Consilar-D24 capsules 1.25mg+5mg, 30pcs

Composition

Active ingredients:

indapamide-1,250 mg;

ramipril-5,000 mg;

excipients:

lactose monohydrate-140,750 mg;

colloidal silicon dioxide-1,500 mg;

calcium stearate-1,500 mg;

solid gelatin capsules: titanium dioxide-2.0%, gelatin – up to 100%.

Pharmacological action

Pharmacotherapy group

Antihypertensive agent combined (diuretic + angiotensin converting enzyme inhibitor (ACE inhibitor)).

ATX code

C09BA05

Pharmacological properties

Pharmacodynamics

A combined antihypertensive drug containing a diuretic from the group of sulfonamide derivatives – indapamide and an angiotensin-converting enzyme (ACE) inhibitor-ramipril. The pharmacological effect of the combination is due to the combination of individual properties of each of the components, which, in turn, enhance the effect of each other. The drug has antihypertensive, diuretic and vasodilating effects.

CONCEALER-D 24 has a pronounced dose-dependent antihypertensive effect on both systolic and diastolic blood pressure (BP). The antihypertensive effect does not depend on the patient’s age and body position. It does not affect the metabolism of lipids and carbohydrates, including in patients with diabetes mellitus.

The antihypertensive effect persists for 24 hours.

A stable reduction in blood pressure is achieved within 1 month with the use of CONCEALAR-D 24 without an increase in heart rate (HR). Discontinuation of treatment does not lead to the development of “withdrawal”syndrome.

Indapamide

Indapamide belongs to the derivatives of sulfonamide with an indole ring and is similar in pharmacological properties to thiazide diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. At the same time, the release 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.

Indapamide reduces the smooth muscle tone of the arteries and has a vasodilating effect, reduces the total peripheral vascular resistance (OPSS). These effects are mediated by a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandin E2, which has vasodilating activity; and inhibition of calcium flow in vascular smooth muscle cells.

Indapamide helps to reduce hypertrophy of the left ventricle of the heart.

Indapamide in monotherapy in doses that do not cause a pronounced diuretic effect, has a 24-hour antihypertensive 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.

In short, medium-term 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-density lipoproteins (LDL) and high-density lipoproteins (HDL);

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

Ramipril

The active metabolite of ramipril, ramiprilate, formed under the influence of liver enzymes, is a long-acting ACE inhibitor (synonyms: kininase II, dipeptidyl carboxydipeptidase I), which is a peptidyl dipeptidase. ACE in blood plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictive effect, and the breakdown of bradykinin, which has a vasodilating effect. Therefore, when taking ramipril orally, the formation of angiotensin II decreases and bradykinin accumulates, which leads to vasodilation and a decrease in blood pressure. Increased activity of the kallikrein-kinin system in blood and tissues causes cardioprotective and endothelioprotective effects of ramipril due to activation of the prostaglandin system and, accordingly, an increase in the synthesis of prostaglandins that stimulate the formation of nitric oxide in endotheliocytes.

Angiotensin II stimulates the production of aldosterone, so taking ramipril leads to a decrease in aldosterone secretion and an increase in the content of potassium ions in the blood plasma.

With a decrease in the concentration of angiotensin II in the blood, its inhibitory effect on renin secretion by the type of negative feedback is eliminated, which leads to an increase in plasma renin activity.

It is assumed that the development of some adverse reactions (in particular, dry cough) is also associated with an increase in bradykinin activity.

In patients with arterial hypertension, taking ramipril leads to a decrease in blood pressure in the “lying” and “standing” positions without a compensatory increase in heart rate. Ramipril significantly reduces OPSS, causing virtually no changes in renal blood flow and glomerular filtration rate. The antihypertensive effect begins to manifest itself 1-2 hours after ingestion of a single dose of ramipril, reaching the highest value after 3-6 hours, and persists for 24 hours. With a course of use, the antihypertensive effect may gradually increase, usually stabilizing by 3-4 weeks of regular ramipril use, and then persist for a long time. Sudden discontinuation of ramipril does not lead to a rapid and significant increase in blood pressure (no “withdrawal”syndrome).

In patients with arterial hypertension, ramipril slows down the development and progression of myocardial and vascular wall hypertrophy.

In patients with a high risk of developing cardiovascular diseases due to vascular lesions (diagnosed coronary heart disease (CHD), a history of peripheral artery obliterating diseases, a history of stroke) or diabetes mellitus with at least one additional risk factor (microalbuminuria, hypertension, increased total cholesterol, decreased HDL cholesterol, smoking), the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke, and mortality from cardiovascular causes. In addition, ramipril reduces overall mortality rates, as well as the need for revascularization procedures, and slows the onset or progression of chronic heart failure.

In the general population of patients, as well as in patients with diabetes mellitus (both with arterial hypertension and normal blood pressure), ramipril significantly reduces the risk of developing nephropathy and microalbuminuria.

Pharmacokinetics

The combined use of indapamide and ramipril does not affect their pharmacokinetic parameters compared to the use of these drugs in monotherapy.

Indapamide

Suction

Released indapamide is rapidly and completely absorbed in the gastrointestinal tract. Simultaneous food intake slightly increases the absorption time of indapamide, without affecting the completeness of absorption. The maximum concentration in blood plasma is reached 1-2 hours after ingestion of a single dose of 2.5 mg. With repeated doses, fluctuations in the concentration of indapamide in blood plasma in the interval between doses of the drug are smoothed out. There is individual variability in indapamide absorption rates.

Distribution

About 79% of indapamide binds to plasma proteins and, due to its high affinity for elastin, is concentrated in the smooth muscle of the vascular walls. It also binds to red blood cell carboxyhydrase without inhibiting the activity of this enzyme.

The equilibrium concentration is reached after 7 days of taking indapamide. With repeated use of indapamide, its accumulation is not observed.

Metabolism

Indapamide is metabolized in the liver.

Deduction

The elimination half-life (T_1/2) is from 14 to 24 hours (average 18 hours). It is excreted as inactive metabolites, mainly by the kidneys (60-80% of the dose taken) and through the intestines (22%). No more than 5% of indapamide is excreted unchanged by the kidneys.

Pharmacokinetics in special patient groups

In patients with renal insufficiency, the pharmacokinetic parameters of indapamide do not change significantly.

Ramipril

Suction

After oral use, ramipril is rapidly absorbed from the gastrointestinal tract (50-60%). Simultaneous food intake slows down its absorption, but does not affect the completeness of absorption.

Distribution

Bioavailability for ramipril after oral use of 2.5-5 mg – 15-28%; for ramiprilat-45%. After oral use of ramipril, the maximum plasma concentrations of ramipril and ramiprilate are reached in 1 and 2-4 hours, respectively. After a daily intake of 5 mg/day, a stable concentration of ramiprilate in blood plasma is reached by day 4. Plasma protein binding for ramipril was 73%, ramiprilate-56%. The volume of distribution of ramipril is 90 liters, ramiprilat – 500 liters.

Metabolism

In the liver, it is metabolized to form the active metabolite ramiprilate (6 times more actively inhibits ACE than ramipril) and inactive metabolites-diketopiperazine ester, diketopiperazine acid, as well as the glucuronides ramipril and ramiprilate. All the metabolites formed, with the exception of ramiprilate, have no pharmacological activity.

The elimination

time of T_1/2 for ramipril is 5.1 hours; in the phase of distribution and elimination, a decrease in the concentration of ramiprilate in blood plasma occurs with T_1/2equal to 3 hours, followed by a transition phase with T_1/215 h, and a prolonged end phase with very low plasma concentrations of ramiprilate and T_1/2of 4-5 days. T_1/2 increases in chronic renal failure.

Excreted by the kidneys-60%, through the intestines-40% (mainly in the form of metabolites).

Pharmacokinetics in special patient groups

In healthy elderly volunteers (65-76 years), the pharmacokinetics of ramipril and ramiprilat did not significantly differ from those in young healthy volunteers.

With impaired renal function, the excretion of ramipril and its metabolites slows down in proportion to a decrease in creatinine clearance (CC); with impaired liver function, the conversion to ramiprilate slows down; with heart failure, the concentration of ramiprilate increases 1.5-1.8 times.

Indications

Arterial hypertension of mild and moderate severity.

Use during pregnancy and lactation

Use during pregnancy

The use of CONCEALAR-D 24 is contraindicated during pregnancy. Before starting treatment, you should make sure that there is no pregnancy. When planning pregnancy or when it occurs during treatment, it is necessary to immediately stop taking CONCEALAR-D 24 and prescribe another therapy with an established safety profile for use during pregnancy.

Indapamide

Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal development delay. In rare cases, newborns develop hypoglycemia and thrombocytopenia while taking diuretics shortly before delivery.

Ramipril

ACE inhibitors can cross the placental barrier. When using ACE inhibitors during pregnancy, there is a risk of impaired fetal kidney development, decreased fetal and newborn blood pressure, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnios, limb contracture, cranial deformity, and lung hypoplasia.

It is recommended that newborns who have been exposed to ACE inhibitors in utero should be closely monitored for hypotension, oliguria, and hyperkalemia. With oliguria, it is necessary to maintain blood pressure and renal perfusion by filling the BCC and using vasoconstrictors. Newborns are at risk for oliguria and neurological disorders, possibly due to decreased renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors (given to pregnant and lactating women).

Use during breastfeeding

The use of CONCEALAR-D 24 is contraindicated during breastfeeding. If treatment with CONCEALER-D 24 is necessary, breast-feeding should be discontinued.

Indapamide

Indapamide is excreted in breast milk. Taking thiazide diuretics causes a decrease in the amount of breast milk or suppression of lactation. A newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia, and”nuclear jaundice”.

Ramipril

In animal studies, ramipril has been shown to be excreted in the milk of lactating animals.

Contraindications

– Hypersensitivity to indapamide, the ramipril, other ACE inhibitors, a derivative of sulfonamide and auxiliary substances that are part of the product;

– a history of angioedema (hereditary or idiopathic and associated with previous therapy with ACE inhibitors);

– hemodynamically significant renal artery stenosis (bilateral or unilateral, in the case of a solitary kidney);

– severe hypotension or condition with unstable hemodynamics;

– simultaneous use of receptor antagonists to angiotensin II in patients with diabetic nephropathy;

– hemodynamically significant stenosis of the aortic or mitral valve, or hypertrophic obstructive cardiomyopathy (HACMP);

– primary hyperaldosteronism;

– severe renal failure (CC less than 30 ml/min);

– hemodialysis;

nephropathy, treatment of which is held by corticosteroids, nonsteroidal anti-inflammatory drugs, immunomodulators, and/or other cytotoxic drugs;

– chronic heart failure in the stage of decompensation (clinical experience is insufficient);

– hemodialysis or hemofiltration using some of membranes with negatively charged surface, such as high-flow membrane of polyacrylnitrile (risk of hypersensitivity reactions);

– LDL apheresis using dextran sulfate (risk of hypersensitivity reactions);

– conducting desensitizing therapy for hypersensitivity reactions to Hymenoptera venoms of insects such as bees, wasps;

– simultaneous use with aliskiren and drugs containing aliskiren in patients with diabetes and/or moderate or severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m 2 of the body surface area);

– acute phase of myocardial infarction in patients with such diseases as:

severe chronic heart failure (NYHA Functional Class IV);

  unstable angina;

life-threatening ventricular arrhythmias;

“pulmonary” heart;

– severe hepatic insufficiency (including encephalopathy);

– hypokalemia;

– concomitant use of drugs that can cause arrhythmia type “pirouette”;

– concomitant use of drugs that lengthen the QT interval (clinical experience is insufficient);

– concomitant use with potassium-sparing diuretics, potassium and lithium in patients with hyperkalemia;

– azotemia, anuria;

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

– pregnancy, the period of breastfeeding;

– age under 18 years (effectiveness and safety not established).

Caution

– simultaneous use with drugs containing aliskiren, or receptor antagonists to angiotensin II (dual blockade of the renin-angiotensin-aldosterone system (RAAS) have an increased risk of a sharp decline HELL of hyperkalemia and worsening renal function);

– a condition in which an excessive decrease in blood pressure is particularly dangerous (in atherosclerotic lesions of the coronary and cerebral arteries);

– severe hypertension, particularly malignant arterial hypertension;

– chronic heart failure (III-IV functional class NYHA classification);

– hemodynamically significant unilateral renal artery stenosis (in the presence of both kidneys) – in these patients, even a slight increase in the concentration of creatinine in the blood plasma may be a manifestation of unilateral deterioration of renal function;

– prior to the use of diuretics;

– reduced volume of circulating blood (BCC), disruption of water and electrolyte balance due to insufficient fluid intake, receiving high doses of diuretics, diet with salt restriction, diarrhoea, vomiting, sweating;

– disorders of the liver (clinical experience is insufficient);

– diabetes mellitus (risk of hyperkalemia);

– disorders of renal function (CC 30-60 ml/min) (risk of hyperkalemia and radiation);

– condition after kidney transplantation;

systemic connective tissue diseases (systemic lupus erythematosus, systemic sclerosis);

– oppression of bone marrow hematopoiesis;

– concomitant therapy mielotoksicnae drugs, immunosuppressive agents, can cause changes in the peripheral blood (possible inhibition of bone marrow hematopoiesis, the development of neutropenia or agranulocytosis);

– renovascular hypertension;

– hyperuricemia and gout;

– lability in blood pressure;

– hyperparathyroidism;

– increase the QT interval;

the old age over 65 years (risk of increased antihypertensive effect);

– in patients of the Negroid race.

Side effects

Classification of the frequency of side effects according to the recommendations of the World Health Organization (WHO):

very often 3 1/10;

often from 3 1/100 to < 1/10;

infrequently from 3 1/1000 to < 1/100;

rarely from 3 1/10000 to < 1/1000;

very rarely < 1/10000, including individual reports;

frequency unknown – according to available data, it is not possible to determine the frequency of occurrence.

Cardiac disorders:

infrequently – myocardial ischemia, including the development of an angina attack or myocardial infarction, tachycardia, arrhythmia, palpitation sensation, peripheral edema;

frequency unknown-pirouette-type arrhythmia (possibly fatal), increased QT interval on the ECG.

Vascular disorders:

often-an excessive decrease in blood pressure, orthostatic hypotension, syncopal states;

infrequently – “hot flashes” of blood to the skin of the face;

rarely – the occurrence or increase of circulatory disorders against the background of stenosing vascular lesions, vasculitis;

frequency unknown-Raynaud’s syndrome.

Nervous system disorders:

often – headache, dizziness (feeling of “lightness” in the head);

infrequently – vertigo, paresthesia, ageusia (loss of taste sensitivity), dysgeusia (violation of taste sensitivity), lethargy;

rarely tremor, impaired balance;

the frequency is unknown – cerebral ischemia, including ischemic stroke and transient ischemic stroke, impaired psychomotor reactions (reduction reaction), a burning sensation, parosmia (impaired sense of smell), fainting.

Visual disturbances:

infrequently-visual disorders, including blurred images;

rarely-conjunctivitis.

Hearing disorders:

rarely – hearing disorders, tinnitus.

Mental disorders:

infrequently – depressed mood, anxiety, nervousness, motor restlessness, sleep disorders, including drowsiness;

rarely-confusion;

frequency unknown-impaired attention.

Respiratory, thoracic and mediastinal disorders:

often – ” dry “cough (worse at night and in the “lying” position), bronchitis, sinusitis, shortness of breath;

infrequently – bronchospasm, including worsening of the course of bronchial asthma, nasal congestion.

Disorders of the digestive system:

often the inflammatory response in the stomach and intestines, indigestion, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting;

infrequently – fatal pancreatitis (pancreatitis cases with a fatal outcome when receiving ACE inhibitors have been observed very rarely), increased activity of pancreatic enzymes in blood plasma, angioedema of the small bowel, pain in the upper abdomen, including those associated with gastritis, constipation, dryness of the mucous membrane of the mouth;

rarely – glossitis;

very rarely – pancreatitis;

frequency unknown – aphthous stomatitis (inflammatory reaction of the mucous membrane of the oral cavity).

Liver and biliary tract disorders:

often – increased activity of alanine aminotransferase;

rarely – increased activity of “liver” enzymes and the concentration of conjugated bilirubin in blood plasma;

rarely – cholestatic jaundice, hepatocellular lesions;

rarely – abnormal liver function;

the frequency is unknown – acute hepatic failure, cholestatic or cytolytic hepatitis (rarely fatal), the possibility of development of hepatic encephalopathy in the case of liver failure.

Kidney and urinary tract disorders:

infrequently-impaired renal function, including the development of acute renal failure, increased urinary excretion, increased pre-existing proteinuria, increased urea and creatinine concentrations in blood plasma;

very rarely-renal failure;

frequency unknown-hyperuricemia, glucosuria.

Genital and breast disorders:

infrequently-erectile dysfunction with transient impotence, decreased libido;

frequency unknown-gynecomastia.

Disorders of the blood and lymphatic system:

very often – eosinophilia;

often-thrombocytopenia, decreased hematocrit;

rarely-leukopenia, including neutropenia and agranulocytosis, erythrocytopenia, decreased hemoglobin concentration;

very rarely-aplastic anemia, hemolytic anemia;

frequency unknown – inhibition of bone marrow hematopoiesis, pancytopenia.

Skin and subcutaneous tissue disorders:

often – skin rash, particularly maculate-papular;

rarely – angioedema, including fatal (edema of the larynx can cause obstruction of the Airways, leading to death), pruritus, hyperhidrosis (excessive sweating), hemorrhagic vasculitis;

rarely exfoliative dermatitis, urticaria, onycholysis;

very rarely – photosensitivity reactions;

the frequency is unknown – toxic epidermal necrolysis, and Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of psoriasis, dermatitis psoriasiform, lichenoid, or pemphigidae (Isaevicha) rash or enanthema, alopecia, exacerbation of systemic lupus erythematosus.

Musculoskeletal and connective tissue disorders:

often-muscle cramps, myalgia;

infrequently-arthralgia.

Endocrine system disorders:

frequency unknown-syndrome of inadequate secretion of antidiuretic hormone.

Metabolic and nutritional disorders:

often – hyperkalemia, hypokalemia, hyponatremia;

infrequently – anorexia, decreased appetite;

very rarely-hypercalcemia;

frequency unknown-hyperglycemia, hypochloremia, accompanied by hypovolemia, dehydration and orthostatic hypotension (simultaneous loss of chlorine ions can lead to compensatory metabolic alkalosis, but the frequency of alkalosis and its severity is insignificant).

Immune system disorders:

the frequency is unknown – anaphylactic or anaphylactoid reactions (when ACE inhibition increases the severity of anaphylactic or anaphylactoid reactions to the poisons of hymenopteran insects, such as bees, wasps), an increase in the titer of antinuclear antibodies.

Common disorders:

often-chest pain, increased fatigue;

infrequently-fever;

rarely-asthenia (weakness).

Interaction

of CONCEALER-D 24

Simultaneous use is contraindicated

With simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in blood plasma and an increase in the cardio – and neurotoxic effects of lithium are possible. The additional use of thiazide diuretics may further increase the concentration of lithium due to a decrease in its excretion, and increase the risk of toxic reactions. Concomitant use of CONCEALAR-D 24 with lithium preparations is contraindicated.

Concomitant use with potassium preparations, potassium-sparing diuretics (amiloride, spironolactone, eplerenone, triamteren), and other drugs that can increase the content of potassium in blood plasma (including trimethoprim, tacrolimus, cyclosporine, heparin) increases the risk of hyperkalemia (especially in patients with diabetes mellitus and patients with renal insufficiency).

Special care should be taken when using the drug at the same time

Baclofen potentiates the antihypertensive effect of indapamide and ramipril (monitoring of blood pressure, renal function and, if necessary, dose adjustment of CONCEALAR-D 24 is required).

Concomitant use with non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors and non-selective NSAIDs, for example, acetylsalicylic acid in doses that have an anti-inflammatory effect (more than 3 g per day), reduces the antihypertensive effect of indapamide and ramipril; increases the risk of impaired renal function, up to the development of acute renal failure; increases the content of potassium in blood plasma in patients with pre-existing renal dysfunction. This combination is recommended to be used with caution, especially in elderly patients. Patients should be compensated for BCC, as well as monitor renal function before and after starting treatment with CONCEALAR-D 24.

Caution should be exercised when used concomitantly

Tricyclic antidepressants, antipsychotics (neuroleptics) enhance the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

Glucocorticosteroids, tetracosactide reduce the antihypertensive effect (fluid retention).

When used concomitantly with other antihypertensive agents, the antihypertensive effect of CONCEALAR-D 24 may be enhanced.

Indapamide

Simultaneous use is contraindicated

Due to the risk of hypokalemia, it is contraindicated to use indapamide simultaneously with medications that can cause pirouette-type arrhythmia, such as antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretilia tosilate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, pimozide), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other substances (bepridil, cisapride, difemanil, erythromycin (intravenously), halofantrin, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (intravenous), methadone, terfenadine). In patients with hypokalemia, it is necessary to use drugs that do not cause arrhythmia of the “pirouette”type.

Special care should be taken when using the drug at the same time

When used concomitantly with amphotericin B (intravenously), gluco-and mineralocorticosteroids (with systemic use), tetracosactide, laxatives that stimulate the motility of the gastrointestinal tract, the risk of hypokalemia increases (additive effect). It is necessary to constantly monitor the content 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 the motility of the gastrointestinal tract.

Hypokalemia increases the toxic effect of cardiac glycosides. With simultaneous use of indapamide and cardiac glycosides, the content of potassium in the blood plasma, ECG indicators should be monitored, and, if necessary, the dose of cardiac glycosides should be adjusted.

Caution should be exercised when used concomitantly

Concomitant use of diuretics with metformin may lead to the development of renal failure, as well as an increased risk of lactic acidosis. Metformin should not be used if the plasma creatinine concentration exceeds 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

While taking diuretics, BCC decreases, and the risk of acute renal failure increases, especially when using high doses of iodine-containing contrast agents. Patients should be compensated for BCC before using iodine-containing contrast agents.

When used concomitantly with calcium supplements, hypercalcemia may develop due to a decrease in the excretion of calcium by the kidneys.

Concomitant use with cyclosporine, tacrolimus increases the risk of impaired renal function (hypercreatinemia).

Ramipril

Simultaneous use is contraindicated

The use of some high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration and the use of dextran sulfate for LDL apheresis increases the risk of severe anaphylactic reactions. If the patient needs these procedures, then other types of membranes should be used (in the case of plasmapheresis and hemofiltration) or the patient should be transferred to antihypertensive drugs of other groups.

Concomitant use of ramipril with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to 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 ramipril with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Special care should be taken when using the drug at the same time

Caution should be exercised when ramipril is co-administered with drugs containing aliskiren and angiotensin II receptor antagonists. Treatment should be carried out under the control of renal function, potassium content and blood pressure.

The combined use of ramipril and telmisartan is not recommended, as it does not provide an increased therapeutic effect compared to the use in monotherapy. In addition, there was a higher incidence of hyperkalemia, renal failure, hypotension and dizziness with combined treatment.

When used concomitantly with hypoglycemic agents, for example, insulins, hypoglycemic agents for oral use (sulfonylureas), due to a decrease in insulin resistance under the influence of ramipril, the hypoglycemic effect of these drugs may increase up to the development of hypoglycemia. Especially careful monitoring of blood glucose concentrations is recommended at the beginning of co-use of hypoglycemic agents with ACE inhibitors.

Patients taking concomitant ACE inhibitors and dipeptidyl peptidase type IV (DPP-IV) inhibitors (gliptins), such as sitagliptin, saxagliptin, vildagliptin, linagliptin, experienced an increased incidence of angioedema.

When ACE inhibitors and mTOR inhibitors (mammalian Target of Rapamycin in mammalian cells) were used simultaneously, for example, temsirolimus, sirolimus, and everolimus, an increase in the incidence of angioedema was observed.

When used concomitantly with sympathomimetics (epinephrine, isoproterenol, dobutamine, dopamine), a decrease in the antihypertensive effect of ramipril is noted, regular blood pressure monitoring is required.

When used concomitantly with other drugs that reduce blood pressure (nitrates, general and local anesthesia, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin), the antihypertensive effect is potentiated.

Combinations of ramipril with RAAS-blocking drugs should be used with caution.

Caution should be exercised when used concomitantly

When used concomitantly with the drug gold (sodium aurothiomalate) for intravenous use, facial hyperemia, nausea, vomiting, and hypotension are rarely possible.

When used concomitantly with sleeping pills, narcotic drugs and painkillers, the antihypertensive effect may increase.

Concomitant use with allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticosteroids and mineralocorticosteroids) and other drugs that may affect hematological parameters increases the risk of developing hematological reactions.

When used concomitantly with sodium chloride, the antihypertensive effect of ramipril may be weakened.

When used concomitantly with ethanol, there is an increase in the symptoms of vasodilation. Ramipril may increase the adverse effects of ethanol on the body.

When used concomitantly with estrogens, there is a weakening of the antihypertensive effect of ramipril (fluid retention).

Concomitant use with other ACE inhibitors increases the risk of developing renal failure (including acute renal failure), hyperkalemia.

Concomitant use of ACE inhibitors with drugs containing co-trimoxazole (trimethoprim + sulfamethoxazole) increases the risk of hyperkalemia.

Concomitant use of ACE inhibitors and the enkephalinase inhibitor racecadotril, used for the treatment of acute diarrhea, increased the risk of angioedema.

Concomitant use of ACE inhibitors with estramustine may increase the risk of angioedema.

How to take, course of use and dosage

Inside, once a day, preferably in the morning.

Capsules should be swallowed whole and washed down with a sufficient amount of water.

The dose is selected depending on the therapeutic effect and tolerability of the drug by the patient.

Treatment with CONCEALER-D 24 is usually long-term, and its duration is determined by the doctor on a case-by-case basis.

Unless otherwise prescribed, the following dosage regimens are recommended for normal renal and hepatic function.

The initial dose is 1 capsule with a dosage of 0.625 mg + 2.5 mg, once in the morning. If when taking the drug CONCEALAR-D 24 in this dose for 2 weeks or more, it is not possible to normalize blood pressure, then the dose can be increased to 1 capsule with a dosage of 1.25 mg + 5 mg of the drug CONCEALAR-D 24 per day.

If the antihypertensive effect of a daily dose of 1.25 mg + 5 mg is insufficient, a new therapy regimen should be selected.

The maximum daily dose is 2 capsules with a dosage of 1.25 mg + 5 mg once a day.

Use of CONCEALAR-D 24 in special groups of patients

Patients with impaired renal function

With a creatinine clearance of 60 ml / min or more, no dose adjustment is required.

For patients with creatinine clearance 30-60 ml/min, the initial dose is 0.625 mg + 2.5 mg per day, the maximum daily dose is 1.25 mg + 5 mg. Treatment should begin with the selection of doses of indapamide and ramipril in monotherapy.

In severe renal insufficiency (creatinine clearance less than 30 ml/min), the use of CONCEALAR-D 24 is contraindicated.

Patients with impaired liver function

For patients with impaired liver function, the maximum daily dose is 1 capsule with a dosage of 0.625 mg + 2.5 mg. Careful medical supervision is required at the beginning of treatment.

In severe hepatic insufficiency, the use of CONCEALAR-D 24 is contraindicated.

Elderly patients (over 65 years of age)

In elderly patients, renal function and plasma potassium levels should be evaluated before starting CONCILAR-D 24.CONCEALAR-D 24 can only be used in patients with normal renal function or minor renal impairment. The dose is selected depending on the degree of reduction in blood pressure, especially with a decrease in BCC and loss of electrolytes, as well as with chronic heart failure (NYHA functional class IV). Such measures can avoid a sharp decrease in blood pressure.

The initial dose is 1 capsule with a dosage of 0.625 mg + 2.5 mg per day.

Overdose

Symptoms

Marked decrease in blood pressure, bradycardia, nausea, vomiting, convulsions, dizziness, drowsiness, confusion, stupor, impaired water and electrolyte balance (hyponatremia, hypokalemia), oliguria up to anuria (due to hypovolemia), acute renal failure.

Treatment

In mild cases of overdose-gastric lavage, taking adsorbents (activated carbon), sodium sulfate (preferably within 30 minutes), followed by restoring the water-electrolyte balance. The function of vital organs should be monitored.

In more severe cases, additional measures are taken to stabilize blood pressure: intravenous use of 0.9% sodium chloride solution, plasma substitutes, installation of a temporary artificial pacemaker for drug-resistant bradycardia. With a pronounced decrease in blood pressure, the use of alpha-adrenergic agonists (norepinephrine, dopamine) can be added to therapy to replenish BCC and restore water and electrolyte balance. In the case of bradycardia, atropine or a temporary artificial pacemaker is recommended. Blood pressure, kidney function, and plasma electrolyte levels should be carefully monitored.

There is no experience of using forced diuresis, changing the pH of urine, hemofiltration or dialysis. Hemodialysis is indicated in cases of renal failure.

Special instructions

Patients with previous diuretic therapy

It is necessary, if possible, to cancel diuretics for 2-3 days (depending on the duration of action of diuretics) before starting treatment with CONCEALAR-D 24, or at least reduce the dose of diuretics taken. Treatment of such patients should begin with taking 1 capsule with a dosage of 0.625 mg + 2.5 mg 1 time a day in the morning. After taking the first dose and after increasing the dose of CONCEALAR-D 24, patients should be under medical supervision for at least 8 hours to avoid an uncontrolled hypotensive reaction.

Ischemic heart disease and cerebrovascular insufficiency

The risk of arterial hypotension exists in all patients, but in patients with coronary heart disease and cerebrovascular insufficiency, special care should be taken when treating with CONCEALAR-D 24. Treatment should start with a daily dose of 0.625 mg + 2.5 mg (starting dose).

Impaired renal function

CONCILAR-D 24 therapy is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min). Some patients with arterial hypertension without previous renal impairment may develop symptoms of acute renal failure during therapy with CONCEALAR-D 24.

In this case, treatment with CONCEALER-D 24 should be discontinued. In the future, you can resume combination therapy using low doses of CONCEALAR-D 24, or use indapamide and ramipril in monotherapy. Such patients need regular monitoring of the potassium content and creatinine concentration in blood plasma every 2 weeks after the start of therapy and every subsequent 2 months of therapy with CONCEALAR-D 24.

Acute renal failure is more likely to occur in patients with severe chronic heart failure or underlying renal dysfunction, including bilateral renal artery stenosis or artery stenosis of a single functioning kidney. CONCILAR-D 24 is contraindicated in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.

Arterial hypotension and impaired water-electrolyte balance

Before starting treatment with CONCEALAR-D 24, hyponatremia and hypovolemia should be eliminated. Hyponatremia is associated with the risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in the content of electrolytes in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients need regular monitoring of blood plasma electrolyte levels. With a marked decrease in blood pressure, an intravenous injection of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continuing therapy. After recovery of BCC and blood pressure, you can resume therapy with CONCEALAR-D 24, using low doses of the drug, or use indapamide and ramipril in monotherapy.

Potassium content

The combined use of indapamide and ramipril may lead to the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. While taking the drug CONCEALAR-D 24, it is necessary to regularly monitor the content of potassium in the blood plasma. In patients with hypokalemia, the use of CONCEALAR-D 24 is contraindicated.

Auxiliary substances

It should be borne in mind that the excipients of CONCEALAR-D 24 include lactose monohydrate. The use of CONCEALAR-D 24 is contraindicated in patients with lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Indapamide

Liver function disorders

When using thiazide and thiazide-like diuretics in patients with impaired liver function, hepatic encephalopathy may develop, especially in the case of impaired water-electrolyte balance. In this case, you should immediately stop taking the drug CONCEALAR-D 24.

Photosensitivity

Photosensitivity reactions have been reported with thiazide and thiazide-like diuretics. If photosensitivity reactions develop while taking CONCEALAR-D 24, treatment should be discontinued. If it is necessary to continue therapy with CONCEALER-D 24, it is recommended to protect exposed areas of the skin from direct exposure to sunlight and artificial ultraviolet rays.

Blood plasma sodium content

Before starting treatment, it is necessary to determine the sodium content in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretic drugs can cause hyponatremia, sometimes leading to extremely severe consequences. Regular monitoring of the sodium content is necessary, since initially a decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most careful monitoring of sodium content is indicated in patients with cirrhosis of the liver and elderly patients.

Potassium content in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia (blood potassium content below 3.4 mmol/k) in patients of the following categories: elderly patients who are weakened or receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the QT interval, patients with cirrhosis of the liver, peripheral edema or ascites, coronary heart disease, heart failure. Hypokalemia in such patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias.

In addition, the increased risk group includes patients with an extended QT interval on the ECG, and it does not matter whether this increase is caused by congenital causes or the action of medications.

Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe arrhythmias and, especially, arrhythmias of the “pirouette” type, which can lead to death. In all the cases described above, it is necessary to regularly monitor the content of potassium in the blood plasma. The first measurement of the potassium content in blood plasma should be carried out within the first week after the start of therapy with CONCEALAR-D 24.

If hypokalemia is detected, appropriate treatment should be prescribed.

Blood plasma calcium content

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in the content of calcium in the blood plasma. Severe hypercalcemia may be a consequence of latent hyperparathyroidism.

You should stop taking CONCEALAR-D 24 before examining the function of the parathyroid glands.

Concentration of glucose in blood plasma

It is necessary to monitor the concentration of glucose in the blood plasma in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

Patients with elevated plasma uric acid concentrations do not have an increased risk of developing gout. In patients with gout, the frequency of seizures may increase or the course of gout may worsen.

Diuretics and renal function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (the concentration of creatinine in blood plasma in adults is lower than 25 mg / l or 220 mmol/l). In elderly patients, the normal concentration of creatinine in blood plasma is calculated taking into account age, body weight and gender.

It should be borne in mind that at the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which, in turn, is caused by loss of fluid and sodium ions against the background of taking diuretics. As a result, the concentration of urea and creatinine in the blood plasma may increase. If the kidney function is not impaired, such temporary functional renal failure usually passes without consequences, but with pre-existing renal failure, the patient’s condition may worsen.

Athletes

Indapamide can give a positive result during doping control.

Ramipril

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis may occur in patients taking ACE inhibitors. The risk of developing neutropenia is dose-dependent and depends on the medication taken and the presence of concomitant diseases. In patients with normal renal function and no other complications, neutropenia rarely develops and resolves on its own after discontinuation of ACE inhibitors. Special care should be taken in patients with systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), as well as in patients treated with immunosuppressants, allopurinol or procainamide, especially in patients with existing renal dysfunction. Such patients may develop a severe infection that does not respond to intensive antibiotic therapy. It is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that if there are any signs of an infectious disease (sore throat, fever), it is necessary to immediately consult a doctor.

Angioedema (angioedema)

In rare cases, angioedema of the face, extremities, lips, tongue, uvula of the upper palate, pharynx and/or larynx may develop against the background of ACE inhibitor therapy. If these symptoms occur, you should immediately stop taking CONCEALAR-D 24. You should monitor the patient’s condition until the signs of edema completely disappear. If the swelling affects only the face and lips, then its manifestations usually go away without special treatment, but antihistamines can be used to more quickly relieve symptoms.

Angioedema, accompanied by swelling of the tongue, pharynx and / or larynx, can lead to airway obstruction and death. In this case, epinephrine (epinephrine) should be immediately administered subcutaneously at a dose of 1: 1000 (0.3 to 0.5 ml) and / or airway patency should be ensured. In the future, such patients should not use ACE inhibitors. Patients who have a history of angioedema that is not associated with ACE inhibitors may have an increased risk of developing angioedema when taking this group of drugs.

In rare cases, intestinal angioedema develops during therapy with ACE inhibitors. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C-1 esterase. The diagnosis is established by computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. In patients with abdominal pain treated with ACE inhibitors, the differential diagnosis should take into account the possibility of developing intestinal angioedema.

Anaphylactoid reactions during desensitization

There are isolated reports of long-term life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions, undergoing desensitization procedures. ACE inhibitors are contraindicated in patients receiving desensitizing therapy with hymenopteran venom, such as bees and wasps. The development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis with dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure with dextran sulfate.

Anaphylactoid reactions during hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flow membranes. Therefore, it is necessary to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group.

Cough

Against the background of therapy with an ACE inhibitor, a dry persistent cough may develop, which disappears after the withdrawal of drugs of this group. If a patient has a dry cough, you should be aware of the possible association of this symptom with taking an ACE inhibitor. If the doctor believes that therapy with an ACE inhibitor is necessary for the patient, taking the drug CONCEALAR-D 24 can be continued.

Risk of hypotension and / or renal failure

In some pathological conditions, significant activation of the RAAS may occur, especially with severe hypovolemia and a decrease in plasma electrolytes (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites. The use of an ACE inhibitor causes blockade of the RAAS and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in blood plasma, indicating the development of acute renal failure. These phenomena are more often observed when taking the first dose of ramipril or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug CONCEALAR-D 24 in a lower dose and then gradually increase the dose.

Diabetes mellitus

When using the drug CONCEALAR-D 24 in patients with diabetes mellitus, receiving hypoglycemic agents for oral use or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood.

Renovascular hypertension

The use of ACE inhibitors has a beneficial effect in patients with renovascular hypertension, both waiting for surgery and when surgery is not possible. Treatment with CONCEALAR-D 24 should be started with a low dose of the drug in a hospital setting, monitoring renal function and blood potassium levels. Some patients may develop functional renal failure, which quickly disappears when the drug is discontinued.

Surgical intervention/General anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a pronounced decrease in blood pressure, especially when using general anesthesia agents that have an antihypertensive effect. It is recommended to stop taking ACE inhibitors 48 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

Anemia

Anemia can develop in patients who have undergone a kidney transplant or in patients undergoing hemodialysis. In this case, the decrease in the concentration of hemoglobin is greater, the higher its initial concentration was. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors. A slight decrease in the hemoglobin concentration occurs during the first 6 months of treatment, then the hemoglobin concentration remains stable and completely recovers after discontinuation of the drug. In such patients, treatment can be continued, but a general blood test should be performed regularly.

Aortic stenosis/Mitral stenosis/Hypertrophic obstructive cardiomyopathy

ACE inhibitors are contraindicated in patients with left ventricular exit tract obstruction, aortic and / or mitral stenosis, and HOCMP.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors, with the progression of which rapid development of fulminant liver necrosis is possible, sometimes with a fatal outcome. If jaundice or a significant increase in the activity of “hepatic” transaminases occurs while taking ACE inhibitors, the patient should stop taking CONCEALAR-D 24.

Hyperkalemia

Hyperkalemia may occur during treatment with ACE inhibitors. Risk factors for hyperkalemia include renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes, and the use of other drugs that increase the potassium content in blood plasma (for example, heparin). Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal. Concomitant use of the above drugs is contraindicated.

Other risk groups

In patients with chronic heart failure (NYHA functional Class IV) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium content), treatment should begin with low doses of CONCEALAR-D 24 and be carried out under the constant supervision of a doctor.

Beta-blockers should not be discontinued in patients with arterial hypertension and CHD: ACE inhibitors should be used together with beta-blockers.

Elderly patients

In elderly patients, renal function and plasma potassium levels should be evaluated before starting CONCILAR-D 24. In order to prevent the development of arterial hypotension, the initial dose of the drug is consistently adjusted in accordance with blood pressure indicators, especially with a decrease in BCC.

Ethnic differences

ACE inhibitors have a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races.

Influence on the ability to drive vehicles and mechanisms

During treatment with CONCEALAR-D 24, it is necessary to refrain from engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, including driving vehicles, since dizziness may occur against the background of taking CONCEALAR-D 24, a decrease in the speed of psychomotor reactions and attention, especially after taking the first dose.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Indapamide, Ramipril

Conditions of release from pharmacies

By prescription

Dosage form

Capsules