Perindopril-SZ, pills 4mg, 30pcs

Composition

1 tablet contains the Active ingredient: perindopril erbumin 4 mg. Auxiliary substances: lactose (milk sugar); microcrystalline cellulose; croscarmellose sodium (primellose); colloidal silicon dioxide (aerosil); magnesium stearate. Description: Tablets are white or almost white in color, round, flat-cylindrical in shape with a chamfer.

Pharmacological action

Pharmacotherapeutic group:

angiotensin-converting enzyme inhibitor (ACE).

ATX code: [C09AA04].

Pharmacological properties.

Pharmacodynamics .

An ACE inhibitor. ACE inhibition leads to a decrease in the level of angiotensin II in the blood plasma, as a result of which the secretion of aldosterone decreases. Perindopril acts through its active metabolite, perindoprilate.

Eliminates the vasoconstrictor effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I to angiotensin II, which has a vasoconstrictor effect, and also causes the degradation of bradykinin and prostaglandin, which have vasodilating activity); reduces the production and release of aldosterone, suppresses the release of norepinephrine from the endings of sympathetic nerve fibers and the formation of endothelin in the vascular wall. A decrease in angiotensin II production is accompanied by an increase in plasma renin activity (due to inhibition of negative feedback).

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. Helps restore the elasticity of large arterial vessels (reducing the formation of excessive amounts of subendothelial collagen), reduces pressure in the pulmonary capillaries, with prolonged use reduces the severity of left ventricular hypertrophy and interstitial fibrosis, normalizes the isoenzyme profile of myosin; normalizes heart function.

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

Increases the concentration of high-density lipoproteins, reduces the concentration of uric acid in patients with hyperuricemia. Increases renal blood flow, does not change the glomerular filtration rate. In patients with chronic heart failure, it causes a significant decrease in the severity of clinical signs of heart failure, increases tolerance to physical activity (according to the bicycle ergometric test), and does not significantly reduce blood pressure.

After ingestion of an average single dose, the maximum antihypertensive effect is achieved in 4-6 hours and persists for 24 hours. Stabilization of the antihypertensive effect is observed after 1 month of therapy and persists for a long time. Discontinuation of treatment is not accompanied by the development of “withdrawal” syndrome.

Pharmacokinetics.

Absorption – 25%, bioavailability-65-70%. The time to reach the maximum concentration in blood plasma is 1 hour, perindoprilat – 3-4 hours. In the process of metabolism,20% is transformed into the active metabolite-perindoprilate (taking perindopril after a meal reduces the proportion of perindoprilate formed – it has no significant clinical significance); the remaining amount is converted into 5 inactive compounds. T 1/2 (half-life) of perindopril is 1 h.

The association of perindoprilat with plasma proteins is insignificant, with ACE-less than 30% (depending on the concentration). The volume of distribution of free perindoprilate is 0.2 l / kg. Perindoprilat is excreted by the kidneys, T 1/2 of the free fraction of the metabolite is 3-5 hours. Dissociation of ACE-associated perindoprilate is slow. As a result, the” effective ” T 1/2 is 25 hours.

Repeated use of perindopril does not lead to its accumulation, and T 1/2 of perindoprilat with repeated use corresponds to the period of its activity. Elimination of perindoprilat slows down in elderly patients, as well as in patients with chronic heart failure and chronic renal failure (in the latter, dose adjustment should be carried out depending on creatinine clearance).

The dialysis clearance of perindopril is 70 ml/min. In patients with cirrhosis of the liver, the hepatic clearance of perindopril decreases by 2 times, while the total amount of perindoprilate formed does not change and no dosage adjustment is required.

Indications

Arterial hypertension, chronic heart failure.

Contraindications

Hypersensitivity to perindopril and other components of the drug or other ACE inhibitors, angioedema in the anamnesis against the background of therapy with inhibitors. ACE inhibitor, hereditary or idiopathic angioedema, pregnancy, lactation, age up to 18 years (efficacy and safety have not been established). With caution: Aortic valve stenosis, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases (including cerebrovascular insufficiency, coronary heart disease, coronary insufficiency – the risk of excessive blood pressure reduction and concomitant ischemia). Severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), inhibition of bone marrow hematopoiesis while taking immunosuppressants (increased probability of neutropenia). Renovascular hypertension, bilateral renal artery stenosis, single kidney artery stenosis, post-kidney transplantation conditions (risk of renal dysfunction and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), hyperkalemia, a sodium-restricted diet, conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting, diuretics), diabetes mellitus, old age, surgery (general anesthesia).

Side effects

-From the cardiovascular system: often-excessive decrease in blood pressure and related symptoms, rarely-arrhythmia, angina pectoris, myocardial infarction and stroke. – From the urinary system: decreased renal function, acute renal failure. – From the respiratory system: often- ” dry ” cough, difficulty breathing; rarely-bronchospasm, rhinorrhea. – From the digestive system: often – nausea, vomiting, abdominal pain, changes in taste, 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 disturbances, muscle cramps, paresthesia; rarely-decreased mood, insomnia; extremely rarely-confusion. – Allergic reactions: often-skin rash, pruritus; rarely-urticaria, angioedema; extremely rarely-erythema multiforme. – Laboratory parameters: often – hypercreatininemia, proteinuria, hyperkalemia; hyperuricemia; rarely (with prolonged use in high doses) – neutropenia, leukopenia, hypohemoglobinemia, thrombocytopenia, decreased hematocrit; extremely rarely – agranulocytosis, pancytopenia, increased activity of “liver” enzymes, hyperbilirubinemia, hemolytic anemia (against the background of glucose-6 deficiency – phosphate dehydrogenase). – Other: increased sweating, impaired sexual function.

Interaction

When used concomitantly with antihypertensive agents, muscle relaxants, and anesthetics, it is possible to increase the antihypertensive effect.

When used concomitantly with loop diuretics, thiazide diuretics, it is possible to increase the antihypertensive effect. Severe hypotension, especially after taking the first dose of a diuretic, appears to occur due to hypovolemia, which leads to a transient increase in the hypotensive effect of perindopril. The risk of impaired renal function increases.

When used concomitantly with sympathomimetics, the antihypertensive effect of perindopril may be reduced.

When used concomitantly with tricyclic antidepressants, antipsychotic drugs (neuroleptics), the risk of postural hypotension increases.

When used concomitantly with indomethacin, the antihypertensive effect of perindopril decreases, apparently due to the inhibition of prostaglandin synthesis under the influence of NSAIDs (which are believed to play a role in the development of the antihypertensive effect of ACE inhibitors).

When used concomitantly with insulin, hypoglycemic agents and sulfonylureas, hypoglycemia may develop due to increased glucose tolerance.

When used concomitantly with potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes, and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), since ACE inhibitors reduce the content of aldosterone, which leads to potassium retention in the body against the background of limiting the excretion of potassium or its additional intake into the body.

When used concomitantly with lithium carbonate, it is possible to reduce the excretion of lithium from the body.

How to take it, course of use and dosage

Inside, in the morning, before eating. The initial dose for the treatment of arterial hypertension is 4 mg / day, if necessary (after 1 month), the dose can be increased to 8 mg/day in one dose.When prescribing ACE inhibitors to patients receiving diuretic therapy, there may be a sharp decrease in blood pressure, for the prevention of which it is recommended to stop taking diuretics 2-3 days before the expected start of therapy with Perindopril or prescribe the drug in lower doses-2 mg 1 time a day.

In patients with renovascular hypertension, the initial dose is 2 mg once a day. If necessary, the dose can be increased later.

In elderly patients, therapy should begin with 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 a non-potassium-sparing diuretic and / or digoxin is recommended to start under close medical supervision, Perindopril should be prescribed at an initial dose of 2 mg 1 time 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 insufficiency: depending on creatinine clearance (CC). With creatinine clearance 30-60 ml / min-2 mg once a day; with creatinine clearance 15-30 ml / min-2 mg every other day; patients on hemodialysis (creatinine clearance less than 15 ml / min) – 2 mg on the day of dialysis. When creatinine clearance is more than 60 ml / min,4 mg per day. Patients with impaired liver function do not need to change the dose of Perindopril.

Overdose

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, electrolyte disturbances (hyperkalemia, hyponatremia), renal failure. Treatment: gastric lavage, restoration of the water-electrolyte state, intravenous use of 0.9% sodium chloride solution. In case of a marked decrease in arterial pressure, the patient should be placed horizontally, lifting his legs up. Hemodialysis is effective (do not use highly permeable polyacrylonitrile membranes). With the development of bradycardia – atropine, it may be necessary to install an artificial pacemaker.

Special instructions

the Risk of arterial hypotension and/or renal insufficiency on the background of the drug increased with significant loss of sodium and water (with a strict salt-free diet, and/or diuretics, diarrhea, vomiting) or renal artery stenosis (blockage in these situations, the renin-angiotensin system can cause, especially when first taking the drug and for the first 2 weeks of treatment, a sudden decrease in arterial blood pressure and chronic kidney failure).

Before starting and during therapy, it is recommended to determine the concentration of creatinine, electrolytes and urea (within 1 month). In patients with arterial hypertension who are already receiving diuretic therapy, it is necessary to stop taking them (3 days before the start of Perindopril use) and, if necessary, add them to treatment again.

In patients with chronic heart failure receiving diuretic therapy, if possible, their dose should also be reduced a few days before the start of use. In patients at risk, especially those with decompensated chronic heart failure, elderly patients, as well as patients with initially low blood pressure, impaired renal function, or receiving high doses of diuretics, the start of the drug should be monitored.

In patients undergoing hemodialysis, the use of polyacrylonitrile membranes should be avoided (anaphylactoid reactions may occur). It is necessary to stop taking before the upcoming surgical treatment for 12 hours and warn the anesthesiologist about taking the drug.

Influence on the ability to drive a car and perform work that requires increased attention.

Due to the risk of developing arterial hypotension and dizziness, ACE inhibitors should be prescribed with caution to people driving vehicles and engaged in activities that require increased attention and rapid motor response.

Form of production

Tablets

Storage conditions

List B. In a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 2 years. Do not use later than the date indicated on the package.

Active ingredient

Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

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