Instructions for use of PERINDOPRIL-LF (PERINDOPRIL-LF)
Dual blockade of the RAAS is associated with an increased risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Dual blockade of the RAAS using ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended, especially in patients with diabetic nephropathy.
In some cases, when the combined use of ACE inhibitors and angiotensin II receptor blockers is absolutely indicated, careful medical supervision and mandatory monitoring of renal function, water and electrolyte balance, and blood pressure are necessary. This applies to the use of candesartan or valsartan as adjunctive therapy to ACE inhibitors in patients with chronic heart failure. Carrying out double blockade of the RAAS under the careful supervision of a specialist and mandatory monitoring of renal function, water-electrolyte balance and blood pressure is possible in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistence of symptoms of chronic heart failure, despite other adequate therapy.
Stable ischemic heart disease
If an episode of unstable angina (severe or not) develops during the first month of treatment with perindopril, the balance between benefit and risk should be carefully assessed before continuing treatment.
Arterial hypotension
ACE inhibitors can cause a decrease in blood pressure. In patients with uncomplicated hypertension, severe hypotension rarely occurs; more often it is observed in patients with hypovolemia - while taking diuretics, limiting salt intake from food, in patients on hemodialysis, with diarrhea or vomiting; in patients with severe renin-dependent hypertension. In patients with clinically significant heart failure with or without concomitant renal failure, clinically significant arterial hypotension was recorded. The risk of its development increases in patients with more severe heart failure, while taking loop diuretics in high doses, with hyponatremia or functional kidney damage. Patients at increased risk of developing clinically significant hypotension require careful monitoring during initiation of therapy and dose adjustment. Similar requirements apply to patients with coronary artery disease or cerebrovascular disease, in whom an excessive decrease in blood pressure can lead to the development of myocardial infarction or acute cerebrovascular accident.
If arterial hypotension develops, the patient should be placed in a horizontal position and, if necessary, given intravenous saline. Transient arterial hypotension is not a contraindication to continued treatment, which can usually be restored without complications after an increase in blood pressure due to an increase in blood volume.
In some patients with congestive heart failure and normal or low blood pressure, treatment with perindopril may lead to an additional decrease in systemic blood pressure. This effect is expected and is not a reason to stop treatment. In case of clinically significant arterial hypotension, dose reduction or discontinuation of treatment with perindopril may be required.
Aortic and mitral valve stenosis/hypertrophic cardiomyopathy
As with other ACE inhibitors, perindopril should be used cautiously in patients with mitral valve stenosis and left ventricular outflow tract stenosis, in particular with aortic stenosis or hypertrophic cardiomyopathy.
Renal dysfunction
In case of impaired renal function (creatinine clearance <60 ml/min), the initial dose of perindopril should be adjusted in accordance with the clinical clearance and depending on the clinical response to treatment. Potassium and creatinine levels are usually monitored routinely in these patients.
In patients with clinically significant heart failure, the development of arterial hypotension after initiation of treatment with ACE inhibitors may lead to some deterioration in renal function. In a similar situation, acute renal failure has been described, which is usually irreversible.
In some patients with bilateral renal artery stenosis or solitary renal artery stenosis treated with ACE inhibitors, increases in serum urea and creatinine levels were detected, which were usually mild and reversible after discontinuation of treatment. This is especially likely in patients with impaired renal function. In the case of renovascular hypertension, there is an increased risk of severe hypotension and renal failure. In such patients, treatment should begin under close medical supervision with a low dose, followed by careful dose titration. Since treatment with diuretics may be a predisposing factor in the development of the above conditions, diuretics should be discontinued during the first weeks of treatment with perindopril, while monitoring renal function.
In some patients with arterial hypertension and no obvious signs of previous vascular damage to the kidneys, increases in serum urea and creatinine levels developed, which were usually mild and transient, especially when perindopril was used concomitantly with diuretics. These manifestations are more likely to develop in patients with pre-existing kidney damage. In such cases, dose reduction and/or discontinuation of diuretic and/or perindopril treatment may be necessary.
Patients on hemodialysis
In patients receiving dialysis using high-flow membranes and concomitant treatment with ACE inhibitors, the development of anaphylactic reactions has been observed. In such cases, consideration should be given to using a different type of dialysate membrane or a different class of antihypertensive drug.
Kidney transplant
There is no experience with the use of perindopril in patients with recent kidney transplantation.
Hypersensitivity/angioedema
Rarely, patients receiving treatment with ACE inhibitors, including perindopril, may develop angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and/or larynx. This phenomenon can develop at any time during treatment. In such cases, treatment with perindopril should be stopped immediately and appropriate monitoring of the condition should be initiated until symptoms cease completely. In cases where swelling of only the face or lips was observed, it usually resolved without treatment, although antihistamines were used to relieve symptoms.
Angioedema in combination with laryngeal edema can lead to death. In case of swelling of the tongue, vocal folds and larynx with a high probability of airway obstruction, emergency treatment should be prescribed immediately. This may include administering epinephrine (adrenaline) and/or maintaining a patent airway. The patient should be under close medical supervision until symptoms disappear completely and permanently.
Patients with a history of angioedema not associated with ACE inhibitors may be at increased risk of such edema when treated with ACE inhibitors. In rare cases, life-threatening anaphylactoid reactions have developed in patients receiving ACE inhibitors during LDL apheresis with dextran sulfate. Such reactions can be avoided by temporarily suspending ACE inhibitor treatment before each apheresis procedure.
Anaphylactic reactions during desensitization
Patients receiving ACE inhibitors during desensitization (for example, to the venom of Hymenoptera - wasps, bees and other insects) developed anaphylactoid reactions. Such reactions can be avoided by temporarily withdrawing ACE inhibitors, but if accidentally reintroduced, these reactions reappear.
Liver failure
In rare cases, treatment with ACE inhibitors is accompanied by a syndrome that begins with cholestatic jaundice and progresses with the development of fulminant liver necrosis, sometimes death. The mechanism of development of this syndrome is unknown. If jaundice develops or liver enzyme levels increase significantly during treatment with ACE inhibitors, the ACE inhibitor should be discontinued and appropriate medical supervision should be provided in the future.
Neutropenia/agranulocytosis/thrombocytopenia/anemia
In patients receiving ACE inhibitors, the development of neutropenia/agranulocytosis, thrombocytopenia and anemia is observed. In patients with normal renal function and without other complicating factors, neutropenia rarely develops. Perindopril should be used very cautiously in patients with collagen diseases, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially in the case of pre-existing renal impairment. Some of these groups of patients develop serious infections, which in many cases do not respond to active antibiotic therapy. When prescribing perindopril to such patients, periodic monitoring of leukocyte levels is recommended. Patients should be informed to report any signs of infection to their physician.
Race
ACE inhibitors are more likely to cause angioedema in blacks compared to patients of other races.
Similar to other ACE inhibitors, perindopril is less effective in lowering blood pressure in blacks compared to patients of other races; a possible explanation is the widespread prevalence of arterial hypertension with low renin levels among representatives of the black race.
Cough
When treated with ACE inhibitors, a cough may develop. Characterized by a non-productive persistent cough, which stops after discontinuation of treatment. Cough caused by an ACE inhibitor should be considered in the differential diagnosis of cough.
Surgery/anesthesia
During major surgery or during anesthesia with drugs that cause hypotension, perindopril may block the formation of angiotensin II due to compensatory release of renin. Treatment should be stopped the day before surgery. If arterial hypotension associated with this mechanism develops, it can be corrected with fluid therapy.
Hyperkalemia
Increases in potassium levels have been observed in some patients during treatment with ACE inhibitors, including perindopril. Patients at risk of developing hyperkalemia include those with renal failure, uncontrolled diabetes mellitus, those taking potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium, and other drugs that increase potassium levels (eg, heparin). If concomitant use of these drugs is necessary, regular monitoring of potassium levels is recommended.
Patients with diabetes mellitus
In patients with diabetes mellitus taking oral hypoglycemic agents or insulin, glycemic levels should be carefully monitored during the first month of treatment with an ACE inhibitor.
Lithium preparations
The combination of lithium and perindopril is generally not recommended.
Potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes
In general, combinations of perindopril and potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes are not recommended.
Excipients
The drug contains lactose, so it should not be prescribed to patients with rare hereditary diseases:
- congenital galactosemia, lactase deficiency, glucose/galactose malabsorption syndrome.
Use in pediatrics
It is not recommended to prescribe the drug to children and adolescents under the age of 18 years,
because There are no data on the effectiveness and safety of perindopril tertbutylamine in this category of patients.
Impact on the ability to drive vehicles and operate machinery
No studies have been conducted on the effect on the ability to drive and operate machines.
If it is necessary to drive vehicles or operate machinery while using the drug, the possibility of dizziness or fatigue should be taken into account.
PERINDOPRIL
special instructions
Stable coronary heart disease (CHD)
If an episode of unstable angina (significant or not) develops during the first month of perindopril therapy, it is necessary to assess the benefit/risk ratio of further use of the drug Perindopril.
Arterial hypotension ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated hypertension, symptomatic hypotension rarely occurs after the first dose. The risk of excessive reduction in blood pressure is increased in patients with reduced blood volume during diuretic therapy, while following a strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or in patients with severe renin-dependent hypertension. Severe arterial hypotension was observed in patients with severe CHF, both in the presence of concomitant renal failure and in its absence. The most common arterial hypotension can develop in patients with more severe CHF, taking loop diuretics in high doses, as well as against the background of hyponatremia or renal failure. Close medical monitoring is recommended for these patients during initiation of therapy and during dosage titration. The same applies to patients with coronary artery disease or cerebrovascular diseases, in whom an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications. If arterial hypotension develops, it is necessary to place the patient in a horizontal position with raised legs, and, if necessary, administer sodium chloride solution intravenously to increase the blood volume. Transient arterial hypotension is not a contraindication for further therapy. After restoration of blood volume and blood pressure, treatment can be continued subject to careful selection of the dose of the drug.
In some patients with CHF and normal or low blood pressure, an additional decrease in blood pressure may occur during perindopril therapy. This effect is expected and is usually not a reason to discontinue the drug. If arterial hypotension is accompanied by clinical manifestations, it may be necessary to reduce the dose or discontinue perindopril.
Renal dysfunction and renovascular hypertension
In patients with renal failure (creatinine clearance less than 60 ml/min), the initial dose of perindopril should be adjusted in accordance with the clinical clearance (see section “Dosage and Administration”) and then depending on the therapeutic response to therapy. For such patients, regular monitoring of potassium and creatinine levels in the blood plasma is necessary.
In patients with symptomatic heart failure, arterial hypotension that develops during the initial period of therapy with ACE inhibitors can lead to deterioration of renal function. Cases of acute renal failure, usually reversible, have sometimes been reported in such patients.
In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney (especially in the presence of renal failure), an increase in serum concentrations of urea and creatinine was observed during therapy with ACE inhibitors, which was reversible after discontinuation of therapy. In patients with renovascular hypertension during therapy with ACE inhibitors, there is an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients should begin under close medical supervision, with small doses of the drug and with further adequate dose selection. During the first weeks of perindopril therapy, diuretics should be discontinued and renal function should be regularly monitored.
In some patients with arterial hypertension, in the presence of previously undetected renal failure, especially with concomitant diuretic therapy, there was a slight and temporary increase in serum urea and creatinine concentrations. In this case, it is recommended to reduce the dose of perindopril and/or discontinue the diuretic.
Anaphylactoid reactions during low-density lipoprotein apheresis (LDL apheresis)
In patients prescribed ACE inhibitors during the procedure of low-density lipoprotein (LDL) apheresis using dextran sulfate, in rare cases, an anaphylactic reaction may develop. It is recommended to temporarily discontinue the ACE inhibitor (at least 24 hours) before each apheresis procedure. Anaphylactic reactions during desensitization There are isolated reports of prolonged life-threatening anaphylactoid reactions in patients taking ACE inhibitors during desensitizing therapy with hymenoptera (bees, wasps) venoms. ACE inhibitors should be prescribed with caution to patients with allergies and those receiving desensitization therapy. However, these reactions can be prevented by temporarily discontinuing the ACE inhibitor at least 24 hours before each desensitization procedure.
Increased sensitivity/angioedema Rare in patients taking ACE inhibitors, incl. perindopril, angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and/or larynx developed. This condition can develop at any time during treatment. If angioedema develops, treatment should be stopped immediately, and the patient should be under medical supervision until symptoms disappear completely. Angioedema of the lips and face usually does not require treatment; Antihistamines can be used to reduce the severity of symptoms.
Angioedema of the tongue, vocal folds, or larynx can be fatal. If angioedema develops, it is necessary to immediately administer epinephrine (adrenaline) subcutaneously and ensure patency of the airway.
ACE inhibitors are more likely to cause angioedema in black patients. Patients with a history of angioedema not associated with the use of ACE inhibitors may be at high risk of developing angioedema while taking an ACE inhibitor.
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors.
In this case, patients experience abdominal pain, possibly in combination with nausea and vomiting; in some cases without previous angioedema of the face and normal C1-esterase levels.
Diagnosed using computed tomography or ultrasound examination of the abdominal organs, or during surgery. Symptoms disappear after discontinuation of ACE inhibitor therapy. In patients receiving ACE inhibitors, the possibility of developing angioedema of the intestine should be taken into account in the differential diagnosis of abdominal pain.
Cough
During therapy with ACE inhibitors, a persistent, unproductive dry cough may develop, which stops after discontinuation of the drug. This should be taken into account in the differential diagnosis of cough.
Elderly patients
In elderly patients, the hypotensive effect of ACE inhibitors may be more pronounced compared to young patients.
It is recommended to begin the course of treatment with low doses and evaluate renal function when starting to take the drug.
Hyperkalemia
During therapy with ACE inhibitors, including perindopril, potassium levels in the blood may increase in some patients. The risk of hyperkalemia is increased in patients with renal and/or heart failure, decompensated diabetes mellitus, and in patients using potassium-sparing diuretics, potassium supplements, or other drugs that cause hyperkalemia (eg, heparin).
If it is necessary to prescribe these drugs simultaneously, it is recommended to regularly monitor the potassium content in the blood serum.
Surgical intervention/general anesthesia
In patients whose condition requires major surgery or general anesthesia with drugs that cause hypotension, ACE inhibitors, including perindopril, may block the formation of angiotensin II with compensatory renin release. One day before surgery, therapy with ACE inhibitors must be discontinued. If the ACE inhibitor cannot be canceled, then arterial hypotension developing according to the described mechanism can be corrected by increasing the volume of blood volume.
Aortic or mitral valve stenosis/hypertrophic obstructive cardiomyopathy
ACE inhibitors, incl. and perindopril should be administered with caution to patients with mitral valve stenosis and left ventricular outflow tract obstruction (aortic valve stenosis and hypertrophic obstructive cardiomyopathy).
Neutropenia/Agranulocytosis/Anemia
Cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitor therapy. With normal renal function in the absence of other complications, neutropenia rarely develops. Perindopril should be used with great caution in patients with systemic connective tissue diseases (for example, systemic lupus erythematosus, scleroderma) who were simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as when combining all of these factors, especially with existing renal impairment. Such patients may develop severe infections that do not respond to intensive antibiotic therapy. When carrying out perindopril therapy in patients with the above factors, it is recommended to periodically monitor the number of leukocytes in the blood and warn the patient about the need to inform the doctor about the appearance of any symptoms of infection.
In patients with congenital deficiency of glucose-6-phosphate dehydrogenase, isolated cases of hemolytic anemia have been reported.
Diabetes
In patients with diabetes mellitus taking oral hypoglycemic agents or insulin, blood glucose concentrations should be carefully monitored during the first few months of ACE inhibitor therapy.
Proteinuria
Proteinuria can develop in patients who already have impaired renal function, as well as during the use of high doses of ACE inhibitors.
Liver failure
During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that begins with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or an increase in the activity of liver transaminases occurs while taking an ACE inhibitor, the ACE inhibitor should be immediately discontinued, and the patient should be under close medical supervision.
Negroid race
The risk of developing angioedema in black patients.
Perindopril-Teva tablet p/p/o 10 mg 30 pcs
Stable IHD If an episode of unstable angina (significant or not) develops during the first month of therapy with Perindopril-Teva, it is necessary to assess the benefit/risk ratio of therapy with this drug. Arterial hypotension ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated hypertension, symptomatic hypotension rarely occurs after the first dose. The risk of excessive reduction in blood pressure is increased in patients with reduced blood volume during diuretic therapy, while following a strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or with severe renin-dependent arterial hypertension. Severe arterial hypotension was observed in patients with severe CHF, both in the presence of concomitant renal failure and in its absence. The most common arterial hypotension can develop in patients with more severe CHF, taking loop diuretics in high doses, as well as against the background of hyponatremia or renal failure. Close medical monitoring is recommended for these patients during initiation of therapy and during dosage titration. The same applies to patients with coronary artery disease or cerebrovascular diseases, in whom an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications.
If arterial hypotension develops, it is necessary to place the patient in a horizontal position with raised legs and, if necessary, administer a 0.9% sodium chloride solution intravenously to increase blood volume. Transient arterial hypotension is not a contraindication for further therapy. After restoration of blood volume and blood pressure, treatment can be continued subject to careful selection of the dose of the drug.
In some patients with CHF and normal or low blood pressure, an additional decrease in blood pressure may occur during therapy with Perindopril-Teva. This effect is expected and is usually not a reason to discontinue the drug. If arterial hypotension is accompanied by clinical manifestations, it may be necessary to reduce the dose or discontinue Perindopril-Teva.
Impaired renal function In patients with renal failure (creatinine clearance less than 60 ml/min), the initial dose of Perindopril-Teva should be adjusted in accordance with the clinical clearance (see section "Method of administration and dosage") and then depending on the therapeutic response. For such patients, regular monitoring of potassium levels and serum creatinine concentrations is necessary.
In patients with symptomatic heart failure, arterial hypotension that develops during the initial period of therapy with ACE inhibitors can lead to deterioration of renal function. Cases of acute renal failure, usually reversible, have sometimes been reported in such patients.
In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney (especially in the presence of renal failure), an increase in serum concentrations of urea and creatinine was observed during therapy with ACE inhibitors, which was reversible after discontinuation of therapy.
In patients with renovascular hypertension during therapy with ACE inhibitors, there is an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients should begin under close medical supervision, with small doses of the drug and with further adequate dose selection. During the first weeks of therapy with Perindopril-Teva, it is necessary to discontinue diuretics and regularly monitor renal function.
In some patients with arterial hypertension in the presence of previously undetected renal failure, especially with concomitant diuretic therapy, there was a slight and temporary increase in serum urea and creatinine concentrations. In this case, it is recommended to reduce the dose of Perindopril-Teva and/or discontinue the diuretic.
Patients on hemodialysis Several cases of persistent, life-threatening anaphylactic reactions have been reported in patients receiving high-flux membrane dialysis and concomitantly taking ACE inhibitors. If hemodialysis is necessary, a different type of membrane must be used.
Kidney transplantation There is no experience with the use of Perindopril-Teva in patients who have recently undergone kidney transplantation.
Hypersensitivity, angioedema Rarely in patients taking ACE inhibitors, incl. perindopril, angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx developed. This condition can develop at any time during treatment. If angioedema develops, treatment should be stopped immediately, and the patient should be under medical supervision until symptoms disappear completely.
Angioedema of the lips and face usually does not require treatment; Antihistamines can be used to reduce the severity of symptoms.
Angioedema of the tongue, vocal folds, or larynx can be fatal. If angioedema develops, it is necessary to immediately administer epinephrine (adrenaline) subcutaneously and ensure airway patency.
Patients with a history of angioedema not associated with the use of ACE inhibitors may be at high risk of developing angioedema while taking an ACE inhibitor.
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 C1-esterase levels. Diagnosis was made using abdominal computed tomography, ultrasound, or surgery.
The symptoms disappeared after stopping taking 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 the low-density lipoprotein apheresis procedure (LDL apheresis) In patients prescribed ACE inhibitors during the LDL apheresis procedure using dextran sulfate, in rare cases, an anaphylactic reaction may develop. It is recommended to temporarily discontinue the ACE inhibitor before each apheresis procedure.
Anaphylactic reactions during desensitization In patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera venom), in very rare cases, life-threatening anaphylactic reactions may develop. It is recommended to temporarily discontinue the ACE inhibitor before each desensitization procedure.
Liver failure During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that begins with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes fatal. The mechanism of development of this syndrome is unclear. If jaundice occurs or an increase in liver enzyme activity occurs while taking an ACE inhibitor, the ACE inhibitor should be discontinued immediately and the patient should be closely monitored. It is also necessary to conduct an appropriate examination.
Neutropenia, agranulocytosis, thrombocytopenia, anemia Cases of neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with ACE inhibitors. With normal renal function in the absence of other complications, neutropenia rarely develops. Perindopril-Teva should be used with great caution in patients with systemic connective tissue diseases (for example, systemic lupus erythematosus, scleroderma) who are simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as when combining all of these factors, especially with existing renal impairment . Such patients may develop severe infections that do not respond to intensive antibiotic therapy. When carrying out therapy with Perindopril-Teva in patients with the above factors, it is recommended to periodically monitor the number of leukocytes in the blood and warn the patient about the need to inform the doctor about the appearance of any symptoms of infection.
In patients with congenital deficiency of glucose-6-phosphate dehydrogenase, isolated cases of hemolytic anemia have been reported.
Black race Like other ACE inhibitors, perindopril is less effective in lowering blood pressure in black patients, possibly due to the higher prevalence of low-renin conditions in this population of patients with arterial hypertension.
Cough During therapy with ACE inhibitors, a persistent, unproductive cough may develop, which stops after discontinuation of the drug. This should be taken into account in the differential diagnosis of cough.
Surgery and general anesthesia In patients whose condition requires major surgery or general anesthesia with drugs that cause hypotension, ACE inhibitors, including perindopril, may block the formation of angiotensin II with compensatory release of renin. One day before surgery, therapy with ACE inhibitors must be discontinued. If the ACE inhibitor cannot be canceled, then arterial hypotension developing according to the described mechanism can be corrected by increasing the volume of blood volume.
Hyperkalemia During therapy with ACE inhibitors, including perindopril, the level of potassium in the blood may increase in some patients. The risk of hyperkalemia is increased in patients with renal and/or heart failure, decompensated diabetes mellitus, and in patients using potassium-sparing diuretics, potassium supplements, or other drugs that cause hyperkalemia (eg, heparin). If it is necessary to prescribe these drugs simultaneously, it is recommended to regularly monitor the potassium content in the blood serum.
Diabetes mellitus In patients with diabetes mellitus taking oral hypoglycemic agents or insulin, blood glucose concentrations should be carefully monitored during the first few months of ACE inhibitor therapy.
Lactose Perindopril-Teva tablets contain lactose. Therefore, patients with hereditary lactose intolerance, lactase deficiency or malabsorption syndrome should not take this drug.
Dual blockade of the RAAS 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, double blockade of the RAAS by combining an ACE inhibitor with ARAII or aliskiren is not recommended.
Combination with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR
Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy Perindopril, 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.
It is not recommended to use ACE inhibitors simultaneously with ARA II antagonists in patients with diabetic nephropathy.
Impact on the ability to drive vehicles and machinery It is necessary to take into account the possibility of developing arterial hypotension or dizziness, which may affect the ability to drive vehicles and work with technical equipment that requires increased concentration and speed of psychomotor reactions.
Perindopril plus, 30 pcs., 1.25 mg+4 mg, tablets
Common to indapamide and perindopril
Renal dysfunction
Therapy is contraindicated in patients with moderate and severe renal failure (creatinine clearance less than 60 ml/min). In some patients with arterial hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of a combination of indapamide and perindopril, or use only one of the drugs.
Such patients require regular monitoring of potassium levels and creatinine concentrations in the blood serum - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, including renal artery stenosis. The drug Perindopril PLUS is not recommended in cases of bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.
Arterial hypotension and water-electrolyte imbalance
In the case of initial hyponatremia, there is a risk of sudden development of arterial hypotension, especially in patients with renal artery stenosis. Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased electrolyte levels in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of blood plasma electrolyte levels.
In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for continued therapy. After restoration of circulating blood volume and blood pressure, therapy can be resumed using low doses of drugs, or only one of the drugs can be used.
Potassium content
The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with any antihypertensive drug or diuretic, regular monitoring of potassium levels in the blood plasma is necessary.
Excipients
It should be taken into account that the excipients of the drug include lactose monohydrate. The drug Perindopril PLUS should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.
Lithium preparations
The simultaneous use of the drug Perindopril PLUS with lithium preparations is not recommended (see section “Interaction with other drugs”).
Childhood
The drug should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of indapamide and perindopril, both separately and together, in patients in this age group.
Perindopril
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence of an increased risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) when ACE inhibitors are used simultaneously with ARB II or aliskiren. Therefore, double blockade of the RAAS by combining an ACE inhibitor with ARA II or aliskiren is not recommended (see sections “Interaction with other drugs” and “Pharmacodynamics”).
If a double blockade is absolutely necessary, then this should be performed under the strict supervision of a specialist with regular monitoring of renal function, plasma electrolytes and blood pressure.
The use of ACE inhibitors in combination with ARA II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements
The simultaneous administration of perindopril 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”).
Neutropenia/agranulocytosis/thrombocytopenia
There are reports of the development of neutropenia/agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors. In patients with normal renal function and without concomitant risk factors, neutropenia rarely occurs. Perindopril should be used with extreme caution against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), as well as while taking immunosuppressants, allopurinol or procainamide, or a combination of these factors, especially in patients with initially impaired renal function .
Some patients developed severe infectious diseases, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should tell their doctor about any signs of infectious diseases (for example, sore throat, fever) (see sections "Interaction with other drugs" and "Side effects").
Anemia
Anemia may develop in patients after kidney transplantation or in those on hemodialysis. In this case, the decrease in hemoglobin is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.
A slight decrease in hemoglobin occurs during the first 6 months, then it remains stable and is completely restored after discontinuation of the drug. In such patients, treatment can be continued, but hematological tests should be performed regularly.
Hypersensitivity/angioedema
When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may occur (see section “Side effects”). This can happen at any time during therapy. If symptoms appear, Perindopril PLUS should be stopped immediately and the patient should be observed until signs of swelling have completely disappeared. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used as symptomatic therapy.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately begin appropriate therapy, for example, subcutaneously administer epinephrine (adrenaline) at a dilution of 1:1000 (0.3 - 0.5 ml) and/or ensure airway patency.
A higher risk of developing angioedema has been reported in black patients.
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 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 C-1 esterase. Diagnosis was made using abdominal computed tomography, ultrasound, or at the time of surgery. Symptoms resolved after discontinuation of 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.
mTOR (mammalian target of rapamycin) inhibitors (eg, sirolimus, everolimus, temsirolimus)
In patients receiving concomitant therapy with mTOR inhibitors, the risk of developing angioedema (including swelling of the airways or tongue with or without respiratory impairment) may be increased (see section "Interaction with other drugs").
Anaphylactoid reactions during desensitization
There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran insect venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions have developed 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.
Hemodialysis
Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive agent of a different pharmacotherapeutic group.
Cough
During therapy with an ACE inhibitor, a dry persistent cough may occur, which disappears after discontinuation of drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible iatrogenic nature of this symptom. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, it is possible to continue taking the drug.
Risk of arterial hypotension and/or renal failure (in patients with heart failure, fluid and electrolyte imbalance, etc.)
In some pathological conditions, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, renal artery stenosis, chronic heart failure or cirrhosis of the liver with edema and ascites.
The use of ACE inhibitors causes blockade of the RAAS and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug and during the first two weeks of therapy. In rare cases, these conditions develop acutely and during other periods of therapy. In such cases, it is recommended to restart therapy at a lower dose and then gradually increase the dose.
Elderly age
Before starting to take perindopril, it is necessary to assess the functional activity of the kidneys and the content of potassium ions in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with low doses of the drug.
Renovascular hypertension
The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors may have a positive effect in this category of patients, both awaiting surgery and in cases where surgery is not possible.
Treatment with Perindopril PLUS is not indicated in patients with diagnosed or suspected renal artery stenosis, because Therapy should be started in a hospital setting with lower doses of the combination of indapamide and perindopril.
Heart failure/severe heart failure
In patients with chronic heart failure (NYHA functional class IV), treatment should begin with lower doses of the combination of indapamide and perindopril and under close medical supervision.
Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: an ACE inhibitor should be added to beta-blocker therapy.
Diabetes
In patients with type 1 diabetes mellitus, a spontaneous increase in potassium levels in the blood is possible. Treatment of such patients with the drug Perindopril PLUS is not indicated, since it should begin with minimal doses and be under constant medical supervision.
During the first month of therapy with ACE inhibitors, plasma glucose concentrations should be carefully monitored in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin (see section "Interaction with other drugs").
Ethnic differences
Perindopril, like other ACE inhibitors. has a clearly less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.
Surgery / General anesthesia
Carrying out general anesthesia against the background of ACE inhibitors can lead to a pronounced decrease in blood pressure, especially when using general anesthesia agents that have an antihypertensive effect.
It is recommended, if possible, to stop taking long-acting ACE inhibitors, including perindopril, the day before surgery. It is necessary to warn the anesthesiologist that the patient is taking ACE inhibitors.
Aortic or mitral stenosis / Hypertrophic obstructive cardiomyopathy
ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.
Liver failure
In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or if there is a significant increase in the activity of liver enzymes while taking ACE inhibitors, the patient should stop taking the ACE inhibitor and consult a doctor (see section “Side Effects”).
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, impaired renal function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute cardiac decompensation, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride ), as well as potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that help increase the content of potassium in the blood plasma (for example, heparins, ACE inhibitors, angiotensin II receptor antagonists, acetylsalicylic acid at a dose of 3 g/day or more, inhibitors cyclooxygenase-2 (COX-2) and non-selective NSAIDs, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim).
The use of potassium supplements, 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 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”).
Indapamide
Hepatic encephalopathy
In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In such a situation, you should immediately stop taking the diuretic.
Water and electrolyte balance
Content of sodium ions in blood plasma
The content of sodium ions in the blood plasma must be determined before starting treatment, and then regularly monitored while taking the drug.
Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and elderly patients (see sections “Side effects” and “Overdose”). Treatment with any diuretics can cause hyponatremia, sometimes with very serious consequences. Hyponatremia accompanied by hypovolemia can lead to dehydration and orthostatic hypotension.
A simultaneous decrease in the content of chlorine ions can lead to the development of secondary compensatory metabolic alkalosis: the frequency of its occurrence and the severity of its manifestations are insignificant.
Content of potassium ions in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/L) should be avoided in the following high-risk patients: elderly patients, malnourished patients (both those receiving and not receiving concomitant drug therapy), patients with cirrhosis (with edema and ascites) , coronary heart disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.
Patients with a prolonged QT interval, either congenital or drug-induced, are also at increased risk.
Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially arrhythmias, which can be fatal. In all the cases described above, more frequent monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion content should be carried out within the first week from the start of therapy.
If hypokalemia is detected, appropriate correction should be made.
Content of calcium ions in blood plasma
Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in calcium levels in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking diuretics.
Plasma glucose concentration
It is necessary to monitor blood glucose concentrations in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
When the concentration of uric acid in the blood plasma increases during therapy, the frequency of gout attacks may increase.
Diuretics and kidney function
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adults below 25 mg/l or 220 µmol/l).
In elderly patients, plasma creatinine levels should be assessed taking into account age, weight and sex, according to the Cockroft formula:
Creatinine clearance (CC) = (140 - age) x weight / 0.814 x plasma creatinine concentration
where: age in years, weight in kg, plasma creatinine concentration in µmol/l.
The formula is suitable for older men; for older women, the result should be multiplied by a factor of 0.85.
At the beginning of diuretic treatment in patients, due to hypovolemia (due to the excretion of water and sodium ions), a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure is not dangerous for patients with initially normal renal function, but its severity may increase in patients with renal failure.
Photosensitivity
While taking thiazide and thiazide-like diuretics, cases of photosensitivity reactions have been reported (see section "Side effects"). If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.
Athletes
Indapamide may give a positive reaction during doping control.
Acute myopia and secondary angle-closure glaucoma
Sulfonamides and their derivatives can cause the development of idiosyncratic reactions leading to temporary (transient) myopia and acute angle-closure glaucoma. Without proper treatment, acute angle-closure glaucoma can lead to vision loss. First of all, you need to stop taking the drug as soon as possible. If intraocular pressure continues to be high, immediate medical or surgical treatment may be required. Risk factors that may lead to the development of acute angle-closure glaucoma include a history of allergies to sulfonamides or penicillin.
