP levels should be carefully monitored and, if necessary, the dose of hypotensive drugs should be adjusted.

Diuretics

In patients taking diuretics, especially fluid- and/or salt-removing diuretics, a significant decrease in BP may be observed at the beginning of ACE inhibitor therapy. The risk of antihypertensive effects may be reduced by withdrawing the diuretic, replenishing fluid or salt loss before initiating therapy with ACE inhibitors. In patients with arterial hypertension with prior diuretic therapy, which may have led to excessive fluid and/or salt excretion, diuretics should be discontinued before starting Equapress.

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

Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ≥3 g/day. Concomitant use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose with anti-inflammatory effect, cyclooxygenase-2 inhibitors (COX-2) and non-selective NSAIDs) may lead to a decrease in the antihypertensive effect of ACE inhibitors. Concomitant use of ACE inhibitors and NSAIDs may lead to worsening of renal function, including the development of acute renal failure and increased serum potassium, especially in patients with reduced renal function. Caution should be exercised when prescribing this combination, especially in elderly patients. Patients should compensate 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 of estramustine with ACE inhibitors is accompanied by an increased risk of angioedema.

DPP-4 inhibitors (glyptins)

Linagliptin, saxagliptin, sitagliptin, vildagliptin – when combined with ACE inhibitors, there is an increased risk of angioedema due to inhibition of dipeptidyl peptidase-4 (DPP-4 ) activity by glyptin.

Racecadotril (encephalinase inhibitor used for the treatment of acute diarrhea)

The risk of angioedema may increase when used concomitantly with ACE inhibitors.

Combinations of drugs requiring caution when using

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

An increase in the antihypertensive effect of the drug is possible. Caution should be exercised when concomitant administration with nitroglycerin, other nitrates, or other vasodilators because additional BP reduction is possible.

Antacids and cholestyramine

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

Tricyclic antidepressants, neuroleptics, general anesthetics, barbiturates, phenothiazine, ethanol

The effect of lisinopril may be enhanced when taken together.

Sympathomimetics

Sympathomimetics may decrease the antihypertensive effect of ACE inhibitors.

Myorelaxants

The concomitant use of muscle relaxants with ACE inhibitors may result in a marked decrease in blood pressure.

Gold preparations

In the use of ACE inhibitors, including lisinopril, by patients receiving intravenous gold preparations (sodium aurothiomalate), rare cases of nitrite reactions (symptomcomplex including facial hyperemia, nausea, vomiting and arterial hypotension) have been described.

Co-trimoxazole (sulfamethoxazole and trimethoprim)

An increased risk of hyperkalemia.

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

The simultaneous use with SSRIs may result in significant hyponatremia.

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

Leukopenia may occur.

Tissue plasminogen activators (alteplase, reteplase, tenecteplase)

Increased risk of angioedema when combined with ACE inhibitors.

Special Instructions

.

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 BP below 90 mm Hg).

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

– Hereditary or idiopathic angioedema.

– Severe renal insufficiency (creatinine clearance < 30 ml/min).

– Hepatic encephalopathy or severe hepatic dysfunction.

– Hypokalemia.

– Hemodynamically significant left ventricular outflow tract obstruction (e.g., severe aortic stenosis, hypertrophic obstructive cardiomyopathy), hemodynamically significant mitral stenosis.

– Hemodynamically unstable heart failure after myocardial infarction.

– Shock (including cardiogenic).

– Unstable angina (except for 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 body surface area).

– Concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.

– Pregnancy and breastfeeding.

– Age less than 18 years (efficacy and safety not established).

– Hereditary lactose intolerance, galactosemia, glucose-galactose malabsorption syndrome.

Side effects

The most common adverse reactions reported with treatment with amlodipine, indapamide, and lisinopril as monotherapy were: Dizziness, headache, somnolence, visual disturbances, tinnitus, palpitations, blood “rushes” to the facial skin, decreased BP (and effects associated with hypotension), cough, shortness of breath Gastrointestinal disorders (abdominal pain, constipation, diarrhea, nausea, dyspepsia, vomiting), maculopapular rash, muscle cramps, swollen ankles, asthenia, edema and fatigue.

The following adverse drug reactions (ADRs) have been reported during the separate use of amlodipine 1, indapamide 2 and lisinopril 3.

The frequency was determined as follows:

Very frequently, 1/10 of prescriptions (≥10%).

Frequent – 1/100 appointments (≥1% and < 10%).

Infrequent – 1/1000 appointments (≥0.1% and < 1%).

Rarely, 1/10000 appointments (≥0.01% and < 0.1%).

Very rarely, less than 1/10000 appointments (< 0.01%).

The frequency is unknown (frequency cannot be estimated from available data).

Within each frequency group, adverse reactions are presented in decreasing order of importance.

Disorders of the blood and lymphatic system

decrease in hemoglobin3(rare), decrease in hematocrit3(rare), suppression of medullary hematopoiesis3(very rare), leukopenia1,2,3(very rare), thrombocytopenia1,2,3(very rare), Agranulocytosis2,3(very rare), aplastic anemia2(very rare), hemolytic anemia2,3(very rare), neutropenia3(very rare), anemia3(very rare), lymphadenopathy3(very rare).

Immune system disorders

Allergic reactions1(very rare), autoimmune disorders3(very rare).

Endocrine system disorders

Inadequate secretion of antidiuretic hormone syndrome3(rare).

Metabolic and nutritional disorders

Hyperglycemia1(very rare), hypoglycemia3(very rare), hypercalcemia2(very rare), decrease in potassium and development of hypokalemia2(frequency unknown), especially significant in patients at risk; hyponatremia2(frequency unknown).

Mental disorders

Mood lability1,3(infrequent), sleep disturbances3(infrequent), hallucinations3(infrequent), insomnia1(infrequent), anxiety1(infrequent), depression1(infrequent),3(frequency unknown), confusion1,3(rare).

Nervous system disorders

Dizziness1,3(often),headache1,3(often),2(rarely),somnolence1(often),increased fatigability2(rarely),vertigo2(rarely),3(infrequently),paresthesia2(rarely),1,3(infrequently),dysgeusia1,3(infrequently),syncope1(infrequently),23(frequency unknown),tremor1(infrequent), hypoesthesia1(infrequent), parosmia (olfactory disturbance)3(rare), muscle hypertonicity1(very rare), peripheral neuropathy1(very rare), extrapyramidal disorders1(frequency unknown).

Visual disturbances

Visual disturbances (including diplopia) 1(often),2(frequency unknown), myopia2(frequency unknown), blurred vision2(frequency unknown).

Hearing and balance disorders

Tinnitus1(infrequent).

Cardiac disorders

palpitations1(often), 3(infrequent), myocardial infarction3(infrequent), 1(very rare), tachycardia3(infrequent), ventricular tachycardia 1(infrequent), arrhythmia1(infrequent), 2(very rare), polymorphic pirouette-type ventricular tachycardia (potentially fatal)2(frequency unknown), bradycardia1(infrequent), atrial fibrillation1(infrequent).

Vascular disorders

Orthostatic hypotension and related symptoms3(often), facial blood flushes1(often), acute cerebral circulation disorder3(infrequent) (due to marked BP reduction in high-risk patient groups), Raynaud’s syndrome3(infrequent), vasculitis1(very rare), hypotension1(infrequent), marked BP reduction2(very rare).

Respiratory system, chest and mediastinum disorders

dyspnea1 (frequent), cough1(infrequent), 3(frequent), rhinitis1,3(infrequent), bronchospasm3(very rare), allergic alveolitis3(very rare), eosinophilic pneumonia3(very rare), sinusitis3(very rare).

Gastrointestinal tract disorders

Abdominal pain1(often), 3(infrequent), nausea1(often),2(rare), 3( infrequent), dyspepsia1(often),3(infrequent), change in defecation rate1(often), diarrhea1,3(frequent), constipation1(often),2(rare), vomiting1,2(infrequent),3(frequent), dry mouth1(infrequent),2,3(rare), pancreatitis1,2,3(very rare), gastritis1(very rare), interstitial angioedema3(very rare), gum hyperplasia1(very rare).

Liver and biliary tract disorders

Hepatitis1(very rare),2(frequency unknown), hepatitis (including hepatic-cellular or cholestatic)3(very rare), jaundice1,3(very rare), liver failure3(very rare), possible development of hepatic encephalopathy in cases of liver failure2(frequency unknown), liver function disorder2(very rare), increased activity of “liver” enzymes*1(very rare).

(*-predominantly due to cholestasis)

Skin and subcutaneous tissue disorders

alopecia1(infrequent), 3(infrequent), hypersensitivity reactions2(frequent), maculopapular rash2(frequent), exanthema1(infrequent), purpura1,2(infrequent), skin depigmentation1(infrequent), hyperhidrosis1(infrequent),3(very rare) pruritus1,3(infrequent), rash1,3(infrequent), urticaria1(infrequent),2(very rare),3(rare), Psoriasis3(rare), erythema multiforme1,3(very rare), angioedema1,2(very rare),3(rare), exfoliative dermatitis1 (very rare), toxic epidermal necrolysis2,3(very rare), Stevens-Johnson syndrome1,2,3(very rare), Quincke’s edema1(very rare), photosensitivity1(very rare), 2(frequency unknown), vesicular vulgaris3(very rare), benign skin lymphadenosis*3(very rare), exacerbation of pre-existing acute systemic lupus erythematosus2(frequency unknown), hypersensitivity/angioneurotic edema of face, hands and feet, lips, tongue, vocal cleft and/or larynx3(rare).

(* – A symptom complex has been reported that may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, positive antinuclear antibody (ANA) reaction, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, skin rash, photosensitization or other skin changes).

Muscular and connective tissue disorders

Muscular cramps1(often), swollen ankles1(often), arthralgia1(infrequent), myalgia1(infrequent), back pain1(infrequent).

Kidney and urinary tract disorders

Renal dysfunction3(often), urinary distress1(infrequent), nycturia1(infrequent), rapid urination1(infrequent), acute renal failure1(rare), renal failure2(very rare), uremia3(rare), oliguria3(very rare), anuria3(very rare).

Genital and mammary disorders

Gynecomastia1(infrequent), 3(rare), impotence1,3(infrequent).

General disorders and disorders at the site of administration

Edema1(very often), increased fatigue1(often),3(infrequent), asthenia1(often),3(infrequent), chest pain1(infrequent), pain1(infrequent), malaise1(infrequent).

Impact on laboratory and instrumental findings:

increased concentration of creatinine and urea3(infrequent), hyperkalemia3(infrequent), hyperbilirubinemia3(rare), increased activity of “liver” enzymes2(frequency unknown), 3(infrequent), hyponatremia3(rare), prolongation of QT interval on ECG2(frequency unknown), increase in uric acid concentration2(frequency unknown), increase in blood glucose concentration2(frequency unknown), decrease or increase in body weight1(infrequent).

If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Amlodipine overdose

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

Treatment: gastric lavage, administration of activated charcoal (especially during the first 2 hours after overdose), keeping the patient in horizontal position with elevated lower extremities, active support of cardiovascular system function, control of cardiac and pulmonary function parameters, control of circulating blood volume and diuresis.

In the absence of contraindications for restoration of vascular tone and BP it may be reasonable to prescribe vasoconstrictors. Intravenous injections of calcium gluconate may help to stop the effects of calcium channel blockade. Since amlodipine is largely bound to serum proteins, hemodialysis is ineffective in the treatment of amlodipine overdose.

Indapamide overdose

Toxic effects of indapamide in overdose have not been noted even in very high doses (up to 40 mg, i.e. 27 times the therapeutic dose).

The signs of acute poisoning with indapamide are primarily associated with disruption of 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 flushing the drug out of the body, gastric lavage, and/or administration of activated charcoal with restoration of the water-electrolyte balance.

Lisinopril overdose

Symptoms: significant decrease in BP, dry mouth, drowsiness, delayed urination, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, intravenous administration of 0.9% sodium chloride solution and, if possible, vasopressors, BP control, control of water-electrolyte balance. Hemodialysis may be performed.