Index of drugs

Treatment of hypertension. Treatment of symptomatic heart failure. Reducing the risk of cardiac events in patients after 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 reducing blood pressure and is partly responsible for specific 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 conversion of perindopril to perindoprilat and therefore its bioavailability. Perindoprilat is excreted in the urine and T_0,5 the free fraction is about 17 h. The stationary 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. Angioedema associated with the use of an ACE inhibitor. Congenital or idiopathic angioedema. II and III trimester of pregnancy. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

If an episode of unstable coronary disease (severe or not) occurs during the first month of treatment with perindopril, the benefit / risk ratio should be carefully assessed before continuing treatment. Because of the risk of hypotension, use caution in patients with a reduced plasma volume, eg as a result of treatment with diuretics, a low-sodium diet, dialysis, diarrhea or vomiting, or in patients with severe renin-dependent hypertension. Symptomatic hypotension has been observed in patients with symptomatic heart failure, with or without renal insufficiency. Its occurrence is more likely in patients with a higher class of heart failure who are using high doses of loop diuretics, in patients with hyponatremia or with renal dysfunction. In patients with an increased risk of symptomatic hypotension, the initial period of application and the dose setting period should be closely monitored. The above claims also apply to patients with ischemic heart disease or patients with cerebral circulation disorders in which excessive hypotension may result in myocardial infarction or cerebrovascular accident. In some patients with congestive heart failure with normal or low blood pressure, additional hypotension may occur after perindopril administration. This effect is expected and usually does not result in discontinuation of treatment. If symptoms of hypotension occur, it may be necessary to reduce the dose or discontinue use.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 exercised when administering perindopril to patients with mitral stenosis or narrowing of the left ventricle outflow path such as aortic stenosis or hypertrophic cardiomyopathy. In patients with impaired renal function (creatinine clearance <60 ml / min), potassium and creatinine should be monitored. 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 transient) may occur. In patients with bilateral renal artery stenosis or stenosis of the artery supplying blood to the only kidney, 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. In the case of coexistence of renovascular hypertension, there is an increased risk of developing severe hypotension and renal failure. Co-administration of diuretics may be a predisposing factor to the above-mentioned complications - treatment with diuretics should be discontinued and the parameters of renal function should be monitored during the first weeks of treatment with perindopril. In some hypertensive patients with no previous renal stenosis, there was an increase in blood urea and serum creatinine, usually mild and transient, especially when the product was given concomitantly with a diuretic. This is more likely in patients with existing renal impairment. Dose reduction and / or discontinuation of the diuretic and / or formulation may be necessary. 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 have these conditions, especially when a renal dysfunction has occurred - 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. Caution in patients at risk of hyperkalemia: patients with renal failure, deterioration of kidney function (age> 70 years), diabetes, dehydration, acute decompensation of heart failure, metabolic acidosis, taking potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes other substances that increase the level of potassium in the blood - if you need to use these medicines at the same time, 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. For patients requiring desensitisation, eg Hymenoptera venom or apheresis, low-density lipoproteins using dextran sulphate, it is recommended to temporarily discontinue ACE inhibitors due to the risk of life-threatening anaphylactoid reactions. Angioedema may occur at any time during treatment, if necessary, discontinue use. 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.The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. It is not recommended for use in children and adolescents <18 years. 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 ACE inhibitors in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effects). 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 (renal dysfunction, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - if exposure to the drug occurred from the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; newborns 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 , weakness. Uncommon: mood or sleep disorders, bronchospasm, dry mouth, angioneurotic edema of the face, limbs, lips, mucous membranes, tongue, glottis and / or larynx, urticaria, muscle cramps, renal failure, impotence, excessive sweating. Rare: increase in liver enzymes, increase in bilirubin in the blood. Very rare: confusion, arrhythmia, angina pectoris and myocardial infarction (probably secondary to excessive hypotension in high-risk patients), stroke (possibly following excessive hypotension in high-risk patients), eosinophilic pneumonia, rhinitis, pancreatitis, cytolytic or cholestatic hepatitis, erythema multiforme, acute renal failure, agranulocytosis, pancytopenia, in patients with G-6-PD deficiency, hemolytic anemia. Frequency unknown: hypoglycaemia, vasculitis. Increases in urea and creatinine in the blood may occur, hyperkalaemia resolves after discontinuation of the drug (especially in the case of concomitant renal failure, severe heart failure and hypertension), decrease in hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia. Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestasis and leads to the development of fulminant hepatic necrosis and (sometimes) death.

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 deficiency and / or water, cardiac decompensation or severe hypertension), an excessive fall in blood pressure may occur after the initial dose in these patients, the recommended starting dose is 2 mg and treatment should be started under close medical supervision. After one month of treatment, the 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, diuretic administration may be reconsidered. In elderly patients, treatment should be started with a dose of 2 mg, which can be increased to 4 mg after one month, and then to 8 mg if necessary, 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 taken in the morning. If the dose is well tolerated, it can be increased after 2 weeks 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 and in other high-risk patients (patients with impaired renal function, with a tendency to electrolyte disorders, 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 disturbances with or without hyponatremia, hypovolaemia or intensely treated with diuretics) should have these disorders disrupted before starting treatment with perindopril. Blood pressure, renal function and serum potassium should be monitored closely, both before and during treatment.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: creatinine clearance ≥60 ml / min - the recommended dose of 4 mg / day; 30 The 4 mg tablets can be divided into equal doses. It is recommended to take tablets in the morning, before meals.