Perindopril PLUS Indapamide, 0.625 mg+2 mg 30 pcs

Indications

Arterial hypertension.

Pharmacological effect

A combined antihypertensive drug containing an angiotensin-converting enzyme (ACE) inhibitor – perindopril and a thiazide-like diuretic – indapamide. The drug has antihypertensive, diuretic and vasodilating effects.

Perindopril PLUS Indapamide has a pronounced dose-dependent antihypertensive effect, independent of the patient’s age and body position and not accompanied by reflex tachycardia. Does not affect lipid metabolism (total cholesterol, low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), high-density lipoproteins (HDL), triglycerides (TG) and carbohydrates), incl. in patients with diabetes mellitus. Reduces the risk of hypokalemia caused by diuretic monotherapy.

The hypotensive effect lasts for 24 hours.

A stable reduction in blood pressure (BP) is achieved within 1 month with the use of the drug Perindopril PLUS Indapamide without an increase in heart rate (HR). Stopping treatment does not lead to the development of withdrawal syndrome.

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, eliminates the vasoconstrictor effect of angiotensin II, and reduces the secretion of aldosterone. The use of perindopril does not lead to sodium and fluid retention and does not cause reflex tachycardia during long-term treatment. The hypotensive effect of perindopril develops in patients with low or normal plasma renin activity. Perindopril acts through its main active metabolite, perindoprilate. Its other metabolites are inactive.

The action of perindopril leads to varicose veins (reduction of preload on the heart), caused by changes in the metabolism of prostaglandins; reduction of total peripheral vascular resistance (TPVR) (reduction of afterload on the heart).

In patients with heart failure, perindopril helps reduce the filling pressure of the left and right ventricles; increased cardiac output and cardiac index; increasing regional blood flow in muscles.

Perindopril is effective for arterial hypertension of any severity: mild, moderate and severe.

The maximum hypotensive effect develops 4-6 hours after a single oral dose and persists throughout the day.

Discontinuation of therapy does not lead to the development of withdrawal syndrome.

It has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances the hypotensive (additive) effect of perindopril.

Indapamide is a sulfonamide derivative and is a diuretic. Inhibits the reabsorption of sodium in the cortical segment of the renal tubules, increasing the excretion of sodium and chlorine by the kidneys, thus leading to increased diuresis. To a lesser extent increases the excretion of potassium and magnesium. Having the ability to selectively block slow calcium channels, indapamide increases the elasticity of arterial walls and reduces peripheral vascular resistance. It has an antihypertensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not increase the hypotensive effect, but increases the risk of adverse events. Indapamide in patients with arterial hypertension does not affect the metabolism of lipids – TG, LDL and HDL; on carbohydrate metabolism, even in patients with diabetes and hypertension.

Pharmacokinetics:

The combined use of perindopril and indapamide does not change their pharmacokinetic parameters compared to taking these drugs separately.

Perindopril

Suction

After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract (GIT). Bioavailability is 65-70%. The maximum concentration (Cmax) in the blood plasma is achieved 3-4 hours after oral administration.

Eating reduces the conversion of perindopril to perindoprilat and the bioavailability of perindopril, so it should be taken 1 time per day in the morning, before breakfast. When taking perindopril 1 time/day. Equilibrium concentration (Css) is reached within 4 days.

Distribution

The binding of perindoprilate to plasma proteins is dose-dependent and amounts to 20%. Perindoprilat easily passes through histohematic barriers, excluding the blood-brain barrier (BBB). Does not cumulate.

Metabolism

It is metabolized in the liver to form the active metabolite perindoprilate. In addition, 5 more inactive metabolites are formed.

Removal

The half-life (T1/2) of perindopril from blood plasma is 1 hour. T1/2 of perindoprilate is about 17 hours. It is excreted by the kidneys.

Pharmacokinetics in special groups of patients

In elderly patients and in patients with renal and heart failure, the elimination of perindoprilate is slowed down.

The dialysis clearance of perindoprilate is 70 ml/min.

The kinetics of perindopril is altered in patients with liver cirrhosis: hepatic clearance is reduced by half. However, the amount of perindoprilate formed does not decrease, which does not require dose adjustment.

Indapamide

Suction

After oral administration, it is quickly and almost completely absorbed from the gastrointestinal tract. Eating slightly slows down absorption, but does not significantly affect the amount of indapamide absorbed. After oral administration in a single dose, Cmax in blood plasma is reached within 1 hour.

Distribution

Plasma protein binding is 79%. Does not cumulate.

Metabolism

Metabolized in the liver.

Removal

T1/2 ranges from 14 to 24 hours (average 18 hours). It is excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of the unchanged drug is about 5%) and by the intestines with bile in the form of inactive metabolites (22%).

Pharmacokinetics in special clinical situations

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

Special instructions

It is not recommended to use the drug simultaneously with lithium preparations.

Therapy with Perindopril PLUS Indapamide is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min).

In some patients with arterial hypertension without previous renal impairment, symptoms of acute renal failure may appear during drug therapy. In this case, treatment with this drug should be stopped. In the future, you can resume combination therapy using low doses of Perindopril PLUS Indapamide, or use perindopril and indapamide in monotherapy. Such patients require regular monitoring of potassium and creatinine concentrations in the blood serum every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Perindopril PLUS Indapamide.

Acute renal failure most often develops in patients with severe chronic heart failure or underlying renal impairment, including bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.

The drug is not recommended for patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney. Hyponatremia is associated with the risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in plasma electrolytes, for example, after prolonged diarrhea or vomiting. Such patients require regular monitoring of plasma electrolytes.

With a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After restoration of BCC and blood pressure, you can resume therapy with Perindopril PLUS Indapamide, using low doses of the drug, or using perindopril and indapamide in monotherapy. The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and a diuretic, regular monitoring of potassium levels in the blood plasma is necessary.

Perindopril

In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop.

In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors.

Perindopril should be prescribed with extreme caution to patients with connective tissue diseases and those simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing renal impairment. Such patients may develop a severe infection that does not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.

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

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

If symptoms of angioedema appear, you should immediately administer subcutaneous epinephrine (adrenaline) at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency. Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.

In patients of the Negroid race, angioedema develops more often than in patients of other races. In rare cases, during therapy with ACE inhibitors, angioedema of the intestine develops. In this case, patients experience 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 C-1-esterase levels.

The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis. There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures.

Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, the development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

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

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69R). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.

During therapy with an ACE inhibitor, a dry cough may occur, which disappears after discontinuation of drugs in this group. If a dry cough appears, you should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the physician believes that ACE inhibitor therapy is necessary for the patient, Perindopril PLUS Indapamide may be continued.

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

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

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration 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.

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthetic agents that have an antihypertensive effect.

It is recommended to stop taking ACE inhibitors, including perindopril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract and with aortic and/or mitral stenosis and HOCM (hypertrophic obstructive cardiomyopathy). In rare cases, while taking ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice or a significant increase in the activity of liver transaminases occurs while taking ACE inhibitors, Perindopril PLUSINDAPAMIDE should be discontinued.

In patients after kidney transplantation or in patients on hemodialysis, anemia may develop. During treatment with ACE inhibitors, including perindopril, hyperkalemia may develop. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing substitutes for table salt and the use of other drugs that increase plasma potassium levels (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. The combined use of the drugs listed above is not recommended; if their use is necessary, therapy should be carried out with extreme caution.

Indapamide

There are reports of cases of increased photosensitivity while taking thiazide and thiazide-like diuretics. If a photosensitivity reaction develops while taking Perindopril PLUS Indapamide, treatment should be discontinued. If it is necessary to resume use of the drug, you should protect exposed skin from direct exposure to sunlight and artificial ultraviolet rays and avoid exposure to the sun.

Before starting treatment with Perindopril PLUS Indapamide, it is necessary to determine the sodium content in the blood plasma and, while taking the drug, regularly monitor electrolytes in the blood plasma (especially in elderly patients). All diuretics can cause hyponatremia, leading to serious complications. Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia (less than 3.4 mmol/l) in elderly patients, debilitated patients, patients with cirrhosis, patients with peripheral edema, ascites, coronary artery disease, and chronic heart failure.

Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia. The high-risk group includes patients with an increased QT interval on the ECG. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially torsade de pointes, which can be fatal. In all the described cases, regular monitoring of potassium levels in the blood plasma is necessary. The first determination of potassium content in blood plasma should be carried out within the first week from the start of drug therapy.

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in calcium levels 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 Perindopril PLUS Indapamide. Glucose concentrations should be monitored in patients with diabetes mellitus.

In patients with increased concentrations of uric acid in the blood plasma during drug therapy, the frequency of exacerbations of gout may increase.

Hypovolemia as a result of a decrease in blood volume or hyponatremia caused by taking diuretics at the beginning of treatment with the drug can lead to a decrease in glomerular filtration rate and be accompanied by an increase in creatinine and urea in the blood plasma.

Indapamide may give a false-positive reaction during doping control.

Use in pediatrics

Perindopril PLUS Indapamide is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of its use.

Impact on the ability to drive vehicles and operate machinery

Care must be taken when driving vehicles and other technical devices that require increased attention and speed of psychomotor reactions (risk of dizziness and fainting).

Active ingredient

Indapamide, Perindopril

Composition

1 tablet contains:

Active substances:

Indapamide 0.625 mg;

Perindopril erbumine 2 mg.

Excipients:

Microcrystalline cellulose – 70.375 mg;

Pregelatinized corn starch – 15 mg;

Crospovidone – 10 mg;

Magnesium stearate – 1 mg;

Colloidal silicon dioxide – 1 mg.

Contraindications

Hypersensitivity to the excipients included in the drug;

Severe renal failure (creatinine clearance <30 ml/min);

Concomitant use with potassium-sparing diuretics, potassium and lithium preparations, and in patients with hyperkalemia;

Concomitant use of drugs that prolong the QT interval;

Due to the lack of sufficient clinical experience, Perindopril plus Indapamide should not be used in patients on hemodialysis, as well as in patients with untreated decompensated heart failure;

Age up to 18 years (efficacy and safety have not been established).

With caution:

The drug should be used for systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma);

During therapy with immunosuppressants (risk of developing neutropenia, agranulocytosis); with suppression of bone marrow hematopoiesis;

A decrease in circulating blood volume (CBV) (due to taking diuretics, a diet with limited salt, vomiting, diarrhea);

For coronary heart disease (CHD);

Cerebrovascular diseases;

Renovascular hypertension;

Chronic heart failure (IV functional class according to the NYHA classification);

With hyperuricemia (especially accompanied by gout and urate nsphrolithiasis);

Blood pressure lability;

During hemodialysis using high-flow polyacrylonitrile membranes (risk of developing anaphylactoid reactions);

Before the LDL apheresis procedure using dextrin sulfate;

Simultaneously with desensitizing therapy with allergens (for example, hymenoptera venom);

In the condition after kidney transplantation;

Stenosis of the aortic and/or mitral valve, hypertrophic obstructive cardiomyopathy;

In elderly patients.

Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.

In patients of the Negroid race, angioedema develops more often than in patients of other races.

Side Effects

Classification of the frequency of side effects (WHO): very common (>1/10). common (>1/100 to 1/1000 to 1/10,000 to <1/1000). very rare (<1/10,000), frequency unknown (frequency cannot be calculated from available data).

From the hematopoietic system: infrequently – eosinophilia, hyponatremia, very rarely – thrombocytopenia, leukopeia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (kidney transplant patients, hemodialysis patients), ACE inhibitors may cause anemia.

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

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

From the organ of hearing: often – tinnitus.

From the cardiovascular system: infrequently – marked decrease in blood pressure (including orthostatic hypotension), palpitations; very rarely – cardiac arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation), angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients; frequency unknown – pirouette-type arrhythmias (possibly fatal), increased QT interval on the ECG.

From the respiratory system: often – during the use of ACE inhibitors, a dry cough may occur, which persists for a long time while taking drugs of this group and disappears after their withdrawal, shortness of breath; infrequently – bronchospasm; very rarely – eosiophilic 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, angioedema of the intestine, cholestatic jaundice; frequency unknown – hepatic encephalopathy in patients with liver failure, increased activity of liver transaminases.

From the skin: often – skin rash, itching, maculopapular rash; uncommon – angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and/or larynx, urticaria, hypersensitivity reactions in patients predisposed to broncho-obstructive and allergic reactions, hemorrhagic vasculitis. In patients with acute form of systemic lupus erythematosus, the course of the disease may worsen; very rarely – erythema multiforme, toxic epidermal necrolysis. Stevens-Johnson syndrome. Cases of photosensitivity reactions have been reported.

From the musculoskeletal system: often – muscle spasms.

From the urinary system: infrequently – renal failure; very rarely – acute renal failure, frequency unknown – hepatitis.

From the reproductive system: infrequently – erectile dysfunction.

Laboratory indicators: rarely – hypercalcemia; frequency unknown – hypokatemia, especially significant for patients at risk; hyponatremia and gyvolemia, leading to dehydration and orthostatic hypotension; increase in the concentration of uric acid and glucose in the blood while taking the drug: a slight increase in the concentration of creatinine in the urine and in the blood plasma, which occurs after discontinuation of therapy, more often in patients with renal artery stenosis, when treating hypertension with diuretics and in the case of renal failure; hyperkalemia, often transient.

Other: often – asthenia; infrequently – increased sweating.

When using ACE inhibitors, a syndrome of impaired secretion of antidiuretic hormone was rarely observed.

Interaction

Concomitant use is not recommended

Lithium preparations: cases of reversible increases in serum lithium concentrations have been reported. The risk of its toxic effect increases while taking an ACE inhibitor.

Concomitant use of a combination of perindopril and indapamide with lithium preparations is not recommended.

In the case of therapy, monitoring of the concentration of lithium in the blood plasma is necessary.

Special caution is required during concomitant use

Baclofen:
potentiates the antihypertensive effect (requires monitoring of blood pressure, renal function and, if necessary, dose adjustment of Perindopril PLUS Indapamide).

The combination of ACE inhibitors with non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs, acetylsalicylic acid in doses that have an anti-inflammatory effect) reduces the antihypertensive effect of ACE inhibitors; increases the risk of renal dysfunction, including the development of acute renal failure; increases serum potassium levels in patients with pre-existing renal impairment.

This combination is recommended to be used with caution, especially in elderly patients.

Patients need to compensate for their blood volume, as well as monitor their renal function before and after starting treatment with Perindopril PLUS Indapamide.

Caution is required during simultaneous use

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

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

When used simultaneously with other antihypertensive drugs, the antihypertensive effect of the drug may be enhanced.

Perindopril

Concomitant use is not recommended

ACE inhibitors reduce diuretic-induced renal potassium loss.

When used together with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements or potassium-containing salt substitutes with ACE inhibitors, an increase in potassium levels in the blood serum may occur, leading to death.

If combined use of an ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be carried out.

The simultaneous use of ACE inhibitors and angiotensin II receptor antagonists with aliskiren is contraindicated in patients with diabetes mellitus and patients with moderate renal failure (creatinine clearance less than 60 ml/min).

When used simultaneously with estramustine, the risk of developing angioedema increases.

Special caution is required during concomitant use

The use of ACE inhibitors may enhance the hypoglycemic effect of oral hypoglycemic agents (sulfonylureas) and insulin in patients with diabetes mellitus; when used together, it is possible to increase glucose tolerance, which may require dose adjustment of oral hypoglycemic agents and insulin.

Baclofen enhances the antihypertensive effect of ACE inhibitors.

With the simultaneous use of potassium-non-sparing diuretics, gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin) – the risk of developing angioedema due to suppression of dipeptidyl peptidase IV activity by gliptin.

When used simultaneously with sympathomimetics, it enhances the antihypertensive effect of ACE inhibitors.

In patients with established atherosclerotic disease, heart failure, or diabetes mellitus with end-organ damage, concomitant therapy with an ACE inhibitor and an angiotensin-converting enzyme inhibitor has been reported to be associated with a higher incidence of hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared with the use of the RAAS-acting drug alone.

Dual blockade (for example, when combining an ACE inhibitor with an ARB) should be limited to selected cases with careful monitoring of renal function, potassium levels and blood pressure.

Caution is required during simultaneous use

With the simultaneous use of allopurinol, cytostatics, immunosuppressants, corticosteroids (for systemic use), procainamide with ACE inhibitors, the risk of developing leukopenia may increase.

In patients whose condition requires major surgery or general anesthesia with drugs that cause hypotension, ACE inhibitors, including perindopril, may block the formation of angiotensin II with compensatory renin release.

One day before surgery, therapy with ACE inhibitors must be discontinued.

If the ACE inhibitor cannot be canceled, then arterial hypotension developing according to the described mechanism can be corrected by increasing the volume of blood volume.

When diuretics are used in high doses, hypovolemia is possible (due to a decrease in blood volume), and the addition of perindopril to therapy can lead to a pronounced decrease in blood pressure.

When prescribing ACE inhibitors, including perindopril. In patients receiving gold (sodium aurothiomalate) intravenously, nitrate-like reactions (nausea, vomiting, marked decrease in blood pressure, facial skin flushing) were noted.

Indapamide

Special caution is required during concomitant use

Due to the risk of hypokalemia, indapamide should be used with caution in combination with drugs that cause torsades de pointes, such as antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol), some antipsychotics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenone (droperidol, haloperidol), other antipsychotics (pimozide); other substances such as bepridil, cisapride, difemanil methyl sulfate, erythromycin (IV), halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine for IV use, methadone, astemizole, terfenadine.

It is necessary to monitor potassium levels in order to avoid hypokalemia, the development of which requires its correction, and to monitor the QT interval on an ECG.

With simultaneous use of indapamide with amphotericin (iv), gluco- and mineralocorticoids (if administered systemically), tetracosactide. laxatives that stimulate gastrointestinal motility increase the risk of hypokalemia (additive effect).

It is necessary to monitor the potassium content in the blood plasma and, if necessary, correct it.

Particular attention should be paid to patients concomitantly receiving cardiac glycosides.

Laxatives that do not stimulate gastrointestinal motility should be used.

Hypokalemia enhances the toxic effect of cardiac glycosides.

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

Caution is required during simultaneous use

When using metformin with diuretics, renal failure may develop.

When used simultaneously with metformin, the risk of developing lactic acidosis increases.

Metformin should not be used if the serum creatinine concentration exceeds 15 mg/L in men and 12 mg/L in women.

While taking diuretics, there is a decrease in blood volume, and the risk of developing acute renal failure increases, especially when using iodine-containing contrast agents in high doses.

Before using iodine-containing contrast agents, it is necessary to compensate for the volumetric volume.

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

When used simultaneously with cyclosporine, the risk of developing renal dysfunction (hypercreatininemia) increases.

Manufacturer

Izvarino Pharma, Russia