Index of drugs

Table. powl. 5 mg and 10 mg: treatment of hypertension; stable ischemic heart disease - a reduction in the risk of cardiac events in patients with a myocardial infarction and / or revascularization. In addition, tabl. powl. 5 mg: treatment of symptomatic heart failure.

1 tabl powl. contains 5 mg or 10 mg Perindopril per week. The preparation 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). After oral administration, perindopril is absorbed quickly and reaches C_max after 1 h. T_0,5 plasma perinodopril is 1 hour. Perindopril is a prodrug. 27% of the administered dose is absorbed into the bloodstream and transformed into the active metabolite - perindoprilat. C_max Perindoprilat in plasma occurs within 3-4 h. The binding of perindoprilat to plasma proteins is 20%. Perindoprilat is mainly associated with angiotensin convertase in a concentration-dependent manner. It is mainly excreted in the urine, T_0,5 in the phase of elimination of its free fraction is about 17 h, and the stationary state is fixed within 4 days. Perindoprilat is removed during dialysis.

Hypersensitivity to perindopril or to any of the excipients or other ACE inhibitors. History of angioneurotic edema associated with previous treatment with ACE inhibitor. Hereditary 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 during the first month of treatment with Perindopril, an unstable angina episode (regardless of its severity), a thorough risk / benefit assessment should be performed before continuing treatment. Patients with an increased risk of symptomatic hypotension (patients with reduced volume of liquids, eg as a result of diuretics, diets with restricted salt, dialysis, diarrhea or vomiting, patients with severe renin-dependent hypertension, patients with heart failure, particularly advanced) at the beginning of treatment and during dose escalation should be closely monitored. Similarly, patients with ischemic heart disease or cerebrovascular disease in whom an excessive reduction in blood pressure can cause a heart attack or cerebrovascular accident. The occurrence of transient hypotension is not a contraindication to the continued use of the drug. In some patients with congestive heart failure with normal or low blood pressure, a significant drop in blood pressure may occur after perindopril administration. This effect is expected and usually does not result in discontinuation of treatment. If hypotension becomes symptomatic, it may be necessary to reduce the dose or discontinue the medicine. Perindopril should be used with caution in patients with mitral stenosis and narrowing of the left ventricle outflow pathway, such as aortic stenosis or hypertrophic cardiomyopathy. In patients with impaired renal function (creatinine clearance <60 ml / min), potassium and creatinine should be routinely monitored. In patients with symptomatic heart failure, hypotension after initiation of ACE inhibitor therapy may result in further impairment of renal function - usually reversible acute renal failure may occur. In some patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney treated with ACE inhibitors, increases in blood urea and serum creatinine, which resolved following discontinuation of treatment, were observed. This particularly applies to patients with impaired renal function.Coexistence of renovascular hypertension increases the risk of severe hypotension and renal failure. In these patients, treatment should be started under close medical supervision from small doses, carefully increasing them. The concomitant use of diuretics may be a predisposing factor to these side effects. During the first weeks of treatment with perindopril, these medicines should be discontinued and renal function monitored. In some hypertensive patients with no overt renal vascular disease, elevations in blood urea and serum creatinine, usually mild and transient, have been observed, particularly when perindopril has been concomitantly administered with a diuretic. This particularly applies to patients with pre-existing renal impairment. Dose reduction and / or discontinuation of diuretics and / or perindopril may be necessary. In patients undergoing dialysis with membranes of high permeability and simultaneously treated with ACE inhibitors anaphylactoid reactions have been observed - consideration should be given to the use of other type of dialysis membranes or an antihypertensive drug from another group. There are no data on the use of the drug in patients who have recently had a kidney transplant. In the event of angioedema, perindopril should be discontinued immediately and the patient should be observed until the symptoms disappear. If angioedema involves the tongue, glottis or larynx, life-saving treatment should be initiated immediately and the patient should be under strict medical supervision until the symptoms have completely and permanently resolved. Angioedema of the gut should be taken into account in the differential diagnosis of abdominal pain in patients treated with ACE inhibitors. Rarely, patients treated with low-density lipoprotein (LDL) apheres treated with ACE inhibitors using dextran sulphate have life-threatening anaphylactoid reactions. These reactions were avoided by temporarily discontinuing ACE inhibitors prior to each apheresis. In patients receiving ACE inhibitors during desensitisation (eg Hymenoptera venom), anaphylactoid reactions may occur. Such reactions can be prevented temporarily by discontinuing the ACE inhibitor before the start of desensitization treatment, but they recur after accidental re-use. In patients receiving ACE inhibitors who have developed cholestatic jaundice or who have a marked increase in liver enzymes, treatment with ACE inhibitors should be discontinued and appropriate medical attention should be sought. Due to the risk of serious infections (sometimes resistant to intensive antibiotic treatment) perindopril should be used with particular caution in patients with vascular collagen, treated with immunosuppressive drugs, Allopurinol or procainamide, or in whom these factors are present, especially if there is a renal dysfunction. These patients should periodically check the number of white blood cells and patients should be advised to report any signs of infection (eg sore throat, fever). ACE inhibitors are more likely to cause angioneurotic edema in black patients than in non-black patients. Perindopril may be less effective in reducing blood pressure in black patients than in non-black patients. In the differential diagnosis of cough, cough caused by the ACE inhibitor should be considered. Perindopril treatment should be discontinued 1 day before planned surgery. If hypotension occurs, they can be corrected by increasing the volume of fluids. Exercise caution in patients with risk factors for hyperkalemia: renal failure, deteriorating renal function, age (> 70 years), diabetes, concomitant conditions, particularly dehydration, acute heart failure, metabolic acidosis and concomitant use of potassium-sparing diuretics (eg spironolactone , eplerenone, triamterene or amiloride), potassium supplements or potassium substitutes with potassium or other drugs that cause an increase in serum potassium (eg heparin) - if concomitant use of the above-mentioned drugs is considered justified, caution should be exercised and regularly monitor serum potassium.In diabetic patients treated with oral antidiabetic agents or insulin, Glucose levels should be closely monitored during the first month of treatment with ACE inhibitors. 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. The efficacy and safety of the medicine in children and adolescents has not been established - use is not recommended. The preparation contains lactose - should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose.

The use of ACE inhibitors in the first trimester of pregnancy is not recommended. The use of ACE inhibitors is contraindicated in the second and third trimester of pregnancy. Patients planning pregnancy should be changed to another antihypertensive drug with an established safety profile for use in pregnancy, unless continuation of treatment with an ACE inhibitor is considered necessary. If pregnancy is confirmed, treatment with ACE inhibitors should be discontinued immediately and other treatments should be initiated as necessary. Exposure to an ACE inhibitor in the second and third trimester of pregnancy has a harmful effect on the fetus (decreased renal function, oligohydramnios, delayed ossification of the skull) and causes harmful effects in newborns (renal failure, hypotension, hyperkalemia). In the case of exposure to an ACE inhibitor from the second trimester of pregnancy, ultrasound control of renal function and skull construction is recommended. Newborns whose mothers have taken ACE inhibitors should be carefully observed because of the possibility of hypotension. Perindopril is not recommended in women who are breastfeeding due to lack of data. You should use a different treatment with a better explored safety profile, especially if the baby being fed is a newborn or a premature baby. In a high dose, perindopril can reduce the fertility of male rats. The effect on human fertility is unknown.

Common: central and peripheral headache and pain, paresthesia, visual disturbances, tinnitus, hypotension and related disorders, cough, shortness of breath, nausea, vomiting, abdominal pain, dysphoria, indigestion, diarrhea, constipation, rash, pruritus, asthenia (feeling exhausted). Uncommon: mood or sleep disorders, bronchospasm, dry mouth, swelling of the face, limbs, lips, mucous membranes, tongue, glottis and / or larynx, urticaria, painful muscle cramps, renal failure, impotence, excessive sweating. Very rare: confusion, arrhythmia, angina and myocardial infarction (probably secondary to excessive reduction of blood pressure in patients at high risk), stroke, possibly secondary to excessive hypotension in patients at high risk, eosinophilic pneumonia, mucositis nose, pancreatitis, cytolytic or cholestatic hepatitis, erythema multiforme, acute renal failure. Frequency unknown: hypoglycaemia, vasculitis. The following may occur: decreases in hemoglobin, hematocrit, thrombocytopenia, leukopenia and / or neutropenia, and, very rarely, cases of agranulocytosis or pancytopenia. In patients with congenital G-6-PD deficiency, cases of haemolytic anemia have been very rarely observed. Increases in blood urea and serum creatinine may occur, hyperkalaemia secondary to discontinuation of the drug, especially in the case of co-existing renal failure, severe heart failure and in hypertension. Increases in liver enzymes and increased serum bilirubin have been observed rarely.

Orally.Hypertension. Perindopril can be used alone or in combination with other antihypertensive agents.The recommended starting dose is 5 mg, once a day, in the morning. In patients with high activity of the renin-angiotensin-aldosterone system (in particular in patients with renovascular hypertension, electrolyte deficiency and / or dehydration, heart failure or severe hypertension) there may be an excessive reduction in blood pressure after the initial dose. The recommended starting dose for these patients is 2.5 mg, and treatment should be started under the supervision of a physician. After a month of treatment, the dose can be increased to 10 mg once a day. When starting treatment with perindopril, symptomatic hypotension may occur. This applies more often to patients who are taking diuretics at the same time. Caution is advised as these patients may have hypovolaemia and / or electrolyte depletion. If possible, the diuretic should be discontinued 2-3 days before starting the treatment. In hypertensive patients for whom diuretic therapy can not be discontinued, perindopril should be started at 2.5 mg. Renal function and serum potassium should be monitored. The further dosage of perindopril should be determined individually, based on the hypotensive response. If necessary, you can resume administration of diuretics. In elderly patients, treatment should start with a 2.5 mg dose, which can then be increased after a month of treatment to 5 mg, and if necessary, to 10 mg, depending on kidney function.Symptomatic heart failure. It is recommended that initiation of perindopril therapy, which is generally administered in combination with diuretics not sparing potassium and / or digitalis (and / or beta blockers), should be under the strict supervision of a physician. The recommended starting dose is 2.5 mg in the morning. The dose may be increased after 2 weeks to 5 mg once a day, as long as it is tolerated. The dose should be adjusted for the patient's clinical response. In patients with severe heart failure, as well as other high-risk patients (patients with impaired renal function and propensity to electrolyte disorders, patients treated concomitantly with diuretics and / or vasodilators), treatment should be started under close medical supervision. In patients at high risk of symptomatic hypotension (eg patients with impaired electrolyte management with or without hyponatremia, dehydrated patients or patients who are intensively treated with diuretics), these disorders should be corrected before initiating therapy. Blood pressure, renal function and serum potassium levels should be closely monitored both at the beginning and during treatment with the preparation.Stable ischemic heart disease. Treatment should be started at a dose of 5 mg once a day for 2 weeks, and then the dose should be increased to 10 mg once a day depending on renal function, provided that the 5 mg dose is well tolerated. In elderly patients, a dose of 2.5 mg once a day for a week should be used followed by 5 mg once a day for another week, before increasing the dose to 10 mg once a day, depending on the kidney function. The dose should only be increased if the lower dose was well tolerated.Patients with impaired renal function. For patients with a creatinine clearance ≥60 ml / min, the recommended dose is 5 mg daily; with a 30-60 ml / min clearance - 2.5 mg per day; with a clearance of 15-30 ml / min - 2.5 mg every other day, patients undergoing hemodialysis clearance <15 ml / min - 2.5 mg on the day of dialysis. Patients undergoing hemodialysis should be administered after dialysis. No dosage adjustment is necessary for patients with hepatic impairment.
It is recommended to take the product in the morning before a meal.