Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
ACE inhibitor. It is a prodrug, from which an active metabolite of perindoprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I into angiotensin II, which is a potent vasoconstrictor. As a result of a decrease in angiotensin II concentration, a secondary increase in plasma renin activity occurs due to elimination of negative feedback during the release of renin and a direct decrease in aldosterone secretion. Due to vasodilator effect, reduces OPSS (afterload), wedging pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases the minute volume of the heart and tolerance to the load.
The hypotensive effect develops within the first hour after taking perindopril, reaches a maximum after 4-8 hours and lasts for 24 hours.
In clinical studies with perindopril (monotherapy or in combination with a diuretic), a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic) and the risk of fatal or disabling strokes is shown; major cardiovascular complications, including myocardial infarction, incl. with lethal outcome;dementia associated with stroke; serious deterioration of cognitive functions. These therapeutic advantages were noted in patients with arterial hypertension and at normal BP, regardless of age, sex, the presence or absence of diabetes mellitus and the type of stroke.
It has been shown that, when perindopril tert-butylamine 8 mg / day (equivalent to 10 mg perindopril arginine) is used in patients with stable ischemic heart disease, there is a significant reduction in the absolute risk of complications provided by the main efficacy criterion (mortality from cardiovascular diseases, incidence of non-fatal myocardial infarction and / or cardiac arrest followed by a successful resuscitation) by 1.9%. In patients who had previous myocardial infarction or coronary revascularization, the absolute risk reduction was 2.2% compared to the placebo group.
Perindopril is used both in the form of monotherapy, and in the form of fixed combinations with indapamide, with amlodipine.
PHARMACOKINETICS
After ingestion, perindopril is rapidly absorbed from the digestive tract. C max is reached after 1 hour. Bioavailability is 65-70%.
In the process of metabolism, perindopril is biotransformed to form an active metabolite - perindoprilat (about 20%) and 5 inactive compounds. C max perindoprilata in plasma is achieved between 3 and 5 hours after administration. The binding of perindoprilat to plasma proteins is insignificant (less than 30%) and depends on the concentration of the active substance. V d of free perindoprilat is close to 0.2 l / kg.
Do not cumulate. The repeated reception does not lead to cumulation and T 1/2 corresponds to the period of its activity.
When you eat while eating, the metabolism of perindopril slows down.
T 1/2 perindopril is 1 hour.
Perindoprilat is excreted from the body by the kidneys; T 1/2 of its free fraction is 3-5 hours.
In elderly patients, as well as in renal and heart failure, excretion of perindoprilat slows down.
INDICATIONS
Arterial hypertension.
Chronic heart failure.
Prevention of recurrent stroke (combination therapy with indapamide) in patients who underwent a stroke or transient cerebral circulation disorder by ischemic type.
Stable IHD: reduced risk of cardiovascular complications in patients with stable coronary artery disease.
DOSING MODE
The initial dose is 1-2 mg / day in 1 dose. Supportive doses - 2-4 mg / day with congestive heart failure, 4 mg (less often - 8 mg) - with arterial hypertension in 1 dose.
In case of violations of the kidney function, a correction of the dosing regimen is required depending on the CK values.
SIDE EFFECT
On the part of the hematopoiesis system: eosinophilia, reduction of hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase.
On the part of metabolism: hypoglycemia, hyperkalemia, reversible after discontinuation of the drug, hyponatremia.
From the nervous system: paresthesia, headache, dizziness, vertigo, sleep disturbance, mood lability, drowsiness, fainting, confusion.
From the sense organs: visual disturbances, noise in the ears.
On the part of the cardiovascular system: excessive BP reduction and associated symptoms, vasculitis, tachycardia, palpitations, heart rhythm disturbances, angina pectoris, myocardial infarction and stroke, possibly due to excessive blood pressure lowering in high-risk patients.
On the part of the respiratory system: cough, dyspnea, bronchospasm, eosinophilic pneumonia, rhinitis.
On the part of the digestive system: constipation, nausea, vomiting, abdominal pain, a taste disorder, dyspepsia, diarrhea, dryness of the oral mucosa, pancreatitis, hepatitis (cholestatic or cytolytic).
From the skin and subcutaneous fat: skin itching, rashes, photosensitivity, pemphigus, increased sweating.
Allergic reactions: angioedema, urticaria, erythema multiforme.
From the musculoskeletal system: muscle spasms, arthralgia, myalgia.
From the urinary system: renal failure, acute renal failure.
On the part of the reproductive system: erectile dysfunction.
Common reactions: asthenia, chest pain, peripheral edema, weakness, fever, falls.
On the part of laboratory indicators: an increase in the activity of hepatic transaminases and bilirubin in the serum, an increase in the concentration of urea and creatinine in the blood plasma.
CONTRAINDICATIONS
An angioneurotic edema in the anamnesis, simultaneous application with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (GFR <60 ml / min / 1.73 m 2 ), pregnancy, lactation, children and adolescents under 18 years, hypersensitivity to perindopril , increased sensitivity to other ACE inhibitors.
PREGNANCY AND LACTATION
Perindopril is contraindicated in pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
In case of violations of the kidney function, a correction of the dosing regimen is required depending on the CK values.
APPLICATION FOR CHILDREN
Contraindicated in childhood.
SPECIAL INSTRUCTIONS
Caution should be applied perindopril with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney; renal failure; systemic diseases of connective tissue; therapy with immunosuppressors, allopurinol, procainamide (risk of neutropenia, agranulocytosis); reduced bcc (taking diuretics, diet with salt restriction, vomiting, diarrhea); angina pectoris; cerebrovascular diseases; Renovascular hypertension; diabetes mellitus; chronic heart failure IV functional class according to NYHA classification; simultaneously with potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for edible salt, with lithium preparations; with hyperkalemia; surgical intervention / general anesthesia; hemodialysis using high-flow membranes; desensitizing therapy; apheresis of LDL;condition after kidney transplantation; aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy; in patients of the Negroid race.
Arterial hypotension, fainting, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in predisposing patients, especially when used with medications that affect RAAS. Therefore, the double blockade of RAAS due to the combination of an ACE inhibitor with an angiotensin II receptor antagonist or aliskiren is not recommended.
Before starting treatment with perindopril, all patients are recommended to study the function of the kidneys.
During treatment with perindopril, kidney function, hepatic enzyme activity in the blood, peripheral blood tests (especially in patients with diffuse connective tissue diseases, in patients receiving immunosuppressive agents, allopurinol) should be monitored regularly. Patients with sodium and liquid deficiency before the start of treatment should be corrected water-electrolyte disorders.
DRUG INTERACTION
The risk of developing hyperkalemia increases with the simultaneous use of perindopril with other drugs that can cause hyperkalemia: aliskiren and aliskiren containing drugs, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparin, immunosuppressants such as cyclosporin or tacrolimus, trimethoprim.
With simultaneous use with aliskiren in patients with diabetes mellitus or kidney dysfunction (GFR <60 mL / min), the risk of hyperkalemia, impaired renal function and increased incidence of cardiovascular morbidity and mortality increases (this combination is contraindicated in patients of these groups).
It is not recommended simultaneous use with aliskiren in patients who do not have diabetes mellitus or renal dysfunction; may increase the risk of hyperkalemia, worsening kidney function and increasing the incidence of cardiovascular morbidity and mortality.
In the literature, it was reported that in patients with established atherosclerotic disease, heart failure or diabetes with target organ damage, simultaneous therapy with an ACE inhibitor and angiotensin II receptor antagonist is associated with a higher incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of only one drug that affects RAAS. Double blockade (for example, with the combination of an ACE inhibitor with an angiotensin II receptor antagonist) should be limited to individual cases with careful monitoring of kidney function, potassium and blood pressure.
Simultaneous use with estramustine can lead to an increased risk of side effects, such as angioedema.
With the simultaneous use of lithium and perindopril preparations, a reversible increase in serum lithium concentration and related toxic effects (this combination is not recommended) is possible.
Simultaneous use with hypoglycemic drugs (insulin, hypoglycemic agents for oral administration) requires extreme caution, because ACE inhibitors, incl. perindopril, may enhance the hypoglycemic effect of these drugs until the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function.
Baclofen increases the antihypertensive effect of perindopril, while simultaneous use may require a dose adjustment of the latter.
In patients receiving diuretics, especially those taking out fluid and / or salts, at the beginning of perindopril therapy, an excessive decrease in blood pressure may occur, the risk of which can be reduced by eliminating the diuretic, replenishing fluid loss or salts before starting perindopril therapy, and using perindopril in low initial dose with a further gradual increase.
In chronic heart failure in the case of diuretics, perindopril should be used in a low dose, possibly after a reduction in the dose of the simultaneously used potassium-sparing diuretic. In all cases, kidney function (creatinine concentration) should be monitored in the first weeks of the use of ACE inhibitors.
The use of eplerenone or spironolactone in doses of 12.5 mg to 50 mg / day and ACE inhibitors (including perindopril) in low doses: in the treatment of heart failure II-IV functional class according to the NYHA classification with the fraction of left ventricular ejection <40% and previously used ACE inhibitors and loop diuretics, there is a risk of developing hyperkalemia (with a possible fatal outcome), especially in case of non-compliance with recommendations for this combination. Before using this combination, you need to make sure there is no hyperkalemia and renal dysfunction. It is recommended to regularly monitor the concentration of creatinine and potassium in the blood - weekly in the first month of treatment and every month thereafter.
Simultaneous use of perindopril with NSAIDs (acetylsalicylic acid in a dose that exerts anti-inflammatory action, inhibitors of COX-2 and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. Simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure, and an increase in potassium in the blood serum, especially in patients with reduced renal function. Use this combination with caution in elderly patients. Patients should receive an adequate amount of fluid; it is recommended to closely monitor the kidney function, both at the beginning and during the treatment.
The hypotensive effect of perindopril may be enhanced by simultaneous use with other antihypertensive drugs, vasodilators, including nitrates of short and prolonged action.
Simultaneous use of glyptins (linagliptin, saxagliptin, sitagliptin, vitagliptin) with ACE inhibitors (including perindopril) may increase the risk of angioedema development due to inhibition of dipeptidyl peptidase IV activity by glyptin.
The simultaneous use of perindopril with tricyclic antidepressants, antipsychotic drugs and general anesthetic agents may lead to an increase in antihypertensive action.
Sympathomimetics can weaken the antihypertensive effect of perindopril.
With the use of ACE inhibitors, incl. Perindopril, in patients receiving IV drugs gold (sodium aurotyomalate), a symptom complex was described, in which hyperemia of the facial skin, nausea, vomiting, arterial hypotension were observed.
