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.
