Perineva Ku-tab - instructions for use, doses, side effects, contraindications

cellulose microcrystalline 10.00 mg, sodium hydrogen carbonate 0.38 mg, mannitol 9.42 mg, aspartame (E 951) 0.75 mg, thaumatin 10% (E 957) 0.05 mg, peppermint flavor²0.80 mg, mint flavor 0.80 mg, crospovidone 5.00 mg, sodium stearyl fumarate 0.80 mg

per 1 tablet of 8 mg

Active substance:

Perindopril erbumin ODT substance-granules 104.00 mg [Active substance of substance-granules:

Perindopril erbumine 8.00 mg Auxiliary substances of granule substance: calcium chloride hexahydrate 2.40 mg¹, hypromellose 6cP 1.60 mg, microcrystalline cellulose 24.00 mg, crospovidone 8.00 mg, mannitol 61.18 mg]

Excipients:

cellulose microcrystalline 20.00 mg, sodium hydrogen carbonate 0.76 mg, mannitol 18.84 mg, aspartame (E 951) 1.5 mg, thaumatin 10% (E 957) 0.10 mg, peppermint flavor²1.60 mg, mint flavor 1.60 mg, crospovidone 10.00 mg, sodium stearyl fumarate 1.60 mg

¹Calcium chloride hexahydrate is taken with an excess, because it partially dissolves in water when preparing the substance - granules and evaporates together with water when drying the granulate. To calculate the theoretical mass of the tablet, the amount of calcium chloride hexahydrate used is 0.61 mg - for tablets 4 mg, 1.22 mg - for tablets 8 mg.

²The flavor of peppermint contains: maltodextrin 78%, acacia gum 9%, sorbitol 3.5%, mint field oil 3.5%, levomentol 0.9%, water q.s. up to 100%.

Description:Round, slightly biconvex tablets white or almost white with a bevel.

Pharmacotherapeutic group:angiotensin-converting enzyme (ACE) inhibitor

ATX: & nbsp

Perindopril

Pharmacodynamics:

Perindopril is an inhibitor of angiotensin-converting enzyme (ACE). It converts angiotensin I into a vasoconstrictor angiotensin II. ACE (kininase II) is an exopeptidase that catalyzes the formation of angiotensin II, which has vasoconstrictive properties, from angiotensin I, and also causes the destruction of the bradykinin vasodilator to an inactive heptapeptide.Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which causes an increase in renin activity of blood plasma (by the mechanism of "negative feedback") and a decrease in the secretion of aldosterone. ACE also inactivates bradykinin, so inhibition of the enzyme leads to an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the system of prostaglandins is activated. It can not be ruled out that this effect is part of the mechanism of antihypertensive action of ACE inhibitors and may be the cause of some side effects of this class of drugs (eg, cough). The action of perindopril is mediated by the active metabolite - perindoprilat. Other metabolites did not have ACE inhibitory activity in vitro.

Arterial hypertension

Perindopril is effective in the treatment of arterial hypertension of any severity. Against the background of the use of perindopril, both systolic and diastolic arterial pressure (BP) decrease in the "lying" and "standing" positions. Perindopril reduces overall peripheral vascular resistance (OPSS), which leads to a decrease in blood pressure, while peripheral blood flow accelerates without changing the heart rate (heart rate).

Kidney blood flow, as a rule, increases, and the glomerular filtration rate (GFR) does not change at the same time.

The antihypertensive effect of perindopril reaches a maximum after 4-6 hours after a single oral intake and lasts for at least 24 hours. At the end of the dosing interval (after 24 hours after ingestion), a residual (about 80%) residual ACE inhibition is observed.

Decrease in blood pressure is achieved quickly enough. In patients with a positive response to treatment, blood pressure normalizes within a month. With continued therapy, the antihypertensive effect persists, and there are no signs of tachyphylaxis (a decrease in the therapeutic effect with repeated use).

Termination of therapy is not accompanied by the development of the "withdrawal" syndrome.

Perindopril reduces left ventricular hypertrophy, has a vasodilating effect, helps restore the elasticity of large arteries and reduces the thickness ratio wewthe diameter of the lumen of small arteries. Perindopril and thiazide diuretics have an additive effect. The simultaneous use of an ACE inhibitor and a thiazide diuretic reduces the risk of hypokalemia in the face of diuretics.

Stable ischemic heart disease (CHD)

Against the background of perindopril 8 mg / day in patients with stable CAD, no signs of heart failure, there is a significant reduction in the absolute risk of complications, provided the main criterion of efficacy (primary endpoint: the death rate from cardiovascular disease, the incidence of nonfatal myocardial infarction and / or cardiac arrest followed by a successful resuscitation) by 1.9%. In patients who had previous myocardial infarction and / or coronary revascularization, the absolute risk reduction was 2.2% compared with placebo.

Pharmacokinetics:

Preparation Perineva Ku tab (dispersible tablet in the mouth) can be used as alternatives to tablets for oral administration.

Suction

After oral administration perindopril quickly absorbed in the gastrointestinal tract, the maximum concentration in the blood plasma (C_max) is achieved after 1 hour. The half-life (T1 / 2) of perindopril from the blood plasma is 1 hour.

Perindopril is a prodrug, does not have pharmacological activity.

27% of the total absorbed perindopril enters the blood stream as an active metabolite - perindoprilat.In addition to perindoprilata, with biotransformation of perindopril, 5 more inactive metabolites are formed. FROM_max Perindoprilata is achieved 3-4 hours after ingestion.

Eating slows the conversion of perindopril to perindoprilat, thus affecting bioavailability. Perindopril should be taken once a day, in the morning, before eating.

Pharmacokinetics is linear in the therapeutic range of doses.

Distribution

The volume of distribution of free perindoprilata is approximately 0.2 l / kg. The association of perindoprilata with plasma proteins is insignificant, is 20%, mainly with ACE; is dose-dependent.

Excretion

Perindoprilat is excreted by the kidneys. The free fraction is 3-5 h, the "effective" T1/2 is approximately 17 hours, and the equilibrium state in the blood plasma is reached within 4 days.

Pharmacokinetics of special groups of patients

Elderly patients

The excretion of perindoprilat is slowed in elderly patients and patients with cardiac or renal insufficiency.

Renal insufficiency

In patients with renal insufficiency, the dose is selected taking into account the degree of impaired renal function (creatinine clearance (CK)).

The dialytic clearance of perindoprilat is 70 ml / min.

Liver failure

In patients with cirrhosis, the liver clearance of perindopril is halved. However, the amount of perindoprilate formed does not decrease, therefore no correction of the dose of the drug is required (see the sections "Dosing and Administration" and "Special instructions").

Indications:

- Arterial hypertension;

- Ischemic heart disease (CHD): reduced risk of cardiovascular complications in patients who had previous myocardial infarction and / or coronary revascularization;

- Chronic heart failure;

- Prevention of recurrent stroke (in combination with indapamide) in patients who underwent a stroke or transient cerebral circulation disorder by ischemic type.

Contraindications:

- Hypersensitivity to perindopril, to other ACE inhibitors and other components of the drug;

- Angioedema in history, associated with the taking of an ACE inhibitor;

- Hereditary / idiopathic angioedema;

- Renal failure (CC less than 60 ml / min) (for this dosage);

- Age under 18 years (effectiveness and safety not established);

- Pregnancy and the period of breastfeeding;

- Congenital intolerance to fructose, tk.preparation Perineva Ku-tab contains sorbitol;

- Simultaneous use of drugs containing aliskiren, in patients with renal insufficiency (CC less than 60 ml / min) and patients with diabetes mellitus.

Carefully:

bilateral stenosis of the renal arteries or the presence of a single functioning kidney (the risk of developing severe arterial hypotension and renal failure), systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma and others), immunosuppressive therapy, allopurinol, procainamide hydrochloride (risk of developing neutropenia , agranulocytosis), decreased circulating blood volume (bcc) (diuretics, diet with restriction of table salt, vomiting, diarrhea), angina pectoris, cerebrovascular disease sciatic diseases, renovascular hypertension, diabetes mellitus, chronic heart failure IV functional class by classification NYHA, application of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for edible salt, lithium preparations, hyperkalemia, surgical intervention / general anesthesia,hemodialysis using highly flowing membranes, desensitizing therapy, low-density lipoprotein (LDL) apheresis with dextran sulphate, the condition after kidney transplantation, aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy (GOKMP), the use of negroid race in patients, phenylketonuria, simultaneous use with drugs containing aliskiren (with a double blockade of RAAS, there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and impaired renal function).

Pregnancy and lactation:

In pregnancy, the use of Perineva® Ku-tab® is contraindicated. When planning pregnancy, the preparation Perineva® Ku-tab® or when it is confirmed, it is necessary to cancel the drug as early as possible and prescribe another antihypertensive therapy with a known safety profile for pregnancy.

The preparation Perineva® Ku-tab® is contraindicated in the II-III trimesters of pregnancy, since the use of the drug during this period can cause fetotoxic effects (decreased kidney function, hypochlorism, oligohydramnion, deceleration of ossification of the fetal bones) and neonatal toxic effects (renal failure, arterial hypotension , hyperkalemia).If the drug was used in the II - III trimesters of pregnancy, then it is necessary to perform ultrasound examination of the kidneys and bones of the fetal skull. It is necessary to observe newborns whose mothers have taken perindopril during pregnancy, to exclude arterial hypotension.

The use of Perineva® Cou-Tab® during breast-feeding is not recommended, due to the lack of data on the possibility of excretion of perindopril in breast milk. If you need to use the drug during this period, breastfeeding should be discontinued.

Dosing and Administration:

Inside, once a day, preferably in the morning, before eating.

The tablet should be put on the tongue and kept in the mouth until completely dissolved (to facilitate swallowing). The tablet after resorption can be washed down with liquid. Tablets are dispersible in the mouth - brittle. Therefore, the tablet should be taken immediately after opening the blister.

Perineva® Cu-tab®, tablets dispersible in the oral cavity, can be used as an alternative to Perineva®, tablets in patients who have difficulty swallowing the tablet.

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

To ensure the following dosing regimen, in particular, to ensure the initial doses of the drug, it is possible to use perindopril erbumine in tablets at a dose of 2 mg.

Arterial hypertension

The drug Perineva® Ku-tab® can be used in monotherapy or as part of a combination therapy.

The recommended initial dose is 4 mg once a day, in the morning.

For patients with severe activation of RAAS (eg, with renovascular hypertension, hypovolemia and / or hyponatremia, CHF in the stage of decompensation or severe degree of arterial hypertension) the initial dose is recommended to be 2 mg once daily.

If necessary, a month after the start of therapy and with good tolerability of the previous dose, the dose can be increased to 8 mg once a day.

The addition of ACE inhibitors to patients taking diuretics can cause symptomatic arterial hypotension. In this regard, it is recommended to conduct therapy with caution,to abolish diuretics 2-3 days before the start of treatment with Perineva® Cu-tab® or start treatment with an initial dose of 2 mg per day in one session. Control is required: blood pressure, kidney function and potassium content in the blood serum. In the future, the dose of the drug may be increased, depending on the dynamics of blood pressure. If necessary, diuretic therapy can be resumed.

Have elderly patients the recommended initial dose is 2 mg once a day. In the future, the dose can be gradually increased to 4 mg and, if necessary, to a maximum of 8 mg once a day, provided that the dose is well tolerated.

Chronic heart failure (CHF)

The recommended initial dose is 2 mg in the morning, under the supervision of the attending physician. After 2 weeks, the dose can be increased to 4 mg per day once a day, under the control of blood pressure. Treatment of CHF with clinical manifestations is usually combined with potassium-sparing diuretics, beta-adrenoblockers and / or digoxin.

After two weeks of therapy, the dose of the drug can be increased to 4 mg once a day, provided that the lower dose is well tolerated and the "response" to the therapy is satisfactory.In patients with a high risk of developing symptomatic arterial hypotension, for example, with a reduced electrolyte content with or without hyponatremia, hypovolemia, or taking diuretics, the listed conditions should be adjusted, if possible, before starting the Perineva® Cu-tab® preparation. Such indicators as: blood pressure, kidney function and potassium content in blood plasma should be monitored both before and during the therapy.

Prevention of recurrent stroke (in combination with indapamide) in patients with cerebrovascular disease in history

The recommended initial dose is 2 mg 1 time per day (morning) for the first 2 weeks, then you should increase the dose to 4 mg for the next 2 weeks before taking indapamide.

Treatment should be started at any time (from 2 weeks to several years) after a stroke.

Coronary heart disease (CHD): reduced risk of developing cardiovascular complications in patients who had previous myocardial infarction and / or coronary revascularization

In patients with stable course of IHD, the recommended initial dose of Perineva® Cu-Tab® is 4 mg once a day.After 2 weeks, the dose is increased to 8 mg per day, provided that the dose is well tolerated at 4 mg per day and that the kidney function is monitored.

Treatment elderly patients should start with a dose of 2 mg once a day for one week, which in a week can be increased to 4 mg per day for the next week. In the future, if necessary, after a week, you can increase the dose to 8 mg per day with mandatory pre-control of kidney function. In elderly patients, the dose of the drug can be increased only if the previous, lower dose is well tolerated.

Patients with impaired renal function

In patients with kidney disease, the dose of Perineva® Cu-tab® is determined depending on the degree of renal dysfunction. Patient monitoring usually involves regular determination of serum potassium and serum creatinine.

Side effects:

Recommended doses:

Creatinine clearance (CC)	Recommended dose
from 60 ml / min. and higher	4 mg per day
from 30 to 60 ml / min.	2 mg per day
from 15 to 30 ml / min.	2 mg every other day
Patients on hemodialysis * (CC less than 15 ml / min.)	2 mg per day of dialysis

* - Dialyz clearance of perindoprilata is 70 ml / min. Perineva® Coupl® should be taken after a dialysis session.

Patients with impaired hepatic function

Correction of the dose in patients with impaired liver function is not required.

It is necessary to take the drug according to the recommendations of your doctor. If you have any questions about the drug, consult your doctor.

Classification of the frequency of development of side effects of the World Organization Health (WHO):

Often >=1/10

often from> = 1/100 to <1/10

infrequently from> = 1/1000 before <1/100

rarely from> = 1/1000 to <1/1000

rarely <1/10000

frequency unknown - can not be estimated on the basis of available data

Table №1. Side effects

	Often	Infrequently	Rarely	Frequency unknown
From the side			decline	eosinophilia
bodies			hemoglobin and
hematopoiesis			hematocrit,

			thrombocytopenia, leukopenia / neutransis anatomy, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital deficit glucose-6- phosphate dehydrogen the basics
From the side exchange of substances:				hypoglycaemia, hyperkalemia, reversible after discontinuation of the drug, hyponatremia
From the side nervous systems	headache, dizziness, vertigo, paresthesia	violations sleep, emotional lability	confusion consciousnesses	drowsiness, fainting
From the sense organs	visual impairment, tinnitus
From the side of the cardiovascular system	excessive decrease in blood pressure, including orthostatic hypotension		heart rhythm disturbances, angina pectoris, myocardial infarction and stroke, due to excessive blood pressure lowering in patients from	vasculitis, tachycardia, sensation palpitation

			high-risk groups
From the side respiratory system:	cough, dyspnea	bronchospasm	eosinophilic pneumonia, rhinitis
From the digestive system:	nausea, vomiting, abdominal pain, taste disorder, indigestion, diarrhea, constipation	dryness of the oral mucosa	pancreatitis, angioedema of the intestine
From the liver and biliary tract:			hepatitis (cholestatic or cytolytic)
From the side dermal integument:	skin rash, itchy skin	angioedema edema face, lips, limbs, mucous shells, language, voice folds and / or larynx, hives	multiform erythema	photosensitivity, eczema
From the musculoskeletal system:	muscle spasms			arthralgia, myalgia
From the side urogenital system:		renal inadequate the	acute renal failure
From the side		impotence

reproductive system:

Other:

asthenia

increased

sweating

pain in the chest,

peripherally

edema

lower

limbs,

weakness,

hyperthermia,

falls

Laboratory indicators:

rarely: increased activity of "hepatic" transaminases and bilirubin concentration in serum;

frequency unknown: increased serum urea and creatinine levels reversible after discontinuation of Perineva® Cu-tab®, especially in patients with renal insufficiency, severe heart failure, and renovascular hypertension.

Adverse reactions noted in clinical trials

In comparison with the group receiving placebo (0.2%), the following serious adverse events were noted in patients in the perindopril group (0.3%): arterial

hypotension (6 cases), angioedema (3 cases) and sudden cardiac arrest (1 case). The frequency of withdrawal of perindopril due to the development of cough, marked decrease in blood pressure or other undesirable reactions was higher in the group receiving perindopril, in comparison with the group receiving placebo: 6.0% and 2.1 %, respectively.

With simultaneous use of ACE inhibitors and intravenous administration of gold preparations (sodium aurotomy malate) describes a symptom complex, which includes: flushing of the facial skin, nausea, vomiting and arterial hypotension.

Overdose:

Data on perindopril overdose are limited.

Symptoms: marked decrease in blood pressure, shock, disturbance of water-electrolyte balance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough.

Treatment: gastric lavage and / or reception of activated charcoal, followed by restoration of the water-electrolyte balance. At a pronounced decrease in blood pressure, the patient should be transferred to the "lying" position on the back with elevated legs and take measures to complete the BCC with the intravenous injection of 0.9% sodium chloride solution and / or catecholamine solution. Perindoprilat, the active metabolite of perindopril, can be removed from the body by hemodialysis. With the development of severe bradycardia, not amenable to drug therapy (incl.atropine), the installation of an artificial pacemaker is shown. It is necessary to monitor the vital functions of the body and the concentration of creatinine and electrolytes in the blood serum.

Interaction:

Diuretics

In patients taking diuretics, especially with excessive excretion of fluid and / or sodium ions, at the beginning of therapy with ACE inhibitors, an excessive decrease in blood pressure may develop, the risk of which can be reduced by eliminating the diuretic, replenishing fluid loss (by intravenous administration of a 0.9% solution sodium chloride), as well as the use of perindopril in lower doses. A further increase in the dose of perindopril should be carried out with caution.

Potassium-sparing diuretics, potassium preparations, potassium-containing foods and potassium-containing substitutes for edible salt

Usually, with the ACE inhibitor therapy, the serum potassium content remains within normal limits, but some patients may develop hyperkalemia. Simultaneous use of ACE inhibitors and potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), preparations of potassium or potassium-containing products and potassium-containing substitutes for edible salt can cause a significant increase in serum potassium content. Therefore, it is not recommended to combine perindopril with the above preparations. Assign these combinations only in the case of hypokalemia, observing the precautions and regularly monitoring the potassium content in the blood serum and the ECG.

Lithium preparations

With simultaneous use of lithium drugs and ACE inhibitors, it is possible to develop a reversible increase in serum lithium concentration and the associated toxic effects. The simultaneous use of ACE inhibitors with thiazide diuretics can further increase serum lithium concentrations and increase the risk of its toxic effects.

If it is necessary to combine therapy, regular monitoring of the concentration of lithium in serum is recommended.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including Acetylsalicylic acid in doses exceeding 3 g / day

Therapy of NSAIDs may reduce the antihypertensive effect of ACE inhibitors.With the simultaneous use of ACE inhibitors and NSAIDs, the risk of impaired renal function is increasing, incl. In rare cases, the development of acute renal failure, as well as an increase in potassium in the blood serum, especially in patients with an existing renal dysfunction. To patients of advanced age to prescribe Perineva® KU-tab® should be used with caution. It is necessary to compensate for the loss of fluid and periodically monitor the kidney function at the beginning of the combination therapy and during treatment.

Other antihypertensives and vasodilators

Simultaneous use of perindopril with other antihypertensive drugs, nitrates of short or prolonged action or vasodilators can enhance the antihypertensive effect of perindopril.

Hypoglycemic agents

Simultaneous use of ACE inhibitors and hypoglycemic agents (insulin or hypoglycemic agents for oral administration) can increase the hypoglycemic effect, up to the development of hypoglycemia. As a rule, this phenomenon occurs in the first weeks of combined therapy in patients with impaired renal function.

Acetylsalicylic acid, thrombolytic agents, beta-blockers and nitrates

Perindopril can be combined with acetylsalicylic acid (as an antiplatelet agent), thrombolytic agents and beta-blockers and / or nitrates.

Tricyclic antidepressants / antipsychotic facilities (antipsychotics) / general anesthetic agents (general anesthetics)

Simultaneous use with ACE inhibitors can lead to an increased antihypertensive effect.

Sympathomimetics

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. Preparations of gold

Preparations containing aliskiren

Simultaneous use of perindopril and preparations containing aliskiren, in patients with diabetes mellitus or renal insufficiency with a CK of less than 60 ml / min is contraindicated.

Special instructions:

IHD: a reduction in the risk of developing cardiovascular complications in patients who have had previous myocardial infarction and / or coronary revascularization

With the development of unstable angina (expressed or not) during the first month of therapy with Perineva® Cu-tab®, the benefits and risks should be assessed before continuing therapy.

ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated arterial hypertension a symptomatic decrease in blood pressure rarely occurs after taking the first dose. The risk of excessive reduction in blood pressure is increased in patients with reduced bcc in the background of diuretic therapy, with strict diet with restriction of table salt, hemodialysis, as well as with diarrhea or vomiting, or in patients with severe hypertension with high renin activity. A marked decrease in blood pressure was observed in patients with CHF IV of the functional class according to the classification NYHA, both in the presence of concomitant renal failure, and in its absence. The most common arterial hypotension can develop in patients with CHF IV functional class by classification NYHA, taking "loop" diuretics in high doses, as well as against hyponatremia or renal insufficiency. We recommend careful medical supervision (control of blood pressure, kidney function and potassium content in blood serum) when titrating the doses of the drug.This approach is also used in patients with ischemic heart disease or cerebrovascular disease, in whom excessive reduction of blood pressure can lead to myocardial infarction or stroke.

With a pronounced decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs and to carry out measures for replenishment of bcc with the intravenous injection of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for further therapy. After the recovery of bcc and blood pressure, treatment can be continued provided that the dose of the drug is carefully selected.

In some patients with CHF and normal or reduced BP during therapy with Perineva® Cu-tab®, an additional reduction in blood pressure is possible. This effect is expected and usually is not a basis for drug discontinuation. If arterial hypotension is accompanied by clinical manifestations, a dose reduction or abolition of Perineva® Cu-tab® may be required.

Stenosis of the aortic and / or mitral valve / hypertrophic obstructive cardiomyopathy (GOKMP)

ACE inhibitors, incl. and perindopril, should be used with caution in patients with stenosis of the mitral valve and obstruction of the outflow tract of the left ventricle (aortic valve stenosis and GOKMP).

Impaired renal function

In patients with renal insufficiency (CC less than 60 ml / min), the initial dose of the drug should be selected according to the QC (see the section "Dosing and Administration") and then, depending on the therapeutic response. For such patients, regular monitoring of serum potassium and serum creatinine is necessary.

In patients with symptomatic heart failure, arterial hypotension, which develops during the initial period of therapy with ACE inhibitors, can lead to impaired renal function. Possible development of acute renal failure, usually reversible.

In some patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney (especially in the presence of renal failure) against the background of therapy with ACE inhibitors, there was an increase in serum concentrations of urea and creatinine, reversible after the abolition of therapy. In patients with renovascular hypertension, with the therapy of ACE inhibitors, there is an increased risk of a marked decrease in blood pressure and renal insufficiency.Treatment of such patients should begin under careful medical supervision, with small doses of perindopril and with further adequate dose selection. As an initial therapy, the preparation Perineva® Ku-tab® should not be used in such patients (for these dosages). During the first weeks of therapy, it is necessary to cancel diuretics and regularly monitor kidney function.

In some patients with arterial hypertension, in the presence of previously unidentified renal failure, especially with concomitant diuretic therapy, there was a slight and temporary increase in the concentration of urea and creatinine in the serum. In this case, it is recommended to reduce the dose of Perineva® Cu-tab® and / or to cancel the diuretic.

Hemodialysis

In patients on dialysis using high-flow membranes (for example, AN 69®), and concurrently taking ACE inhibitors, several cases of persistent, life-threatening anaphylactic reactions were noted. If you need hemodialysis, you need to use a different type of membrane.

Kidney Transplantation

Experience with perindopril in patients after a recent transplantation of the kidney is absent.

Increased sensitivity / angioedema

Rarely in patients taking ACE inhibitors, incl. perindopril, it is possible to develop an angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and / or larynx. With the development of angioneurotic edema treatment should be immediately stopped, the patient should be under medical supervision until the symptoms disappear completely. Angioedema of the lips and face usually does not require treatment and passes by itself; To reduce the severity of symptoms, you can use antihistamines.

Angioedema, swelling of the tongue, vocal cords or larynx can lead to death. Swelling of the tongue, vocal cords or larynx may be accompanied by the development of airway obstruction. With the development of angioedema, immediately subcutaneously epinephrine (epinephrine) and ensure airway patency.

Patients with a history of angioedema, who are not associated with the use of ACE inhibitors, may be at increased risk of developing angioedema when taking drugs of this group.

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain, possibly in combination with nausea or vomiting; in some cases without a previous angioedema and a normal level of C1-esterase. Diagnosed with computer tomography or ultrasound examination of the abdominal organs, or during a surgical procedure. Symptoms disappear after discontinuing therapy with an ACE inhibitor. Patients receiving ACE inhibitors should consider the possibility of angioedema edema in the differential diagnosis of abdominal pain.

Anaphylactoid reactions during the procedure of apheresis of low density lipoproteins (LDL)

In patients receiving ACE inhibitors, amid the procedure of apheresis of LDL with the use of dextran sulfate, in rare cases, the development of anaphylactoid reactions is possible. It is recommended that the ACE inhibitor be temporarily withdrawn before each procedure for LDL apheresis.

Anaphylactic reactions during desensitization

In patients receiving ACE inhibitors during the course of desensitization (for example, the venom of Hymenoptera insects), in very rare cases development of long-term, life-threatening anaphylactoid reactions is possible. It should be used with caution in patients predisposed to allergic reactions. It is recommended that the ACE inhibitor be temporarily withdrawn before each desensitization procedure begins.

Liver failure

During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that starts with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice appears during the administration of an ACE inhibitor or there is a significant increase in the activity of "liver" enzymes, the ACE inhibitor should be immediately discontinued and the patient should be closely monitored.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

In patients on the background of therapy with ACE inhibitors, cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia were noted. With normal kidney function, in the absence of other complications, neutropenia develops rarely.Perineva® Cu-tab® should be used with extreme caution in patients with systemic connective tissue diseases (eg, systemic lupus erythematosus, scleroderma) who are simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, and also at a combination of all listed factors, especially at an existing infringement of function of kidneys. Such patients may develop severe infections that do not respond to intensive antibiotic therapy. When carrying out therapy with Perineva® Cu-tab®, these patients should regularly monitor the number of leukocytes in the blood serum. Patients should inform the doctor of any signs of infectious diseases (eg, sore throat, fever).

Ethnic differences

The risk of angioedema development in patients of the Negroid race is higher. Like other ACE inhibitors, perindopril is less effective in reducing blood pressure in patients of the Negroid race, possibly because of the greater prevalence of low-grade conditions in the population of this group of patients with hypertension.

Cough

Against the background of therapy with ACE inhibitors, a persistent, unproductive cough may develop which stops after the drug is discontinued. This should be taken into account in the differential diagnosis of cough.

Surgery / general anesthesia

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 the surgery, therapy with ACE inhibitors should 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. It is necessary to warn the surgeon that the patient is taking ACE inhibitors.

Hyperkalemia

Against the background of therapy with ACE inhibitors, including perindopril, in some patients may be increasedwthe content of potassium in the blood serum. Risk factors for hyperkalemia are renal and / or heart failure, diabetes mellitus in decompensation stage, simultaneous intake of potassium-sparing diuretics, potassium preparations,or potassium-containing substitutes for edible salt, or other drugs that cause hyperkalemia (eg, heparin), especially in patients with impaired renal function. Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If it is necessary to simultaneously use these drugs, it is recommended to regularly monitor the potassium content in the blood serum.

Diabetes

In patients with diabetes mellitus, who take hypoglycemic agents for ingestion or insulin, during the first month of therapy with ACE inhibitors, the concentration of glucose in the blood should be carefully monitored.

Lithium preparations

It is not recommended simultaneous use with lithium preparations.

Potassium-sparing diuretics, preparations containing potassium and potassium-containing substitutes for edible salt

It is not recommended simultaneous use with ACE inhibitors.

Special information on excipients

The drug Perineva® Ku-tab® contains sorbitol, therefore, in patients with congenital fructose intolerance, the use of the drug is contraindicated.

The drug Perineva® Ku-tab® is not recommended for patients with phenylketonuria, tk. contains aspartame.

Effect on the ability to drive transp. cf. and fur:The drug Perineva® Cou-tab® should be used with caution in patients whose activity is related to the management of vehicles or requires an increased concentration of attention and speed of psychomotor reactions, in connection with the danger of developing arterial hypotension and dizziness.

Form release / dosage:

Tablets are dispersible in the oral cavity 4 mg, 8 mg.

For 7 or 10 tablets in a contour mesh package (blister) from the combined material OPA / Al / PVC and PET / aluminum foil (peel off foil).

4, 8, 12 contour cell packs (blisters) of 7 tablets or 3, 5, 6, 9, 10 contour cell packs (blisters) of 10 tablets together with instructions for use are placed in a pack of cardboard.

Packaging:tablets, dispersible in the oral cavity, 4 mg, 8 mg (blister (contour pack)) 7 x 4/8/12 (cardboard pack) tablets dispersible in the oral cavity, 4 mg, 8 mg (blister (contourcell) ) 10 х 3/5/6/9/10 (a pack of cardboard)

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002312

Date of registration:25.11.2013

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Perineva® Ku-tab® (Perineva® Q-tab®)