Perindopril, 4 mg 30 pcs

Perindopril is an ACE inhibitor (it interacts with the zinc ions in the ACE molecule and causes its inactivation). Perindopril acts through its active metabolite perindoprilat. Eliminates the vasoconstrictor effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I into angiotensin II, which has a vasoconstrictor effect, and causes degradation of bradykinin and prostaglandins that have vasodilator activity); reduces the production and release

aldosterone, inhibits the release of noradrenaline from sympathetic nerve fiber endings and the formation of endothelin in the vascular wall. Reduction of angiotensin II formation is accompanied by an increase in plasma renin activity (due to inhibition of negative feedback). ACE suppression is accompanied by increased activity of both circulating and tissue kallikrein-kinin system as well as prostaglandin system.

It promotes restoration of elasticity of large arterial vessels (decrease of formation of excessive amount of subendothelial collagen), reduces pressure in pulmonary capillaries, with long-term prescription it reduces expression of left ventricular myocardial hypertrophy and interstitial fibrosis, normalizes myosin isoenzyme profile; normalizes heart function.

Limits preload and postload (reduces systolic and diastolic blood pressure (BP) in “lying” and “standing” position), filling pressure of the left and right ventricles, total peripheral vascular resistance (TPR); increases minute blood volume (MOB) and cardiac index, does not increase heart rate (HR) (in patients with chronic heart failure (CHF) moderately reduces HR), increases 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, does not change glomerular filtration rate.

Indications

Arterial hypertension.
Chronic heart failure.

Active ingredient

Composition

1 tablet contains perindopril erbumin – 4 mg.

How to take, the dosage

The initial dose for treatment of arterial hypertension is 4 mg/day; if necessary (after 1 month), the dose may be increased to 8 mg/day in a single dose.

When ACE inhibitors are prescribed in patients receiving diuretic therapy, a sharp decrease in BP may be noted. To prevent this, it is recommended to discontinue diuretics 2-3 days before the intended start of therapy with Perindopril or to prescribe the drug in lower doses of 2 mg once daily.

In patients with renovascular hypertension, the initial dose is 2 mg once daily. If necessary, the dose can be subsequently increased.

In elderly patients, therapy should be started with a dose of 2 mg daily and then, if necessary, gradually increased up to a maximum dose of 8 mg daily.

The treatment of patients with chronic heart failure in combination with a non-caliber diuretic and/or digoxin is recommended to start under close medical supervision, Perindopril should be prescribed in an initial dose of 2 mg once daily, in the morning.
Later, after 1-2 weeks of therapy, the drug dose may be increased to 4 mg once daily.

In patients with impaired renal function the dose should be adjusted according to the degree of renal failure: depending on creatinine clearance.

If creatinine clearance is greater than 60 ml/min, 4 mg of perindopril daily. If creatinine clearance is 30-60 ml/min – 2 mg once daily; if creatinine clearance is 15-30 ml/min – 2 mg every other day; patients on hemodialysis (creatinine clearance less than 15 ml/min) – 2 mg per day of dialysis.

Patients with impaired liver function do not need dose changes.

Interaction

Baclofen, tricyclic antidepressants, antipsychotic drugs (neuroleptics), saluretics increase the hypotensive effect and increase the risk of orthostatic hypotension (additive effect).

Antacids decrease the bioavailability of ACE inhibitors.

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

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

In concomitant use with lithium preparations, its excretion from the body may be delayed (regular monitoring of lithium in the blood is necessary).

Diuretics, drugs for general anesthesia and muscle relaxants, ethanol increase the risk of excessive reduction of blood pressure. The risk of clinically significant arterial hypotension may be reduced by discontinuing diuretics several days prior to treatment with perindopril.

Myelotoxic drugs – increase myelotoxic effect.

Special Instructions

The risk of arterial hypotension and/or renal insufficiency against the background of the drug increases with significant sodium and water loss (strict salt-free diet, and/or use of diuretics, diarrhea, vomiting) or renal artery stenosis (blockade of the renin-angiotensin system in these situations may lead, especially during the first drug administration and during the first 2 weeks of treatment, to a sudden decrease of blood pressure and development of chronic renal insufficiency). It is recommended to determine creatinine, electrolyte and urea concentrations before and during therapy (within 1 month).

In patients with arterial hypertension who are already receiving therapy with diuretics, it is necessary to stop their administration (3 days before Perindopril administration) and, if necessary, to add them again to the treatment in future.

In patients with chronic heart failure receiving therapy with diuretics, if possible, their dose should also be reduced a few days before starting.

In patients at risk, especially those with decompensated chronic heart failure, elderly patients, and patients with baseline low blood pressure, impaired renal function, or those receiving high doses of diuretics, initiation of the drug should be under medical supervision.

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

Contraindications

Hypersensitivity to perindopril and other components of Perindopril or other ACE inhibitors, history of angioedema during therapy with ACE inhibitors, hereditary or idiopathic angioedema, pregnancy, lactation, age under 18 years (effectiveness and safety not established).

With caution:

Aortic valve stenosis, hypertrophic obstructive cardiomyopathy, cerebro- and cardiovascular disease (including cerebrovascular insufficiency, coronary heart disease, coronary artery disease – risk of excessive blood pressure drop and concomitant ischemia).

Severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), suppression of medullary hematopoiesis while taking immunosuppressants (increased possibility of neutropenia).

Renovascular hypertension, bilateral renal artery stenosis, artery stenosis of the single kidney, conditions after renal transplantation (risk of renal dysfunction and agranulocytosis), chronic renal failure (especially accompanied with hyperkalemia), hyperkalemia, diet with sodium restriction, conditions accompanied with decreased volume of circulating blood (including diarrhea, vomiting, diarrhea and hypertension).including diarrhea, vomiting, use of diuretics), diabetes, elderly age, surgical interventions (general anesthesia).

Side effects

The incidence of side effects is estimated on the basis of: often – 1-10%; rarely – 0.1-1%; extremely rare, including isolated reports – less than 0.1%.

Cardiovascular system: often – excessive decrease in blood pressure and related symptoms, rarely – arrhythmia, angina pectoris, myocardial infarction and stroke.

Urinary system disorders: decreased renal function and acute renal failure.

Respiratory system disorders: often – “dry” cough, difficulty in breathing; rarely – bronchospasm, rhinorrhea.

Gastrointestinal system: frequently – nausea, vomiting, abdominal pain, change in taste, diarrhea or constipation, dry mouth, decreased appetite, cholestatic jaundice, pancreatitis, intestinal edema.

The central nervous system: often – headache, asthenia, fatigue, dizziness, tinnitus, visual disturbances, muscle cramps, paresthesias; rarely – decreased mood, insomnia; extremely rare – confusion.

Allergic reactions: common – skin rash, itching, rarely – urticaria, angioedema; very rare – erythema multiforme.

Laboratory indices: frequent – hypercreatininemia, proteinuria, hyperkalemia; hyperuricemia; rare (with prolonged use in high doses) – neutropenia, leukopenia, hypogemoglobinemia, thrombocytopenia, reduced hematocrit; Very rarely – agranulocytosis, pancytopenia, increased “liver” enzymes activity, hyperbilirubinemia, hemolytic anemia (with glucose-6-phosphate dehydrogenase deficiency).

Others: increased sweating, impaired sexual function.

Overdose

Symptoms: BP decrease, shock, stupor, bradycardia, electrolyte disturbances, renal failure.

Treatment: gastric lavage, enterosorbents, restoration of water-electrolyte balance, intravenous injection of 0.9% sodium chloride solution. In case of marked BP decrease, the patient should be placed in a horizontal position with elevated legs.

Hemodialysis is effective (do not use highly permeable polyacrylonitrile membranes). If bradycardia develops – atropine. Temporary implantation of a pacemaker is indicated in severe cases. It is necessary to monitor and correct vital body functions.

Similarities