Perindopril PLUS Indapamide - instructions for use, dose, side effects, contraindications

Tablet core composition: active substance: perindopril erbumine 2,000 mg; indapamide 0.625 mg; Excipients: microcrystalline cellulose 70,375 mg; starch corn pregelatinized 15,000 mg; crospovidone 10,000 mg; magnesium stearate 1,000 mg; silicon colloid dioxide 1,000 mg.

Composition of the tablet shell: Opapray II green (85F21738) polyvinyl alcohol 40,000%, titanium dioxide 24.345%, macrogol-3350 20.200%, talc 14.800%, indigo carmine aluminum varnish 0.540%, quinoline yellow 0.115%.

1 tablet, film-coated, 1.25 mg + 4 mg, contains:

Tablet core composition: aactive substance: perindopril erbumine 4,000 mg; indapamide 1,250 mg; Excipients: microcrystalline cellulose 67.750 mg; starch corn pregelatinized 15,000 mg; crospovidone 10,000 mg; magnesium stearate 1,000 mg; silicon colloid dioxide 1,000 mg.

Composition of the tablet shell: Opapray II yellow (85F38201) - polyvinyl alcohol 40,000%, titanium dioxide 24,480%, macrogol-3350 20,200%, talc 14,800%, iron oxide yellow 0.500%, iron oxide red 0.020%.

1 tablet, film-coated, 2.5 mg + 8 mg contains:

Tablet core composition: aactive substance: perindopril erbumine 8,000 mg; indapamide 2,500 mg; Excipients: microcrystalline cellulose 62,500 mg; starch corn pregelatinized 15,000 mg; crospovidone 10,000 mg; magnesium stearate 1,000 mg;silicon colloid dioxide 1,000 mg.

Composition of the tablet shell: Opapray II white (85F48105) polyvinyl alcohol 46.900%, macrogol-3350 23.600%, talc 17.400%, titanium dioxide 12.100%.

Description:

Tablets 0.625 mg + 2 mg

Tablets are round, biconvex, covered with a film membrane from gray-green to green with a grayish hue. On the cross section - the core is white or almost white

Tablets 1.25 mg + 4 mg

The tablets are round, biconvex, covered with a film coat from light yellow with a pinkish hue to yellow with a pinkish tinge. On the cross section - the core is white or almost white.

Tablets 2.5 mg + 8 mg

The tablets are round, biconvex, covered with a film coat of white or almost white color. On the cross section - the core is white or almost white.

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

ATX: & nbsp

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

Pharmacodynamics:

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

Perindopril PLUS Indapamide has a pronounced dose-dependent antihypertensive effect, independent of the age and position of the patient's body and not accompanied by reflex tachycardia. Does not affect the metabolism of lipids (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 due to monotherapy with a diuretic.

The hypotensive effect persists for 24 hours.

A stable decrease in blood pressure (BP) is achieved within 1 month against the background of the drug Perindopril PLUS Indapamide without increasing the heart rate (heart rate). Termination of treatment does not lead to the development of the "withdrawal" syndrome.

Perindopril - ACE inhibitor, the mechanism of its action is associated with the inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictive effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to the retention of sodium and liquid, does not cause reflex tachycardia in long-term treatment.The hypotensive effect of perindopril is developed in patients with low or normal renin activity of blood plasma. Perindopril acts through its main active metabolite - perindoprilata. Its other metabolites are inactive.

The action of perindopril leads to widening of the veins (decrease in preload on the heart), caused by a change in the metabolism of prostaglandins; reduction of total peripheral resistance of blood vessels (OPSS) (decrease in postload on the heart).

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

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

The maximum hypotensive effect develops 4-6 hours after a single oral intake and persists for 24 hours.

Termination of therapy does not lead to the development of the "withdrawal" syndrome.

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 refers to derivatives of sulfonamide, 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. Possessing the ability to selectively block slow calcium channels, indapamide increases the elasticity of the walls of the arteries and reduces the OPSS. Has antihypertensive effect in doses that do not have a pronounced diuretic effect. An increase in the dose of indapamide does not entail an increase in the hypotensive effect, but increases the risk of developing undesirable phenomena. Indapamide in patients with hypertension does not affect the metabolism of lipids - TG, LDL and HDL; on the metabolism of carbohydrates, even in patients with diabetes mellitus and hypertension.

Pharmacokinetics:

The combined use of perindopril and indapamide does not alter their pharmacokinetic parameters, as compared to the separate administration of these drugs.

Perindopril

Suction

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

Eating a meal reduces the conversion of perindopril to perindoprilat and the bioavailability of perindopril, so it should be taken 1 time / day in the morning, before breakfast. When taking perindopril 1 time / day. The equilibrium concentration (C_ss) is achieved within 4 days.

Distribution

Binding to blood plasma proteins perindoprilata has a dose-dependent character and is 20%. Perindoprilat easily passes through the histohematological barriers, excluding the blood-brain barrier (BBB). Do not cumulate.

Metabolism

In the liver is metabolized with the formation of an active metabolite perindoprilata. In addition, 5 more inactive metabolites are formed.

Excretion

The half-life (T_1/2) of perindopril from blood plasma is 1 h. T_1/2 perindoprilata is about 17 hours. It is excreted by the kidneys.

Pharmacokinetics in specific patient groups

In patients of advanced age, in patients with renal and cardiac failure, excretion of perindoprilate is slowed.

The dialytic clearance of perindoprilat is 70 ml / min.

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

Indapamide

Suction

After oral administration, it is quickly and almost completely absorbed from the digestive tract. Eating somewhat slows down absorption, but does not significantly affect the amount of absorbed indapamide. After oral administration in a single dose of C_m_Oh in blood plasma is achieved after 1 h.

Distribution

Binding to plasma proteins is 79%. Do not cumulate.

Metabolism

Metabolised in the liver.

Excretion

T_1/2is from 14 to 24 hours (an average of 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 the intestine with bile in the form of inactive metabolites (22%).

Pharmacokinetics in special clinical cases

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

Indications:

Arterial hypertension.

Contraindications:

Perindopril

- Hypersensitivity to perindopril and other ACE inhibitors;

- angioedema (angioedema) in the anamnesis associated with the administration of an ACE inhibitor;

- hereditary / idiopathic angioedema;

- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;

- simultaneous administration of ACE inhibitors with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and renal insufficiency (creatinine clearance less than 60 ml / min);

- pregnancy;

- the period of breastfeeding;

- age to 18 years (efficacy and safety not established).

Indapamide

- Pincreased sensitivity to indapamide and other sulfonamide derivatives;

- severe hepatic insufficiency (including with encephalopathy);

- hypokalemia;

- simultaneous use with drugs that can cause arrhythmia such as "pirouette";

- pregnancy and the period of breastfeeding;

- age to 18 years (efficacy and safety not established).

Perindopril PLUS Indapamide

- PHigh sensitivity to the auxiliary substances included in the preparation;

- severe renal failure (CK <30 mL / min);

- simultaneous administration with potassium-sparing diuretics, potassium and lithium preparations, and in patients with hyperkalemia;

- simultaneous reception of drugs that extend the interval QT Due to lack of sufficient clinical experience, the drug Perindopril PLUS Indapamide should not be used in patients on hemodialysis, as well as in patients with untreated heart failure in the stage of decompensation;

- age to 18 years (efficacy and safety not established).

Carefully:

It should be used in cases of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); on the background of immunosuppressant therapy (risk of neutropenia, agranulocytosis); when oppression of bone marrow hematopoiesis; decrease in the volume of circulating blood (BCC) (due to taking diuretics, diets with restriction of table salt, vomiting, diarrhea); with ischemic heart disease (CHD); cerebrovascular diseases; Renovascular hypertension; chronic heart failure (IV functional class by classification NYHA); with hyperuricemia (especially accompanied by gout and urate nephrolithiasis); lability of blood pressure; when hemodialysis using high-flow polyacrylonitrile membranes (risk of anaphylactoid reactions); before the procedure for apheresis of LDL with dextran sulfate; simultaneously with the conduct of desensitizing therapy with allergens (for example,the poison of Hymenoptera insects); after the kidney transplantation; stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy; in elderly patients. Patients with a history of Quincke 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 patients of the Negroid race angioneurotic edema develops more often than in patients of other races.

Pregnancy and lactation:

Perindopril PLUS Indapamide contraindicated in pregnancy.

When planning pregnancy or when it comes on the background of taking the drug should immediately stop taking the drug and prescribe another antihypertensive therapy. Appropriate controlled trials of ACE inhibitors in pregnant women have not been conducted. The available limited data on the effect of the drug in the first trimester of pregnancy indicate that the drug did not lead to malformations associated with fetotoxicity.

Do not use Perindopril PLUS Indapamide in the first trimester of pregnancy. Perindopril PLUS Indapamide contraindicated in the II and III trimesters of pregnancy.

It is known that prolonged exposure to ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, delayed ossification of the skull bones) and development of complications in the newborn (such as kidney failure, arterial hypotension, hyperkalemia).

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 Perindopril PLUS Indapamide in the II or III trimesters of pregnancy, it is recommended to perform ultrasound examination of the fetus to assess the condition of the skull bones and kidney function.

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

Perindopril PLUS Indapamide contraindicated during breastfeeding. It is not known whether perindopril in breast milk.

Indapamide is 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.

If you need to use Perindopril PLUS Indapamide during breastfeeding should stop breastfeeding.

Dosing and Administration:

Assign inside 1 time / day, preferably in the morning before breakfast, squeezed with enough liquid.

Doses are given for the ratio of indapamide / perindopril.

Initial dose of Perindopril PLUS Indapamide - 0.625 mg / 2 mg (1 tablet) 1 time / day. If after 1 month of taking the drug, you can not achieve adequate control of blood pressure, then the dose should be increased to 1.25 mg / 4 mg (1 tablet) 1 time / day.

Patients with renal insufficiency (SC 60 ml / min or more) dose adjustment is not required. For patients with KK 30-60 ml / min the maximum dose of the drug Perindopril PLUS Indapamide is 0.625 mg / 2 mg (1 tablet) 1 time / day, treatment should begin with the selection of doses of perindopril and indapamide in monotherapy. With QC less than 30 ml / min, the drug Perindopril PLUS Indapamide it is contraindicated (see section "Contraindications").

Patients with moderate impaired hepatic function correction of the dose is not required. Patients with severe impairment of liver function using the drug Perindopril PLUS Indapamide it is contraindicated.

For elderly patients initial dose of Perindopril PLUS Indapamide is 0.625 mg / 2 mg (1 tablet) 1 time / day.

In elderly patients before starting the drug Perindopril PLUS Indapamide it is necessary to evaluate the function of the kidneys and the content of potassium in the blood plasma. The initial dose of the drug Perindopril PLUS Indapamide are selected depending on the degree of BP reduction, especially with a decrease in BCC and in chronic heart failure (IV functional class by classification NYHA). Such measures allow to avoid a sharp decrease in blood pressure.

The risk of arterial hypotension exists in all patients, but special care should be taken when using the drug Perindopril PLUS Indapamide in patients with ischemic heart disease and insufficiency of cerebral circulation.In such patients, drug treatment should be given at a dose of 0.625 mg / 2 mg (initial dose).

In patients with diagnosed or suspected renal artery stenosis, treatment with Perindopril PLUS Indapamide should begin in a hospital with a dose of 0.625 mg / 2 mg under the control of kidney function and potassium content in blood plasma. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.

In patients with chronic heart failure (IV functional class by classification NYHA) treatment with Perindopril PLUS Indapamide it is necessary to start with an initial dose of 0.625 mg / 2 mg under medical supervision.

Side effects:

Classification of the incidence of adverse events (WHO): very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1/100), rarely (> 1/10 000 to <1/1000), very rarely (from <1/10 000), the frequency is unknown (the frequency can not be calculated from the available data).

On the part of the hematopoiesis system: infrequently - eosinophilia, hyponatremia, 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 (CNS): often - paresthesia, headache, dizziness, vertigo; infrequently - sleep disturbance, mood lability; very rarely confusion; frequency unknown - faint.

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 cardiovascular system: infrequent - marked decrease in blood pressure (including orthostatic hypotension), a feeling of palpitations; very rarely - heart rhythm disturbances (including bradycardia, ventricular tachycardia, atrial fibrillation), angina pectoris and myocardial infarction, possibly due to excess BP reduction in patients at high risk; the frequency is unknown - arrhythmias of the "pirouette" type (possibly with a lethal outcome), an increase in the QT interval on the ECG.

From the respiratory system: often - against the background of the use of ACE inhibitors may occur a dry cough, long-lasting during the intake of drugs of this group and disappearing 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; the frequency is unknown - hepatic encephalopathy in patients with hepatic insufficiency, increased activity of "liver" transaminases.

From the skin: often - skin rash, itching, maculopapular rash; infrequently - angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and / or larynx, urticaria, hypersensitivity reactions in patients predisposed to bronchial 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 reaction are noted.

From the musculoskeletal system: often - muscle spasms.

From the urinary system: infrequent - renal insufficiency; very rarely - acute renal failure; frequency is unknown - hepatitis.

From the side of the reproductive system: infrequently erectile dysfunction.

Laboratory indicators: rarely - hypercalcemia; frequency unknown - hypokalemia, especially significant for patients at risk; hyponatremia and hypovolemia leading to dehydration and orthostatic hypotension; increase in the concentration of uric acid and glucose in the blood at the time of taking the drug; 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; hyperkalaemia, often transient.

Other: often - asthenia; infrequently - increased sweating

With the use of ACE inhibitors, the syndrome of impaired secretion of antidiuretic hormone was rarely observed.

Overdose:

Symptoms: marked decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in bcc); there are violations of water-electrolyte balance (low content of sodium and potassium in the blood plasma).

Treatment: gastric lavage and / or the administration of activated carbon, restoration of the water-electrolyte balance in a hospital. With a pronounced decrease in blood pressure, the patient must be transferred to a position lying on his back with his legs raised upwards; further measures should be taken to increase the BCC (introduction of a 0.9% solution of sodium chloride in the IV). Perindoprilat, the active metabolite of perindopril, can be eliminated from the body by dialysis.

Interaction:

Perindopril PLUS Indapamide

Simultaneous use is not recommended

With the simultaneous use of lithium drugs and ACE inhibitors, cases of reversible increase in serum lithium concentration were recorded.

Simultaneous reception of thiazide diuretics can promote an increase in the concentration of lithium and the risk of its toxic effect against the background of taking an inhibitor ACE.

Simultaneous reception of a combination of perindopril and indapamide with lithium preparations is not recommended. In case of therapy, it is necessary to monitor the concentration of lithium in the blood plasma.

With simultaneous application, special care is required

Baclofen potentiates antihypertensive effect (requires control of blood pressure, kidney function and, if necessary, dose adjustment Perindopril PLUS Indapamide).

The combination of ACE inhibitors with nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs, acetylsalicylic acid in doses that have anti-inflammatory effect) reduces the antihypertensive effect of ACE inhibitors; increases the risk of impaired renal function, up to the development of acute renal failure; increases the potassium content in the blood serum in patients with pre-existing renal dysfunction. This combination is recommended for use with caution, especially in elderly patients. Patients should be compensated for BCC, as well as to monitor kidney function before and after treatment with Perindopril PLUS Indapamide.

With simultaneous application, care is required

Tricyclic antidepressants, antipsychotics (antipsychotics) increase 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 agents, the antihypertensive effect of Perindopril PLUS Indapamide.

Perindopril

Simultaneous use is not recommended

ACE inhibitors reduce potassium-induced kidney loss caused by a diuretic. With the combined use of potassium-sparing diuretics (spironolactone, triamterene. amiloride. eplerenone), potassium or potassium-containing salt substitutes with ACE inhibitors, potassium levels in the blood serum can be increased right up to a lethal outcome. If the combined use of an ACE inhibitor and the above drugs is required (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.

PpoThe simultaneous use of ACE inhibitors and angiotensin II receptor antagonists with aliskiren in patients with diabetes mellitus and patients with moderate renal insufficiency (CC less than 60 ml / min) is concomitant.

Simultaneous use with estramustine is accompanied by an increased risk of angioedema development.

With simultaneous application, special care is required

The use of ACE inhibitors can enhance the hypoglycemic effect of hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin in patients with diabetes mellitus; when they are used together, there may be an increase in glucose tolerance, which may require correction of doses of hypoglycemic agents for ingestion and insulin.

Baclofen increases the antihypertensive effect of ACE inhibitors.

With the simultaneous use of potassium-non-sparing diuretics, glyptins (linaglyptin, saxagliptin, sitagliptin, vildagliptin) - the risk of angioedema development due to suppression of dipeptidyl peptidase IV activity by glyptin.

With simultaneous use with sympathomimetics enhances the antihypertensive effect of ACE inhibitors.

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 ARAII is associated with a higher incidence of arterial hypotension, fainting, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of only one drug that affects RAAS. Double blockade (eg, with the combination of an ACE inhibitor with an APAII) should be limited to individual cases with careful monitoring of kidney function, potassium and blood pressure.

With simultaneous application, care is required

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

In patients whose condition requires extensive surgical intervention or general anesthesia with drugs that cause arterial hypotension, ACE inhibitors, including perindopril, can block the formation of angiotensin II with compensatory release of renin. The day before surgery or therapy with ACE inhibitors must be canceled. If the ACE inhibitor can not be canceled, then the arterial hypotension, which develops according to the mechanism described, can be corrected by an increase in BCC.

When diuretics are used in high doses, hypovolemia is possible (due to a decrease in BCC), and the addition of perindopril to therapy is associated with a marked decrease in blood pressure.

With the appointment of ACE inhibitors, incl. perindopril. patients receiving a drug of gold (sodium aurothiomalate) IV, nitrate-like reactions were noted (nausea, vomiting, marked decrease in blood pressure, hyperemia of the facial skin).

Indapamide

With simultaneous application, special care is required

Because of the risk of hypokalemia, indapamide should be used with caution in conjunction with drugs that cause ventricular arrhythmia such as pirouettes, such as antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide. brethil tosylate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenone (droperidol, haloperidol), other neuroleptics (pimozide); other substances such as bepridil, cisapride, difemanyl methyl sulfate, erythromycin (w / w). halofantrine, misolastine, moxifloxacin, pentamidine, sparfloxacin, wincamine with / in application, methadone, astemizole, terfenadine. It is necessary to control the potassium content in order to avoid hypokalemia, in the course of which it is necessary to correct it, to monitor the interval QT na ECG.

With the simultaneous use of indapamide with amphotericin B (IV), gluco- and mineralocorticoids (for systemic administration), tetracosactide. laxatives, stimulating the motility of the gastrointestinal tract, increases 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.

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, the parameters of the ECG and, if necessary, adjust the dose of cardiac glycosides.

With simultaneous application, care is required

When metformin with diuretics is used, it is possible to develop renal failure.

With the simultaneous use of e metformin, the risk of developing lactic acidosis increases. Do not follow the apply metforminif the serum creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Against the background of taking diuretics, there is a decrease in BCC, the risk of developing acute renal failure increases, especially when using iodine-containing contrast media in high doses. Before using iodine-containing contrast agents, BCC should be compensated.

With simultaneous application with calcium preparations, the development of hypercalcemia is possible, due to a decrease in the excretion of calcium by the kidneys.

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

Special instructions:

Perindopril PLUS Indapamide

It is not recommended simultaneous use of the drug Perindopril PLUS Indapamide with lithium preparations.

Therapy with Perindopril PLUS Indapamide 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 in the background of therapy with Perindopril PLUS Indapamide there may be symptoms of acute renal failure. In this case, treatment with Perindopril PLUS Indapamide should be discontinued. In the future it is possible to resume combined therapy, using low doses of Perindopril PLUS Indapamide, or use drugs perindopril and indapamide in monotherapy. Such patients need regular monitoring of potassium content and concentration Creatinine in the blood serum every 2 weeks after initiation of therapy and every subsequent 2 months of therapy with Perindopril PLUS Indapamide.

Acute renal failure often develops in patients with severe chronic heart failure or with an initial impairment of kidney function, incl. with bilateral stenosis of the renal arteries or stenosis of the artery the only functioning kidney. Taking Perindopril PLUS Indapamide not recommended for patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney.

Hyponatremia is associated with a risk of a sudden drop in blood pressure (especially in patients with bilateral stenosis of the renal arteries or arterial stenosis 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. Such patients need regular monitoring of electrolytes in 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, one can resume therapy with Perindopril PLUS Indapamide, using low doses of the drug, or using drugs 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 insufficiency. As in the case of combined use of antihypertensive drugs and a diuretic, regular monitoring of the potassium content in the blood plasma is necessary.

Perindopril

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

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

When taking ACE inhibitors, incl. 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 discontinued immediately. Patient status should be monitored until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually go away by itself or to treat the symptoms you can use antihistamines preparations. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

When symptoms of angioedema develop, immediately enter epinephrine (epinephrine) in a dilution of 1: 1000 (0.3 or 0.5 ml) and / or provide airway patency.

Patients with a history of Quincke 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 patients of the Negroid race angioneurotic edema develops more often than in patients of other races.

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 in combination with nausea and vomiting,in some cases without a previous angioedema and at a normal level of C-1-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, the differential diagnosis should take into account the possibility of developing angioedema of the intestine. 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). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving immunotherapy with venom of Hymenoptera. Nevertheless, 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.

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

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.

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 therapy with an ACE inhibitor is necessary for the patient, taking Perindopril PLUS Indapamide can be continued.

With liver cirrhosis accompanied by edema and ascites, arterial hypotension, chronic heart failure, a 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 a background of a salt-free diet or a long-term intake of diuretics).

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

When prescribing Perindopril PLUS Indapamide patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin during the first month of therapy should 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.

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 taking ACE inhibitors, incl. perindopril, 12 hours prior to surgery, warning the anesthetist 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 GOKMP (hypertrophic obstructive cardiomyopathy).

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

In patients after kidney transplantation or in patients on hemodialysis, anemia may develop.

During treatment with ACE inhibitors, incl. and perindopril may develop hyperkalemia. Risk factors for hyperkalemia are renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in decompensation,metabolic acidosis), simultaneous administration 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, sometimes with a fatal outcome. Combined use of the above drugs is not recommended, if necessary, the use of therapy should be done with extreme caution.

Indapamide

There are reports of cases of increased photosensitivity against thiazide and thiazide-like diuretics. With the development of photosensitivity reaction against the background of the drug Perindopril PLUS Indapamide treatment should be discontinued. If necessary, renew the use of Perindopril PLUS Indapamide, it is necessary to protect the exposed areas of the skin from direct exposure to sunlight and artificial ultraviolet rays.

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

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, chronic heart failure. 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 ventricular arrhythmias such as pirouettes, which can be lethal. In all cases described, 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 initiation of therapy with Perindopril PLUS Indapamide.

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 examining the function of parathyroid glands, you should discontinue taking Perindopril PLUS Indapamide.

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

In patients with a high concentration of uric acid in the blood plasma on the background of therapy with the drug Perindopril PLUS Indapamide possibly an increase in the frequency of exacerbation of gout.

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

Indapamide can give a false positive reaction during doping control.

Pediatric Use

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

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

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

Form release / dosage:

Film-coated tablets, 0.625 mg + 2 mg, 1.25 mg + 4 mg and 2.5 mg + 8 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 3, 6 or 9 contour cell packs, together with instructions for medical use, put in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002488

Date of registration:04.06.2014

Date of cancellation:2019-06-04

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Representation: & nbspIZVARIN PHARMA LLC IZVARIN PHARMA LLC Russia

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Perindopril PLUS Indapamide (Perindopril PLUS Indapamide)