Perindopril Plus Indapamid

General characteristics. Structure:

Active ingredients: 0,625 mg of an indapamid + 2 mg of a perindopril of an erbumin, 1,25 mg of an indapamid + 4 mg of a perindopril of an erbumin, 2,5 mg of an indapamid + 8 mg of a perindopril of an erbumin.

Excipients: cellulose microcrystallic, starch corn prezhelatinizirovanny, кросповидон, magnesium stearate, silicon dioxide colloid.

Structure of a film cover: опадрай the II yellow (85F38201), including polyvinyl alcohol - 40%, titanium dioxide - 24.48%, a macrogoal-3350 - 20.2%, talc - 14.8%, ferrous oxide of yellow 0.5%, ferrous oxide of red 0.02%.

Pharmacological properties:

Pharmacodynamics. Perindopril-Indapamid Richter represents a combination of a perindopril of an erbumin and an indapamid. The combination of a perindopril and an indapamid renders dozozavisimy anti-hypertensive effect on diastolic and systolic to the ABP in a prone position and standing, regardless of age. Effect of drug remains during 24 h. The lasting therapeutic effect develops less, than in 1 month from the beginning of therapy and is not followed by tachycardia. The termination of treatment is not followed by development of a syndrome of "cancellation".

Perindopril. Inhibitor of an angiotensin-converting enzyme (APF) reduces formation of II angiotensin of angiotensin I. Decrease in content of angiotensin II leads to direct reduction of allocation of Aldosteronum. Reduces degradation of bradikinin and increases synthesis of prostaglandins. Reduces the general peripheric vascular resistance, the ABP, preloading, pressure in pulmonary capillaries, causes increase in minute volume of blood and increase in tolerance of a myocardium to loadings in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by influence on fabric renin-angiotensin-aldosteronovuyu system. At prolonged use the hypertrophy of a myocardium and walls of arteries of resistive type decreases. Improves blood supply of a myocardium in the conditions of ischemia.

APF inhibitors extend life expectancy at patients with chronic heart failure, slow down progressing of dysfunction of a left ventricle at the patients who had a myocardial infarction without clinical displays of heart failure.

The maximum anti-hypertensive effect develops in 4-6 h after reception of a single dose and remains at least for days: the ratio of residual effect and maximum makes about 80%. At patients who answered treatment arterial pressure is normalized within a month and remains during a long span without development of tachycardia. After the termination of reception of a perindopril the syndrome of "cancellation" does not arise.

Indapamid. Indapamid treats sulfonamide derivatives, the containing indole ring. On pharmacological properties it is close to thiazide diuretics which effect is connected with inhibition of a reabsorption of ions of sodium in a cortical segment of a nephronic loop. Indapamid increases removal by kidneys of ions of sodium, chlorine and, to a lesser extent, potassium ions and magnesium that is followed by strengthening of a diuresis. Indapamid has anti-hypertensive effect in the doses which do not have the expressed diuretic effect. Besides, anti-hypertensive action is connected with ability of drug to increase elasticity of walls of arteries and to reduce the general peripheric vascular resistance (GPVR).

The mechanism of action of an indapamid is caused by change of transmembrane current of ions (first of all - calcium) that leads to relaxation of smooth muscle cells of vessels, and also strengthening of synthesis of PGE2 prostaglandins and PGI2 prostacyclin (a vazodilatator and inhibitor of aggregation of thrombocytes).

Indapamid promotes reduction of a hypertrophy of a left ventricle of heart.

The lasting anti-hypertensive effect remaining during 24 h develops in monotherapies; at the same time moderate strengthening of a diuresis is observed.

Irrespective of use duration индапамид does not influence indicators of a lipidic profile in a blood plasma (triglycerides, cholesterol of lipoproteins of the low density (HS/LPNP), cholesterol of lipoproteins of the high density (HS/LPVP)). Indapamid does not influence indicators of carbohydrate metabolism (including at patients with arterial hypertension and a diabetes mellitus).

Renders therapeutic effect in the doses which are not possessing the expressed diuretic action.

At use of an indapamid in high doses anti-hypertensive action amplifies, but the diuresis increases.

Perindopril + Indapamid. The combination of a perindopril and an indapamid in one medicine allows to prevent development of the undesirable side effects caused by one of active agents. So APF inhibitor leads to decrease in risk of development of a hypopotassemia against the background of diuretic reception.

Pharmacokinetics. At joint reception of a perindopril and indapamid their pharmacokinetic properties in comparison with separate reception of these drugs do not change.

Perindopril. After oral administration perindoprit quickly it is soaked up, Cmax in a blood plasma is reached throughout 1 p. T1/2 - 1 h Perindopril is pro-medicine. 27% of total quantity of the adsorbed perindopril are defined in blood in the form of an active metabolite - a perindoprilat. Except an active metabolite - - perindoprit a perindoprilat forms 5 inactive metabolites. Cmax of a perindoprilat in a blood plasma is reached in 3-4 h after intake. The use of food slows down transformation of a perindopril in периндоприлат, and, therefore, and bioavailability of drug therefore the perindopril эрбумин should be accepted once, in the morning, before food. Between a dose of a perindopril and its concentration in a blood plasma there is a linear interrelation. Vd of an untied perindoprilat makes about 0.2 l/kg. Linkng of a perindoprilat with proteins of a blood plasma, mainly with APF, makes 20%, but this indicator depends on concentration.

Perindoprilat is brought from an organism by kidneys. Final T1/2 makes several hours, the stage of equilibrium concentration to a vplazma of blood comes in 4 days from an initiation of treatment.

Removal of a perindoprilat at elderly patients, and also at a heart and renal failure is slowed down. At a vzavisimost renal failure from its expressiveness (clearance of creatinine) dose adjustment is required. The dialysis clearance of a perindoprilat makes 70 ml/min. The kinetics of a perindopril changes at patients with cirrhosis: at them the hepatic clearance of a perindopril decreases twice. Nevertheless, the quantity of the formed perindoprilat does not decrease therefore such patients do not need to adjust a dose.

Indapamid. Indapamid is quickly and completely adsorbed from a digestive tract. Cmax in a blood plasma at the person is observed in 1 h after oral administration of drug.

T1/2 makes 14-24 h (on average, 18 h). At repeated administration of drug of cumulation in an organism does not occur. Indapamid is brought in the form of inactive metabolites, generally by kidneys (70%), and also through intestines (22%). The pharmacokinetics at patients with a renal failure does not change.

Indications to use:

— essential arterial hypertension (at patients to whom the combination therapy is shown).

Route of administration and doses:

Inside, it is preferable in the morning, on an empty stomach, on 1 tablet of drug Perindopril-Indapamid Richter according to the picked-up dose of 1 times/days.

Purpose of the combined drug in a certain dose perhaps after titration of a dose on separate components of drug in monotherapy. With therapeutic effect it is necessary to consider the possibility at once to pass from monotherapy to treatment with drug Perindopril-Indapamid Richter.

At patients of advanced age. Treatment should be begun taking into account decrease in the ABP and function of kidneys.

At a renal failure. At a heavy renal failure (clearance of creatinine less than 30 ml/min.) treatment by drug Perindopril-Indapamid Richter contraindicated. At a moderate renal failure (clearance of creatinine of 30-60 ml/min.) it is recommended to begin therapy with the combined drug depending on the ABP. Higher than 60 ml/min. dose adjustment is not required to patients with clearance of creatinine at regular control of concentration of creatinine and content of potassium.

At a liver failure. At heavy abnormal liver functions treatment by this drug contraindicated.

At moderately expressed liver failure dose adjustment is not required.

Children and teenagers up to 18 years. Perindopril-Indapamid Richter should not accept children and teenagers in view of the fact that efficiency and safety perindoprit also an indapamid in this age group as separately, and in combination with other active ingredients, were not studied.

Features of use:

Use at pregnancy and feeding by a breast. Pregnancy. It is not necessary to apply during the first trimester of pregnancy. At identification of the fact of pregnancy or at its planning it is necessary to pass to an alternative way of treatment as soon as possible.

Controlled researches at people were not conducted, however, among special cases of use of APF inhibitors in the first trimester of pregnancy of data on a fetotoksichnost of drug and development of the pathologies described below it is not revealed.

Use Perindopril-Indapamid Richter in the second and third trimesters of pregnancy is contraindicated.

Prolonged use of APF inhibitors in the second and third trimesters of pregnancy affects development of the growing fruit. Toxic action in the prenatal period is expressed in depression of function of kidneys, an oligoamnios, braking of process of ossification of a skull; in the neonatal period it is shown by a renal failure, hypotension, a hyperpotassemia.

At long influence of tiazid in the third trimester of pregnancy the volume of the circulating blood at mother, as well as uteroplacental blood circulation therefore fetoplacental ischemia can develop can decrease and be slowed down fetation.

Besides, in rare instances at newborns at short-term influence the hypoglycemia and thrombocytopenia can develop.

If appointment in the second trimester and on later durations of gestation is necessary, use of drug has to be followed by ultrasonic control of a condition of renal function and a skull.

Feeding period breast. Drug use Perindopril-Indapamid Richter during feeding by a breast contraindicated.

Researches of release of drug with breast milk were not conducted, however it is known that индапамид is allocated with breast milk. Indapamid on pharmacological properties is close to thiazide diuretics which are known that they reduce and even suppress development of breast milk. Also there can be hypersensitivity to sulphonamide drugs, a hypopotassemia and a kernicterus. Manifestation of heavy side reactions at the babies who are on breastfeeding whose mothers accept any of the above-stated components therefore breastfeeding or treatment (taking into account importance degree for mother) should be stopped is possible.

Use at abnormal liver functions. At heavy abnormal liver functions treatment by this drug contraindicated.

At moderately expressed liver failure dose adjustment is not required.

Use at renal failures. At a heavy renal failure (clearance of creatinine less than 30 ml/min.) treatment by drug Perindopril-Indapamid Richter contraindicated. At a moderate renal failure (clearance of creatinine of 30-60 ml/min.) it is recommended to begin therapy with the combined drug depending on the ABP. Higher than 60 ml/min. dose adjustment is not required to patients with clearance of creatinine at regular control of concentration of creatinine and content of potassium.

Use for children. Perindopril-Indapamid Richter should not accept children and teenagers in view of the fact that efficiency and safety perindoprit also an indapamid in this age group as separately, and in combination with other active ingredients, were not studied.

Use for elderly patients. Treatment at elderly patients should be begun taking into account decrease in the ABP and function of kidneys.

The general instructions for a perindopril and an indapamid. Lithium. It is not recommended to appoint perindoprit and индапамид in combination with lithium drugs. Connected with perindoprily

Risk of development of a neutropenia/agranulocytosis in patients with an immunodeficiency. The risk of development of a neutropenia directly depends on a dose and on the accepted drug, and also a clinical condition of the patient. At patients without associated diseases the neutropenia arises seldom, the risk of its development increases at patients with a renal failure, general diseases of connecting fabric, for example, at a system lupus erythematosus, a scleroderma, and treatment by immunodepressants. This state is reversible after cancellation of APF inhibitors (including perindoprit). Strict observance of instructions on the mode of a drug dosing is the best way to avoid developed the described complication.

At the same time, appointing such patients APF inhibitor (including perindoprit), it is necessary to estimate carefully a ratio of risk and the expected advantage.

Quincke's disease (Quincke's edema). The Quincke's disease, extremities, lips, language, a throat and/or voice folds at the patients accepting APF inhibitors (including perindoprit), meets seldom. In such cases treatment perindoprily should be stopped immediately, it is necessary to watch a condition of the patient up to total disappearance of symptoms of hypostasis.

The Quincke's disease which is localized in a face and lips usually does not demand special treatment. It is possible to apply antihistamines to removal of symptoms.

In combination with throat hypostasis the Quincke's disease poses a threat for life. At a paraglossa, voice folds or a throat obstruction of respiratory tracts can develop. At emergence of such symptoms it is necessary to enter immediately subcutaneously solution of Epinephrinum (adrenaline) in cultivation 1:1000 (from 0.3 ml to 0.5 ml) in combination with other appropriate measures. Further such patients of APF inhibitors should avoid appointment.

At patients with the Quincke's edema in the anamnesis which is not connected with reception of APF inhibitors, development of a Quincke's disease at reception of APF inhibitors (including perindoprit) it is considerable more possibly.

Anaphylactoid reactions at stings of insects. In some cases desensitizations against allergens of Hymenoptera treatment (APF inhibitors was followed by hypersensitivity reactions. Similar can be avoided if it is previously temporary to interrupt reception of APF inhibitors.

Hemodialysis. The hemodialysis at which high-flowing membranes are used (polyacryle - nitrile) can lead to development of anaphylactic reactions in the patients accepting APF inhibitors (the paraglossa and lips which is followed by an asthma and decrease in the ABP). It is necessary to avoid a hemodialysis combination to use high-flowing (polyacryle - nitrile) membranes and treatment by APF inhibitors (including perindoprit).

Kaliysberegayushchy diuretic means, potassium salts. Simultaneous use of a perindopril and kaliysberegayushchy diuretics with potassium salts is not recommended.

Connected with indapamidy. At an abnormal liver function reception of thiazide diuretics can cause hepatic encephalopathy. At emergence of a similar complication reception of diuretics should be stopped immediately.

Sultoprid. It is not recommended to combine use of an indapamid and sultoprid.

The general for a perindopril and an indapamid. Renal failure. At a heavy renal failure (clearance of creatinine <30 ml/min.) drug use Perindopril-Indapamid Richter contraindicated.

At development of clinical manifestations of a renal failure or identification in the patient of these laboratory researches, testimonial of a renal failure, treatment should be stopped. Afterwards therapy can be continued or in a smaller dose, or one of drug components at regular control of concentration of creatinine and content of potassium - 2 weeks later from an initiation of treatment and further each two months. About cases of a renal failure it is reported, mainly, at patients with chronic heart failure or the basic disease leading to a renal failure including a renal artery stenosis.

At a bilateral renal artery stenosis or a stenosis of an artery of the only functioning kidney Perindopril-Indapamid Richter is not recommended to carry out treatment by drug.

Arterial hypotension and disturbance of water and electrolytic balance. At the reduced content of sodium (especially at patients with a stenosis of renal arteries), perhaps sudden development of arterial hypotension. The risk of excessive decrease in the ABP is increased at patients with a reduced volume of the circulating blood that is noted at observance of a rigid electrolyte-deficient diet, at a hemodialysis, and also at vomiting and diarrhea.

It is necessary to control systematically emergence of symptoms of decrease in OTsK and disturbance of water and electrolytic balance, to regularly determine the content of electrolytes in blood serum.

Tranzitorny arterial hypotension at the first administration of drug Perindopril-Indapamid Richter is not a contraindication for further continuation of therapy.

After recovery of OTsK and the ABP it is possible to resume therapy, applying low doses of a combination perindoprit also an indapamid, or to use drugs in monotherapy.

Maintenance of potassium ions. At a concomitant use of drug Perindopril-Indapamid Richter development of a hypopotassemia, especially at patients with a diabetes mellitus and a renal failure is possible. As well as at reception of any combined hypotensive drug containing diuretic it is regularly necessary to control the content of potassium in a blood plasma.

Lactoses monohydrate. It is necessary to consider that Perindopril-Indapamid Richter contains lactoses monohydrate. Thereof Perindopril-Indapamid Richter patients should not accept with insufficiency of lactase, a lactose intolerance, a syndrome of glyukozo/galaktozny malabsorption.

Perindopril. Cough. Against the background of therapy dry cough can arise APF inhibitor. Cough it is long remains against the background of administration of drugs of this group and disappears after their cancellation. At emergence in the patient of dry cough it is necessary to remember possible communication of this symptom with APF inhibitor reception. If the doctor considers that therapy by APF inhibitor is necessary for the patient, administration of drug can be continued (it important at differential diagnosis of cough!).

Perindopril (as well as other APF inhibitors), has less expressed hypotensive effect at patients of negroid race in comparison with representatives of other races.

Children and teenagers up to 18 years. Data on efficiency and safety were perindoprit also by an indapamida in this age group as separately, and in combination with other active ingredients, were not studied.

Risk of development of an arterial gipotepziya and/or renal failure (in cases of chronic heart failure, disturbance water элетролитного balance, etc.):

At patients with initial decrease in the ABP and existence of a renal artery stenosis, congestive heart failure or the cirrhosis which is followed by hypostases and ascites activation system renin-angiotensin-aldosteronovoy is observed. This activation is especially expressed at a hypovolemia and water and electrolytic disturbances (at observance of a rigid electrolyte-deficient diet or long treatment by diuretics).

As a result the expressed decrease in the ABP can be noted and/or raise concentration of creatinine in plasma that is the certificate of a renal failure. In rare instances the disease can proceed sharply and for a long time. Treatment should be begun with lower doses and to increase them gradually.

Patients of advanced age. Treatment should be begun after the preliminary research of content of potassium and function of kidneys. The initial dose is selected taking into account extent of decrease in the ABP, considering possible decrease in volume of the circulating blood and disturbance of water and electrolytic balance. These measures will allow to avoid sharp decrease in the ABP.

Atherosclerosis. The risk of development of arterial hypotension exists at all patients, however the special attention to themselves is required by patients with an ischemic heart disease or insufficiency of cerebral circulation. In this case treatment should be begun with lower dose.

Renovascular hypertensia. Method of treatment of renovascular hypertensia is revascularization. Nevertheless, use of APF inhibitors has favorable effect at patients as expecting an operative measure, and in that case when carrying out surgical intervention is impossible. Treatment should be begun with low doses of drug, in the conditions of a hospital at regular control of function of kidneys and contents of potassium in view of the fact that at some patients the acute renal failure can develop. This state was reversible at treatment cancellation.

Other risk groups. Patients with heavy heart failure (the IV functional class on NYHA classification) or to patients with a diabetes mellitus of the I type (danger of spontaneous increase in content of potassium) should begin treatment with a low dose of drug and under constant medical observation. Patients with arterial hypertension and chronic heart failure should not stop reception of beta adrenoblockers: APF inhibitors should be applied in combination with beta adrenoblockers.

Anemia. Anemia can develop at patients after transplantation of a kidney or at the patients who are on dialysis.

Decrease in hemoglobin of subjects is more, than its initial indicator was higher. This effect is not dozozavisimy, but can be connected with the mechanism of effect of APF inhibitors.

Insignificant decrease in hemoglobin is noted within 1-6 months then it remains stable and is completely recovered after drug withdrawal. Treatment can be continued on condition of regular control of hemoglobin of blood.

Surgical intervention / general anesthesia. APF inhibitors can cause the expressed decrease in the ABP when carrying out the general anesthesia, especially in cases when the entered anesthetic has potentially hypotensive property. It is recommended to stop reception of APF inhibitors of long action, including perindoprit, for 12 h to surgical intervention.

Aortal stenosis hypertrophic subaortic stenosis. With care it is necessary to appoint APF inhibitors at patients with obstruction of an output path of a left ventricle.

Liver failure. In rare instances reception of APF inhibitors is connected with a syndrome which begins with cholestatic jaundice, it is transformed to fulminantny necrotic hepatitis and (sometimes) leads to a lethal outcome. The mechanism of this state is not revealed. The patients accepting APF inhibitors at which jaundice or substantial increase of activity of "hepatic" enzymes comes to light should cancel reception of APF inhibitors and to undergo the corresponding medical examination.

Hyperpotassemia. At some patients accepting APF inhibitors, including perindoprit, increase in content of potassium in blood serum was noted. Patients with a renal failure, a diabetes mellitus, and also those who receive the accompanying treatment by kaliysberegayushchy diuretics, kaliysoderzhashchy additives or kaliysoderzhashchy substitutes of salt have a risk of development of a hyperpotassemia. In risk group there are also patients, (The accepting other medicines which increase the content of potassium (for example, heparin). Simultaneous use of above-mentioned drugs is allowed (in urgent cases at regular control of content of potassium in blood serum. Drug is not recommended to be used in cases of the increased content of potassium in the I blood.

Indapamid. Hyponatremia. Prior to the beginning of and during treatment it is necessary to control the content of sodium in a blood plasma, further such researches have to be conducted regularly. Reception of any diuretic drugs can lead to decrease in content of sodium in a blood plasma, in some cases asymptomatic that, in turn, promotes development of a number of serious complications. Most often the hyponatremia arises at the patients entering into risk group, for example, of patients of advanced age or patients with cirrhosis.

Content of potassium. At treatment by thiazide and tiazidopodobny diuretics it is necessary to consider a possibility of development of a hypopotassemia. It is not necessary to allow decrease in content of potassium lower than 3.4 mmol/l at the elderly and/or weakened people, regardless of use of several drugs by them, patients with the cirrhosis which is followed by hypostases and ascites, patients with an ischemic heart disease or heart failure. This category of patients concerns to group of the increased risk.

Decrease in content of potassium increases risk of development of disturbances of a cordial rhythm. Patients with the extended QT interval on an ECG treat group of high risk. The hypopotassemia, as well as bradycardia, promotes development of heavy disturbances of a cordial rhythm, up to arrhythmia like "pirouette" which can lead to a lethal outcome. Regular control of content of potassium in a blood plasma is anyway necessary: the first research is conducted a week later after an initiation of treatment. At the revealed decrease in content of potassium in a blood plasma drug dose adjustment is required.

Content of calcium. Reception of thiazide and tiazidopodobny diuretics can reduce calcium excretion kidneys that leads to the temporary and moderately expressed increase in content of calcium in a blood plasma. In case of not diagnosed hyperparathyreosis increase in content of calcium in a blood plasma can be considerable. In this case treatment has to be stopped before the end of a research of function of epithelial bodies.

Concentration of glucose in blood. Control of this indicator is important for patients with a diabetes mellitus, especially against the background of a hypopotassemia.

Uric acid. At patients with high concentration of uric acid in a blood plasma the probability of development of an attack of gout or an aggravation of its latent form increases.

Function of kidneys and diuretics. Fully efficiency of thiazide and tiazidopodobny diuretics is shown only on condition of normal function of kidneys. They are also effective at creatinine level lower than 25 mg/l, i.e. adults have 220 m of mol/l.

When calculating the clearance of creatinine (CC) in a blood plasma at elderly people on Kokroft's formula the age, weight and a sex of the patient is taken into account:

KK = (140 - age) x body weight / 0.814 x concentration of creatinine in a blood plasma, where: the age is expressed advanced in years, body weight - in kilograms, concentration of creatinine in plasma - in mmol/l.

This formula is suitable for patients of male advanced age. When calculating an indicator for women the correction factor 0.85 is used.

In an initiation of treatment owing to a hypovolemia because of loss of water and sodium reduction in the rate of glomerular filtering is noted. As a result of it can raise concentration of urea and creatinine in blood serum.

Such temporary functional renal failure does not influence function of kidneys at patients with normal function of kidneys, but, nevertheless, can strengthen the existing renal failure.

Athletes. Indapamid can give positive reaction when carrying out a drug test.

Influence on ability to control of vehicles and work with the equipment. индапамид, perindoprit, both in monotherapy, and in a combination with each other, does not exert negative impact on speed of response. Nevertheless, some patients can have episodes of arterial hypotension that can have an adverse effect on ability to manage the mechanisms demanding the high speed of physical and mental reactions (especially at the beginning of a course of treatment or in combination with other hypotensive drugs).

Side effects:

The side effects which are listed below are presented on system and organ classes according to classification of MedDRA and with the following frequency: frequent (from ≥1/100 to <1/10); rare (from ≥1/10000 to <1/1000); very rare (<1/10000)

From cardiovascular system: rare - excessive decrease in the ABP, orthostatic hypotension.

From a nervous system: rare - paresthesias, a headache, weakness, dizziness, sleep disorders, lability of mood.

From respiratory system, bodies of a chest tag and a mediastinum: frequent - dry persistent cough which disappears at cancellation of APF inhibitors.

From the alimentary system: frequent - a lock, dryness in a mouth, nausea, an abdominal pain, anorexia, disturbance of flavoring feelings; very rare - pancreatitis. At patients with a liver failure development of hepatic encephalopathy is possible.

From skin and hypodermic cellulose: rare - at the patients predisposed to allergic reactions hypersensitivity manifestation, mainly in the form of dermatological reactions is possible: skin rash, makulopapulezny rashes, purpura, aggravation of a current of a system lupus erythematosus; very rare - a Quincke's disease (Quincke's edema).

From a musculoskeletal system and connecting fabric: rare - spasms.

Laboratory indicators: as a result of reception of a perindopril the hypopotassemia (content of potassium in a blood plasma less than 3.4 mmol/l), especially at patients with a diabetes mellitus or a renal failure can develop in combinations with indapamidy. Decrease in content of sodium in a blood plasma and a hypovolemia owing to dehydration and orthostatic hypotension is possible; increase in concentration of uric acid and glucose in blood; insignificant increase in concentration of creatinine in urine and in a blood plasma, reversible after drug withdrawal, is the most probable at a stenosis of renal arteries, treatment of arterial hypertension diuretics, a renal failure; increase in content of potassium (usually temporary); rare - the increased content of calcium in a blood plasma; very rare - thrombocytopenia, a leukopenia, an agranulocytosis, aplastic anemia, hemolitic anemia, at some patients (after transplantation of a kidney, at the patients who are on a hemodialysis) against the background of reception of APF inhibitors can develop anemia.

Interaction with other medicines:

The combinations which are not recommended for use:

Perindopril-Indapamid Richter.

Lithium drugs. At a concomitant use of drugs of lithium and APF inhibitors increase the content of lithium in blood serum and its toxicity. In combination with thiazide diuretics toxic effect of lithium even more amplifies and its concentration in serum increases. This combination is not recommended. If the combined therapy including APF inhibitors and drugs of lithium cannot be cancelled, it is necessary to control carefully concentration of lithium and if necessary to adjust a drug dose.

Perindopril. Kaliysberegayushchy diuretics (Spironolactonum, Triamterenum both in monotherapy, and in a combination) or potassium drugs

APF inhibitors reduce potassium removal by kidneys. Kaliysberegayushchy diuretics, for example, спироиолактон, Triamterenum or amiloride, and also the nutritional supplements and substitutes of salt containing potassium can increase considerably the content of potassium in blood serum (potentially lethal phenomenon - risk of development of a hyperpotassemia). At simultaneous use of the specified means for patients with a hypopotassemia, treatment has to be followed by constant control of content of potassium in a blood plasma and parameters of the electrocardiogram (ECG).

Indapamid. Sultoprid. At simultaneous use of a sultoprid and indapamid development of ventricular arrhythmia, especially the pirouette type, owing to a hypopotassemia is possible.

The combinations requiring extra care and attention:

Perindopril-Indapamid Richter

Baclofenum. Strengthening of hypotensive action. Control of the ABP and function of kidneys is required; if necessary it is necessary to carry out dose adjustment of hypotensive drug.

Non-steroidal anti-inflammatory drugs (NPVP) (including high doses of acetylsalicylic acid). Simultaneous use of drug with NPVP promotes a delay of liquid and sodium in an organism and to decrease in hypotensive effect of drug at some patients. At patients of advanced age or at patients with the expressed dehydration development of an acute renal failure is possible (owing to decrease in glomerular filtering). Patients need to offset loss of liquid and from the very beginning of treatment it is recommended to control function of kidneys.

Hypoglycemic means (insulin, sulphonylurea derivatives). At simultaneous use with APF inhibitors hypoglycemic effect of insulin or derivatives of sulphonylurea at patients a diabetes mellitus can amplify.

Development of a hypoglycemia is observed very seldom (increase in tolerance to glucose that leads to decrease in need for insulin).

Indapamid. The drugs provoking development of ventricular arrhythmia like "pirouette". In view of a possible hypopotassemia индапамид it is necessary to apply with care in combination with drugs which provoke ventricular arrhythmia like "pirouette". Treat them: antiarrhytmic drugs of the class IA (quinidine, Disopyramidum); class III (Amiodaronum, дофетилид, ибутилид, bretylium tosylate), соталол; some neuroleptics (Chlorpromazinum, циамемазин, levomepromazinum, thioridazine, трифлуоперазин); benzamides (амисульприд, сульприд, тиаприд); phenyl propyl ketone derivatives (Droperidolum, haloperidol), other neuroleptics (Pimozidum); other drugs (bepridit, цизаприд, difemantit, erythromycin for in/in introductions, галофантрин, мизоластин, moxifloxacin, певтамидин, спарфлоксацин, Vincaminum for in/in introductions, methadone, астемизол, терфенадин). At the same time control of an interval of QT and content of potassium is necessary. In case of need it is necessary to carry out correction of a condition of the patient.

The drugs reducing the content of potassium. Amphotericinum of B (in/in), system glyuko-and mineralokortikosteroida, тетракозактид, the purgatives stimulating motility of intestines: development of a hypopotassemia (the additive effect) is possible. Control and necessary correction of content of potassium is required. The special attention is required by therapy together with cardiac glycosides. It is not necessary to appoint drug together with the purgatives stimulating motility of intestines.

Cardiac glycosides. Against the background of decrease in content of potassium toxic effect of cardiac glycosides amplifies. Therapy is carried out under control of content of potassium and an ECG. If necessary it is necessary to adjust the carried-out therapy.

Imipraminopodobny (tricyclic) antidepressants, neuroleptics. Strengthening of hypotensive action, increase in risk of development of orthostatic hypotension (additive effect).

Glucocorticosteroids, тетракозактид. Decrease in hypotensive action (the delay of water and electrolytes caused by glucocorticosteroids).

Other hypotensive drugs. At simultaneous use of drug Perindopril-Indapamid Richter with others (more expressed decrease in the ABP happens hypotensive drugs.

Allopyrinolum, cytostatic or immunosuppressive drugs, glucocorticosteroids or procaineamide

At simultaneous use with APF inhibitors development of a leukopenia is possible.

Means for the general anesthesia. APF inhibitors strengthen anti-hypertensive action of some means for the general anesthesia.

Diuretics (thiazide or "loopback"). At reception of high doses of diuretics before an initiation of treatment perindoprily decrease in OTsK and development of a hypovolemia and arterial hypotension is possible.

Metforminum. The aggravation of lactic acidosis against the background of a renal failure connected with reception of diuretic means, especially "loopback" diuretics. Metforminum it is not necessary to appoint at creatinine level in a blood plasma higher than 15 mg/l (135 mmol/l) at men and women have 12 mg/l (110 mmol/l).

X-ray contrast substances. In cases of decrease in OTsK caused by reception of diuretics development of an acute renal failure is possible, especially at use of high doses of iodinated X-ray contrast substance. Before use of iodinated X-ray contrast substances it is necessary to compensate the volume of the circulating blood.

Calcium drugs. Risk of development of a hypercalcemia, owing to decrease in its removal by kidneys.

Cyclosporine. There is a risk of development of a giperkreatininemiya without change of concentration of cyclosporine in blood even if the raised excretion of water and electrolytes is not noted.

Contraindications:

— hypersensitivity to a perindopril or other APF inhibitors, an indapamid and other derivatives of sulfonamide, other components of drug;

— a Quincke's disease (Quincke's edema) in the anamnesis against the background of reception of APF inhibitors;

— hereditary/idiopathic Quincke's disease;

— pregnancy;

— heavy renal failure (clearance of creatinine less than 30 ml/min.);

— hepatic encephalopathy;

— heavy liver failure;

— hypopotassemia;

— simultaneous use with antiarrhytmic drugs with risk of development of arrhythmia like "pirouette";

— feeding period breast;

— drug contains lactose. Perindopril-Indapamid Richter patients should not accept with insufficiency of lactase, a lactose intolerance, a galactosemia or a syndrome of glyukozo/galaktozny malabsorption;

In a type of insufficiency of therapeutic experience, Perindopril-Indapamid Richter it is not necessary to appoint drug:

— to the patients who are on dialysis;

— to patients with chronic heart failure of the IV functional class on classification of NYHA in a decompensation stage.

With care: Aortal stenosis / a hypertrophic subaortic stenosis (GOKMP), a bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney, a state after transplantation of kidneys, a renal failure (clearance of creatinine more than 30 ml/min.), primary hyper aldosteronism, arterial hypotension, renovascular hypertensia, a marrow hypoplasia, a hyponatremia (the increased risk of development of arterial hypotension in the patients who are on a low-salt or electrolyte-deficient diet), hypovolemic states (including diarrhea, vomiting), general diseases of connecting fabric (including, a system lupus erythematosus, a scleroderma), a diabetes mellitus, gout, oppression of a marrowy hemopoiesis, a hyperuricemia, a hyperpotassemia, coronary heart disease, cerebrovascular diseases (including insufficiency of cerebral circulation), heavy chronic heart failure (the III functional class on NYHA classification), liver failure, advanced age.

Overdose:

Symptoms: the expressed decrease in the ABP, nausea, vomiting, spasms, dizziness, sleeplessness, an oliguria (owing to a hypovolemia can pass into an anury), electrolytic disturbances.

Treatment: gastric lavage, reception of absorbent carbon. In case of the expressed decrease in the ABP the patient should give horizontal position with the raised legs. Correction of water and electrolytic balance. If necessary are carried out to injections of isotonic solution or other methods of replacement therapy are applied.

Treatment is carried out in a hospital to an absolute recovery.

Perindoprilat can be removed from an organism by means of dialysis.

Storage conditions:

To store drug in unavailable to children, in the dry and protected from light place at a temperature not above 30 °C. A period of validity - 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

On 10, 30, 60 or 90 pieces of tablets in blister strip packagings and cardboard packs.