Indapamide Perindopril-Teva pills 0.625mg+2.5mg, 30pcs

Composition

1 tablet contains:

active ingredients:

indapamide 0.625 mg,

perindopril tosylate 2.50 mg;

excipients:

lactose monohydrate 74.056 mg,

corn starch 2.70 mgmg,

sodium bicarbonate 0.793 mg,

pregelatinized corn starch 7.20 mg,

povidone-K 30 1.80 mg,

magnesium stearate 0.90 mg;

tablet shell:  Opadray II white 85F18422 (partially hydrolyzed polyvinyl alcohol 1,800 mg, titanium dioxide (E 171) 1,125 mg, macrogol-3350 0.909 mg, talc 0.666 mg).

Pharmacological action

Combined antihypertensive agent (diuretic+ACE inhibitor)ATX: C. 09. B. A. 04 Perindopril in combination with diuretics Pharmacodynamics : The drug Indapamide/Perindopril-Teva is a combination drug containing a perindopril-angiotensin converting enzyme (ACE) inhibitor and an indapamide – thiazide-like diuretic. The synergistic effect of perindopril and indapamide determines the pharmacological properties of the drug,

Perindopril is an ACE inhibitor, the mechanism of action of which is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, which has a vasoconstrictive effect, and also destroying bradykinin, which has a vasodilating effect, to an inactive heptapeptide.

As a result, perindopril reduces the secretion of aldosterone, increases the activity of renin in blood plasma according to the principle of a figurative connection; with prolonged use, it reduces total peripheral vascular resistance (OPSS), which is mainly due to the effect on blood vessels in the muscles and kidneys. These effects are not accompanied by salt and fluid retention or the development of reflex tachycardia.

Perindopril has a therapeutic effect due to the active metabolite-perindoprilat. Other metabolites are inactive.

Perindopril normalizes heart function by promoting venous dilation (reduced preload) by altering prostaglandin metabolism and reducing total peripheral vascular resistance (OPSS) (reduced afterload).

In patients with chronic heart failure (CHF) perindopril reduces the filling pressure in the left and right ventricles of the heart, reduces OPSS, increases cardiac output and increases the cardiac index, increases peripheral blood flow in the muscles. Indapamide belongs to the group of sulfonamides and is similar in pharmacological properties to thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment of the renal tubules, increasing the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium by the kidneys, increasing diuresis and lowering blood pressure (BP).

Antihypertensive effect

The combination of indapamide/perindopril has a dose-dependent antihypertensive effect on both diastolic and systolic blood pressure in the “standing” and “lying” positions. The antihypertensive effect persists for 24 hours. The therapeutic effect occurs less than 1 month after the start of treatment and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal symptoms. The combination of indapamide/perindopril reduces the degree of left ventricular hypertrophy (LVH), improves the elasticity of the arteries, reduces OPSS, and does not affect the metabolism of lipids (total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglycerides). The effect of the drug on cardiovascular morbidity and mortality has not been studied. The effect of the indapamide/perindopril combination on LVH compared to enalapril has been proven. There was a more pronounced antihypertensive effect when receiving indapamide/perindopril combination therapy compared to enalapril.

Perindopril is effective in the treatment of arterial hypertension of any severity. The antihypertensive effect is achieved a maximum of 4-6 hours after a single oral dose and lasts for 24 hours. 24 hours after taking perindopril, there is a pronounced (about 80%) residual ACE inhibition. Perindopril has an antihypertensive effect in both patients with low and normal plasma renin activity.

Perindopril has a vasodilating effect, helps restore the elasticity of large vessels and the structure of the vascular wall of small arteries. It also reduces left ventricular hypertrophy.

Concomitant use of thiazide diuretics increases the antihypertensive effect.

Indapamide in monotherapy has an antihypertensive effect for 24 hours in doses that have a minimal diuretic effect. Indapamide improves the elasticity of large arteries, reduces OPSS, and reduces left ventricular hypertrophy. Increasing the dose of indapamide does not increase the antihypertensive effect, but increases the risk of adverse events. Indapamide does not affect lipid metabolism (total cholesterol, HDL and LDL cholesterol, triglycerides) and carbohydrate metabolism. Pharmacokinetics:

The combined use of perindopril and indapamide does not change their pharmacokinetic characteristics in comparison with separate use of these drugs.

Perindopril after oral use is rapidly absorbed in the gastrointestinal tract (GIT) and reaches a maximum concentration in blood plasma (Cmax) within 1 hour.

Perindopril has no pharmacokinetic activity. Approximately 27% of the total amount of oral perindopril enters the bloodstream as the active metabolite of perindoprilat. In addition to perindoprilat,5 more metabolites are formed that do not have pharmacological activity. Cmax of perindoprilat is reached in 3-4 hours.

Taking perindopril during a meal is accompanied by a decrease in the conversion of perindopril to perindoprilat, and its bioavailability decreases accordingly. Therefore, perindopril should be taken once a day, before meals.

There is a linear dependence of the concentration of perindopril in blood plasma on its dose. The volume of distribution of free perindoprilate is 0.2 l/kg. The association with plasma proteins is insignificant, the association of perindoprilat, mainly with ACE is less than 20% and depends on its concentration.

Perindopril is excreted by the kidneys. The “effective” half-life (T1 / 2) of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days.

Elimination of perindopril slows down in the elderly and in patients with heart and kidney failure.

The dialysis clearance of perindopril is 70 ml/min.

In patients with cirrhosis of the liver, the “hepatic” clearance of perindopril decreases by 2 times, while the total amount of perindoprilate formed does not decrease and no dosage adjustment is required.

Indapamide is rapidly and completely absorbed from the gastrointestinal tract (GIT). Cmax of indapamide is reached in blood plasma after 1 hour. Binding to plasma proteins is 79%. T 1/2 is 14-24 hours (average 18 hours). Repeated use of indapamide does not lead to its accumulation in the body. It is mainly excreted by the kidneys (70%) and through the intestines (22%) in the form of inactive metabolites.

The pharmacokinetics of indapamide do not change in patients with renal insufficiency.

Indications

Arterial hypertension.

Contraindications

Perindopril

Hypersensitivity to perindopril and other ACE inhibitors, indapamide and other sulfonamide derivatives, and other components of the drug; pregnancy; breastfeeding; a history of angioedema (including hereditary/idiopathic angioedema or angioedema due to taking other ACE inhibitors); concomitant use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR)

Indapamide

Hypersensitivity to indapamide and other sulfonamide derivatives; severe renal insufficiency (creatinine clearance less than 30 ml / min); severe hepatic insufficiency, including hepatic encephalopathy; hypokalemia; concomitant use with antiarrhythmic agents and other drugs capable of causing pirouette-type arrhythmia; pregnancy, breast-feeding, age up to 18 years (efficacy and safety have not been established).

Concomitant use of the drug with potassium-sparing diuretics, potassium and lithium preparations is not recommended, and in patients with increased potassium content in blood plasma. Due to the lack of sufficient experience, it should not be used in patients with untreated decompensated heart failure, hereditary lactose intolerance, lactase deficiency or malabsorption syndrome.

With caution:

Renovascular hypertension; bilateral renal artery stenosis; single kidney artery stenosis; chronic heart failure (CHF) (NYHA functional class IV); decreased circulating blood volume (BCC) (due to a salt-free diet and / or previous diuretic therapy, vomiting, diarrhea), angina pectoris, cerebrovascular diseases (including cerebral circulatory failure): aortic valve stenosis, hypertrophic obstructive cardiomyopathy (HOCMP); renal failure (creatinine clearance less than 60 ml/min, but more than 30 ml/min); hemodialysis using high-flow polyacrylonitrile membranes (for example, AN69®); before the LDL apheresis procedure; simultaneous desensitizing therapy; condition after kidney transplantation; systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), immunosuppressant therapy (risk of neutropenia, agranulocytosis), bone marrow suppression, surgery/general anesthesia; diabetes mellitus; hyperuricemia (especially with gout or urate nephrolithiasis); lability of blood pressure, elderly age.

Side effects

the Frequency of adverse reactions that can occur during therapy, as shown in the following gradation: very often (> 1 /10); often (>1/100, <1/10); infrequently (>1/1000. <1/100); rare (>1/10000, <1/1000); very rare (< 1/10000); unknown frequency (frequency cannot be estimated according to the available data).

Blood and lymphatic system disorders: very rarely – thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (patients after kidney transplantation, patients on hemodialysis), ACE inhibitors can cause anemia.

From the central nervous system: often-paresthesia, headache, dizziness, vertigo; infrequently-sleep disturbance, mood lability; very rarely-confusion; unknown frequency-fainting.

From the side of the organ of vision: often-visual impairment.

From the side of the hearing organ: often-tinnitus.

From the cardiovascular system: infrequently-a marked decrease in blood pressure, including orthostatic hypotension; very rarely-a violation of the heart rhythm, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina and myocardial infarction, possibly due to an excessive decrease in blood pressure in high – risk patients; unknown frequency-arrhythmia of the “pirouette” type (possibly fatal).

Respiratory, thoracic and mediastinal disorders: often-against the background of the use of ACE inhibitors, a dry cough may occur, which persists for a long time during taking drugs of this group and disappears after their withdrawal, shortness of breath; infrequently – bronchospasm; very rarely – eosinophilic pneumonia, rhinitis.

From the digestive system: often-dryness of the oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste perception, decreased appetite, dyspepsia, constipation, diarrhea; very rarely – pancreatitis, intestinal angioedema, cholestatic jaundice; unknown frequency – hepatic encephalopathy in patients with hepatic insufficiency.

From the side of the skin and subcutaneous fat: often – skin rash, pruritus, maculopapular rash; infrequently – angioedema of the face, lips, extremities, tongue mucosa, vocal folds and/or larynx, urticaria; hypersensitivity reactions in patients predisposed to bronchoobstructive and allergic reactions; hemorrhagic vasculitis; in patients with acute systemic lupus erythematosus may worsen the course of the disease; very rarely – erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity reaction.

Musculoskeletal and connective tissue disorders: often-muscle spasm.

From the urinary system: infrequently – renal failure; very rarely-acute renal failure.

From the side of the reproductive system: infrequently-impotence.

Other: often-asthenia; infrequently-increased sweating.

Laboratory parameters: rarely – hypercalcemia; unknown frequency – increased QT interval on the ECG; increased uric acid and glucose concentrations in the blood while taking the drug; increased activity of “liver” enzymes; a slight increase in creatinine concentration in the urine and blood plasma, passing after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of arterial hypertension with diuretics and in the case of renal failure; hypokalemia, especially significant for patients at risk; hyperkalemia, often transient; hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension.

Interaction

Indapamide/perindopril

Undesirable combination of medications

Lithium preparations

With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the content of lithium in blood plasma and associated toxic effects may occur. Additional use of thiazide diuretics may further increase the lithium content and increase the risk of toxicity. Concomitant use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of such therapy, regular monitoring of the lithium content in the blood plasma is necessary (see the section “Special instructions”).

A combination of drugs that requires special attention

Baclofen

When used concomitantly with baclofen, it is possible to increase the antihypertensive effect. Blood pressure and renal function should be monitored, and the dose of antihypertensive drugs should be adjusted if necessary.

A combination of medications that requires attention

Tricyclic antidepressants, antipsychotic drugs (neuroleptics)

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

Glucocorticosteroids (corticosteroids), tetracosactide

It is possible to reduce the antihypertensive effect (fluid retention and sodium ions as a result of the action of corticosteroids).

Other antihypertensive drugs

It is possible to increase the antihypertensive effect.

Perindopril

Simultaneous use is contraindicated

Aliskiren

Patients with diabetes mellitus or impaired renal function (GFR less than 60 ml/min) have an increased risk of hyperkalemia, deterioration of renal function, and increased incidence of cardiovascular morbidity and mortality.

Undesirable combination of medications

Aliskiren

Patients who do not have diabetes mellitus or impaired renal function may have an increased risk of hyperkalemia, impaired renal function, and increased incidence of cardiovascular morbidity and mortality.

Potassium-sparing diuretics (amiloride, spironolactone, eplerenone, triamterene both in monotherapy and in combination therapy) and potassium preparations ACE inhibitors reduce diuretic-induced potassium loss. Potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene, or amiloride) or potassium-containing salt substitutes can lead to a significant increase in the potassium content in the blood plasma, up to a fatal outcome. If simultaneous use of an ACE inhibitor and the above drugs is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

A combination of drugs that requires special attention

Hypoglycemic drugs for oral use (sulfonylurea derivatives) and insulin

The following effects have been described for captopril and enalapril. ACE inhibitors may increase the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. The development of hypoglycemia is very rare (due to an increase in glucose tolerance and a decrease in the need for insulin).

Nonsteroidal anti-inflammatory drugs (NSAIDs), including high doses of acetylsalicylic acid (more than 3 g / day)

Concomitant use of ACE inhibitors and NSAIDs (acetylsalicylic acid at a dose that has an anti-inflammatory effect, cyclooxygenase-2 inhibitors and non-selective NSAIDs) may lead to a decrease in the antihypertensive effect. Concomitant use of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when using this combination, especially in elderly patients. Patients need to compensate for fluid loss and regularly monitor kidney function, both at the beginning of treatment and throughout the entire treatment process.

Allopurinol, cytostatic and immunosuppressive drugs, corticosteroids (for systemic use) and procainamide

Concomitant use with ACE inhibitors may be associated with an increased risk of leukopenia.

Preparations for general anesthesia

Concomitant use of ACE inhibitors and general anaesthetics may lead to an increased antihypertensive effect.

Diuretics (thiazide and loop)

The use of diuretics in high doses can lead to hypovolemia, and the addition of perindopril to therapy can lead to arterial hypotension.

Gold preparations

When using ACE inhibitors, including perindopril, patients receiving intravenous gold preparation (sodium aurothiomalate) may rarely develop reactions similar to those that occur with the use of nitrates (redness of the face, nausea, vomiting, hypotension).

Double blockade of the RAAS

In the literature, it has been reported that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and ARA II is associated with a higher incidence of hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared to using only one drug that affects the RAAS. Double blockade (for example, when an ACE inhibitor is combined with ARA II) should be limited to individual cases with careful monitoring of renal function, potassium content and blood pressure.

Ektramustin

Concomitant use may lead to an increased risk of side effects, such as angioedema.

Gliptins (lipagliptin, saxagliptin, sitagliptin, vitagliptin)

Concomitant use with ACE inhibitors may increase the risk of angioedema due to the suppression of dipeptidyl peptidase IV (DPP-IV) activity by gliptin.

Sympathomimetics

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors. When using this combination, the effectiveness of ACE inhibitors should be regularly evaluated.

Indapamide

A combination of drugs that requires special attention

Drugs that can cause pirouette-type arrhythmia

Due to the fact that there is a risk of hypokalemia, caution should be exercised with simultaneous use of indapamide with drugs that can cause arrhythmia type “pirouette”, for example, antiarrhythmic drugs of class IA (quinidine, gedragingen, disopyramide), anti-arrhythmic drugs class III (amiodarone, dofetilide, ibutilide, bretilia tosylate) with sotalol, some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide), other drugs, such as bepridil, cisapride, was diphemanil metilsulfate, erythromycin/in, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine has on/in, methadone, astemizole, terfenadine, Should be monitored and, if necessary, to adjust the content of potassium in the blood plasma, and also to carry out monitoring of the QT interval.

Drugs that can cause hypokalemia

Amphotericin B (IV), gluco-and mineralocorticosteroids (with systemic use), tetracosactide. laxatives that stimulate gastrointestinal motility increase the risk of hypokalemia (additive effect). It is necessary to monitor the content of potassium in the blood plasma, if necessary – its correction. Special attention should be paid to patients receiving concomitant cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.

Cardiac Glycosides

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

A combination of medications that requires attention

Metformin

Functional renal failure, which may occur during the use of diuretics, especially “loop”, when used simultaneously with metformin increases the 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.

Iodine-containing radiopaque substances

Dehydration of the body while taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast agents, patients need to compensate for fluid loss.

Calcium Salts

With simultaneous use, hypercalcemia may develop due to a decrease in calcium excretion by the kidneys.

Cyclosporine

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

How to take, course of use and dosage

Inside, once a day, preferably in the morning before meals, with a sufficient amount of water.

The dose of the drug is selected individually for each patient, depending on the patient’s condition and individual response to treatment.

The recommended starting dose is 1 tablet at a dosage of 0.625 mg+2.5 mg once a day. If the desired antihypertensive effect is not achieved 1 month after the start of therapy, the dose of the drug should be increased to 1 tablet at a dosage of 1.25 mg+5 mg.

Elderly patients

The recommended starting dose is 1 tablet at a dosage of 0.625 mg+2.5 mg once a day.

In the absence of the desired antihypertensive effect, after a study of renal function, you can proceed to the use of a dose of 1 tablet in a dosage of 1.25 mg+5 mg.

Patients with renal insufficiency

In patients with mild renal insufficiency (creatinine clearance greater than 60 ml/min), no dose adjustment is required.

In patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min), the maximum daily dose is 1 tablet at a dosage of 0.625 mg+2.5 mg.

In severe renal insufficiency (creatinine clearance less than 30 ml/min), the use of Indapamide/Perindopril-Teva is contraindicated (see section Contraindications).

Regular monitoring of the potassium content and creatinine concentration in the blood plasma should be carried out.

Patients with impaired liver function

No dose adjustment is required in patients with severe or moderate hepatic impairment.

In severe hepatic impairment, the drug Indapamide/Perindopril-Teva is contraindicated (see section “Contraindications”).

If you miss taking one or more doses at the next dose, the drug Indapamide/Perindopril-Teva should be taken at the usual dose; a higher dose should not be taken, i. e. the dose should not be doubled.

Overdose

Symptoms: marked decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria turning into anuria (decrease in BCC), violation of water and electrolyte balance (hypokalemia, hyponatremia).

Treatment: gastric lavage and / or the use of activated carbon, restoration of water and electrolyte balance. With a pronounced decrease in blood pressure, the patient should be transferred to the “lying” position with the legs raised up, if necessary, measures should be taken to replenish the BCC (for example, intravenous (IV) use of 0.9% sodium chloride solution). Perindoprilat can be removed from the body by dialysis.

Special instructions

The drug Indapamide/Perindopril-Teva

Lithium preparations

Concomitant use of Indapamide is not recommended/Perindopril-Teva with lithium preparations.

Impaired renal function

Indapamide therapy/Perindopril-Teva is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min). In some patients with arterial hypertension without previous renal impairment during Indapamide therapy/Perindopril-Teva may show signs of acute renal failure. In this case, treatment with Indapamide/Perindopril-Teva should be discontinued. In the future, you can resume therapy by using either low doses of Indapamide/Perindopril-Teva, or the drugs perindopril and indapamide in monotherapy. In such patients, it is necessary to regularly monitor the potassium content and serum creatinine concentration 2 weeks after the start of therapy and then every subsequent 2 months of Indapamide therapy. /Perindopril-Teva.

Acute renal failure is more likely to occur in patients with severe CHF or initial renal impairment, including bilateral renal artery stenosis or artery stenosis of a single functioning kidney.

Taking the drug Indapamide/Perindopril-Teva is usually not recommended in cases of bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.

Reduced blood pressure and impaired water-electrolyte balance

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. In such patients, it is necessary to regularly monitor the content of electrolytes in the blood plasma. With a pronounced decrease in blood pressure, an intravenous injection of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After BCC and BP are restored, Indapamide therapy can be resumed/Perindopril-Teva, using either low doses of the drug, or using perindopril and indapamide in monotherapy.

Potassium content

Use of Indapamide/Perindopril-Teva does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. Blood plasma potassium levels should be monitored regularly.

Auxiliary substances

It should be borne in mind that the excipients of the drug Indapamide/Perindopril-Teva contains lactose monohydrate, so the drug is contraindicated in patients with hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Perindopril

Neutropenia/agranulocytosis

Patients taking ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia. In patients with normal renal function and no other complications, neutropenia rarely develops and resolves on its own after discontinuation of ACE inhibitors.

Perindopril should be used with caution in patients with connective tissue disease and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially in patients with existing renal dysfunction. These patients may develop severe infections that do not respond to intensive antibiotic therapy. In the case of using perindopril, it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that in case of any signs of an infectious and inflammatory disease (sore throat, fever), it is necessary to immediately consult a doctor.

Angioedema (angioedema)

When taking ACE inhibitors, including perindopril, in rare cases, angioedema of the face, lips, tongue, uvula of the upper palate and/or larynx may develop. If these symptoms occur, the drug should be stopped immediately and the patient should be monitored until the signs of edema disappear completely.

If angioedema has spread only to the face and lips, then its manifestations usually go away on their own, or antihistamines can be used to treat its symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

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, angioedema of the intestine develops during therapy with ACE inhibitors. At the same time, patients have abdominal pain as an isolated symptom or accompanied by nausea and vomiting, in some cases without previous angioedema of the face and with normal C1-esterase activity. 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 angioedema of the intestine.

Anaphylactoid reactions during desensitization procedures

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 avoided in patients receiving hymenopteran venom immunotherapy. 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 dextrin sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes.

Hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69®). Therefore, it is advisable to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group.

Potassium-sparing diuretics and potassium supplements

Simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes is not recommended.

Cough

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of drugs of this group. If a dry cough occurs, 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 Indapamide/Perindopril-Teva can be continued.

Under 18 years of age

The drug Indapamide/Perindopril-Teva is contraindicated in children under 18 years of age due to the lack of data on the effectiveness and safety of use.

Risk of arterial hypotension and / or renal failure in patients with CHF, impaired water-electrolyte balance, etc.

With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension, CHF, there may be a significant activation of the renin-angiotensin-aldosterone system (RAAS), especially with severe hypovolemia and a decrease in the content of electrolytes in blood plasma (against the background of a salt-free diet or long-term use of diuretics).

The use of an ACE inhibitor may cause blockade of the RAAS, and therefore a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in blood plasma is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose of Indapamide/Perindopril-Teva or during the first 2 weeks of therapy.

Elderly patients

Before starting the drug Indapamide/Perindopril-Teva should monitor renal function and blood potassium levels. The initial dose of Indapamide/Perindopril-Teva is selected depending on the degree of BP reduction, especially with a decrease in BCC and CHF (NYHA functional class IV). Such measures allow you to avoid a sharp decrease in blood pressure,

Atherosclerosis

The risk of hypotension exists in all patients, but special care should be taken when using Indapamide/Perindopril-Teva in patients with ischemic heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with the recommended starting dose of Indapamide/Perindopril-Teva.

Patients with renovascular hypertension

Revascularization is used to treat renovascular hypertension. However, ACE inhibitors have a beneficial effect in patients with renovascular hypertension, both waiting for surgery, and in patients who cannot perform such surgery.

Treatment with Indapamide/Perindopril therapy for patients with diagnosed or suspected renal artery stenosis should be initiated in a hospital setting with the recommended starting dose of Indapamide/Perindopril-Teva, monitoring kidney function and potassium content in blood plasma. Some patients may develop functional acute renal failure, which is reversible after discontinuation of the drug.

Other risk groups

In patients with CHF (NYHA functional class IV) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium content), treatment should begin with the recommended starting dose of Indapamide/Perindopril-Teva and under the supervision of a doctor.

When using the drug Indapamide/Perindopril-Teva in patients with diabetes mellitus receiving hypoglycemic drugs for oral use or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood.

Perindopril (like other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races.

Surgical interventions/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 a hypotensive effect. It is recommended to stop taking ACE inhibitors, including perindopril,12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

Aortic stenosis/HOCMP

ACE inhibitors should be used with caution in patients with left ventricular exit tract obstruction.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors, with the progression of which fulminant liver necrosis develops, including with a fatal outcome. If jaundice occurs or there is a significant increase in the activity of “hepatic” transaminases while taking ACE inhibitors, take Indapamide/Perindopril-Teva should be discontinued.

Anemia

It may develop in patients after a kidney transplant or in patients undergoing hemodialysis.

Hyperkalemia

Hyperkalemia may occur during treatment with ACE inhibitors, including perindopril. 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, including death.The combined use of the above drugs should be carried out with caution.

Indapamide

The use of thiazide and thiazide-like diuretics in patients with impaired liver function may lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.

Photosensitivity

Increased photosensitivity has been reported with thiazide and thiazide-like diuretics. With the development of a photosensitivity reaction against the background of taking the drug Indapamide/Perindopril-Teva treatment should be discontinued. If there is a need to resume the use of Indapamide/Perindopril-Teva, it is necessary to protect exposed areas of the skin from direct exposure to sunlight and artificial ultraviolet rays.

Water-electrolyte balance

Blood plasma sodium content

Before starting treatment with Indapamide/Perindopril-Teva is necessary to determine the sodium content in the blood plasma and regularly monitor the content of electrolytes in the blood plasma while taking the drug. All diuretics can cause hyponatremia, leading to serious complications.

Potassium content in blood plasma

Treatment with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia (less than 3.4 mmol/l) in elderly patients, emaciated patients, patients with cirrhosis of the liver, patients with peripheral edema, ascites, CHD, CHF. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

The increased risk group includes patients with an extended QT interval on the ECG. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially pirouette-type arrhythmias, which can lead to death. In all these cases, regular monitoring of the potassium content in the blood plasma is necessary. The first determination of the potassium content in the blood plasma should be carried out within the first week after the start of therapy with Indapamide/Perindopril-Teva.

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. Before studying the function of the parathyroid glands, you should stop taking Indapamide/Perindopril-Teva.

Concentration of glucose in blood plasma

Glucose concentrations should be monitored in patients with diabetes mellitus.

Uric acid concentration

In patients with elevated plasma uric acid concentrations during Indapamide therapy/Perindopril-Teva may increase the frequency of gout exacerbation.

Diuretics and renal function

The full effectiveness of thiazide and thiazide-like diuretics is manifested only under the condition of normal renal function. They are also effective if the creatinine concentration is less than 25 mg / l, i. e. 220 mmol / l in adults.

In elderly patients, the concentration of creatinine in the blood plasma should be adjusted for the age, body weight and gender of the patient according to the Cockcroft formula:

KK = (140 – age (years)) x body weight (kg)/ 0.814 x creatinine concentration (mol / l).

This formula is suitable for elderly male patients. When calculating the CC for women, a coefficient of 0.85 is used.

Hypovolemia due to a decrease in BCC or hyponatremia caused by diuretics at the beginning of treatment with Indapamide/Perindopril-Teva can lead to a decrease in the glomerular filtration rate and be accompanied by an increase in the concentration of creatinine and urea in blood plasma.

Such temporary functional renal failure does not adversely affect normal renal function, but may worsen pre-existing renal failure.

Athletes

Indapamide may give a false positive reaction during doping control. Influence on the ability to drive vehicles and mechanisms:Neither indapamide nor perindopril, either in monotherapy or in combination with each other, have a negative effect on the concentration of attention and the speed of psychomotor reactions. However, some patients, especially at the beginning of treatment or in combination with other antihypertensive drugs, may experience episodes of pronounced or sharp decrease in blood pressure, dizziness, which may reduce the ability to drive vehicles and operate mechanisms.

Form of production

Film-coated tablets,0.625 mg+2.5 mg.

Storage conditions

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

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Indapamide, Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Angina, Heart failure, Hypertension, Prevention of heart attacks and strokes