Perindopril-SZ - instructions for use, doses, side effects, contraindications

ACE inhibitor. Suppression of ACE leads to a decrease in angiotensin II in the blood plasma, resulting in a decrease in the secretion of aldosterone. Perindopril acts through its active metabolite perindoprilata: Eliminates the vasoconstrictive effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I to angiotensin II, which has a vasoconstrictive effect, and also causes bradykinin and prostaglandin that have vasodilating activity); reduces the production and release of aldosterone, inhibits the release of norepinephrine from the endings of sympathetic nerve fibers and the formation of endothelin in the vessel wall.Reduction of the formation of angiotensin II is accompanied by an increase in the activity of renin of the blood plasma (due to the inhibition of negative feedback). Suppression of ACE is accompanied by an increase in the activity of both circulating and tissue kallikrein-kinin system, while the system of prostaglandins is also activated.

Helps restore the elasticity of large arterial vessels (reducing the formation of excessive amounts of subendothelial collagen), reduces pressure in the pulmonary capillaries, with long-term administration reduces the severity of myocardial hypertrophy of the left ventricle and interstitial fibrosis, normalizes the isozyme profile of myosin; normalizes the work of the heart.

Reduces preload and postnagruzku (reduces systolic and diastolic blood pressure in the "lying" and "standing"), the filling pressure of the left and right ventricles, the total peripheral resistance of the vessels; increases the minute volume of blood circulation and cardiac index without changing the heart rate (in patients with chronic heart failure), does not increase the heart rate, increases the regional blood flow in the muscles.

Increases the concentration of high density lipoproteins, in patients with hyperuricemia reduces the concentration of uric acid. Increases renal blood flow, not changes the skrage glomerular filtering.

In patients with chronic heart failure causes a significant decrease in the severity of clinical signs of heart failure, increases tolerance to physical activity (according to veloergometric test), does not reliably reduce blood pressure. After ingestion of the median single dose, the maximum hypotensive effect is achieved after 4-6 hours and persists for 24 hours. Stabilization of the hypotensive effect occurs after 1 month of therapy and persists for a long time. The termination of treatment is not accompanied by the development of the "withdrawal" syndrome.

Pharmacokinetics:

Absorption is 25%, bioavailability is 65-70%. Time to reach the maximum concentration in the plasma blood - 1 h, perindoprilata - 3-4 h.

In the process of metabolism, 20% is transformed into an active metabolite - perindoprilat (the intake of perindopril after meals reduces the proportion of perindoprilat that is formed - it has no significant clinical significance); The rest is in 5 inactive connections. T1 / 2 (half-life) of perindopril - 1 hour.The relationship between perindoprilata and blood plasma proteins is insignificant, with an ACE of less than 30% (dependent on concentration). Volume distribution of free perindoprilata - 0.2 l / kg.

Perindoprilat is excreted kidneys, T1 / 2 free fraction of the metabolite - 3-5 hours. Dissociation of perindoprilat, associated with ACE, is slow. Therefore, the "effective" T1 / 2 is 25 hours. Repeated administration of perindopril does not lead to its cumulation, and T1 / 2 perindoprilata with repeated admission corresponds to the period of its activity.

The excretion of perindoprilat is slowed in elderly patients, as well as in patients with chronic heart failure and chronic renal insufficiency (in the latter, dose adjustment should be performed depending on the creatinine clearance). The dialytic clearance of perindopril is 70 ml / min.

In patients with liver cirrhosis, the liver clearance of perindopril is reduced by a factor of 2, while the total amount of perindoprilat formed does not change and correction of the dosing regimen is not required.

Indications:Arterial hypertension; chronic heart failure.

Contraindications:

Hypersensitivity to perindopril and other components of the drug or other ACE inhibitors, angioedema in a history of therapy with ACE inhibitors,hereditary or idiopathic angioedema, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Carefully:

Stenosis of the aortic valve, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases (including cerebral circulatory insufficiency, coronary heart disease, coronary insufficiency - the risk of excessive decrease in arterial pressure and concomitant ischemia.

Heavy autoimmune systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis against immunosuppressant therapy (increased probability of neutropenia development).

Renovascular hypertension, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, condition after kidney transplantation (risk of renal and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), hyperkalemia, diet with sodium restriction, conditions accompanied by a decrease in the volume of circulating blood (incl.diarrhea, vomiting, diuretics), diabetes mellitus, advanced age, surgical intervention (general anesthesia).

Pregnancy and lactation:contraindicated

Dosing and Administration:

Inside, in the morning, before eating.

The initial dose for the treatment of hypertension is 4 mg / day, if necessary (after 1 month) the dose can be increased to 8 mg / day in one session.

With the appointment of ACE inhibitors, patients who are receiving diuretic therapy may experience a sharp decrease in blood pressure, for the prevention of which it is recommended to stop taking diuretics 2-3 days before the expected initiation of therapy with Perindopril or to prescribe the drug at lower doses - 2 mg once a day.

In patients with renovascular hypertension, the initial dose is 2 mg 1 time per day. If necessary, the dose may be increased later.

In elderly patients, therapy should be started at a dose of 2 mg per day, and then, if necessary, gradually increase it up to a maximum dose of 8 mg per day.

Treatment of patients with heart failure in combination with non-potassium-sparing diuretic and / or digoxin is recommended to begin under careful medical supervision, Perin was prescribed to administer in an initial dose of 2 mg once a day, in the morning.

In the future, after 1-2 weeks of therapy, the dose of the drug can be increased to 4 mg once a day.

In patients with impaired renal function, the dose of the drug should be selected taking into account the degree of renal failure: depending on the clearance of creatinine (CC).

With KK 30-60 ml / min - 2 mg once a day; with QC 15-30 ml / min - 2 mg every other day; patients on hemodialysis (QC less than 15 ml / min) - 2 mg per day of dialysis. With SC more than 60 ml / min 4 mg per day.

Perindopril to patients with impaired liver function, dose changes are not required.

Side effects:From the side of the cardiovascular system: often - excessive reduction in blood pressure and related symptoms, rarely - arrhythmia, angina, myocardial infarction and stroke.

From the urinary system: decreased kidney function, acute renal failure.

On the part of the respiratory system: often - a "dry" cough, difficulty breathing; rarely - bronchospasm, rhinorrhea.

From the digestive system: often - nausea, vomiting, abdominal pain, taste change, diarrhea or constipation, dry mouth, decreased appetite, cholestatic jaundice, pancreatitis, intestinal edema.

From the central nervous system: often - headache, asthenia, fatigue, dizziness, ringing in the ears, visual impairment, muscle cramps, paresthesia; rarely - decreased mood, insomnia; very rarely confusion.

Allergic reactions: often - skin rash, itching; rarely - hives, angioedema; extremely rarely - multiforme exudative erythema.

Laboratory indicators: often - hypercreatininaemia, proteinuria, hyperkalemia; hyperuricemia; rarely (with prolonged use in high doses) - neutropenia, leukopenia, hypohemoglobinaemia, thrombocytopenia, a decrease in hematocrit; extremely rare - agranulocytosis, pancytopenia, increased activity of "hepatic" enzymes, hyperbilirubinemia, hemolytic anemia (against the background of deficiency of glucose-6-phosphate dehydrogenase).

Other: increased sweating, violation of sexual function.

Overdose:

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, electrolyte disorders (hyperkalaemia, hyponatremia), renal failure.

Treatment: gastric lavage, restoration of the water-electrolyte state, intravenous injection of 0.9% sodium chloride solution.In the case of a marked decrease in blood pressure, the patient should be placed horizontally, lifting his legs up. Effective hemodialysis (do not use high permeability polyacrylnitrile membranes). With the development of bradycardia - atropine, an artificial pacemaker may be required.

Interaction:

Increases the severity of hypoglycemic action of insulin and sulfonylurea derivatives.

Baclofen, tricyclic antidepressants, antipsychotic drugs (antipsychotics), saluretics increase the hypotensive effect and increase the risk of orthostatic hypotension (additive effect), antacids reduce the bioavailability of ACE inhibitors.

Glucocorticosteroids, nonsteroidal anti-inflammatory drugs reduce the severity of hypotensive action (fluid retention and electrolytes).

Potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations increase the risk of hyperkalemia. It is not recommended simultaneous use of drugs that can cause hyperkalemia, and ACE inhibitors, except in cases of severe hypokalemia (control of potassium in the blood serum).

With simultaneous use with lithium preparations, it is possible to slow its removal from the body (regular monitoring of lithium content in the blood is necessary).

Diuretics, medicines for general anesthesia and muscle relaxants, ethanol increase the risk of excessive blood pressure lowering. The risk of developing clinically pronounced arterial hypotension can be reduced by stopping diuretics several days before starting treatment with perindopril.

Special instructions:

The risk of arterial hypotension and / or renal failure increases with a significant loss of sodium and water (strict salt-free diet, and / or diuretics, diarrhea, vomiting) or renal artery stenosis (blockade in these situations of the renin-angiotensin system may result , especially with the first intake of the drug and during the first 2 weeks of treatment, to a sudden decrease in blood pressure and the development of chronic kidney failure).

Before and during the therapy it is recommended to determine the concentration of creatinine, electrolytes and urea (within 1 month).

In patients with hypertension who are already receiving diuretic therapy, it is necessary to stop taking them (3 days before the appointment of Perindopril) and, if necessary, further add to treatment again.

In patients with chronic heart failure who receive diuretic therapy, if possible, their dose should also be reduced several days before the start of admission.

In patients at risk, especially with chronic heart insufficiency in the stage of decompensation, elderly patients, as well as patients with initially low blood pressure, impaired renal function or receiving large doses of diuretics, the beginning of the drug should be controlled.

Patients on hemodialysis should avoid the use of polyacrylonitrile membranes (possibly the development of anaphylactoid reactions). It is necessary to stop taking before the forthcoming surgical treatment for 12 hours and to warn the anesthesiologist about taking the drug.

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

In connection with the danger of developing arterial hypotension and dizziness,ACE inhibitors should be cautiously prescribed to persons managing motor vehicles and engaged in activities requiring increased attention and rapid motor reaction.

Form release / dosage:

Tablets of 2 mg and 4 mg.

For 10 or 30 tablets in a contour cell packaging.

For 30 tablets in a polymer jar or vial polymer.

Each bank, bottle, 3, 5 contour cell packs of 10 tablets or

1, 2 contour cell packs per 30 tablets together with instructions for

application in a cardboard bundle.

Packaging:(10) - polymer cans (1) - packs cardboard
(10) - cans of light-protective glass (1) - packs cardboard
(10) - packings, cellular, outline (1) - packs, cardboard
(10) - packings cellular planimetric (10) - packs cardboard
(10) - packings, cell planimetric (1000) - cardboard boxes
(10) - packings, cellular, outline (2) - packs, cardboard
(10) - packings, cellular outline (200) - cardboard boxes
(10) - packings, cellular, outline (3) - packs, cardboard
(10) - packings, cellular planimetric (5) - packs cardboard
(10) - polymer bottles (1) - packs of cardboard
(100) - polymer cans (1) - packs of cardboard
(100) - cans of light-protective glass (1) - packs cardboard
(100) - polymer bottles (1) - packs of cardboard
(15) - polymer cans (1) - packs cardboard
(15) - cans of light-protective glass (1) - packs cardboard
(15) - polymer bottles (1) - packs cardboard
(20) - polymer cans (1) - cardboard packs
(20) - cans of light-protective glass (1) - packs cardboard
(20) - polymer bottles (1) - packs of cardboard
(30) - polymer cans (1) - packs of cardboard
(30) - cans of light-protective glass (1) - packs cardboard
(30) - polymer bottles (1) - packs cardboard
(50) - polymer cans (1) - cardboard packs
(50) - cans of light-protective glass (1) - packs cardboard
(50) - polymer bottles (1) - packs cardboard

Storage conditions:

List B. In a dry, the dark place, at a temperature not inyshe 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-006978/08

Date of registration:01.09.2008

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp29.08.2015

Illustrated instructions

Instructions

Perindopril-SZ (Perindopril-SZ)