Index of drugs

Treatment of hypertension. Treatment of symptomatic heart failure. Reducing the risk of cardiac events in patients with a history of myocardial infarction and / or 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); drug contains lactose.

Perindopril is converted into the active metabolite - perindoprilat - ACE inhibitor (an enzyme that catalyzes the conversion of angiotensin I to vasopressor angiotensin II, as well as the breakdown of bradykinin acting vasodilating). Suppression of ACE activity results in a decrease in plasma angiotensin II, which leads to an increase in plasma renin activity (by inhibiting the negative feedback regulating renin secretion) and to reducing the secretion of aldosterone. Because ACE inactivates bradykinin, suppression of ACE activity also increases the activity of circulating and local kallikrein-kinin systems (and thus also activation of the prostaglandin system); it is possible that this mechanism is involved in the reduction of blood pressure by ACE inhibitors and is partly responsible for certain side effects (eg cough). The maximum antihypertensive effect occurs after 4-6 h after a single dose and persists for 24 hours. Perindopril is rapidly absorbed from the gastrointestinal tract, reaching C_max after about 1 hour. About 27% of the total amount of perindopril absorbed is converted into the active metabolite - perindopril. The maximum concentration of perindoprilat in the blood is reached within 3-4 h. Food reduces the bioavailability of perindoprilat. In addition to active perindoprilat, there are 5 other metabolites, all inactive. Perindoprilat is excreted in the urine and T_0,5 the free fraction is about 17 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.

Blood pressure and renal function should be monitored at the beginning as well as during treatment with perindopril. 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. Particularly cautiously use in patients with highly energized renin-angiotensin-aldosterone system, due to the risk of significant hypotension (closely monitor initiation of treatment and dose adjustment) - this applies to patients: fluid deficiency and / or hyponatremia (as a result of diuretic therapy, dialysis, restriction of salt in the diet, diarrhea or vomiting); with severe renin-dependent hypertension; with symptomatic heart failure with concomitant or impaired renal function; with renal arterial hypertension (with bilateral renal artery stenosis or stenosis of the artery of the sole kidney); with impaired renal function. 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).If hypotension occurs during treatment with perindopril, the patient should be positioned on the back and, if necessary, given a saline infusion of physiological saline. Transient hypotension is not a contraindication to the administration of subsequent doses of perindopril, which can usually be administered without difficulty when the blood pressure increases after increasing the volume of fluids. If hypotension during treatment becomes symptomatic, it may be necessary to reduce the dose or discontinue treatment with perindopril. Since the use of diuretics may contribute to the occurrence of hypotension, it may be necessary to reduce the dose and / or discontinue diuretic therapy. Caution should be exercised when administering perindopril to patients with mitral stenosis and impaired left ventricular outflow, such as aortic stenosis or hypertrophic cardiomyopathy. In patients with impaired renal function (creatinine clearance <60 ml / min), monitoring of potassium and creatinine should be monitored during perindopril treatment. In patients with symptomatic heart failure, the occurrence of hypotension after initiation of ACE inhibitor therapy may result in further impairment of renal function; acute renal failure (usually reversible) may occur. In patients with bilateral renal artery stenosis or stenosis of the artery supplying blood to a single kidney treated with an ACE inhibitor, an increase in serum urea and creatinine was observed (these changes were generally transient after discontinuation of the drug); this particularly applies to patients with renal failure. There are no data available on the use of perindopril in patients who have recently had a kidney transplant. Special care should be taken in patients with vascular collagen, using immunosuppressive drugs, taking Allopurinol or procainamide or in patients who co-exist with these factors, in particular coexistence of renal impairment - monitor the patient for infection and periodically control the number of white blood cells. In diabetic patients treated with oral antidiabetic agents or insulin, blood Glucose monitoring should be closely monitored during the first month of treatment with an ACE inhibitor. Exercise caution in patients at risk of hyperkalaemia: renal failure,> 70 years of age, uncontrolled diabetes, dehydrated, acute heart failure, metabolic acidosis, as well as people taking potassium salts, potassium sparing diuretics and other potassium blood - if you need to use these medicines simultaneously, your blood potassium levels should be closely monitored. Co-administration of perindopril and lithium is not recommended. In patients undergoing dialysis with high permeability, there is a high likelihood of anaphylactoid reactions - consideration should be given to using an antihypertensive agent from another group or other type of dialysis membranes. In patients requiring venom desease desensitization or LDL-apheresis treatment with dextran sulphate, it is recommended to temporarily discontinue ACE inhibitors due to the risk of life-threatening anaphylactoid reactions. In patients who develop angioneurotic edema of the face, limbs, lips, tongue, mucous membranes, glottis and or larynx, the drug should be immediately discontinued, appropriate therapy should be instituted and the patient monitored until the signs of edema have completely resolved (fatal angioedema has been observed associated with laryngeal or tongue swelling). Angioedema of the gut should be taken into account in the differential diagnosis of abdominal pain in patients treated with ACE inhibitors. The black patients are more likely to have angioedema. In black patients, perindopril may be less effective. In case of jaundice or a significant increase in liver enzymes, perindopril should be discontinued and appropriate treatment should be given. In the differential diagnosis of cough, cough induced by ACE inhibitors should be considered. Use in children and adolescents <18 years 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.

The use of perindopril in the first trimester of pregnancy is not recommended (there is a risk of teratogenicity). Use in the second and third trimester of pregnancy is contraindicated. Perindopril used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - when exposure to the drug occurred from the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension. The drug is not recommended during breast-feeding.

Common: headache, dizziness of central and peripheral origin, paresthesia, visual disturbances, tinnitus, hypotension and disorders associated with it, cough, shortness of breath, nausea, vomiting, abdominal pain, taste disturbances, indigestion, diarrhea, constipation, rash, pruritus , asthenia. Uncommon: mood or sleep disorders, bronchospasm, dry mouth, swelling of the face, limbs, lips, mucous membranes, tongue, glottis and / or larynx, urticaria, muscle cramps, renal failure, impotence, excessive sweating. Very rare: confusion, arrhythmia, angina and myocardial infarction (probably secondary to excessive hypotension in high-risk patients), stroke (probably secondary to excessive hypotension in high-risk patients), eosinophilic pneumonia, rhinitis pancreatitis, cytolytic or cholestatic hepatitis, erythema multiforme, acute renal failure, decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, pancytopenia; hemolytic anemia - in patients with congenital deficiency of glucose-6-phosphate dehydrogenase. Frequency unknown: hypoglycaemia, vasculitis. There may be an increase in urea and creatinine in the blood, hyperkalemia which resolves after discontinuation of the drug, especially in the case of co-existing renal failure, severe heart failure and in renovascular hypertension. Increases in liver enzymes and increased bilirubin in the blood have been observed rarely.

Orally.Hypertension. Perindopril can be used alone 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, you can resume administration of diuretics. 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 before increasing the dose to 8 mg once a day, depending on 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 (CCr): CCr ≥ 60 ml / min - the recommended dose of 4 mg / day; 30 The tablets can be divided in half. It is recommended to take the product in the morning before a meal.