Nosological classification (ICD-10)
Description of the dosage form
Round biconvex tablets of white color.
Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II.
ACE, or kininase II, is exopeptidase, which carries out both the conversion of angiotensin I into a vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilator, to inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone.
Since ACE inactivates bradykinin, ACE inhibition is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the PG system is also activated. It is possible that this effect is part of the mechanism of the antihypertensive effect of ACE inhibitors, as well as the mechanism of development of certain side effects of drugs of this class (for example, cough).
Perindopril has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites do not inhibit ACE in vitro.
Clinical efficacy and safety
Perindopril is effective in the treatment of hypertension of any degree of severity. Against the background of the use of the drug, there is a decrease in both the SBP and DBP in the prone and standing position.
Perindopril reduces OPSS, which leads to a decrease in blood pressure, while the peripheral blood flow is accelerated without changing the heart rate.
As a rule, perindopril leads to an increase in renal blood flow, while the glomerular filtration rate does not change.
The antihypertensive effect of the drug reaches a maximum after 4–6 hours after a single dose and remains for 24 hours. Within 24 hours after ingestion, a pronounced (about 80%) residual inhibition of ACE is observed.
Reduced blood pressure is achieved quite quickly. In patients with a positive response to treatment, normalization of blood pressure occurs within a month and persists without developing tachycardia.
Discontinuation of treatment is not accompanied by the development of withdrawal syndrome.
Perindopril has a vasodilating effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.
The simultaneous appointment of thiazide diuretics increases the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also leads to a reduction in the risk of hypokalemia in patients receiving diuretics.
Perindopril normalizes heart function, reducing preload and afterload.
In patients with chronic heart failure who received perindopril, were identified:
– decrease in filling pressure in the left and right ventricles of the heart;
– increase in cardiac output and increase in cardiac index.
A study of the drug compared with placebo showed that changes in blood pressure after the first dose of Prestarium ® A 2.5 mg in patients with chronic heart failure (functional class II – III according to the NYHA classification) did not statistically differ from changes in blood pressure observed after taking placebo
The results of the PROGRESS study, where the effect of active therapy with perindopril (monotherapy or in combination with indapamide) for 4 years on the risk of recurrent stroke in patients with a history of cerebrovascular disease was assessed. After the administration period of perindopril tertbutylamine, 2 mg (equivalent to perindopril arginine 2.5 mg) once a day for two weeks and then 4 mg (equivalent to perindopril arginine 5 mg) once a day for the next two weeks, 6,105 patients were randomized into two groups: placebo (n = 3054) and perindopril tertbutylamine 4 mg each (corresponding to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n = 3051).
Indapamide was further prescribed to patients who did not have direct indications or contraindications for the use of diuretics. This therapy was prescribed in addition to standard therapy for stroke and / or arterial hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular disease (stroke or transient ischemic attack) in the past 5 years. The value of blood pressure was not an inclusion criterion: 2916 patients had arterial hypertension and 3189 patients had normal blood pressure. After 3.9 years of therapy, the value of blood pressure (SBP / DBP) decreased by an average of 9/4 mm Hg. Art. A significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic) was also shown to be about 28% (95% CI (17; 38), p ® A
chronic heart failure;
prevention of recurrent stroke (combination therapy with indapamide) in patients who have had a stroke or transient cerebral circulation in ischemic type;
stable coronary heart disease: reduced risk of cardiovascular complications in patients with stable coronary artery disease.
Hypersensitivity to the active substance, other ACE inhibitors and excipients (see. “Composition”), which is part of the drug;
history of angioedema (angioedema) associated with taking an ACE inhibitor;
hereditary / idiopathic angioedema;
pregnancy (see “Use during pregnancy and breastfeeding”);
breastfeeding period (see. “Use during pregnancy and lactation”);
simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) 2) (see “Special instructions” and “Interaction”);
lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
age up to 18 years (efficacy and safety have not been established).
Precautions: (see also “Special Instructions” and “Interaction”): bilateral renal artery stenosis or the presence of only one functioning kidney, renal failure, systemic connective tissue diseases (systemic lupus erythematosus, scleroderma), therapy with immunosuppressants, allopurinol, procainamide ( risk of developing neutropenia, agranulocytosis), reduced BCC (diuretic intake, salt-free diet, vomiting, diarrhea), angina pectoris, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic serum renal failure IV functional class according to NYHA classification, simultaneous use of potassium-saving diuretics, potassium preparations, potassium-containing substitutes for salt and lithium, hyperkalemia, surgical intervention / general anesthesia, hemodialysis using high-flow membranes, desensitizing therapy, apneresis after LDL, condition after transplantation, kidneys, kidneys, kidney transplantation, kidney transplantation stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, use of the Negroid race in patients.
Use during pregnancy and lactation
Prestarium ® A is contraindicated for use in pregnancy (see “Contraindications”).
Prestarium ® A should not be used in the first trimester of pregnancy. When planning pregnancy or when it occurs during the use of Prestarium ® A, you should immediately stop taking the drug and, if necessary, prescribe another antihypertensive therapy with a proven safety profile during pregnancy.
It is known that the effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to a violation of its development (decreased renal function, oligohydramnios, slowing down of ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).
If the patient received ACE inhibitors during the II or III trimester of pregnancy, it is recommended to conduct an ultrasound examination of the newborn to assess the state of the bones of the skull and kidney function.
It is not known whether perindopril passes into breast milk. In this connection, the use of the drug Prestarium ® A during breastfeeding is not recommended. If the use of the drug is necessary during lactation, breastfeeding should be canceled.
In preclinical studies it was shown that perindopril does not affect reproductive function in rats of both sexes.
The safety profile of perindopril is consistent with the safety profile of ACE inhibitors.
The most frequent adverse events reported in clinical trials and observed with perindopril are: dizziness, headache, paresthesia, vertigo, visual disturbances, tinnitus, excessive blood pressure reduction, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disturbance, dyspepsia, nausea, vomiting, pruritus, skin rash, muscle cramps and asthenia.
The frequency of adverse reactions that were noted during clinical trials and / or post-registration use of perindopril is given in the form of the following gradation: very often (≥1 / 10); often (≥1 / 100, ® A can be used both in monotherapy and as part of combination therapy.
The recommended initial dose is 5 mg 1 time per day.
In patients with pronounced activation of the RAAS system (especially in case of renovascular hypertension, hypovolemia and / or reduction of plasma electrolytes, decompensation of chronic heart failure or severe arterial hypertension), a pronounced decrease in blood pressure may occur after taking the first dose of the drug. At the beginning of therapy, such patients should be under close medical supervision. The recommended initial dose for these patients is 2.5 mg 1 time per day. If necessary, one month after the start of therapy, you can increase the dose of the drug to 10 mg 1 time per day.
At the beginning of therapy with Prestarium ® A, symptomatic arterial hypotension may occur. In patients receiving diuretics at the same time, the risk of arterial hypotension is higher due to possible hypovolemia and a decrease in the electrolyte content of blood plasma. Caution must be exercised when using the drug Prestarium ® A in this group of patients.
It is recommended, if possible, to stop taking diuretics 2-3 days before the intended start of therapy with Prestarium ® A (see “Special Instructions”).
If it is impossible to cancel diuretics, the initial dose of Prestarium ® A should be 2.5 mg. It is necessary to monitor the kidney function and the content of potassium in the serum. In the future, if necessary, the dose of the drug may be increased. If necessary, diuretic administration can be resumed.
In elderly patients, treatment should begin with a dose of 2.5 mg / day. If necessary, one month after the start of therapy, the dose can be increased to 5 mg / day, and then up to a maximum dose of 10 mg / day, taking into account the condition of the kidney function (see Table 1).
The maximum daily dose is 10 mg.
Treatment of patients with chronic heart failure with Prestarium ® A in combination with non-potassium-sparing diuretics and / or digoxin and / or beta-blockers, it is recommended to start under close medical supervision, prescribing the drug in an initial dose of 2.5 mg once a day, in the morning. After 2 weeks of treatment, the dose of the drug can be increased to 5 mg once a day, provided that the dose of 2.5 mg is well tolerated and the response to the therapy is satisfactory.
In patients with a high risk of developing symptomatic arterial hypotension, for example, with a reduced electrolyte content with or without hyponatremia, hypovolemia, or diuretics, before the start of Prestarium ® A, these conditions should be corrected.
Indicators such as blood pressure, kidney function and the content of potassium in the blood plasma should be monitored both before and during the treatment.
Prevention of recurrent stroke (combination therapy with indapamide)
In patients with a history of cerebrovascular diseases, treatment with Prestarium ® A should be started with a dose of 2.5 mg for the first two weeks, then increasing the dose to 5 mg over the next two weeks before using indapamide.
Therapy should begin at any time (from two weeks to several years) after a stroke.
Ischemic heart disease: reduced risk of cardiovascular complications in patients who have previously suffered a myocardial infarction and / or coronary revascularization
In patients with a stable course of IHD, Prestarium ® A therapy should be started with a dose of 5 mg 1 time per day.
After 2 weeks, with good tolerability of the drug and taking into account the state of kidney function, the dose can be increased to 10 mg 1 time per day.
Elderly patients should begin therapy with a dose of 2.5 mg 1 time per day for 1 week, then 5 mg 1 time per day during the next week. Then, taking into account the state of kidney function, the dose can be increased to 10 mg 1 time per day (see table. 1). It is possible to increase the dose of the drug only if it is well tolerated at the previously recommended dose.
Special patient groups
In patients with renal insufficiency, the dose of the drug should be selected taking into account Cl creatinine.
Dosage of the drug Prestarium ® A in renal failure
* Dialysis clearance of perindoprilat – 70 ml / min. The drug should be taken after the procedure dialysis.
Patients with impaired liver function dose adjustment is not required (see “Pharmacokinetics” and “Special instructions”).
Age up to 18 years
Prestarium ® A should not be prescribed to children and adolescents under 18 years of age due to the lack of data on the efficacy and safety of using the drug in patients of this age group.
Data on drug overdose is limited.
Symptoms: marked decrease in blood pressure, shock, impaired water and electrolyte balance, renal failure, hyperventilation, tachycardia, feeling of heartbeat, bradycardia, dizziness, anxiety, cough.
Treatment: emergency measures are reduced to the removal of the drug from the body – gastric lavage and / or the appointment of activated carbon, followed by the restoration of water and electrolyte balance.
With a significant decrease in blood pressure should transfer the patient to the supine position with his legs elevated. If necessary, you should enter in / in 0.9% sodium chloride solution. If necessary, you can enter / in the solution of catecholamines. Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis. With the development of treatment-resistant bradycardia, it may be necessary to install an artificial pacemaker. It is necessary to constantly monitor the indicators of the main vital functions of the body, the concentration of creatinine and electrolytes in the serum.
IHD: a reduction in the risk of cardiovascular complications in patients who have previously suffered a myocardial infarction and / or coronary revascularization. With the development of unstable angina during the first month of therapy with Prestarium ® A, the advantages and risks should be assessed before continuing therapy.
Hypotension. ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive reduction in blood pressure is increased in patients with reduced BCC, which can be observed during diuretic therapy, with a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see “Interaction” and “Side effects”). In patients with an increased risk of developing symptomatic arterial hypotension, blood pressure, kidney function and serum potassium levels should be carefully monitored during therapy with Prestarium ® A.
A similar approach is used in patients with coronary artery disease and cerebrovascular diseases, in whom severe hypotension can lead to myocardial infarction or impaired cerebral circulation.
If arterial hypotension develops, the patient should be placed in a supine position with legs elevated. If necessary, the BCC should be replenished with IV injection of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further administration of the drug. After the restoration of BCC and blood pressure treatment can be continued.
In some patients with chronic heart failure (CHF) and normal or decreased blood pressure, Prestarium ® A may cause an additional decrease in blood pressure. This effect is predictable and usually does not require cessation of therapy. If symptoms appear, a pronounced decrease in blood pressure should reduce the dose of the drug or stop taking it.
Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy. Prestarium ® A, like other ACE inhibitors, should be used with caution in patients with obstruction of the left ventricular output tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.
Impaired renal function. Patients with renal insufficiency (Cl creatinine ® A are chosen depending on the value of Cl creatinine (see “Dosage and administration”) and then depending on the therapeutic effect. For these patients, regular monitoring of Cl creatinine and serum potassium is necessary (see “Side effects”).
Hypotension, which sometimes develops at the beginning of the use of ACE inhibitors in patients with symptomatic CHF, can lead to a deterioration in renal function. Perhaps the development of acute renal failure, as a rule, reversible.
In patients with bilateral renal artery stenosis or arterial stenosis of a single kidney (especially in the presence of renal failure) during therapy with ACE inhibitors, it is possible to increase the concentration of urea and serum creatinine, usually taking place when therapy is canceled. The additional presence of renovascular hypertension leads to an increased risk of severe arterial hypotension and renal failure in these patients.
The treatment of these patients begins under close medical supervision with the use of low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and regular monitoring of the content of potassium and creatinine in the blood plasma should be carried out during the first few weeks of therapy.
In some patients with arterial hypertension without indicating the presence of a prior kidney disease, the concentration of urea and creatinine in the blood serum may increase, especially with the simultaneous use of diuretics. These changes are usually expressed slightly and are reversible. The likelihood of developing these disorders is higher in patients with renal insufficiency in history. In such cases, you may need to cancel or reduce the dose of Prestarium ® A and / or diuretic.
Hemodialysis. In patients on hemodialysis using high-flow membranes (for example, AN69®), there have been cases of anaphylactic reactions during therapy with ACE inhibitors. The use of ACE inhibitors when using this type of membrane should be avoided.
Kidney transplantation. Data on the use of the drug Prestarium ® A in patients after kidney transplantation are not available.
Hypersensitivity / angioedema. When taking ACE inhibitors,
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords or larynx can lead to airway obstruction. When these symptoms appear, emergency treatment is required, in
In patients with a history of angioedema, not associated with the use of ACE inhibitors, the risk of its development may be increased when taking drugs of this group (see “Contraindications”).
In rare cases, against the background of therapy with ACE inhibitors, angioedema of the intestines develops. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without prior angioedema of the face and with a normal level of C1-esterase. The diagnosis is established using computed tomography of the abdominal area, ultrasound, or during surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain, receiving ACE inhibitors, when conducting a differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestines (see “Side effects”).
Anaphylactoid reactions during LDL apheresis. In rare cases, patients receiving ACE inhibitors may experience life-threatening anaphylactoid reactions when performing an apheresis procedure for LDL using dextran sulfate. To prevent an anaphylactoid reaction, the ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Anaphylactoid reactions during desensitization. There are separate reports on the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy, for example, venom insect venom. ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors in patients receiving immunotherapy with bee venom should be avoided. However, this reaction can be avoided by temporarily canceling the ACE inhibitor before the desensitization procedure begins.
Liver dysfunction. In rare cases, while taking ACE inhibitors, the syndrome of cholestatic jaundice with transition to fulminant necrosis of the liver was observed, sometimes with a fatal outcome. The mechanism for the development of this syndrome is unclear. With the appearance of jaundice or a significant increase in the activity of liver enzymes in the background of taking ACE inhibitors, the drug should be stopped (see “Side effects”), the patient should be under appropriate medical supervision.
Neutropenia / agranulocytosis / thrombocytopenia / anemia. Neutropenia / agranulocytosis, thrombocytopenia and anemia can occur while taking ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. With extreme caution should be used Prestarium ® A in patients with systemic diseases of the connective tissue, in patients receiving immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.
Some patients had severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Prestarium ® A, it is recommended that such patients periodically monitor their white blood cell counts. Patients should inform the doctor about any signs of infectious diseases (for example, sore throat, fever).
Ethnic differences. It should be borne in mind that patients of the Negroid race are more likely to develop angioedema. Like other ACE inhibitors, Prestarium ® A is less effective in reducing blood pressure in Negroid patients.
This effect is probably associated with a pronounced predominance of low-rootine status in patients of the Negroid race with arterial hypertension.
Cough. During therapy with an ACE inhibitor, persistent dry cough may occur, which stops after discontinuation of the drug. This should be considered when conducting a differential diagnosis of cough.
Surgical intervention / general anesthesia. The use of ACE inhibitors in patients who are to undergo surgery using general anesthesia can lead to a pronounced decrease in blood pressure, especially when using drugs for general anesthesia that have an antihypertensive effect. Reception of the drug Prestarium ® A should be stopped one day before the surgical intervention. With the development of arterial hypotension should maintain blood pressure by replenishing the BCC. It is necessary to warn the surgeon / anesthesiologist that the patient is taking ACE inhibitors.
Hyperkalemia. May develop during treatment with ACE inhibitors, in
Patients with diabetes. When prescribing the drug to patients with diabetes mellitus, receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy it is necessary to regularly monitor the concentration of glucose in the blood (see. “Interaction”).
Lithium preparations. Simultaneous use of Prestarium ® A and lithium preparations is not recommended (see “Interaction”).
Potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes and food additives. The simultaneous prescription of Prestarium ® A and potassium-sparing diuretics, as well as potassium preparations, potassium-containing food salt substitutes and food additives is not recommended (see “Interaction”).
Double blockade of RAAS. Cases of arterial hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure) have been reported in susceptible patients, especially when used concurrently with medications that affect this system. Therefore, a double blockade of RAAS as a result of a combination of an ACE inhibitor with ARA II or aliskiren is not recommended.
Combination with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR 2) (see “Contraindications” and “Interaction”).
Influence on the ability to drive vehicles and perform work requiring high speed mental and physical reactions. Prestarium ® A should be used with caution to patients driving vehicles and engaging in activities that require increased concentration and quick reaction, due to the risk of arterial hypotension and dizziness.
Tablets dispersible in the mouth, 2.5 mg, 5 mg and 10 mg. At 30 tab. in a polypropylene bottle equipped with a dispenser and a stopper containing a moisture-absorbing gel. 1 bottle with 30 tabl .. with instructions for medical use is placed in a cardboard box with the control of the first opening.
The registration certificate is issued by Servier Laboratories, France.
Produced by Servier (Ireland) Industries Ltd, Ireland.
Ireland, County Wicklow, Arklow, Goree Road, Manlands.
For all questions please contact the representative office of JSC “Servier Laboratory”.
Representation of Servier Laboratory JSC
115054, Moscow, Paveletskaya Sq., 2,
Tel: (495) 937-07-00; Fax: (495) 937-07-01.
The instructions enclosed in the pack additionally indicate the logo of the Servier Labs firm.
Pharmacy sales terms
Storage conditions of the drug Prestarium ® A
Keep out of the reach of children.
The shelf life of the drug Prestarium ® A
Do not use after the expiration date printed on the package.