Perineva pills 8mg, 30pcs

Composition

1 tablet 2 mg / 4 mg / 8 mg contains:

Active ingredient:

Perindopril erbumin 2,000 mg / 4,000 mg/8,000 mg

Auxiliary substances:

Calcium chloride hexahydrate, lactose monohydrate, crospovidone, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate

Pharmacological action

angiotensin converting enzyme (ACE)inhibitor

Clinical Pharmacology

Pharmacodynamics

Mechanism of action

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II. ACE inhibitor (kininase II) is an exopeptidase that converts angiotensin I to the vasoconstrictor angiotensin II, and destroys bradykinin, which has a vasodilating effect, to an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone.

Since ACE inhibits bradykinin, ACE inhibition is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin systems, while the prostaglandin system is also activated. It is possible that this effect is part of the mechanism of the antihypertensive action of ACE inhibitors, as well as the mechanism of the development of some side effects of drugs of this class (for example, cough). Perindopril has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites do not have an ACE inhibitory effect in vitro.

Clinical efficacy and safety

Arterial hypertension

Perindopril is effective in the treatment of arterial hypertension of any severity. Against the background of the use of perindopril, there is a decrease in both systolic and diastolic blood pressure (BP) in the patient’s “lying” and “standing”positions.

Perindopril reduces total peripheral vascular resistance (OPSS), which leads to a decrease in blood pressure, while peripheral blood flow accelerates without changing the heart rate (HR).

As a rule, perindopril leads to an increase in renal blood flow, the glomerular filtration rate (GFR) does not change.

The antihypertensive effect of the drug reaches a maximum in 4-6 hours after a single oral use and persists for 24 hours. 24 hours after oral use, there is a pronounced (about 87-100%) residual ACE inhibition. Blood pressure reduction is achieved fairly quickly. In patients with a positive response to treatment, blood pressure normalizes within a month and persists without developing tachycardia.

Discontinuation of treatment is not accompanied by the development of “withdrawal” syndrome.

Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

Concomitant use of thiazide diuretics increases the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia when taking diuretics.

Chronic heart failure (CHF)

Perindopril normalizes heart function, reducing preload and afterload.

In patients with CHF treated with perindopril, a decrease in filling pressure in the left and right ventricles of the heart, a decrease in OPSS, an increase in cardiac output, and an increase in the cardiac index were detected. Perindopril at a dose of 2 mg did not significantly reduce blood pressure in patients with CHF (NYHA functional class II-III).

Cerebrovasculardiseases

When taking perindopril at a dose of 4 mg, as well as in combination with indapamide, there is a reduced risk of developing a second stroke (both ischemic and hemorrhagic), as well as an additional risk reduction:

· fatal or disabling strokes·

* major cardiovascular complications, including myocardial infarction, including fatal outcomes;

· stroke-related dementia;

· severe cognitive impairment.

Stable coronary heart disease (CHD)

When using perindopril at a dose of 8 mg / day in patients with stable coronary heart disease, there is a significant reduction in the absolute risk of complications provided for by the main criterion of effectiveness (mortality from cardiovascular diseases, the frequency of non-fatal myocardial infarction and / or cardiac arrest followed by successful resuscitation).

Pharmacokinetics

Suction

When taken orally, perindopril is rapidly absorbed in the gastrointestinal tract, the maximum concentration (withmgax) in blood plasma is reached after 1 hour. Theplasma half-life of perindopril is 1 hour.

Perindopril has no pharmacological activity. Approximately 27% of the total amount of absorbed perindopril enters the bloodstream as the active metabolite of perindoprilat. In addition to perindoprilat,5 more metabolites are formed that do not have pharmacological activity. C_{– max} of perindoprilat in blood plasma is reached 3-4 hours after oral use.

Food intake slows down the conversion of perindopril to perindoprilate, thus affecting bioavailability. Therefore, the drug Perineva® should be taken orally 1 time a day, in the morning, before meals.

A linear relationship was demonstrated between the dose of perindopril and its exposure in blood plasma.

Distribution

The volume of distribution of free perindoprilate is approximately 0.2 l / kg. The association of perindoprilat with plasma proteins, mainly with ACE, is less than 30% and is dose-dependent.

Deduction

Perindoprilat is excreted by the kidneys. The_half-life of the free fraction is 3-5 hours. The “effective”_half-life is approximately 17 hours, and the equilibrium state in the blood plasma is reached within 4 days.

Pharmacokinetics in selected groups of patients

Elimination of perindoprilat is slowed in elderly patients, as well as in patients with heart and renal insufficiency.

The dialysis clearance of perindoprilat is 70 ml/min.

In patients with cirrhosis of the liver, the hepatic clearance of perindopril decreases by 2 times. However, the amount of perindoprilate produced does not decrease, and no dose adjustment of Perineva® is required (see sections” Dosage and use”, “Special instructions”).

Indications

* Arterial hypertension.

* Chronic heart failure.

* Prevention of recurrent stroke (combined therapy with indapamide) in patients who have had a stroke or transient ischemic cerebrovascular accident.

·  Stable CHD: reducing the risk of cardiovascular complications in patients with stable CHD.

Use during pregnancy and lactation

Pregnancy

The drug Perineva® is contraindicated for use during pregnancy (see the section “Contraindications”).

When planning pregnancy or when it occurs during the use of Perineva®, you should immediately stop taking the drug and, if necessary, prescribe another antihypertensive therapy with a proven safety profile for use during pregnancy.

It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to impaired development (decreased renal function, oligohydramnios, slowing of ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia).

If the patient received ACE inhibitors in the second or third trimester of pregnancy, it is recommended to conduct an ultrasound examination of the newborn to assess the condition of the skull bones and kidney function.

Breast-feeding period

It is not known whether perindopril passes into breast milk. In this regard, the use of Perineva® during breastfeeding is contraindicated.

If the use of Perineva® is necessary during breastfeeding, then breast-feeding should be discontinued.

Fertility

Preclinical studies have shown no effect of perindopril on reproductive function in rats of both sexes.

Contraindications

·  Hypersensitivity to the Active ingredient, other ACE inhibitors and excipients (see the section “Composition”) that make up the drug.

* Lactase deficiency, lactose intolerance, glucose-galactose deficiency syndrome (Perineva ® contains lactose).

* Hereditary / idiopathic angioedema.

· A history of angioedema (angioedema) associated with taking an ACE inhibitor.

· Significant bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney.

* Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and / or moderate to severe renal impairment (GFRsections “Special instructions”, “Interaction with other medicinal products”).

* Concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.

* Concomitant use with neutral endopeptidase inhibitors (for example, with drugs containing sacubitril) due to a high risk of angioedema.

* Extracorporeal treatments that cause blood to come into contact with negatively charged surfaces.

* Pregnancy (see the section “Use during pregnancy and lactation”).

· Breast-feeding period (see the section “Use during pregnancy and lactation”).

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

Side effects

The safety profile of perindopril is consistent with that of ACE inhibitors.

The most common adverse events reported in clinical trials and observed with perindopril are: dizziness, headache, paresthesia, vertigo, visual disturbances, tinnitus, marked decrease in blood pressure, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disorders, dyspepsia, nausea, vomiting, pruritus, skin rash, muscle spasms and asthenia.

Classification of the incidence of side effects recommended by the World Health Organization (WHO):

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

Disorders of the blood and lymphatic system:

infrequently*: eosinophilia;

very rarely: decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency (see section “Special instructions”).

Metabolic and nutritional disorders:

infrequently*: hypoglycemia (see sections “Interaction with other drugs”, “Special instructions”), hyperkalemia that is reversible after discontinuation of the drug (see section” Special instructions”), hyponatremia.

Nervous system disorders:

common: paresthesia, headache, dizziness, vertigo;

uncommon: drowsiness*, fainting*;

very rare: confusion.

Mental disorders:

infrequently: sleep disorders, mood lability.

Visual disturbances:

common: visual disturbances.

Hearing disorders and labyrinth disorders:

common: tinnitus.

Cardiac disorders:

infrequently*: tachycardia, palpitation sensation;

very rarely: cardiac arrhythmias, angina pectoris, myocardial infarction, possibly due to a marked decrease in blood pressure in high-risk patients (see section “Special instructions”).

Vascular disorders:

often: severe lowering of blood pressure and associated symptoms;

infrequently*: vasculitis;

very rarely: stroke, possibly due to severe lowering of blood pressure in high-risk patients (see section “Special instructions”);

frequency unknown: Raynaud’s syndrome.

Respiratory, thoracic and mediastinal disorders:

common: cough, shortness of breath;

uncommon: bronchospasm;

very rare: eosinophilic pneumonia, rhinitis.

Disorders of the digestive system:

often: constipation, nausea, vomiting, abdominal pain, taste disorders, dyspepsia, diarrhea;

infrequently: dry oral mucosa;

very rarely: pancreatitis.

Liver and biliary tract disorders:

very rare: hepatitis (cholestatic or cytolytic) (see section “Special instructions”).

Skin and subcutaneous tissue disorders:

common: pruritus, skin rash;

infrequent: angioedema of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal folds and / or larynx, urticaria (see section “Special instructions”), photosensitivity*, pemphigus*, increased sweating;

rarely: exacerbation of psoriasis*;

very rarely: erythema multiforme.

Musculoskeletal and connective tissue disorders:

often: muscle spasm;

infrequently*: arthralgia, myalgia.

Kidney and urinary tract disorders:

Infrequently: renal failure;

very rarely: acute renal failure (ARF).

Genital and breast disorders:

infrequently: erectile dysfunction.

General disorders and disorders at the injection site:

common: asthenia;

uncommon: chest pain*, peripheral edema*, weakness*, fever*, falls*.

Laboratory and instrumental data:

Infrequently*: increased plasma urea and creatinine concentrations;

rarely: increased activity of “hepatic” transaminases and serum bilirubin concentrations.

* Assessment of the frequency of adverse reactions identified by spontaneous reports was carried out based on the results of clinical studies.

Cases of inadequate antidiuretic hormone secretion syndrome (ADH SNA) have been reported with other ACE inhibitors. The syndrome of inadequate ADH secretion can be considered as a very rare but possible complication associated with ACE inhibitor therapy, including perindopril.

Adverse events reported in clinical trials

Only serious adverse events were recorded in the clinical trial. Serious adverse events were reported in patients in the perindopril group and in patients in the placebo group. In the perindopril group, patients showed a marked decrease in blood pressure, angioedema, and sudden cardiac arrest. The frequency of withdrawal of perindopril due to coughing, a marked decrease in blood pressure, or other cases of intolerance was higher in the perindopril group compared to the placebo group.

Interaction

Simultaneous use is contraindicated

Concomitant use of ACE inhibitors with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area). Concomitant use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy. Extracorporeal methods of treatment.

Neutral endopeptidase inhibitors

An increased risk of angioedema has been reported when ACE inhibitors are co-administered with neutral endopeptidase inhibitors such as sacubitril and racecadotril (an enkephalinase inhibitor).

Concomitant use of ACE inhibitors with drugs containing sacubitril (a neprilysin inhibitor) increases the risk of angioedema, and therefore the simultaneous use of these drugs is contraindicated. ACE inhibitors should be prescribed no earlier than 36 hours after discontinuation of drugs containing sacubitril. It is contraindicated to prescribe drugs containing sacubitril to patients receiving ACE inhibitors, as well as within 36 hours after discontinuation of ACE inhibitors.

Medications that cause hyperkalemia

Certain medications or drugs of other pharmacological classes may increase the risk of hyperkalemia: aliskiren and aliskiren-containing drugs, potassium salts, potassium-sparing diuretics, ACE inhibitors, ARA II, nonsteroidal anti-inflammatory drugs (NSAIDs), heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim, co-trimoxazole (trimethoprim + sulfamethoxazole). The combination of these medications increases the risk of hyperkalemia.

Double blockade of the RAAS

In the literature, it has been reported that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and ARA II is associated with a higher incidence of hypotension, syncope, hyperkalemia, or deterioration of renal function (including acute renal failure) compared to the use of only one drug that affects the RAAS. Concomitant use of ACE inhibitors with aliskiren and drugs containing aliskiren is not recommended in patients without diabetes mellitus and/or without moderate or severe renal impairment (and is contraindicated in patients with diabetes mellitus and/or moderate or severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area)). Concomitant use of ACE inhibitors with ARA II is not recommended in patients without diabetic nephropathy (and is contraindicated in patients with diabetic nephropathy).

Simultaneous use is not recommended

(see also the section “Special instructions”)

Aliskiren

Patients who do not have a history of diabetes mellitus and/or moderate renal impairment may have an increased risk of hyperkalemia, deterioration of renal function, and increased incidence of cardiovascular morbidity and mortality.

Extracorporeal methods of treatment

Extracorporeal treatments that cause blood to come into contact with negatively charged surfaces, such as dialysis or hemofiltration with certain high-flow membranes (such as polyacrylonitrile membranes) and LDL apheresis with dextran sulfate, increase the risk of severe anaphylactoid reactions. If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Estramustin

Concomitant use may lead to an increased risk of angioedema.

Racecadotril (an enkephalinase inhibitor used to treat acute diarrhea)

Concomitant use of ACE inhibitors with racecadotril increases the risk of angioedema.

Cyclosporine

Concomitant use with ACE inhibitors may increase the risk of hyperkalemia. Monitoring of the potassium content in the blood serum is recommended.

Heparin

Hyperkalemia may occur when ACE inhibitors are co-administered with heparin. Monitoring of the potassium content in the blood serum is recommended.

Co-trimoxazole (trimethoprim + sulfamethoxazole)

Trimethoprim is known to act as a potassium-sparing diuretic (such as amiloride). Therefore, concomitant use with perindopril is not recommended.

mTOR inhibitors (mammalian Target of Rapamycin-target of rapamycin in mammalian cells), for example, temsirolimus, sirolimus, everolimus

Patients taking concomitant mTOR inhibitors have an increased risk of developing angioedema.

Potassium-sparing diuretics (such as triamterene, amiloride, spironolactone and its derivative eplerenone), potassium salts

Features of spironolactone use in heart failure-see the section ” Potassium-sparing diuretics (eplerenone, spironolactone)” in this section.

Development of hyperkalemia (with a possible fatal outcome), especially with impaired renal function (additional effects associated with hyperkalemia).

Concomitant use of perindopril with the above-mentioned medicinal products is not recommended (see the section “Special instructions”). If, however, concomitant use is indicated, they should be used with caution and regular monitoring of serum potassium levels.

Lithium preparations

With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in serum lithium content and associated toxic effects may occur. Concomitant use of perindopril and lithium preparations is not recommended. If such therapy is necessary, the lithium content in the blood plasma should be regularly monitored (see the section “Special instructions”).

Simultaneous use that requires extreme caution

Hypoglycemic agents (insulin, hypoglycemic agents for oral use)

The use of ACE inhibitors may increase the hypoglycemic effect of insulin and oral hypoglycemic agents up to the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function.

Baclofen

Increases the antihypertensive effect of ACE inhibitors. Blood pressure levels should be carefully monitored and, if necessary, the dosage of antihypertensive drugs should be adjusted.

Potassium-sparing diuretics

Patients receiving diuretics, especially those that remove fluids and / or salts, may experience a marked decrease in blood pressure at the beginning of perindopril therapy, the risk of which can be reduced by discontinuing the diuretic, replenishing the loss of fluid or salts before starting perindopril therapy, and prescribing perindopril in a low dose with a further gradual increase.

In patients with arterial hypertension, the use of diuretics, especially those that remove fluid and / or salts, should either be discontinued before starting the use of an ACE inhibitor (while a potassium-sparing diuretic may be re-prescribed later), or an ACE inhibitor should be prescribed at a low dose with a further gradual increase.

In patients with CHF, when using diuretics, an ACE inhibitor should be prescribed at a low dose, possibly after reducing the dose of the potassium-sparing diuretic used simultaneously. In all cases, renal function (serum creatinine) should be monitored during the first weeks of ACE inhibitor use.

Potassium-sparing diuretics (eplerenone, spironolactone)

Use of eplerenone or spironolactone in doses from 12.5 mg to 50 mg per day and low doses of ACE inhibitors

In patients with CHF of NYHA functional class II-IV with left ventricular ejection fraction

Before using this combination of medications, it is necessary to make sure that there is no hyperkalemia and impaired renal function. It is recommended to regularly monitor the concentration of creatinine and potassium in the blood serum: weekly in the first month of treatment and monthly thereafter.

NSAIDs, including high doses of acetylsalicylic acid (more than 3 g / day)

Concomitant use of ACE inhibitors with NSAIDs (acetylsalicylic acid at a dose that has an anti-inflammatory effect, cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of ACE inhibitors. Concomitant use of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when using this combination, especially in elderly patients. Patients should receive an adequate amount of fluid. It is recommended to carefully monitor kidney function both at the beginning and during treatment.

Tissue plasminogen activators

Observational studies have revealed an increased incidence of angioedema in patients taking ACE inhibitors after the use of alteplase for thrombolytic therapy of ischemic stroke.

Simultaneous use that requires caution

Antihypertensive drugs and vasodilators

The antihypertensive effect of perindopril may be enhanced when used concomitantly with other antihypertensive, vasodilating agents, including short-and long-acting nitrates.

Dipeptidyl peptidase type 4 (DPP-4) inhibitors – gliptins (for example, linagliptin, saxagliptin, sitagliptin, vildagliptin)

Concomitant use with ACE inhibitors may increase the risk of angioedema.

Tricyclic antidepressants, antipsychotics (neuroleptics) and general anaesthetics

Concomitant use with ACE inhibitors may lead to increased antihypertensive effects (see section “Special instructions”).

Sympathomimetics

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.

Gold preparations

When ACE inhibitors, including perindopril, were co-administered with gold (sodium aurothiomalate intravenously), a symptom complex was described, including facial skin hyperemia, nausea, vomiting, and hypotension.

How to take it, course of use and dosage

Inside,1 tablet 1 time a day, preferably in the morning, before meals.

When choosing the dose, you should take into account the specific clinical situation (see the section “Special instructions”) and the degree of blood pressure reduction during therapy.

Arterial hypertension

The drug Perineva® can be used both in monotherapy and in combination therapy.

The recommended starting dose is 4 mg once a day.

In patients with severe activity of the renin-angiotensin-aldosterone system (RAAS) (especially in patients with renovascular hypertension, hypovolemia and / or decreased plasma electrolytes, decompensation of CHF or severe arterial hypertension) after taking the first dose of the drug, a pronounced decrease in blood pressure may develop. At the beginning of therapy, such patients should be under close medical supervision. The recommended starting dose for such patients is 2 mg once a day.

If necessary, a month after the start of therapy, you can increase the dose of the drug to 8 mg once a day.

At the beginning of therapy with Perineva®, symptomatic hypotension may develop. In patients receiving concomitant diuretics, the risk of hypotension is higher due to possible hypovolemia and a decrease in plasma electrolytes. Caution should be exercised when using Perineva in this group of patients. It is recommended, if possible, to stop taking diuretics 2-3 days before the expected start of therapy with Perineva® (see the section “Special instructions”).

If diuretics cannot be discontinued, the initial dose of Perineva® should be 2 mg per day. At the same time, it is necessary to monitor the function of the kidneys and the content of potassium in the blood serum. In the future, if necessary, the dose of Perineva® can be increased. If necessary, you can resume taking diuretics.

In elderly patients, treatment should begin with a dose of 2 mg per day. If necessary, one month after the start of therapy, the dose can be increased to 4 mg per day, and then to a maximum dose of 8 mg per day, taking into account the state of renal function (see Table 1).

The maximum daily dose is 8 mg

. Chronicheart failure

Treatment of patients with CHF with Perineva® in combination with potassium-sparing diuretics and/or digoxin, and / or beta-blockers is recommended to begin under close medical supervision, prescribing Perineva® at an initial dose of 2 mg 1 time a day, in the morning. After 2 weeks of treatment, the dose of Perineva® can be increased to 4 mg once a day, provided that the 2 mg dose is well tolerated and the response to the therapy is satisfactory.

In patients at high risk of developing symptomatic arterial hypotension (for example, patients with impaired water-electrolyte balance with or without hyponatremia, patients with hypovolemia, or patients taking high doses of diuretics), if possible, water-electrolyte balance disorders and hypovolemia should be eliminated before starting Perineva®. It is recommended to carefully monitor blood pressure, kidney function, and serum potassium levels before and during therapy.

Prevention of recurrent stroke (combination therapy with indapamide)

In patients with a history of cerebrovascular disease, treatment with Perineva should begin with a daily dose of 2 mg for the first 2 weeks, then increase the dose to 4 mg for the next 2 weeks before using indapamide.

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

Stable CHD: reduced risk of cardiovascular complications in patients who have previously had a myocardial infarction and / or coronary revascularization

In patients with a stable course of coronary artery disease, therapy with Perineva® should begin with a dose of 4 mg once a day.

After 2 weeks, if the drug is well tolerated and taking into account the state of renal function, the dose can be increased to 8 mg once a day.

Elderly patients should start therapy with a dose of 2 mg once a day for the 1st week, then 4 mg once a day for the next week. Then, taking into account the state of renal function, the dose can be increased to 8 mg once a day (see Table 1). You can increase the dose of the drug only if it is well tolerated at the previously recommended dose.

Special patient groups

Kidney failure

In patients with renal insufficiency, the dose of Perineva® should be selected based on creatinine clearance (CC).

Table 1. Dosage of Perineva® for renal insufficiency

creatinine clearance (ml / min)	The recommended dose
is ≥ 60	4 mg / day
? 30 and < 60	2 mg / day
? 15 and < 30	2 mg every other day
	2 mg per dialysis day

* Dialysis clearance of perindoprilat is 70 ml/min. Perineva® should be taken after the dialysis procedure.

Liver failure

Patients with impaired liver function do not need to adjust the dose (see the sections ” Pharmacological properties. Pharmacokinetics“, “Special instructions”).

Under 18 years of age

Perineva® should not be used in children and adolescents under 18 years of age, as there are no data on the efficacy and safety of perindopril in patients of this age group (see the section “Contraindications”).

Overdose

Data on drug overdose are limited.

Symptoms

Marked decrease in blood pressure, shock, impaired water-electrolyte balance, renal failure, hyperventilation, tachycardia, palpitation, bradycardia, dizziness, anxiety, cough.

Treatment

Emergency measures are limited to removing the drug from the body: gastric lavage and / or taking activated carbon, followed by restoring the water-electrolyte balance.

With a marked decrease in blood pressure, the patient should be transferred to the “lying” position on his back with his legs raised. If necessary,0.9% sodium chloride solution should be administered intravenously (iv). If necessary, a solution of catecholamines can be administered intravenously. Perindoprilate, the active metabolite of perindopril, can be removed from the body by dialysis. If therapy-resistant bradycardia develops, it may be necessary to implant an electrocardiostimulator.It is necessary to constantly monitor the indicators of the main vital functions of the body, the concentration of creatinine and the content of electrolytes in the blood serum.

Description

Tablets 2 mg. Round, slightly biconvex tablets of white or almost white color, with a chamfer.

Tablets 4 mg. Oval, slightly biconvex tablets of white or almost white color, with a chamfer, with a risk on one side.

Tablets of 8 mg. Round, slightly biconvex tablets of white or almost white color, with a chamfer, with a risk on one side.

Special instructions

(see also sections “Interaction with other medicinal products”, “Special instructions”)

Bilateral renal artery stenosis, the presence of only one functioning kidney, renal failure, systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc. ), immunosuppressive therapy, allopurinol, procainamide (risk of neutropenia, agranulocytosis), reduced circulating blood volume (BCC) (diuretics, salt-free diet, vomiting, diarrhea), angina pectoris, cerebrovascular diseases, cardiovascular hypertension, diabetes mellitus, NYHA functional class IV CHF, concomitant use of potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes, lithium preparations, hyperkalemia, surgery/general anesthesia, hemodialysis using high-flow membranes, desensitizing therapy, low-density lipoprotein (LDL) apheresis, post-kidney transplantation condition, aortic stenosis/mitral valve failure stenosis/hypertrophic obstructive cardiomyopathy (HOCMP), use in black patients, congenital glucose-6-phosphate dehydrogenase deficiency.

Perineva® should not be used in children and adolescents under 18 years of age, as there are no data on the efficacy and safety of perindopril in patients of this age group.

In elderly patients, treatment should begin with a dose of 2 mg per day. If necessary, one month after the start of therapy, the dose can be increased to 4 mg per day, and then to a maximum dose of 8 mg per day, taking into account the state of renal function (see Table 1).

The maximum daily dose is 8 mg.

Kidney failure

In patients with renal insufficiency, the dose of Perineva® should be selected based on creatinine clearance (CC).

Table 1. Dosage of Perineva® for renal insufficiency

creatinine clearance (ml / min)	The recommended dose
is ≥ 60	4 mg / day
? 30 and < 60	2 mg / day
? 15 and < 30	2 mg every other day
	2 mg per dialysis day

* Dialysis clearance of perindoprilat is 70 ml/min. Perineva® should be taken after the dialysis procedure.

Liver failure

No dose adjustment is required in patients with hepatic impairment.

CHD: reducing the risk of cardiovascular complications in patients who have previously had a myocardial infarction and / or coronary revascularization

If unstable angina develops during the first month of Perineva therapy, the benefits and risks should be evaluated to decide whether to continue therapy.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with an uncomplicated course of arterial hypertension. The risk of a marked decrease in blood pressure is increased in patients with reduced BCC, which can be observed against the background of diuretic therapy, with a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see the sections “Interaction with other drugs” and “Side effects”). In patients with an increased risk of developing symptomatic hypotension, blood pressure, renal function, and serum potassium should be carefully monitored during Perineva therapy.

This approach is also used in patients with CHD and cerebrovascular diseases, in which severe hypotension can lead to myocardial infarction or impaired cerebral circulation.

In case of hypotension, the patient should be placed in a supine position with the legs raised. If necessary, the BCC should be replenished by intravenous use of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further use of the drug. After recovery of BCC and blood pressure, treatment can be continued.

In some patients with CHF and normal or reduced blood pressure, Perineva may cause an additional reduction in blood pressure. This effect is predictable and usually does not require discontinuation of therapy. If symptoms of a marked decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.

Mitral stenosis/aortic stenosis/HOCMP

Perineva®, like other ACE inhibitors, should be used with caution in patients with left ventricular exit tract obstruction (aortic stenosis, HOCMP), as well as in patients with mitral stenosis.

Impaired renal function

Patients with renal insufficiency (CC For such patients, regular monitoring of serum creatinine and potassium levels is necessary (see section “Side effects”).

Hypotension, which sometimes develops at the beginning of ACE inhibitor therapy in patients with symptomatic CHF, can lead to deterioration of renal function. It is possible to develop acute renal failure, usually reversible. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal insufficiency), an increase in serum urea and creatinine concentrations may occur during therapy with ACE inhibitors, which usually passes when therapy is discontinued.The additional presence of renovascular hypertension leads to an increased risk of severe hypotension and renal failure in these patients.

Treatment of such patients begins under close medical supervision with the use of low doses of the drug and further adequate selection of doses. Diuretic therapy should be temporarily discontinued and regular monitoring of serum potassium and creatinine levels should be performed during the first few weeks of therapy.

In some patients with arterial hypertension, the concentration of urea and creatinine in the blood serum may increase without indicating the presence of previous renal vascular disease, especially with simultaneous use of diuretics. These changes are usually minor and reversible. Patients with a history of renal insufficiency are more likely to develop these disorders. In such cases, it may be necessary to cancel or reduce the dose of Perineva® and / or a diuretic.

Hemodialysis

Patients undergoing hemodialysis using high-flow membranes (for example, AN69®) have been reported to develop anaphylactic reactions during therapy with ACE inhibitors. ACE inhibitors should be avoided when using this type of membrane.

Kidney transplantation

There are no data on the use of perindopril in patients after kidney transplantation.

Hypersensitivity, angioedema

When using ACE inhibitors, including perindopril, in rare cases and in any period of therapy, angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may develop (see the section “Side effects”). If symptoms occur, Perineva should be discontinued immediately and the patient should be monitored until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually go away on their own, although antihistamines can be used to treat the symptoms.

Angioedema accompanied by laryngeal edema can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If these symptoms occur, emergency therapy is required, including subcutaneous use of epinephrine (epinephrine) and / or airway patency. The patient should be under medical supervision until complete and persistent disappearance of symptoms.

Patients with a history of angioedema that is not associated with ACE inhibitors may have an increased risk of developing angioedema when using drugs in this group (see the section “Contraindications”).

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal activity of C1-esterase. The diagnosis was made using computed tomography of the abdominal cavity, ultrasound, or surgical intervention. Symptoms disappeared after discontinuation of ACE inhibitor therapy. Therefore, in patients with abdominal pain receiving ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema of the intestine (see the section “Side effects”).

Neutral endopeptidase inhibitors

Concomitant use of ACE inhibitors with drugs containing sacubitril (a neprilysin inhibitor) increases the risk of angioedema, and therefore the simultaneous use of these drugs is contraindicated. ACE inhibitors should be prescribed no earlier than 36 hours after discontinuation of drugs containing sacubitril. It is contraindicated to prescribe drugs containing sacubitril to patients receiving ACE inhibitors, as well as within 36 hours after discontinuation of ACE inhibitors.

Tissue plasminogen activators

Observational studies have revealed an increased incidence of angioedema in patients taking ACE inhibitors after the use of alteplase for thrombolytic therapy of ischemic stroke.

An increased risk of angioedema was observed in patients taking ACE inhibitors and medications such as mTOR inhibitors (temsirolimus, sirolimus, everolimus), DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin), estramustine, neutral endopeptidase inhibitors (racecadotril, sacubitril) and tissue plasminogen activators.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis with dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There have been isolated reports of anaphylactoid reactions in patients treated with ACE inhibitors during desensitizing therapy, such as hymenopteran venom. ACE inhibitors should be used with caution in patients predisposed to allergic reactions, undergoing desensitization procedures. ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily discontinuing the ACE inhibitor prior to the desensitization procedure.

Impaired liver function

In rare cases, against the background of ACE inhibitors, a syndrome of cholestatic jaundice development with transition to fulminant liver necrosis was observed, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of “liver” enzymes in blood plasma occurs against the background of the use of ACE inhibitors, the drug should be discontinued (see the section “Side effects”), the patient should be under appropriate medical supervision.

Neutropenia/agranulocytosis / thrombocytopenia/anemia

Neutropenia/agranulocytosis, thrombocytopenia, and anemia may occur with ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other aggravating factors. Perineva should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.

Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When using Perineva® in such patients, it is recommended to periodically monitor the number of white blood cells in the blood. Patients should inform the doctor about any signs of infectious diseases (for example, sore throat, fever).

Ethnic differences

It should be borne in mind that patients of the black race have a higher risk of developing angioedema. Like other ACE inhibitors, Perineva is less effective in reducing blood pressure in black patients.

This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Cough

Against the background of therapy with ACE inhibitors, persistent dry cough may occur, which stops after discontinuation of the drug. This should be taken into account when conducting a differential diagnosis of cough.

Surgical intervention, general anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a marked decrease in blood pressure, especially when using general anesthesia drugs that have an antihypertensive effect. Perineva® should be discontinued one day before surgery. With the development of arterial hypotension, blood pressure should be maintained by filling the BCC. The surgeon/anaesthetist should be advised that the patient is taking ACE inhibitors.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include impaired renal function, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), potassium supplements/preparations or potassium-containing salt substitutes, as well as the use of other drugs that contribute to an increase in serum potassium (for example, heparin trimethoprim or co-trimoxazole (trimethoprim + sulfamethoxazole) and especially aldosterone antagonists or angiotensin receptor blockers). The use of potassium supplements/preparations, potassium-sparing diuretics, potassium-containing salt substitutes can lead to a significant increase in serum potassium, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal, cardiac arrhythmias. If simultaneous use of Perineva® and the above-mentioned drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of serum potassium (see the section “Interaction with other drugs”).

Diabetes mellitus

When using perindopril in patients with diabetes mellitus receiving hypoglycemic agents for oral use or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood (see the section “Interaction with other drugs”).

Lithium preparations

Concomitant use of Perineva® and lithium preparations is not recommended (see section “Interaction with other medicinal products”).

Potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes and food additives

Although serum potassium levels usually remain within normal limits, hyperkalemia may occur in some patients receiving perindopril.

Concomitant use of potassium-sparing diuretics (such as spironolactone, triamterene, amiloride), potassium preparations, or potassium-containing supplements or salt substitutes may result in hyperkalemia.

Caution should also be exercised when prescribing perindopril concomitantly with other drugs that increase serum potassium, such as heparin, trimethoprim, and co-trimoxazole (trimethoprim + sulfamethoxazole), since trimethoprim is known to act as a potassium-sparing diuretic (such as amiloride). Therefore, the combination of perindopril with the above drugs is not recommended.

If the simultaneous use of perindopril and the above-mentioned drugs is necessary, care should be taken and the serum potassium content should be regularly monitored.

Double blockade of the RAAS

Hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure)have been reported in susceptible patients, especially when used concomitantly with medications that affect this system. Concomitant use of ACE inhibitors with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients. Concomitant use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Primary aldosteronism

Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting by inhibiting RAAS. Therefore, the use of Perineva® in this group of patients is not recommended.

Special information on excipients

Perineva ® contains lactose, so its use is contraindicated in patients with congenital galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Perineva® should be used with caution in patients driving vehicles and engaging in activities that require increased concentration and rapid response, due to the risk of hypotension and dizziness.

Form of production

Tablets,2 mg,4 mg,8 mg.

During production at KRKA-RUS LLC, Russia:

10,14,30 tablets in a contour cell package made of a combined material OPA / Al / PVC and aluminum foil or PVC/PE/PVDH and aluminum foil.

3,6,9 contour cell packages (10 tablets each); 1,2,4,7 contour cell packages (14 tablets each); 1,2,3 contour cell packages (30 tablets each) together with the instructions for use are placed in a cardboard pack.

During production at JSC “KRKA, D. D., Novo Mesto”, Slovenia:

10,14,30 tablets in a blister of combined OPA/Al/PVC material and aluminum foil.

3,6,9 blisters (10 tablets each); 1,2,4,7 blisters (14 tablets each); 1,2,3 blisters (30 tablets each) together with the instructions for use are placed in a cardboard pack.

Storage conditions

At a temperature not exceeding 25 ° C, in the original packaging.

Keep out of reach of children.

Shelf

life is 3 years.

Do not use the drug after the expiration date.

Active ingredient

Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Prevention of heart attacks and strokes, Heart failure, Hypertension, Angina