Pharmacological properties of the drug Prestarium
Perindopril is an inhibitor of ACE, the enzyme that converts angiotensin I to angiotensin II. ACE, or kinase, is an exopeptidase that promotes the conversion of angiotensin I to the vasoconstrictor angiotensin II, and also causes the breakdown of bradykinin, which has vasodilatory properties, into an inactive heptapeptide. ACE inhibition leads to a decrease in the concentration of angiotensin II, an increase in plasma renin activity and a decrease in aldosterone secretion. Because ACE inactivates bradykinin, ACE inhibition results in increased bradykinin levels, circulating and tissue kallikrein-kinin system activity, and activation of the prostaglandin system. This mechanism of action determines the reduction in blood pressure by ACE inhibitors and is partly responsible for the appearance of some of their side effects (dry cough). Perindopril increases the level of bradykinin, which leads to improved endothelial function and vascular relaxation and plays a leading role in reducing cardiovascular remodeling and improving the fibrinolytic balance of the blood. Perindopril helps to dilate peripheral blood vessels and reduce their resistance. Peripheral blood flow increases, but heart rate does not increase. When using perindopril, renal blood flow usually increases, but the glomerular filtration rate does not change. Due to its complex mechanism of action, perindopril reduces high blood pressure. The action of perindopril is carried out through its active metabolite - perindoprilate. Hypertension (arterial hypertension) Perindopril effectively reduces blood pressure in all degrees of hypertension (arterial hypertension): mild, moderate and severe; reduces systolic and diastolic blood pressure. Perindopril is effective for 24 hours. The maximum hypotensive effect is achieved 4–6 hours after a single dose of the drug. The T/P ratio (peak/plateau) of perindopril is 87–100%. Perindopril reduces blood pressure from the very beginning of treatment, stabilization of blood pressure levels occurs over 1 month and persists for a long time without the occurrence of tachyphylaxis. When you stop taking the drug, no withdrawal effect is noted. In addition to effectively lowering blood pressure, perindopril improves the elasticity of large-caliber arteries, corrects structural changes in small-caliber arteries, reduces left ventricular hypertrophy, prevents the progression of atherosclerosis and has anti-ischemic properties. Heart failure Perindopril reduces cardiac function by reducing pre- and afterload on the heart. Studies involving patients with heart failure have demonstrated a decrease in filling pressure in the right and left ventricles, a decrease in peripheral vascular resistance, and an increase in cardiac index and cardiac output. In comparative studies using placebo and other ACE inhibitors, perindopril at an initial dose of 2.5 mg in patients with mild to moderate heart failure did not cause hypotension after the first dose compared to placebo. Patients with cerebrovascular disease The PROGRESS study of more than 6,000 patients demonstrated the benefit of 4 years of treatment of patients with a history of stroke or transient cerebrovascular accident with perindopril tertbutylamine 4 mg, which is equivalent to perindopril arginine 5 mg (Prestarium 5 mg), in preventing recurrent stroke in patients with cerebral vascular diseases (in monotherapy or in combination with the diuretic indapamide in addition to basic therapy). There was a statistically significant reduction in the risk of: recurrent ischemic and hemorrhagic stroke by 28% (including hemorrhagic stroke by 50%); cases of fatal or disabling stroke by 33%; dementia and severe cognitive impairment associated with stroke, by 34 and 45%, respectively; myocardial infarction by 38%; heart failure by 26%. These therapeutic results were noted regardless of the presence of concomitant hypertension (arterial hypertension) or diabetes mellitus, age and gender, and type of stroke. Prevention of cardiovascular complications in patients with documented stable coronary artery disease. The four-year EUROPA study involving 12,218 patients demonstrated that treatment with perindopril tertbutylamine 8 mg, which is equivalent to perindopril arginine 10 mg (Prestarium 10 mg): significantly reduced the likelihood of fatal and non-fatal myocardial infarction by 24%; significantly reduces the likelihood of developing heart failure requiring hospitalization by 39%. Bioequivalence studies confirmed the bioequivalence between perindopril arginine at doses of 2.5; 5; 10 mg and perindopril tertbutylamine in doses of 2; 4; 8 mg. After oral administration, perindopril is rapidly absorbed, the maximum concentration in the blood plasma is reached within 1 hour. The half-life of perindopril from the blood plasma is 1 hour. Perindopril is a prodrug. 27% of the total amount of perindopril taken is determined in the blood in the form of an active metabolite - perindoprilate. In addition to the active metabolite, 5 more inactive metabolites of the drug have been identified. The maximum concentration of perindoprilate in the blood plasma is achieved 3–4 hours after administration. Concomitant food intake somewhat slows down the conversion of perindopril to perindoprilat, so perindopril arginine should be taken before meals. There is a linear relationship between the dose of perindopril and its concentration in the blood plasma. In blood plasma, perindoprilat is found in the form of free and ACE-bound fractions (the latter is responsible for the antihypertensive effect of the drug). The binding of perindoprilate to plasma proteins (mainly ACE) is 20%, this figure is dose-dependent. Perindoprilat is excreted in the urine; the half-life of its free fraction is 17 hours. The state of equilibrium concentration in the blood plasma is achieved after 4 days from the start of treatment. The elimination of perindoprilate is slowed down in the elderly and in patients with heart and kidney failure. Doses of the drug for patients with renal failure are recommended to be selected taking into account the degree of failure and creatinine clearance. Dialysis clearance of perindoprilate is 70 ml/min. The pharmacokinetics of perindopril changes in patients with liver cirrhosis. The hepatic clearance of perindopril is reduced by half, but the amount of perindoprilate formed does not decrease, so dose adjustment is not required in such patients.
Prestarium®
IHD: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and/or coronary revascularization
If unstable angina develops during the first month of therapy with Prestarium®, the benefits and risks should be assessed before continuing therapy.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without concomitant diseases. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, following a strict salt-free diet, hemodialysis, vomiting and diarrhea, as well as in patients with severe arterial hypertension with high plasma renin activity (see sections “Interaction with other drugs” and “Special instructions”).
In most cases, episodes of pronounced decrease in blood pressure are observed in patients with severe chronic heart failure, both in the presence of concomitant renal failure and in its absence. This side effect is most often observed in patients receiving loop diuretics in high doses, as well as in patients with hyponatremia or impaired renal function.
At the beginning of therapy and when increasing the dose of Prestarium®, patients should be under close medical supervision (see sections “Dosage and Administration” and “Side Effects”). A similar approach should be used in patients with angina pectoris and cerebrovascular diseases, in whom severe arterial hypotension can lead to the development of myocardial infarction or cerebrovascular complications.
If there is a significant decrease in blood pressure, the patient should be transferred to the “lying” position on his back with his legs elevated and immediately replenish the blood volume (for example, intravenous infusion of 0.9% sodium chloride solution). Intravenous administration of angiotensin II and/or catecholamines is also possible. A pronounced decrease in blood pressure when taking the drug for the first time is not an obstacle to further use of the drug. After restoration of blood volume and blood pressure, treatment can be continued with careful selection of doses of the drug Prestarium®.
In some patients with chronic heart failure and normal or low blood pressure, Prestarium® may cause an additional decrease in blood pressure. This effect is predictable and does not usually require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.
Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy
Prestarium®, like other ACE inhibitors, should be used with caution in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.
Renal dysfunction
For patients with renal failure (creatinine clearance less than 60 ml/min.), the initial dose of Prestarium® is selected depending on the clearance value (see section “Method of administration and dosage”) and then depending on the therapeutic effect. For such patients, regular monitoring of QC and potassium levels in the blood plasma is necessary (see section “Side Effects”).
Hypotension, which sometimes develops when starting ACE inhibitors in patients with symptomatic chronic heart failure, can lead to deterioration of renal function. Acute renal failure may develop, usually reversible.
In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood plasma, which usually resolves when therapy is discontinued.
The additional presence of renovascular hypertension causes an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients begins under close medical supervision using low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and serum potassium and creatinine levels monitored regularly during the first few weeks of therapy.
In some patients with arterial hypertension, in the presence of previously undetected renal failure, especially with simultaneous use of diuretics, the concentration of urea and creatinine in the blood serum may increase. These changes are usually mild and reversible. In such cases, it may be necessary to discontinue or reduce the dose of Prestarium® and/or diuretic.
Hemodialysis
Several cases of persistent, life-threatening anaphylactic reactions have been reported in patients undergoing hemodialysis using high-flux membranes (eg, AN69®). Prescription of ACE inhibitors should be avoided when using this type of membrane.
Kidney transplantation
There are no data on the use of Prestarium® after kidney transplantation.
Hypersensitivity/angioedema
In patients taking ACE inhibitors, in rare cases, especially during the first few weeks of therapy, angioedema of the face, extremities, lips, tongue, glottis and/or larynx may develop. In rare cases, severe angioedema may occur during prolonged use of an ACE inhibitor. If these symptoms appear, the use of the drug Prestarium® should be stopped immediately, and drugs of another pharmacotherapeutic group should be used as a replacement.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. When it develops, emergency therapy includes, among other prescriptions, immediate subcutaneous administration of a solution of epinephrine (adrenaline) 1:1000 (1 mg/ml) 0.3-0.5 ml or slow intravenous administration (in accordance with the preparation instructions infusion solution) under ECG and blood pressure control. The patient should be hospitalized for treatment and observation for at least 12-24 hours until complete regression of symptoms.
Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section “Contraindications”).
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal activity of the C-1 esterase enzyme. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.
Anaphylactic reactions during low-density lipoprotein (LDL) apheresis
In rare cases, life-threatening anaphylactic reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein apheresis with dextran sulfate. To prevent an anaphylactic reaction, ACE inhibitor therapy should be temporarily discontinued before each LDL apheresis procedure using dextran sulfate.
Anaphylactic reactions during desensitization
There are isolated reports of the development of life-threatening anaphylactic reactions in patients receiving ACE inhibitors during desensitizing therapy with bee venom (bees, wasps). ACE inhibitors should be used with caution in patients with a predisposition to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily discontinuing the ACE inhibitor before starting the desensitization procedure.
Liver dysfunction
Taking ACE inhibitors is sometimes associated with a syndrome starting with the development of cholestatic jaundice, progressing to fulminant hepatic necrosis, and (sometimes) death. The mechanism of development of this syndrome is unclear. If symptoms of jaundice or increased activity of liver enzymes appear in patients taking ACE inhibitors, drug therapy should be discontinued and appropriate examination should be carried out (see section “Side Effects”).
Neutropenia/agranulocytosis/thrombocytopenia/anemia
During therapy with ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. With normal renal function and the absence of other complications, neutropenia rarely occurs. ACE inhibitors are used only in emergency cases in the presence of systemic vasculitis, immunosuppressive therapy, taking allopurinol or procainamide, as well as when combining all of these factors, especially against the background of previous renal failure. There is a risk of developing severe infectious diseases that are resistant to intensive antibiotic therapy. When carrying out therapy with Prestarium® in patients with the above factors, it is necessary to regularly monitor the leukocyte count.
Ethnic differences
It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, Prestarium® is less effective in lowering blood pressure in black patients.
This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.
Cough
During therapy with an ACE inhibitor, a dry, non-productive cough may occur, which stops after discontinuation of the drug.
Surgery/general anesthesia
The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthetic agents that have an antihypertensive effect. Taking Prestarium® should be stopped one day before surgery. If arterial hypotension develops, blood pressure should be maintained by replenishing blood volume.
It is necessary to warn the anesthesiologist that the patient is taking ACE inhibitors.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, especially if the patient has renal and/or heart failure or latent diabetes mellitus. The use of potassium supplements, potassium-sparing diuretics, and other drugs associated with a risk of potassium elevation (eg, heparin) is generally not recommended due to the potential for severe hyperkalemia. If the combined use of these drugs is necessary, then therapy should be accompanied by regular monitoring of potassium levels in the blood serum.
Diabetes
In patients taking oral hypoglycemic agents or insulin, plasma glucose concentrations should be regularly monitored during the first month of therapy with ACE inhibitors (see section “Interaction with other drugs”).
Lithium preparations
The combined use of Prestarium® and lithium preparations is not recommended (see section “Interaction with other drugs”).
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements
Concomitant use with ACE inhibitors is not recommended (see section “Interaction with other drugs”).
Use of the drug Prestarium
Take orally 1 time per day before meals, preferably in the morning. The dose is selected individually for each patient, taking into account the indications for use and blood pressure level. Use in patients at risk - see SPECIAL INSTRUCTIONS. Tablets of 10 mg (Prestarium 10 mg) cannot be divided; 5 mg tablets (Prestarium 5 mg) can be divided. AH (arterial hypertension) Prestarium 5 or 10 mg can be prescribed as monotherapy or in combination with antihypertensive drugs of other classes. The recommended starting dose is 5 mg (Prestarium 5 mg). Patients with high activity of the renin-angiotensin-aldosterone system (especially patients with renovascular hypertension, water-electrolyte imbalance, decompensated heart failure or severe hypertension (arterial hypertension), as well as elderly patients) due to the possibility of a sudden decrease in blood pressure (arterial hypotension of the first dose) it is recommended to begin treatment with a dose of 2.5 mg under the supervision of a physician, if necessary, in a hospital setting. If necessary and well tolerated, the dose is gradually (over 1 month) increased to 5–10 mg (1 tablet Prestarium 5 mg or Prestarium 10 mg/day). Heart failure The recommended starting dose is 2.5 mg 1 time per day before meals, preferably in the morning. After 2 weeks, if well tolerated, the dose can be increased to 5 mg and switched to Prestarium 5 mg. Use in patients at risk - see SPECIAL INSTRUCTIONS. Prevention of recurrent stroke in patients with cerebrovascular diseases (according to the results of the PROGRESS study). The recommended starting dose is 2.5 mg (1/2 t of Prestarium 5 mg tablet) once a day before meals, preferably in the morning. After 2 weeks of treatment, the dose is increased to 5 mg (Prestarium 5 mg). If the hypotensive effect is insufficient, it can be prescribed in combination with indapamide or switched to the use of a fixed combination of perindopril and indapamide (Prestarium arginine Combi). Treatment begins from 2 weeks to several years after the initial stroke. Prevention of cardiovascular complications in patients with proven stable coronary artery disease Long-term therapy reduces the risk of myocardial infarction and heart failure (according to the results of the 4-year EUROPA study). Treatment begins with a dose of 5 mg/day (1 tablet of Prestarium 5 mg), preferably in the morning. After 2 weeks, if well tolerated, the dose is increased to 10 mg and switched to long-term use of the drug Prestarium 10 mg. Prestarium 10 mg at a dose of 1 tablet per day is prescribed for long-term therapy in patients with proven stable coronary artery disease, regardless of concomitant pathology, age and additional therapy. In elderly patients with proven stable coronary artery disease, treatment begins with a dose of 2.5 mg once a day before meals, preferably in the morning; after 1 week of treatment, the dose is increased to 5 mg (Prestarium 5 mg); after 2 weeks of treatment, if well tolerated, the dose is increased to 10 mg (Prestarium 10 mg), in which the drug is continued to be taken for a long time.
Side effects of the drug Prestarium
The following side effects may occur while using perindopril. From the blood system: decreased hemoglobin levels and hematocrit, thrombocytopenia, leukopenia/neutropenia, anemia, agranulocytosis, pancytopenia. In patients with congenital deficiency of the enzyme glucose-6-phosphate dehydrogenase (G-6PDH), isolated cases of hemolytic anemia have been reported. From the central nervous system and peripheral nervous system: headache, asthenia, dizziness, paresthesia; very rarely - mood and sleep disorders. From the organ of vision: visual impairment. On the part of the hearing organ: tinnitus. From the cardiovascular system: arterial hypotension (especially after taking the first dose); very rarely - due to a sudden decrease in blood pressure, arrhythmia, stable angina, myocardial infarction, stroke may occur in high-risk patients (see SPECIAL INSTRUCTIONS). From the respiratory system: dry cough, shortness of breath; uncommon - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis. From the digestive system: nausea, vomiting, abdominal pain, diarrhea, constipation, dry mouth; very rarely - pancreatitis. From the hepatobiliary system: very rarely - hepatitis, jaundice (see SPECIAL INSTRUCTIONS). From the urinary system: infrequently - worsening chronic renal failure; very rarely - acute renal failure. Allergic reactions and skin reactions: skin rashes, erythema; uncommon - angioedema; very rarely - erythema multiforme. Other manifestations: asthenia, muscle cramps, rarely - impotence, sweating. Laboratory indicators: possible increase in the concentration of potassium, creatinine and urea in the blood serum, especially in patients with severe heart failure and renovascular hypertension. Rarely - increased activity of liver transaminases and bilirubin levels in the blood plasma.
Special instructions for the use of the drug Prestarium
The use of the drug in the first trimester of pregnancy is not recommended. If pregnancy is planned or established, the drug should be discontinued. The use of the drug in the II–III trimester of pregnancy is contraindicated. The use of perindopril during breastfeeding is not recommended due to the lack of data on the excretion of perindopril in breast milk. Perindopril is not recommended for use in children and adolescents due to the lack of appropriate studies in these patient groups. Before starting to use the drug and during its use, it is necessary to monitor blood pressure, renal function and potassium levels in the blood plasma. Effect on potassium levels in the blood Plasma potassium levels may fluctuate in patients taking ACE inhibitors. In patients at risk of hyperkalemia, namely in patients with renal failure, uncontrolled diabetes mellitus, hyperkalemia may occur. First-dose hypotension When using ACE inhibitors after taking the first dose, a sudden decrease in blood pressure may occur (first-dose hypotension). Hypotension usually occurs in patients with concomitant disorders - hypovolemia, sodium deficiency caused by the use of diuretics, a salt-free diet, vomiting, diarrhea, in patients with severe renin-dependent hypertension (arterial hypertension) and with symptoms of heart failure with or without concomitant renal failure), especially in patients with severe heart failure, taking loop diuretics in high doses, having electrolyte imbalance or impaired renal function of functional origin. Patients with fluid and electrolyte imbalances are recommended to correct them before starting treatment with perindopril. In patients at risk of developing arterial hypotension, initial therapy and further dose increases should be carried out under medical supervision. Use in patients with ischemic heart disease and cerebrovascular diseases. The above recommendations regarding initiation of treatment should be followed to avoid a possible sudden decrease in blood pressure, which in such patients can lead to the development of myocardial infarction or stroke. In the presence of severe heart failure and in other patients at risk, treatment should be started under the supervision of a physician. If, while taking perindopril, the patient experiences hypotension at the first dose, the patient should be placed in a horizontal position with a low head and the blood volume should be restored with an infusion of isotonic sodium chloride solution. Transient hypotension after taking the first dose is not a contraindication for further increasing the dose if, after restoration of the water-electrolyte balance and normalization of the patient's condition, there is a need for a further reduction in blood pressure. In order to reduce the risk of developing symptomatic arterial hypotension, patients taking diuretics are recommended to stop taking them 2-3 days before starting treatment with perindopril; if this is not possible, treatment should be started with a minimum dose of 2.5 mg (Prestarium 2.5 mg). It is necessary to monitor kidney function and the level of potassium in the blood plasma. Further increases in the dose are carried out under the control of blood pressure levels. If necessary, resume the use of diuretics. Aortic or mitral valve stenosis, hypertrophic cardiomyopathy All ACE inhibitors should be administered with caution to patients with mitral valve stenosis or left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy). Use in patients with renal failure In patients with renal failure (creatinine clearance ≤60 ml/min), the dose should be adjusted taking into account creatinine clearance and the patient's response to treatment. Periodic monitoring of serum potassium and creatinine levels is also recommended.
Creatinine clearance, ml/min | Recommended dosage |
| ≥60 | 5 mg/day |
| 30–60 | 2.5 mg/day |
| 15–30 | 2.5 mg every other day |
| ≤15, hemodialysis patients | 2.5 mg/day of dialysis |
Dialysis clearance of perindoprilate is 70 ml/min. Perindopril is not prescribed to patients undergoing hemodialysis using high-flow polyacrylic membranes due to the possibility of an anaphylactoid reaction. Some patients with bilateral renal artery stenosis or solitary renal artery stenosis may experience increased plasma urea and creatinine levels, especially in the presence of renal failure. Changes in indicators are reversible and normalize after cessation of treatment. In the presence of renovascular hypertension, such patients have an increased risk of developing symptomatic hypotension and renal failure. Treatment in such patients is recommended to begin under the supervision of a physician with a low dose and if well tolerated, with further titration of the dose upward. In some patients who did not have renal disease before starting treatment, an increase in plasma urea and creatinine levels when using perindopril, especially in combination with diuretics, may indicate that the patient has impaired renal function before starting treatment. In this case, it may be necessary to reduce the dose or discontinue the diuretic or ACE inhibitor. In patients with heart failure, the occurrence of arterial hypotension at the beginning of treatment with an ACE inhibitor may lead to further impairment of renal function. Use in patients with diabetes: Patients using insulin or oral hypoglycemic agents while taking ACE inhibitors should monitor blood glucose levels, especially during the first month of use (see also INTERACTIONS) . Use in patients with liver failure No dose adjustment is required. If a patient experiences jaundice or a significant increase in liver enzymes while taking an ACE inhibitor, the ACE inhibitor should be discontinued and the patient should be closely monitored medically. Use in patients with collagenosis and in those taking allopurinol, immunosuppressants, procainamide Should be used with caution, especially in the presence of impaired renal function. Cough Since the drug contains an ACE inhibitor, during its use a dry cough may occur, which disappears after discontinuation of the drug. If necessary, treatment can be continued. Surgical interventions and anesthesia The anesthesiologist should be informed about the use of any ACE inhibitor if the patient is scheduled to undergo anesthesia or surgery. Treatment with an ACE inhibitor should be discontinued the day before surgery (see INTERACTIONS). Lactose intolerance The drug contains lactose, therefore it is not recommended to prescribe the drug to patients with congenital galactose intolerance, glucose-galactose malabsorption syndrome, or Lapp lactase deficiency. Plasmapheresis In patients with elevated LDL levels, when plasmapheresis is performed using dextran sulfate while using an ACE inhibitor, life-threatening anaphylactoid reactions may occur. The development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor before starting plasmapheresis. Carrying out desensitization In patients taking ACE inhibitors, anaphylactoid reactions may occur during specific desensitization to bee venom. The development of these reactions can be prevented by temporarily stopping taking the ACE inhibitor. These reactions may occur during provocative tests. Effect on psychomotor reactions When driving vehicles or working with machinery, the possibility of developing dizziness or weakness due to a sharp decrease in blood pressure should be taken into account.
Prestarium A
Use during pregnancy and breastfeeding
Prestarium® A is contraindicated for use during pregnancy.
Prestarium® A should not be used in the first trimester of pregnancy. If you are planning pregnancy or if it occurs while using the drug Prestarium® A, you should immediately stop taking the drug and, if necessary, prescribe alternative antihypertensive therapy with a proven safety profile for use during pregnancy.
It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).
If the patient received ACE inhibitors in the second or third trimester of pregnancy, it is recommended to conduct an ultrasound examination of the newborn to assess the condition of the skull bones and kidney function.
It is not known whether perindopril is excreted in breast milk, therefore the use of Prestarium® A during lactation (breastfeeding) is not recommended. If the use of the drug is necessary during lactation, then breastfeeding should be discontinued.
Fertility
Preclinical studies have shown no effect of perindopril on reproductive function in rats of both sexes.
Use for liver dysfunction
In patients with liver cirrhosis, the hepatic clearance of perindopril is reduced by 2 times. However, the amount of perindoprilate formed does not decrease and no changes in the dose of the drug are required.
When prescribing the drug to patients with impaired liver function, no dose changes are required.
Use for renal impairment
The drug should be used with caution in cases of bilateral renal artery stenosis or the presence of only one functioning kidney; renal failure.
There are no data on the use of Prestarium® A in patients after kidney transplantation.
If renal function is impaired, the dose of Prestarium® A should be selected taking into account the degree of renal failure and under regular monitoring of potassium and QC levels.
| CC (ml/min) | Recommended dose |
| CC ≥60 | 5 mg/day |
| 30<КК<60 | 2.5 mg/day |
| 15<КК<30 | 2.5 mg every other day |
| Patients on hemodialysis * CC <15 | 2.5 mg per day of dialysis |
* dialysis clearance of perindoprilate: 70 ml/min. The drug should be taken after the dialysis procedure.
Use in children
The use of the drug is contraindicated in patients under the age of 18 years (the effectiveness and safety of use have not been established).
Use in elderly patients
For arterial hypertension in elderly patients, treatment should begin with a dose of 2.5 mg/day. If necessary, a month after the start of therapy, the dose can be increased to 5 mg/day, and then to a maximum dose of 10 mg/day, taking into account the state of renal function.
For coronary artery disease, to reduce the risk of cardiovascular complications in patients who have previously suffered a myocardial infarction and/or coronary revascularization, elderly patients should begin therapy with a dose of 2.5 mg 1 time / day for 1 week, then 5 mg 1 time / day in over the next week. Then, taking into account the state of renal function, the dose can be increased to 10 mg 1 time / day (see table). The dose of the drug can be increased only if it is well tolerated at the previously recommended dose.
special instructions
IHD: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and/or coronary revascularization
In patients with coronary artery disease, if an episode of unstable angina occurs during the first month of therapy with Prestarium® A, the benefits and risks should be assessed before continuing treatment.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during therapy with diuretics, while following a strict salt-free diet, hemodialysis, vomiting and diarrhea, as well as in patients with severe arterial hypertension with high renin activity. In patients at increased risk of developing symptomatic hypotension, blood pressure, renal function, and serum potassium levels should be carefully monitored during therapy with Prestarium® A. A similar approach is also used in patients with coronary artery disease or cerebrovascular disease, in whom severe hypotension may lead to to the development of myocardial infarction or cerebrovascular complications.
If arterial hypotension develops, the patient should be placed in a horizontal position with a low headboard. If necessary, the blood volume should be replenished using intravenous administration of saline. Transient arterial hypotension is not an obstacle to further use of the drug. After restoration of blood volume and blood pressure, treatment can be continued.
In some patients with chronic heart failure and normal or low blood pressure, Prestarium® A may cause an additional decrease in blood pressure. This effect is predictable and does not usually require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.
Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy
Prestarium® A, like other ACE inhibitors, should be prescribed with caution to patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.
Renal dysfunction
In patients with renal failure (creatinine clearance <60 ml/min), the initial dose of Prestarium® A should be adjusted depending on the clearance value and then depending on the therapeutic effect. For such patients, regular monitoring of serum creatinine and potassium concentrations is necessary.
Hypotension, which sometimes develops when initiating ACE inhibitors in patients with symptomatic chronic heart failure, can lead to deterioration of renal function. Acute renal failure may develop, usually reversible.
In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood serum, which usually resolves when therapy is discontinued. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients. Treatment of such patients begins under close medical supervision using low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and plasma potassium and creatinine levels should be regularly monitored during the first few weeks of therapy.
In some patients with arterial hypertension without indication of pre-existing renal vascular disease, serum urea and creatinine concentrations may increase, especially with simultaneous use of diuretics. These changes are usually mild and reversible. The likelihood of developing these disorders is higher in patients with a history of renal failure. In such cases, it may be necessary to discontinue or reduce the dose of Prestarium® A and/or the diuretic.
Hemodialysis
In patients undergoing hemodialysis using high-flux membranes (eg, AN69®), several cases of persistent, life-threatening anaphylactic reactions have been reported during therapy with ACE inhibitors. Prescription of ACE inhibitors should be avoided when using this type of membrane.
Kidney transplant
There are no data on the use of Prestarium® A in patients after kidney transplantation.
Hypersensitivity/angioedema
When using ACE inhibitors, incl. perindopril, in rare cases and during any period of therapy, the development of angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may be observed. If symptoms appear, use of the drug should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. When such symptoms appear, emergency treatment is required, incl. subcutaneous administration of epinephrine (adrenaline) and/or ensuring airway patency. The patient should be under medical supervision until symptoms disappear completely and permanently.
Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis was made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy, such as hymenoptera venom. ACE inhibitors should be used with caution in patients susceptible to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily discontinuing the ACE inhibitor before starting the desensitization procedure.
Liver dysfunction
In rare cases, during the use of ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs during the use of ACE inhibitors, the drug should be stopped and the patient should be under appropriate medical supervision.
Neutropenia/agranulocytosis/thrombocytopenia/anemia
Neutropenia/agranulocytosis, thrombocytopenia and anemia may occur during the use of ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Prestarium® A should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.
Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Prestarium® A in such patients, it is recommended to periodically monitor the level of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Ethnic differences
It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, perindopril is less effective as an antihypertensive agent in black patients. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.
Cough
During therapy with an ACE inhibitor, a persistent dry cough may occur, which stops after discontinuation of the drug. This should be taken into account when carrying out the differential diagnosis of cough.
Surgery/general anesthesia
The use of ACE inhibitors in patients whose condition requires surgery and/or general anesthesia may lead to an excessive decrease in blood pressure, especially when using drugs for general anesthesia that have an antihypertensive effect. Taking Prestarium® A should be stopped one day before surgery. If arterial hypotension develops, blood pressure should be maintained by replenishing blood volume. It is necessary to warn the surgeon/anesthesiologist that the patient is taking ACE inhibitors.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, incl. perindopril. Risk factors for hyperkalemia are renal failure, decreased renal function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride) , potassium supplements/preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase potassium levels in the blood (for example, heparin). The use of potassium supplements/preparations, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If simultaneous use of Prestarium® A and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of potassium levels in the blood serum.
Patients with diabetes mellitus
When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic drugs for oral administration or insulin, during the first month of therapy it is necessary to regularly monitor the concentration of glucose in the blood.
Lithium preparations
The simultaneous use of Prestarium® A and lithium preparations is not recommended.
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements
The simultaneous administration of Prestarium® A and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended.
Double blockade of the RAAS
Cases of hypotension, syncope, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used concomitantly with drugs that affect this system. Therefore, dual blockade of the RAAS by combining an ACE inhibitor with an angiotensin II receptor antagonist or aliskiren is not recommended.
Combination with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR <60 ml/min/1.73 m2).
Impact on the ability to drive vehicles and operate machinery
Prestarium® A should be prescribed with caution to patients driving vehicles and engaging in activities that require increased concentration and speed of psychomotor reactions, due to the risk of developing arterial hypotension and dizziness.
Interactions of the drug Prestarium
Diuretics. In patients with fluid and electrolyte imbalances taking diuretics, a sharp decrease in blood pressure may occur when an ACE inhibitor is prescribed. To reduce the risk of arterial hypotension, such patients are advised to stop treatment with diuretics and restore water and electrolyte balance before starting treatment with perindopril. Concomitant use with potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium salts can cause hyperkalemia. The above-mentioned drugs are not recommended for simultaneous use with perindopril. If these drugs are prescribed, they should be used with caution. It is necessary to regularly monitor the level of potassium in the blood plasma. NSAIDs, including acetylsalicylic acid at a dose of ≥3 g/day , reduce the antihypertensive effect of ACE inhibitors, while having a synergistic effect on increasing the level of potassium in the blood plasma, and can also cause renal dysfunction. This effect is reversible. In isolated cases, renal failure may occur in patients with a history of impaired renal function (elderly people, patients with fluid and electrolyte imbalance). When using ACE inhibitors with lithium , a reversible increase in the concentration of lithium in the blood plasma is possible and, accordingly, an increase in the risk of its toxic effect. The use of thiazide diuretics increases the likelihood of lithium toxicity when used with ACE inhibitors. It is not recommended to use perindopril simultaneously with lithium preparations. If it is necessary to prescribe such a combination, it is necessary to monitor the level of lithium in the blood plasma. Antihypertensives and vasodilators . The simultaneous use of antihypertensive drugs, nitroglycerin, other nitrates and vasodilators may enhance the antihypertensive effect of perindopril. Antidiabetic agents. The simultaneous use of ACE inhibitors and drugs that lower blood glucose levels (insulin, oral hypoglycemic agents) may cause a further decrease in blood glucose levels and the risk of hypoglycemia, especially in the first weeks of treatment and in patients with renal failure. Tricyclic antidepressants/antipsychotics/anaesthetics. Concomitant use of certain anesthetics, tricyclic antidepressants or antipsychotics with ACE inhibitors may lead to a further decrease in blood pressure. Sympathomimetics: the antihypertensive effect of ACE inhibitors may be weakened.
Prestarium A, 5 mg, film-coated tablets, 30 pcs.
IHD: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and/or coronary revascularization
If unstable angina develops during the first month of therapy with Prestarium® A, the benefits and risks should be assessed before continuing therapy.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see sections “Interaction” with other drugs" and "Side effects"). Symptomatic hypotension may occur in patients with clinical manifestations of heart failure, both with and without renal failure. This risk is more likely in patients with severe heart failure, as a reaction to high-dose loop diuretics, hyponatremia, or functional renal failure. In patients at increased risk of developing symptomatic arterial hypotension, blood pressure, renal 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 arterial hypotension can lead to myocardial infarction or cerebrovascular accident.
If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, the volume of circulating blood should be replenished with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of blood volume and blood pressure, treatment can be continued.
In some patients with chronic heart failure (CHF) and normal or low blood pressure, Prestarium® A may cause an additional decrease in blood pressure. This effect is predictable and does not usually require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.
Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy
Prestarium® A, like other ACE inhibitors, should be administered with caution to the left ventricle (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.
Renal dysfunction
For patients with renal failure (creatinine clearance less than 60 ml/min), the initial dose of Prestarium® A is selected depending on the clearance value (see section “Method of administration and dosage”) and then depending on the therapeutic effect.
For such patients, regular monitoring of serum creatinine and potassium concentrations is necessary (see section “Side Effects”).
Hypotension, which sometimes develops when starting ACE inhibitors in patients with symptomatic CHF, can lead to deterioration of renal function. Acute renal failure may develop, usually reversible. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood serum, which usually resolves when therapy is discontinued. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients.
Treatment of such patients begins under close medical supervision using low doses of the drug and further adequate selection of doses.
Treatment with diuretics should be temporarily discontinued and plasma potassium and creatinine levels should be regularly monitored during the first few weeks of therapy.
In some patients with arterial hypertension without indication of pre-existing renal vascular disease, serum urea and creatinine concentrations may increase, especially with simultaneous use of diuretics. These changes are usually mild and reversible. The likelihood of developing these disorders is higher in patients with a history of renal failure. In such cases, it may be necessary to discontinue or reduce the dose of Prestarium® A and/or the diuretic.
Hemodialysis
In patients undergoing hemodialysis using high-flow membranes, cases of anaphylactic reactions have been reported during therapy with ACE inhibitors. Prescription of ACE inhibitors should be avoided when using this type of membrane. In such situations, consideration should be given to prescribing a different class of antihypertensive drug or using a different type of dialysis membrane.
Kidney transplant
There are no data on the use of Prestarium® A in patients after kidney transplantation.
Hypersensitivity/angioedema
When taking ACE inhibitors, including perindopril, in rare cases and during any period of therapy, the development of angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may be observed (see section “Side effects”). action"). If symptoms appear, the drug should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the vocal fold tongue or larynx can lead to airway obstruction. When such symptoms appear, emergency treatment is required, including subcutaneous administration of epinephrine (adrenaline) and/or ensuring airway patency. The patient should be under medical supervision until symptoms disappear completely and permanently.
Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section "Contraindications").
In rare cases, angioedema of the intestine developed during therapy with AP inhibitors. In this case, patients experienced abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. Diagnosis was made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine (see section “Side effects”).
Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy, for example, with hymenoptera venom. In these patients, such reactions were prevented by temporary discontinuation of ACE inhibitors, but with accidental or careless resumption of treatment, the reactions could develop again.
Liver dysfunction
In rare cases, while taking ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, you should stop taking the drug (see section “Side Effects”), the patient should be under appropriate medical supervision.
Neutropenia/ agranulocytosis/ thrombocytopenia/ anemia
While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Prestarium® A should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially in the presence of underlying renal impairment.
Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Prestarium® A to such patients, it is recommended to periodically monitor the level of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Ethnic differences
It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors,
Prestarium® A is less effective in lowering blood pressure in patients of the Negroid race.
This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.
Cough
During therapy with an ACE inhibitor, a persistent dry cough may occur, which stops after discontinuation of the drug. This should be taken into account when carrying out the differential diagnosis of cough.
Surgery/general anesthesia
In patients who are planning to undergo major surgery or use anesthetic agents that cause arterial hypotension, the use of perindopril may block the formation of angiotensin II against the background of compensatory release of renin. Treatment should be stopped one day before surgery. If arterial hypotension develops according to this mechanism, blood pressure should be maintained by replenishing blood volume.
Hyperkalemia
May develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, decreased renal function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride) , potassium supplements/preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase potassium levels in the blood (for example, heparin). The use of potassium supplements/preparations, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal heart rhythm problems. If simultaneous use of Prestarium® A and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of potassium levels in the blood serum (see section “Interaction with other drugs”).
Patients with diabetes mellitus
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 section “Interaction with other drugs”).
Lithium preparations
The simultaneous use of Prestarium® A and lithium preparations is not recommended (see section “Interaction with other drugs”).
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements
The simultaneous administration of Prestarium® A and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended (see section “Interaction with other drugs”).
Double blockade of the RAAS
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Thus, double blockade of the RAAS by combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections “Interaction with other drugs” and “Pharmacodynamics”). If dual block therapy is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, blood electrolytes and blood pressure.
ACE inhibitors should not be used in combination with angiotensin II receptor antagonists in patients with diabetic nephropathy.
Impact on the ability to drive vehicles and perform work that requires high speed of mental and physical reactions
Prestarium® A should be used with caution in patients driving vehicles and engaging in activities that require increased concentration and quick reaction, due to the risk of developing arterial hypotension and dizziness.
Prestarium drug overdose, symptoms and treatment
Symptoms of an overdose of any ACE inhibitors are severe hypotension, circulatory shock, tachycardia, bradycardia, electrolyte imbalance, renal failure, hyperventilation, dizziness, anxiety. In case of overdose, the patient should be hospitalized and under the supervision of a physician. The level of electrolytes and creatinine in the blood plasma should be monitored. Treatment depends on the nature and severity of symptoms. It is necessary to reduce the absorption of the ACE inhibitor by gastric lavage and the administration of enterosorbents. In case of severe arterial hypotension, the patient must be placed in a horizontal position with the head down and the blood volume must be restored by infusion of isotonic sodium chloride solution. If necessary, angiotensin II and/or catecholamines are administered intravenously. In severe cases, temporary implantation of a cardiac pacemaker is indicated. It is necessary to monitor and correct the vital functions of the body. Perindopril can be removed from the body using hemodialysis. The use of high-flow membranes is not recommended.
