Indapamide / Perindopril-Teva - instructions for use, dose, side effects, contraindications

auxiliary substancesa: lactose monohydrate 74,056 mg / 148,112 mg, corn starch 2,70 mg / 5.40 mg, sodium bicarbonate 0.793 mg / 1.586 mg, corn pregelatinized corn starch 7.20 mg / 14.40 mg, povidone-K30 1.80 mg / 3 , 60 mg, magnesium stearate 0.90 mg / 1.80 mg;

sheath for tablets 0.625 mg + 2.5 mg, 1.25 mg + 5 mg: Foam II white 85F18422 (polyvinyl alcohol partially hydrolyzed 1,800 mg / 3,600 mg, titanium dioxide (E171) 1,125 mg / 2,250 mg, macrogol-3350 0.909 mg / 1.818 mg, talc 0.666 mg / 1.332 mg).

Description:

Tablets, film-coated, 0.625 mg + 2.5 mg: oBiconvex tablets coated with a white film coating. On one side is the dividing risk.

Tablets, film-coated, 1.25 mg + 5 mg: aboutbiconvex tablets, covered with a film coating of white color. On one side is the dividing risk and engraving "P", "I".

Pharmacotherapeutic group:antihypertensive agent combined (diuretic + ACE inhibitor)

ATX: & nbsp

C.09.B.A.04 Perindopril in combination with diuretics

Pharmacodynamics:

The preparation Indapamide / Perindopril-Teva is a combined preparation containing perindopril - angiotensin-converting enzyme (ACE) inhibitor and indapamide a thiazide-like diuretic.The synergistic action of perindopril and indapamide determines the pharmacological properties of the drug,

Perindopril - ACE inhibitor, the mechanism of its action is associated with the inhibition of ACE activity, which leads to a decrease in the formation of angiotensin II, which has a vasoconstrictive effect, and also destroys 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 by the principle of figurative communication; with prolonged use reduces the overall peripheral vascular resistance (OPSS), which is due mainly to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by a delay in salts and fluid or the development of reflex tachycardia.

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

Perindopril normalizes the heart, contributing to the expansion of veins (decreased preload) by changing the metabolism of prostaglandins and reducing the overall peripheral vascular resistance (OPCC) (decreased afterload).

In chronic heart failure (CHF) perindopril reduces the filling pressure in the left and right ventricles of the heart, reduces the OPSS, increases cardiac output and increases the cardiac index, increases peripheral blood flow in the muscles.

Indapamide belongs to the group of sulfonamides and on pharmacological properties is close to thiazide diuretics. Indapamide inhibits the reabsorption of sodium in the cortical segment of the renal tubules, increasing the release of sodium, chlorine and, to a lesser extent, potassium and magnesium by the kidneys, enhancing diuresis and lowering blood pressure (BP).

Antihypertensive action

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. Termination of treatment does not cause withdrawal syndrome. The combination of indapamide / perindopril reduces the degree of left ventricular hypertrophy (LVH), improves the elasticity of the arteries, reduces OPSS,does not affect the metabolism of lipids (total cholesterol, high-density cholesterol-lipoproteins (HDL-C) and low-density cholesterol-lipoproteins (LDL-C), triglycerides). The effect of the drug on cardiovascular morbidity and mortality was not studied. The effect of indapamide / perindopril combination on LVH compared with enalapril has been demonstrated. A more pronounced antihypertensive effect was observed against the background of the combination therapy of indapamide / perindopril compared to enalapril.

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

Perindopril has a vasodilating effect, contributes to the restoration of the elasticity of large vessels and the structure of the vascular wall of small arteries.And also reduces the hypertrophy of the left ventricle.

The concomitant use of thiazide diuretics enhances the antihypertensive effect.

Indapamide with 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, reduces hypertrophy of the left ventricle. An increase in the dose of indapamide does not entail an increase in the antihypertensive effect, but increases the risk of developing undesirable phenomena. Indapamide does not affect the metabolism of lipids (total cholesterol, HDL-C and LDL-C, triglycerides) and carbohydrate metabolism.

Pharmacokinetics:

The combined use of perindopril and indapamide does not change their pharmacokinetic characteristics as compared with the separate administration of these drugs.

Perindopril after intake quickly absorbed in the gastrointestinal tract (GIT) and reaches the maximum concentration in the blood plasma (C_max) for 1 hour.

Perindopril does not have pharmacokinetic activity. Approximately 27% of the total amount of perindopril ingested enters the bloodstream as an active metabolite of perindoprilat.In addition to perindoprilata, another 5 metabolites are formed that do not have pharmacological activity. FROM_max Perindoprilata is achieved in 3-4 hours.

The intake of perindopril during meals is accompanied by a decrease in the conversion of perindopril to perindoprilat, and its bioavailability decreases accordingly. therefore perindopril should be taken 1 time per day, before eating.

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

Perindopril is excreted by the kidneys. The "effective" half-life (T_1/2) of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days.

The excretion of perindopril slows down in old age and in patients with cardiac and renal insufficiency.

The dialytic clearance of perindopril is 70 ml / min.

In patients with cirrhosis of the liver, the "hepatic" clearance of perindopril is reduced by a factor of 2, with the total amount of perindoprilate formed not decreasing and correction of the dosing regimen is not required.

Indapamide quickly and completely absorbed from the gastrointestinal tract (GIT). FROM_mOh indapamide is achieved in blood plasma after 1 hour. Relationship with blood plasma proteins - 79%. T₁_/₂is 14-24 hours (an average of 18 hours). Repeated administration of indapamide does not lead to its cumulation in the body. It is excreted mainly by the kidneys (70%) and through the intestine (22%) in the form of inactive metabolites.

The pharmacokinetics of indapamide does 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; the period of breastfeeding; angioedema in the anamnesis (including hereditary / idiopathic angioedema or angioedema due to the administration of other ACE inhibitors); simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate (GFR) <60 ml / min / 1.73 m²); age to 18 years (efficacy and safety not established).

Indapamide

Hypersensitivity to indapamide and other sulfonamide derivatives; severe renal failure (creatinine clearance (CK) less than 30 ml / min); severe hepatic insufficiency, including hepatic encephalopathy; hypokalemia; simultaneous use with antiarrhythmic drugs and other drugs that can cause arrhythmia such as "pirouette"; pregnancy, the period of breastfeeding, age to 18 years (efficacy and safety not established).

It is not recommended simultaneous use of the drug with potassium-sparing diuretics, potassium and lithium preparations, and in patients with elevated levels of potassium in the 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.

Carefully:

Renovascular hypertension; bilateral stenosis of the renal arteries; stenosis of the artery of a single kidney; chronic heart failure (CHF) (IV functional class by classification NYHA); decrease in circulating blood volume (due to a salt-free diet and / or previous diuretic therapy, vomiting, diarrhea), stenocardia, cerebrovascular diseases (including cerebral circulatory insufficiency): aortic valve stenosis, hypertrophic obstructive cardiomyopathy (GOKMP); renal failure (CC less than 60 ml / min, but more than 30 ml / min); hemodialysis using high-density polyacrylonitrile membranes (for example, AN69®); before the procedure for apheresis of LDL; simultaneous desensitizing therapy; condition after kidney transplantation; systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), immunosuppressant therapy (risk of developing neutropenia, agranulocytosis), bone marrow depression, surgical intervention / general anesthesia; diabetes; hyperuricemia (especially with gout or urate nephrolithiasis); lability of blood pressure, old age.

Pregnancy and lactation:

Pregnancy

The use of Indapamide / Perindopril-Teva is contraindicated in pregnancy.

When planning pregnancy or when it comes on the background of taking the drug should immediately stop taking the drug and apply other antihypertensive therapy.

Perindopril

There was no corresponding controlled study of perindopril in pregnant women. The limited data available on the effects of perindopril in the first trimester of pregnancy suggest that perindopril did not lead to malformations associated with fetotoxicity.

Do not use Indapamide / Perindopril-Teva in the first trimester of pregnancy. The drug Indapamide / Perindopril-Teva is contraindicated in the second and third trimesters of pregnancy.

It is known that the long-term effect of ACE inhibitors on fetus II and III trimester of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, slowing ossification of the bones of the skull) and development of complications in the newborn (kidney failure, arterial hypotension, hyperkalemia).

In newborns whose mothers received therapy with ACE inhibitors, hypotension may be observed, and therefore newborns should be under careful medical supervision.

Indapamide

Long-term use of thiazide diuretics in the III trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and delayed fetal development. In rare cases, against the background of diuretics shortly before delivery, neonates develop hypoglycemia and thrombocytopenia.

If the patient received Indapamide / Perindopril-Teva during II or III trimesters of pregnancy, it is recommended to perform newborn ultrasound to assess the condition of the skull and kidney function.

Breastfeeding period

The drug Indapamide / Perindopril-Teva is contraindicated in the period of breastfeeding.

It is not known whether perindopril with breast milk.

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

It is necessary to evaluate the importance of therapy for the mother and decide to terminate Breastfeeding or discontinuation of the drug.

Dosing and Administration:

Inside, once a day, preferably in the morning before eating, squeezed with enough 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 initial dose is 1 tablet at a dosage of 0.625 mg + 2.5 mg once daily. If, after 1 month after the initiation of therapy, the desired antihypertensive effect is not achieved, the dose should be increased to 1 tablet at a dosage of 1.25 mg + 5 mg.

Elderly patients

The recommended initial 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 examining the function of the kidneys, you can proceed to the use of a dose of 1 tablet at a dosage of 1.25 mg + 5 mg.

Patients with renal insufficiency

In patients with mild renal insufficiency (QC greater than 60 ml / min), dose adjustment is not required.

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

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

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

Patients with impaired hepatic function

With a fragile and moderate degree of impaired liver function, dose adjustment is not required.

With a severe degree of impaired liver function, the drug Indapamide / Perindopril-Teva is contraindicated (see section "Contraindications").

If you miss a dose of one or more doses in the next dose, Indapamide / Perindopril-Teva should be taken in the usual dose; You can not take a higher dose, i.e. you can not double the dose.

Side effects:

The frequency of adverse reactions that may occur during therapy is given in the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000. <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); unknown frequency (the frequency of development can not be calculated from the available data).

From the side of the blood and lymphatic system: 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 (see section "Special instructions").

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 - impaired vision.

From the side of the hearing organ: often - noise in the ears.

From the side of the cardiovascular system: infrequent - marked decrease in blood pressure, including orthostatic hypotension; very rarely - a violation of the rhythm of the heart, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina and myocardial infarction, possibly due to excessive reduction in blood pressure in patients at high risk (see section "Special instructions"); unknown frequency - arrhythmia of the "pirouette" type (possibly fatal) (see sections "Special instructions", "Interaction with other medicinal products").

From the respiratory system, chest and mediastinum: often - against the background of the use of ACE inhibitors may occur a dry cough that persists long during the intake of drugs of this group and disappears after their withdrawal, dyspnea; 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, decreased appetite, indigestion, constipation, diarrhea; very rarely - pancreatitis, angioedema, intestinal edema, cholestatic jaundice (see section "Special instructions"); unknown frequency - hepatic encephalopathy in patients with hepatic insufficiency (see the sections "Contraindications" and "Special instructions").

From the skin and subcutaneous fat: often - skin rash, itching, maculopapular rash; infrequently - angioedema, swelling of the face, lips, extremities, tongue mucosa, vocal folds and / or larynx, urticaria (see section "Special instructions"); reactions of hypersensitivity in patients predisposed to bronchial obstructive and allergic reactions; hemorrhagic vasculitis; in patients withthe acute form of systemic lupus erythematosus may worsen the course of the disease; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity reaction (see section "Special instructions").

From the musculoskeletal system and connective tissue: often - muscle spasm.

Co side of the urinary system: infrequent - renal insufficiency; very rarely acute renal failure.

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

Other: often - asthenia; infrequently - increased sweating.

Laboratory indicators: rarely - hypercalcemia; unknown frequency - increase in the QT interval on the ECG (see section "Special instructions", "Interaction with other medicinal products"); increase in the concentration of uric acid and glucose in the blood at the time of taking the drug; increased activity of "hepatic" enzymes; a slight increase in the concentration of creatinine in the urine and in the blood plasma, which occurs after the abolition of therapy, more often in patients with renal artery stenosis, in the treatment of arterial hypertension with diuretics and in the case of kidney failure; Hypokalemia, especially significant for patients at risk (see p.section "Special instructions"); hyperkalaemia, more often transient; hyponatremia and hypovolemia leading to dehydration and orthostatic hypotension.

Overdose:

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

Treatment: gastric lavage and / or use of activated charcoal, restoration of water-electrolyte balance. With a pronounced decrease in blood pressure, the patient should be placed in the "lying" position with the legs raised upwards, and, if necessary, measures aimed at replenishment of the bcc (for example, intravenous (intravenous) injection of 0.9% sodium chloride solution). Perindoprilat can be removed from the body by dialysis.

Interaction:

Indapamide / Perindopril

Unwanted combination of drugs

Lithium preparations

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

A combination of drugs that requires special attention

Baclofen

With simultaneous use with baclofen, an increase in antihypertensive action is possible. It is necessary to monitor blood pressure and kidney function, if necessary, correction of the dose of antihypertensive drugs.

A combination of drugs that requires attention

Tricyclic antidepressants, antipsychotic drugs (antipsychotics)

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

Glucocorticosteroids (GCS), tetracosactide

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

Other antihypertensive drugs

It is possible to increase the antihypertensive effect.

Perindopril

Simultaneous use is contraindicated

Aliskiren

In patients with diabetes mellitus or renal dysfunction (GFR less than 60 mL / min), the risk of hyperkalemia, impaired renal function, and increased incidence of cardiovascular morbidity and mortality increases.

Unwanted combination of drugs

Aliskiren

In patients without diabetes mellitus or renal dysfunction, there may be an increased risk of hyperkalemia, impaired renal function, and an increased incidence of cardiovascular morbidity and mortality.

Potassium-sparing diuretics (amiloride, spironolactone, eplerenone, triamterene as in monotherapy, and in the combination therapy) and potassium preparations

ACE inhibitors reduce diuretic-induced loss of potassium. 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 lethal 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 potassium levels in the blood plasma and ECG parameters should be performed.

A combination of drugs that requires special attention

Hypoglycemic drugs for oral administration (derivatives of sulfonylureas) and insulin

The following effects were described for captopril and enalapril. ACE inhibitors can enhance 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 insulin requirements).

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

Simultaneous use of ACE inhibitors and NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, cyclooxygenase-2 inhibitors and nonselective NSAIDs) can lead to a decrease in the antihypertensive effect. The concomitant use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function. Care should be taken 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 therapy process.

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

Simultaneous use with ACE inhibitors may be accompanied by an increased risk of leukopenia.

Preparations for general anesthesia

Simultaneous use of ACE inhibitors and agents for general anesthesia can lead to an increase in antihypertensive effect.

Diuretics (thiazide and "loop")

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

Preparations of gold

With the use of ACE inhibitors, including perindopril in patients receiving an intravenous drug of gold (sodium aurotomy malate), reactions similar to those that occur with the use of nitrates (reddening of the face, nausea, vomiting, arterial hypotension) can rarely develop.

Double blockade of RAAS

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

Ectramustine

Simultaneous application can lead to an increased risk of side effects, such as angioedema.

Glyptins (lipagliptin, saxagliptin, sitagliptin, vitagliptin)

Co-administration with ACE inhibitors may increase the risk of developing angioedema due to suppression of dipeptidyl peptidase IV (DPP-IV) activity with glyptin.

Sympathomimetics

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. When using this combination, the efficacy of ACE inhibitors should be evaluated regularly.

Indapamide

A combination of drugs that requires special attention

Preparations, They can cause arrhythmia such as "pirouette"

In connection with the fact that there is a risk of development of hypokalemia,caution should be exercised while using indapamide with drugs capable of causing piruet-type arrhythmias, for example, antiarrhythmic drugs of class IA (quinidine, hydroquinidine, disopyramide), antiarrhythmic drugs of the class III (amiodarone, dofetilide, ibutilide, brethil tosylate), 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, dipemanyl methyl sulfate, erythromycin in / in, halofantrine, misolastine, moxifloxacin, pentamidine, sparfloxacin, wincamine in / in, methadone, astemizole, terfenadine, should monitor and, if necessary, adjust the potassium content in blood plasma, as well as monitor the QT interval.

Medications that can cause hypokalemia

Amphotericin B (IV), gluco- and mineralocorticosteroids (with systemic application), tetracosactide. laxatives, stimulating the motility of the gastrointestinal tract, increase the risk of hypokalemia (additive effect). It is necessary to control the content of potassium in the blood plasma, if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. You should use laxatives that do not stimulate the motility of the gastrointestinal tract.

Cardiac glycosides

Hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium content in the blood plasma and the parameters of the ECG and, if necessary, adjust the therapy.

A combination of drugs that requires attention

Metformin

Functional renal failure, which can occur with the use of diuretics, especially "loop", while using with metformin increases the risk of lactic acidosis. Do not use metformin, if the creatinine concentration in the blood plasma exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-containing radiopaque substances

Dehydration of the body against the background of 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 must compensate for fluid loss.

Salts of calcium

With simultaneous application, it is possible to develop hypercalcemia due to decreased calcium excretion by the kidneys.

Cyclosporin

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

Special instructions:

The drug Indapamide / Perindopril-Teva

Preparations lithiI

It is not recommended simultaneous use of the drug Indapamide / Perindopril-Teva with lithium preparations.

Impaired renal function

Indapamide / Perindopril-Teva therapy is contraindicated in patients with severe renal insufficiency (CC less than 30 ml / min). In some patients with hypertension without a previous impairment of kidney function, Indapamide / 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, using either low doses of the drug Indapamide / Perindopril-Teva, or drugs perindopril and indapamide in monotherapy. In these patients, it is necessary to carry out regular monitoring of potassium and creatinine serum concentration 2 weeks after initiation of therapy and then every 2 months following therapy with Indapamide / Perindopril-Teva.

Acute renal failure often develops in patients with severe CHF or an initial impairment of kidney function, incl. with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney.

The drug Indapamide / Perindopril-Teva is usually not recommended in case of bilateral renal artery stenosis or stenosis of the artery only functioning kidney.

Reduction of blood pressure and violation of water-electrolyte balance

Hyponatremia is associated with a risk of a sudden drop in blood pressure (especially in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney). Therefore, when observing patients dynamically, attention should be paid to the possible symptoms of dehydration and a decrease in the electrolyte content 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 marked decrease in blood pressure, you may need to / in the introduction of 0.9% solution of sodium chloride.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After the recovery of bcc and blood pressure, it is possible to resume therapy with Indapamide / Perindopril-Teva using either low-dose drugs or perindopril and indapamide in monotherapy.

The content of potassium

The use of Indapamide / Perindopril-Teva does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. Regularly monitor the potassium content in the blood plasma.

Excipients

It should be borne in mind that at Ingredients of the preparation Indapamide / Perindopril-Teva include lactose monohydrate, therefore the drug is contraindicated in patients with hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Perindopril

Neutropenia / agranulocytosis

In patients taking ACE inhibitors, there may be cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia.In patients with normal renal function and the absence of other complications, neutropenia develops rarely and passes on its own after the withdrawal of ACE inhibitors.

Perindopril should be used with caution in patients with connective tissue disease and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing impairments of kidney function. Such patients can develop severe infections that are not amenable to intensive antibiotic therapy. In the case of perindopril it is recommended to periodically monitor the amount of white blood cells in the blood. The patient should be warned that at If there are any signs of an infectious-inflammatory disease (sore throat, fever), you should immediately consult a doctor.

Angioedema (edema of Quincke)

When taking ACE inhibitors, including perindopril, in rare cases, development of an angioedema of the face, lips, tongue, tongue of the upper palate and / or larynx can be observed. If these symptoms appear, the drug should be stopped immediately, the patient should be observed until the signs of edema disappear completely.

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

Patients with a history of Quincke's edema who are not associated with the administration of ACE inhibitors may be at increased risk of developing it with this group of drugs.

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or are accompanied by nausea and vomiting, in some cases without a previous angioedema and with normal activity C1-esterase. The diagnosis is established by means of computed tomography of the abdominal cavity, ultrasound examination or at the time of surgical intervention. Symptoms disappear after stopping the intake of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, a differential diagnosis should take into accountthe possibility of angioedema edema development of the intestine.

Anaphylactoid reactions during desensitization procedures

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with Hepaticoptera insects (bees, wasps). The use of ACE inhibitors should be avoided in patients receiving immunotherapy with venom of Hymenoptera. The development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.

Anaphylactoid reactions during apheresis of LDL

In rare cases, patients receiving ACE inhibitors may experience life-threatening anaphylactoid reactions during LDL-apheresis with dextrin sulfate. To prevent the anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each procedure for LDL apheresis using high-flow membranes.

Hemodialysis

In patients receiving ACE inhibitors, hemodialysis using high-flow membranes (for example,AN69®), anaphylactoid reactions were noted. Therefore, it is desirable to use a different type of membrane or to use an antihypertensive drug of another pharmacotherapeutic group.

Potassium-sparing diuretics and potassium preparations

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

Cough

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of this group. When dry cough occurs, remember the possible association of this symptom with the administration of an ACE inhibitor. If the doctor believes that ACE inhibitor therapy is necessary for the patient, taking Indapamide / Perindopril-Teva may be continued.

Age under 18 years old

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

The risk of arterial hypotension and / or renal failure in patients with heart failure, a violation of the water-electrolyte balance, etc.

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

The use of an ACE inhibitor can cause blockade of the RAAS, in this connection, a sharp decrease in blood pressure and / or an increase in plasma creatinine concentration, indicating the development of acute renal failure, is more likely to occur with 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 be evaluated by the kidney function and the potassium content in the blood plasma. The initial dose of the drug Indapamide / Perindopril-Teva is selected depending on the degree of BP reduction, especially with a decrease in bcc and CHF (IV functional class by classification NYHA). Such measures allow to avoid a sharp decrease in blood pressure,

Atherosclerosis

The risk of arterial hypotension exists in all patients, but special care should be taken when using Indapamide / Perindopril-Teva in patients with coronary artery disease and cerebral circulatory insufficiency.In such patients, treatment should begin with the recommended initial dose of Indapamide / Perindopril-Teva.

Patients with Renovascular Hypertension

Revascularization is used to treat renovascular hypertension. Nevertheless, ACE inhibitors have a beneficial effect in patients with renovascular hypertension, both anticipating surgical intervention, and in patients whose conduct is not possible.

Treatment with Indapamide / Perindopril-Teva in patients with diagnosed or suspected renal artery stenosis should begin in a hospital with the recommended initial dose of Indapamide / Perindopril-Teva, controlling kidney function and potassium levels in the blood plasma. Some patients may develop functional acute renal failure, which is reversible after drug withdrawal.

Other risk groups

In patients with CHF (IV functional class by classificationNYHA) and patients with type 1 diabetes mellitus (the risk of spontaneous increase in potassium content) treatment should start with the recommended initial dose of the drug 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 ingestion or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood.

Perindopril (as well as other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

Surgical interventions / general anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetics, which have an antihypertensive effect. It is recommended to stop the use of ACE inhibitors, including perindopril, 12 hours before surgery, warning the anesthesia doctor about the use of inhibitors APF.

Aortic stenosis / GOKMP

ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract.

Liver failure

In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs,with the progression of which fulminant hepatic necrosis develops, including fatal outcome. When jaundice or a significant increase in the activity of "liver" transaminases against the background of taking ACE inhibitors, the drug Indapamide / Perindopril-Teva should be discontinued.

Anemia

It can develop in patients after kidney transplantation or in patients on hemodialysis.

Hyperkalemia

In the treatment of ACE inhibitors, including perindopril, hyperkalemia may develop. Risk factors for hyperkalemia are renal failure, elderly age, diabetes mellitus, some concomitant conditions (decreased BCC, acute heart failure in decompensation, metabolic acidosis), simultaneous intake of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes for edible salt and the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, including fatalities.Combined use of the above drugs should be done with caution.

Indapamide

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

Photosensitivity

There are reports of cases of increased photosensitivity against thiazide and thiazide-like diuretics. With the development of 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 the drug Indapamide / Perindopril-Teva, it should protect the exposed areas of the skin from direct exposure to sunlight and artificial ultraviolet rays.

Water-electrolyte balance

The content of sodium in the blood plasma

Before starting treatment with the drug Indapamide / Perindopril-Teva it is necessary to determine the sodium content in the blood plasma and on the background of taking the drug to conduct regular monitoring of the content of electrolytes in the blood plasma. All diuretics are capable of causing hyponatremia, leading to serious complications.

The content of potassium in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia (less than 3.4 mmol / L) in elderly patients, depleted patients, patients with cirrhosis, patients with peripheral edema, ascites, IHD, XCH. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

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

Calcium in the blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of latent hyperparathyroidism.Before the study of the function of parathyroid glands, you should cancel the use of the drug Indapamide / Perindopril-Teva.

The concentration of glucose in the blood plasma

It is necessary to monitor the concentration of glucose in patients with diabetes mellitus.

Concentration of uric acid

In patients with a high concentration of uric acid in blood plasma against the background of therapy with the drug Indapamide / Perindopril-Teva may increase the frequency of exacerbation of the gout.

Diuretic drugs and kidney function

The effectiveness of thiazide and thiazide-like diuretics is fully manifested only under the condition of normal kidney function. They are also effective in the case of a creatinine concentration of 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 taking into account the patient's age, body weight and sex Cockcroft formula:

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

This formula is suitable for elderly male patients. When calculating QA for women, the coefficient is 0.85.

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

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

Athletes

Indapamide can give a false positive reaction during doping control.

Effect on the ability to drive transp. cf. and fur:

Neither indapamide, nor perindopril, both in monotherapy and in combination with each other, do not have a negative effect on the concentration of attention and the speed of psychomotor reactions. Nevertheless, in some patients, especially at beginning of treatment, or in combination with other antihypertensive drugs, there may be episodes of severe or severe BP depression, dizziness, which may reduce the ability to drive vehicles and control mechanisms.

Form release / dosage:

Tablets, film-coated, 0.625 mg + 2.5 mg, 1.25 mg + 5 mg.

Packaging:

For 30 tablets in a white polypropylene container with a polyethylene lid with a drying insert, equipped with a polyethylene limiter with the control of the first opening.

1 The container together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003156

Date of registration:25.08.2015

Date of cancellation:2020-08-25

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Indapamide / Perindopril-Teva (Indapamide / Perindopril-Teva)