Index of drugs

Treatment of hypertension. Treatment of symptomatic heart failure. Reducing the risk of cardiac events in patients after myocardial infarction and / or after revascularization.

1 tabl contains 4 mg Perindopril with tert-butylamine (corresponding to 3.338 mg perindopril) or 8 mg perindopril with tert-butylamine (corresponding to 6.676 mg perindopril). The preparation contains lactose.

Perindopril is converted into the active metabolite - Perindopril, which is an inhibitor of ACE (angiotensin converting enzyme I to angiotensin II). Suppression of ACE activity results in a decrease in angiotensin II concentration in the plasma, which leads to increased plasma renin activity, decreased aldosterone secretion and increased circulating activity as well as local kallikrein-kinin systems. The maximum antihypertensive effect occurs after 4-6 h after a single dose and persists for at least 24 h. After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract and reaches a maximum blood concentration after 1 h. The bioavailability is 65-70%. About 20% of the total amount of perindopril absorbed is converted into perindoprilat, the active metabolite. T_0,5 perindopril is 1 hour. The maximum concentration of perindoprilat in the blood is reached within 3-4 h. Food reduces the bioavailability of perindopril. Perindoprilat is excreted in the urine and T_0,5 the free fraction is 3-5 h, whereas the bound fraction is 25 h. When repeatedly administered, steady state is achieved within 4 days. Elimination of perindoprilat is slower in the elderly and in patients with heart or kidney failure. Perindoprilat is removed from the circulation by dialysis.

Hypersensitivity to perindopril, other ACE inhibitors or other components of the preparation. History of angioneurotic edema associated with previous treatment with ACE inhibitors. Hereditary or idiopathic angioneurotic edema. II and III trimester of pregnancy.

If an episode of unstable angina (severe or not) occurs during the first month of treatment with perindopril, the benefit-risk of continuing therapy should be considered. Due to the risk of hypotension, particularly cautiously use in patients with fluid deficiency (as a result of diuretic therapy, dialysis, dietary salt restriction, diarrhea or vomiting), severe hypertensive arterial hypertension, symptomatic heart failure with coexisting renal dysfunction or without, with hyponatraemia and in patients with impaired renal function - starting treatment and adjusting the dose should be closely monitored. Similar recommendations should be used in patients with ischemic heart disease and cerebrovascular disorders, in which a significant reduction in blood pressure may lead to a myocardial infarction or cerebrovascular accident. Caution should also be exercised in patients undergoing major surgery or under general anesthesia with hypotensive agents; treatment with the preparation should be discontinued 1 day before the planned surgery (hypotension can be compensated by increasing the intravascular volume). Caution should be used in patients with bilateral renal artery stenosis or stenosis of the artery of the sole kidney. In patients with renovascular hypertension and renal artery stenosis there is an increased risk of significant hypotension and renal failure - treatment should be started with small doses after close medical supervision and dose should be carefully increased; in the first weeks of treatment with perindopril, diuretic should be discontinued and renal function should be monitored. It should be used with caution in patients with mitral valve stenosis and narrowing of the left ventricle outflow pathway, e.g. as aortic valve stenosis or hypertrophic cardiomyopathy.Use with caution in patients with vascular collagen, patients taking immunosuppressant, Allopurinol or procainamide (risk of neutropenia); with a history of angioneurotic edema, unrelated to the use of an ACE inhibitor; with the risk of hyperkalemia (including patients with renal insufficiency, diabetes, while taking potassium sparing diuretics, potassium supplements or potassium substitutes containing potassium or other drugs that increase the level of potassium in the blood). There is no experience regarding the use of perindopril in patients who have recently undergone kidney transplantation. In dialysis patients with dialysis membranes of high permeability and simultaneously treated with ACE inhibitors, anaphylactoid reactions have been observed - consideration should be given to the use of other types of dialysis membranes or antihypertensive agents from other groups. The preparation should be discontinued before LDL-apheresis with dextran sulphate or before the start of desensitization treatment due to the risk of life-threatening anaphylactoid reactions. ACE inhibitors are more likely to cause angioneurotic edema in black patients than in non-black patients. Perindopril may be less effective in lowering blood pressure in black patients. Patients receiving ACE inhibitors who develop jaundice or have significantly increased liver enzymes should discontinue ACE inhibitors. The preparation should be discontinued in the event of angioedema and the patient should be monitored until the symptoms have completely resolved. The efficacy and safety of the preparation in children has not been established - the use in this group of patients is not recommended. Due to the lactose content, the preparation should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

Perindopril should not be used during the first trimester of pregnancy. The drug is contraindicated in the second and third trimester of pregnancy. Administration of the preparation during the second and third trimester of pregnancy results in renal dysfunction, oligohydramnios, skull ossification retardation and renal failure, hypotension and hyperkalemia in the newborn. In the case of exposure to perindopril, starting from the second trimester of pregnancy, ultrasound examination of the kidneys and skull is recommended. Newborns whose mothers have taken ACE inhibitors should be monitored for hypotension. It is not recommended to use the product during breastfeeding.

Common: pain and dizziness, paresthesia; blurred vision; Tinnitus; hypotension and symptomatic hypotension; cough, shortness of breath; nausea, vomiting, abdominal pain, indigestion, diarrhea and constipation; rash, pruritus; muscle cramps; asthenia. Uncommon: mood disorders or sleep disorders; bronchial spasm; dryness of the oral mucosa; angioneurotic edema of the face, limbs, lips, mucous membranes, tongue, glottis or larynx, urticaria; renal failure; impotence; excessive sweating. Very rare: confusion; arrhythmia, angina, myocardial infarction and stroke (probably secondary to increased hypotension in high-risk patients); eosinophilic pneumonia, rhinitis; inflammation of the pancreas; cytolytic or cholestatic hepatitis; erythema multiforme; acute renal failure; decreases in hemoglobin and hematocrit, thrombocytopenia, leukopenia, neutropenia, agranulocytosis or pancytopenia, cases of hemolytic anemia in patients with congenital G-6-PD deficiency. Increases in urea and creatinine in the blood may occur as well as hyperkalemia which resolves after discontinuation of the preparation (especially in patients with renal failure, severe heart failure, renovascular hypertension). In isolated cases: increased liver enzymes and bilirubin in the blood. Rarely, the use of ACE inhibitor is associated with the onset of syndrome starting with cholestasis jaundice developing into fulminant hepatic necrosis, sometimes leading to death.

Orally.Hypertension. The product can be used as monotherapy or in combination with other antihypertensive medicines from other groups. The recommended starting dose is 4 mg once a day in the morning.In patients with high activity of the renin-angiotensin-aldosterone system (in particular with renovascular hypertension, electrolyte and / or fluid deficiency, decompensated heart failure or severe hypertension), excessive hypotension may occur after the initial dose - in these patients patients, the recommended starting dose is 2 mg, and treatment should be started under close medical supervision. After a month of treatment, the daily dose can be increased to 8 mg once a day. Concomitant use of diuretics: if possible, diuretic therapy should be discontinued 2-3 days before commencing therapy with perindopril; in patients who can not discontinue diuretic therapy, the treatment should be started with a dose of 2 mg, renal function and potassium levels should be monitored. The further dosage of perindopril should be adjusted to changes in blood pressure in response to treatment. If necessary, treatment with diuretics can be restarted. In elderly patients, treatment should be started with a dose of 2 mg, which can be gradually increased to 4 mg after the first month of treatment and, if necessary, to 8 mg, depending on renal function.Symptomatic heart failure. It is recommended to start treatment with perindopril, generally given in combination with a diuretic, non-potassium and / or Digoxin and / or β-blocker, under close medical supervision from an initial dose of 2 mg once a day in the morning. If this dose is well tolerated, it may be increased by 2 mg, not earlier than after 2 weeks, up to 4 mg once a day. The dose should be adjusted depending on the clinical response of the patient. In patients with severe heart failure or in other high-risk patients (patients with impaired renal function and with a tendency to electrolyte disturbances, patients treated concomitantly with diuretics and / or vasodilators), treatment should be started under close medical supervision . Patients with a high risk of symptomatic hypotension (eg patients with electrolyte depletion with or without hyponatraemia, dehydrated patients or patients undergoing intensive diuretic treatment should have these disorders discharged prior to commencing treatment with perindopril.Stable coronary heart disease. Treatment with perindopril should be started with 4 mg once a day for 2 weeks, and then increased to 8 mg once a day, depending on kidney function and on condition that the 4 mg dose is well tolerated. Elderly patients should receive 2 mg once a day for a week, followed by 4 mg once a day for the Next week. The dose may be increased to 8 mg once a day depending on your kidney function. The dose can only be increased if the previous lower dose is well tolerated.Special groups of patients. In patients with renal insufficiency, the dosage should be adjusted based on the creatinine clearance: creatinine clearance ≥60 ml / min - the recommended dose of 4 mg / day; clearance 30-60 ml / min - 2 mg / day; clearance 15-30 ml / min - 2 mg every other day, clearance <15 ml / min - 2 mg on the day of dialysis, the dose should be administered after dialysis. No dosage adjustment is necessary in patients with hepatic impairment.
The tablets can be divided in half. It is recommended to take the product in the morning before a meal.