Stable ischemic heart disease (CHD)
When the episode of unstable angina develops (significant or not) during the first month of therapy with the drug KOVEREX®, it is necessary to evaluate the benefit / risk ratiowhen using this drug.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated arterial hypertension, symptomatic arterial hypotension rarely occurs after taking the first dose. The risk of excessive reduction in blood pressure is increased in patients with a reduced bcc against diuretic therapy, with strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or in patients with severe renin-dependent hypertension. The expressed 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 hyponatremia or kidney failure. These patients are recommended careful medical supervision at the beginning of therapy and when titrating doses of the drug. The same applies to patients with IHD or cerebrovascular disease, in whom excessive reduction of blood pressure can lead to myocardial infarction or cerebrovascular complications.In the case of development of arterial hypotension, it is necessary to give the patient a horizontal position with raised legs, and if necessary, administer a solution of sodium chloride intravenously to increase the BCC. Transient arterial hypotension is not a contraindication for further therapy. After the recovery of bcc and blood pressure, treatment can be continued provided that the dose of the drug is carefully selected.
In some patients with CHF and normal or low blood pressure during therapy with COWREEX®, an additional decrease in blood pressure may occur. This effect is expected and usually is not a basis for drug discontinuation. If arterial hypotension is accompanied by clinical manifestations, a dose reduction or withdrawal of the KOVEREX® preparation may be required.
Renal impairment and renal vascular hypertension
In patients with renal insufficiency (KC less than 60 ml / min) the initial dose of the drug KOVEREKS ® should be matched in accordance with QC (see the section "Method of administration and dose") and then - depending on the therapeutic response to the therapy. For such patients, regular monitoring of serum potassium and serum creatinine is necessary.
In patients with symptomatic heart failure, arterial hypotension, which develops during the initial period of therapy with ACE inhibitors, can lead to impaired renal function. In these patients, sometimes there were cases of acute renal failure, usually reversible.
In some patients with bilateral renal artery stenosis or stenosis of the renal artery to a solitary kidney (especially in the presence of renal failure) during therapy with ACE inhibitors was an increase in serum concentrations of urea and creatinine, reversible after discontinuation of therapy. Patients with renovascular hypertension during therapy with ACE inhibitors are at increased risk of severe hypotension and renal insufficiency. Treatment of such patients should start under close medical supervision with low doses and with further adequate dose selection. During the first weeks of therapy with KOVEREKS® to cancel diuretics and regular monitoring of renal function.
Some patients with hypertension, the presence of previously undetected kidney failure,especially with concomitant diuretic therapy, there was a slight and temporary increase in the concentration of urea and creatinine in the blood serum. In this case, it is recommended to reduce the dose of KOVEREX® and / or to cancel the diuretic.
Anaphylactoid reactions during the procedure of apheresis of low-density lipoproteins (LDL-apheresis)
In patients with the appointment of ACE inhibitors against the background of the procedure for the apheresis of low density lipoprotein (LDL) with dextran-sulfate absorption, in rare cases, the development of an anaphylactic reaction. It is recommended that the ACE inhibitor be temporarily withdrawn (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 poisons of Hymenoptera (bees, wasps). ACE inhibitors should be given with caution to patients with allergies and receiving desensitizing therapy; these drugs should not be prescribed with immunotherapy with poisons.However, these reactions can be prevented by the temporary withdrawal of the ACE inhibitor at least 24 hours before each desensitization procedure.
Hypersensitivity / angioedema
Rarely, in patients taking ACE inhibitors, incl. perindopril, developed angioedema, facial edema, extremities, lips, mucous membranes, tongue, glottis and / or larynx. This condition can develop at any time of treatment. With the development of angioedema, treatment should immediately be discontinued, the patient should be under medical supervision until the symptoms disappear completely. Angioedema of the lips and face usually does not require treatment; To reduce the severity of symptoms, you can use antihistamines.
Angioedema, swelling of the tongue, glottis or larynx can lead to death. With the development of angioedema, immediately subcutaneously epinephrine (epinephrine) and ensure airway patency.
ACE inhibitors often cause angioedema in patients of the Negroid race. Patients with an angioneurotic edema in the anamnesis,not associated with the use of ACE inhibitors, may be at high risk of developing angioedema while taking an ACE inhibitor.
Cough
Against the background of therapy with ACE inhibitors, a persistent, unproductive dry cough may develop, which stops after the drug is discontinued. This should be taken into account in the differential diagnosis of cough.
Elderly patients
Some elderly patients may give an increased response to ACE inhibitors compared to younger patients. It is recommended to start treatment with low doses and assess kidney function at the beginning of the drug.
Children
Since the efficacy and tolerability of perindopril in children under 18 years of age is not established, such patients should not prescribe the drug KOVEREX®.
Hyperkalemia
Against the background of therapy with ACE inhibitors, including perindopril, in some patients the potassium content in the blood can increase. The risk of hyperkalemia is elevated in patients with renal and / or heart failure, decompensated diabetes mellitus, and in patients using potassium-sparing diuretics, potassium preparations or other drugs that cause hyperkalemia (eg, heparin).If it is necessary to simultaneously prescribe these drugs, it is recommended to regularly monitor the potassium content in the blood serum.
Surgery / general anesthesia
In patients whose condition requires extensive surgical intervention or anesthesia with drugs that cause arterial hypotension, ACE inhibitors, including perindopril, can block the formation of angiotensin II with compensatory release of renin. The day before the surgery, therapy with ACE inhibitors should be canceled. If the ACE inhibitor can not be canceled, then the arterial hypotension, which develops according to the mechanism described, can be corrected by an increase in BCC.
Stenosis of the aortic or mitral valve / 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
In patients on the background of therapy with ACE inhibitors, cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia were noted. With normal kidney function, in the absence of other complications, neutropenia develops rarely. The drug KOVEREKS ® must be used with great care in patients with systemic connective tissue diseases (eg, systemic lupus erythematosus, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as when combining all of these factors, especially if there is an existing impairment of kidney function. Such patients may develop severe infections that do not respond to intensive antibiotic therapy. When carrying out therapy with KOVEREX® in patients with the above factors it is recommended to periodically monitor the amount of white blood cells 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 development of hemolytic anemia were noted.
Diabetes
In patients with diabetes who take hypoglycemic agents for ingestion or insulin, in the first few months of therapy with ACE inhibitors, the concentration of glucose in the blood should be carefully monitored.
Proteinuria
Proteinuria can develop in patients already having impaired renal function, as well as during the administration of high doses of ACE inhibitors.
Liver failure
During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that starts with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice appears during the administration of an ACE inhibitor or an increase in the activity of "liver" enzymes occurs, the ACE inhibitor should be immediately discontinued and the patient should be closely monitored. It is also necessary to conduct an appropriate examination.
Negroid race
The risk of angioedema development in patients of the Negroid race is higher. Like other ACE inhibitors, perindopril less effective in reducing blood pressure in patients of the Negroid race,due to the greater prevalence of low-grade conditions in the population of this group of patients with hypertension.