Noliprel® A
The use of Noliprel ® A 2.5 mg + 0.625 mg, containing a low dose of indapamide and perindopril arginine, is not accompanied by a significant reduction in the incidence of side effects, with the exception of hypokalemia, compared with perindopril and indapamide in the lowest permitted doses (see " Side effect"). At the beginning of therapy with two antihypertensive drugs, which the patient did not receive earlier, one can not exclude the increased risk of idiosyncrasy. Careful observation of the patient makes it possible to minimize this risk.
Impaired renal function
Therapy is contraindicated in patients with severe renal failure (CC less than 30 ml / min).In some patients with hypertension without a previous obvious violation of kidney function against the background of therapy, there may be laboratory signs of functional renal failure. In this case, treatment should be discontinued. In the future, you can resume combination therapy, using low doses of drugs, or use drugs in monotherapy.
Such patients need regular monitoring of the level of potassium and creatinine in the blood serum - 2 weeks after the start of therapy and then every 2 months. Renal failure often occurs in patients with severe chronic heart failure or an initial impairment of kidney function, including with renal artery stenosis.
Arterial hypotension and disturbance of water-electrolyte balance
Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with artery stenosis of a single kidney and bilateral stenosis of the renal arteries). Therefore, in the dynamic observation of patients should pay attention to possible symptoms of dehydration and reduce the level of electrolytes in the blood plasma, for example,after diarrhea or vomiting. Such patients need regular monitoring of the level of plasma electrolytes.
With severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for the continuation of therapy. After recovering the volume of circulating blood and blood pressure, you can resume therapy using low doses of drugs, or use drugs in monotherapy.
Potassium level
The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. As in the case of combined use of antihypertensive drugs and diuretic, regular monitoring of the potassium level in the blood plasma is necessary.
Excipients
It should be borne in mind that the composition of excipients of the drug includes lactose monohydrate. You should not assign Noliprel® and patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.
Lithium preparations
Simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see the section "Contraindications", "Interaction with other drugs").
Perindopril
Neutropenia / agranulocytosis
The risk of developing neutropenia against the background of the administration of ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma). After the withdrawal of ACE inhibitors, neutropenia signs pass independently.
To avoid the development of such reactions it is recommended to strictly follow the recommended dose. In the appointment of ACE inhibitors, this group of patients should carefully balance the benefit / risk factor.
Angioedema (edema of Quincke)
When taking ACE inhibitors, including perindopril, in rare cases, development of angioedema of the face, limbs, lips, tongue, glottis and / or larynx can be observed.If symptoms appear, the perindopril should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the edema affects only the face and lips, then its manifestations usually pass independently, although antihistamines may be used to treat its symptoms.
Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, glottis or larynx can lead to airway obstruction. When such symptoms occur, immediately enter subcutaneously epinephrine (epinephrine) in a dilution of 1: 1000 (0.3 or 0.5 ml) and / or provide airway patency.
Patients with a history of Quincke edema who are not associated with the administration of ACE inhibitors may be at increased risk of developing it with the use of this group of drugs (see section "Contraindications").
In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine.
Anaphylactoid reactions during desensitization
There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the poison of Hymenoptera insects (bees, wasps).ACE inhibitors should be used with caution in allergic patients who undergo desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving immunotherapy with venom of Hymenoptera. However, the anaphylactoid reaction can be avoided by temporarily lifting the ACE inhibitor at least 24 hours before the procedure.
Anaphylactoid reactions during apheresis of LDL
In rare cases in patients receiving ACE inhibitors, when performing low-density lipoprotein (LDL) apheresis using dextran sulfate, life-threatening anaphylactoid reactions may develop in hemodialysis patients using high-flow membranes. To prevent the anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued at least 24 hours before the apheresis procedure.
Cough
Against the background of therapy with an ACE inhibitor, dry cough may occur. Cough persists for a long time against the background of taking this group's drugs and disappears after their withdrawal. When a patient has a dry cough, remember the possible iatrogenic nature of this symptom.If the attending physician believes that therapy with an ACE inhibitor is necessary for the patient, the drug may be continued.
Children and teens
The drug should not be given to children and adolescents under the age of 18 due to the lack of data on the efficacy and safety of perindopril in the form of monotherapy or as part of combination therapy in patients of this age group.
The risk of arterial hypotension and / or renal failure (in patients with heart failure, a violation of water-electrolyte balance, etc.).)
In some pathological conditions, a significant activation of the renin-angiotensin-aldosterone system can occur, especially in severe hypovolemia and a decrease in the level of plasma electrolytes (against a background of a salt-free diet or long-term diuretics), in patients with initially low blood pressure, with bilateral stenosis of the renal arteries or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites. The use of an ACE inhibitor causes blockade of this system and therefore can be accompanied by a sharp decrease in blood pressure and / or an increase in the level of creatinine in the blood plasma, indicating the development of functional renal failure.These phenomena are more often observed with the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop rapidly in other periods of therapy. In such cases, when the therapy is resumed, it is recommended to use the drug in a lower dose and then gradually increase the dose.
Elderly patients
Before you start taking the drug, you need to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected, given the degree of BP reduction, especially in the case of dehydration and loss of electrolytes. Such measures allow to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of hypotension exists in all patients but particular care should be taken using the drug in patients with ischemic heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with low doses.
Patients with Renovascular Hypertension
The method of treating reninvascular hypertension is revascularization. Nevertheless, the use of ACE inhibitors has a beneficial effect in this category of patients,as waiting for surgery, and in the case when surgical intervention can not be carried out.
Treatment with Noliprel® A in patients with diagnosed or suspected bilateral stenosis of the renal arteries or stenosis of the single kidney artery should begin with a low dose of the drug in a hospital setting, monitoring the kidney function and the concentration of potassium in the blood plasma. In some patients, functional renal failure may develop, which disappears when the drug is withdrawn.
Other risk groups
In patients with severe heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (the risk of spontaneous increase in potassium concentration) treatment should start with a low dose of the drug and under constant medical supervision.
Patients with arterial hypertension with ischemic heart disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers.
Anemia
Anemia can develop in patients after kidney transplantation or in people on hemodialysis.At the same time, the decrease in hemoglobin concentration is greater, the higher its initial value was. This effect, apparently, is not dose-dependent, but may be related to the mechanism of action of ACE inhibitors.
A slight decrease in hemoglobin concentration occurs within the first 6 months, then it remains stable and completely restored after the drug is discontinued. In such patients, treatment can be continued, however, hematological analyzes should be carried out regularly.
Surgery / General Anesthesia
The use of ACE inhibitors in patients undergoing surgery with the use of general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetic agents that have an antihypertensive effect.
It is recommended to stop taking long-acting ACE inhibitors, including perindopril, the day before the surgery. It is necessary to warn the anesthesia doctor that the patient is taking ACE inhibitors.
Aortic stenosis / Hypertrophic cardiomyopathy
ACE inhibitors should be administered with caution to patients with left ventricular outflow obstruction.
Liver failure
In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, rapid development of liver necrosis, sometimes fatal, is possible. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors should stop taking the drug and see a doctor (see section "Side effect").
Indapamide
In the presence of violations of the liver, the use of thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, stop taking the medication immediately.
Water-electrolyte balance
The content of sodium priests in blood plasma
Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug should regularly monitor this figure. All diuretic drugs can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary.More frequent monitoring of sodium ions is indicated for patients with cirrhosis of the liver and elderly people (see section "Side effect" and "Overdose").
The content of potassium ions in the blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. It is necessary to avoid hypokalemia (less than 3.4 mmol / L) in the following categories of patients at high risk: elderly, depleted patients or receiving concomitant medication, patients with cirrhosis, peripheral edema or ascites, coronary heart disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias.
Patients with an increased QT interval also belong to the high-risk group, and it does not matter whether this increase is due to congenital causes or effects of drugs.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias such as pirouettes, which can be fatal. In all the cases described above, more regular monitoring of the potassium ion content inblood plasma. The first measurement of the concentration of potassium ions should be carried out within the first week from the start of therapy.
If hypokalemia is detected, appropriate treatment should be prescribed.
The content of calcium ions in the blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism. Before the study of the function of the parathyroid gland, diuretic drugs should be withdrawn.
The content of glucose in the blood plasma
It is necessary to monitor the blood glucose level in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
In patients with elevated uric acid levels in blood plasma, the frequency of gout attacks may increase with therapy.
Diuretics and kidney function
Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine levels in adults below 25 mg / L or 220 μmol / L in plasma in adults).
At the beginning of treatment with diuretics in patients due to hypovolemia and hyponatremia may be a temporary reduction in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, however, in patients with renal insufficiency, its severity may increase.
Photosensitivity
Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported. In the case of the development of reactions photosensitivity against the background of taking the drug should stop treatment. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.
Athletes
Indapamide can give a positive reaction during doping control.