Perindopril, indapamide
The use of Noliprel ® 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 dose permitted for use (see section "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.
Lithium preparations
The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see.section "Interaction with other drugs").
Impaired renal function
Therapy is contraindicated in patients with severe renal failure (CC less than 30 ml / min). In some patients with AH without previous obvious impairment of renal function against the background of therapy, laboratory signs of functional renal failure may appear. 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 potassium and serum creatinine level - 2 weeks after the beginning of therapy and then every 2 months. Renal failure often occurs in patients with severe heart failure or an initial impairment of kidney function, including stenosis of one or two renal arteries.
As a rule, the use of perindopril and indapamide is not recommended for patients with bilateral stenosis of the renal arteries or stenosis of a single functioning kidney.
Arterial hypotension and disturbance of water-electrolyte balance
Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with stenosis of one or two renal arteries). Therefore, when observing patients dynamically, attention should be paid to possible symptoms of dehydration and a decrease in 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. Do not prescribe Noliprel® to patients with hereditary intolerance to galactose, lactase deficiency, and glucose-galactose malabsorption.
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.
With extreme caution should be applied perindopril in patients with diffuse connective tissue diseases, with the use of immunosuppressive drugs, allopurinol or procainamide and with simultaneous exposure to these factors, especially in patients with initial renal impairment.Some patients experienced severe infectious lesions, in some cases, resistant to intensive antibiotic therapy. When appointing perindopril to such patients - it is recommended to periodically monitor the number of leukocytes in the blood. Patients should inform the doctor of any signs of infectious diseases (eg, angina, fever).
Hypersensitivity / angioedema (angioedema)
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 not associated with the administration of ACE inhibitors may be at increased risk of developing it with the use of drugs of this group (see the section "Contraindications"),
In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without a prior angioedema and at a normal level of C-1 esterase. The diagnosis is established using computed tomography of the abdominal region, ultrasound or at the time of surgery. Symptoms disappear after stopping the intake of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema edema of 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, life-threatening anaphylactoid reactions may develop during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued before each apheresis procedure.
Hemodialysis
In patients receiving ACE inhibitors, anaphylactoid reactions were noted in hemodialysis using high-flow membranes (eg AN69®).Therefore, it is desirable to use a different type of membrane or to use an antihypertensive drug of another pharmacotherapeutic group.
Potassium-sparing diuretics and potassium preparations
As a rule, the combined use of perindopril and potassium-sparing diuretics, as well as potassium and potassium-containing substitutes for edible salt is not recommended (see section "Interaction with other drugs").
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 dry cough occurs in a patient, one should keep in mind the possible connection of this symptom with the administration of an ACE inhibitor. If the attending physician believes that therapy with an ACE inhibitor is necessary for the patient, the drug may be continued.
Children and teens
Noliprel® should not be given to children and adolescents under the age of 18 due to a 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 states, a significant activation of the renin-angiotensin-aldosterone system can occur, especially with 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, stenosis of one or two renal arteries, chronic heart failure or cirrhosis of the liver with the presence of 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 patients who are waiting for surgery, and in the case when it is impossible to perform such an operation.
Treatment with Noliprel® for patients with diagnosed or suspected renal artery stenosis 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 chronic heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (the risk of spontaneous increase in potassium concentration), treatment should begin with a low dose of the drug (half a pill) and under constant medical supervision.
Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers.
Patients with diabetes mellitus
When prescribing a drug for patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin, during the first month of therapy, the blood glucose level must be carefully monitored.
Ethnic differences
Perindopril, like other ACE inhibitors, obviously has a less pronounced hypotensive effect in patients of the Negroid race compared with representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race are more likely to have low renin activity.
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 the use of long-acting ACE inhibitors, including perindopril, 12 hours before the surgery.
Aortic stenosis / mitral stenosis / Hypertrophic cardiomyopathy
ACE inhibitors should be administered with caution to patients with left ventricular outflow obstruction.
Liver failure
In rare cases, with the administration of ACE inhibitors occurs. cholestatic jaundice. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. When 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").
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.
Hyperkalemia
Hyperkalemia can develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, decreased kidney function, advanced age, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of heart failure, metabolic acidosis), concurrent administration of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes for edible salt, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). The use of potassium, potassium-sparing diuretics, potassium-containing substitutes for edible salt can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances.If a combination of the above drugs is required, treatment should be carried out with caution, against a background of regular monitoring of potassium in the blood serum (see section "Interaction with other drugs").
Indapamide
With the appointment of thiazide and thiazide-like diuretics, patients with impaired hepatic function may develop hepatic encephalopathy. In this case, the taking of diuretics should be stopped immediately.
Photosensitivity
Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported (see the "Side effect" section). In the case of developing photosensitivity reactions 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 UV rays.
Water-electrolyte balance
Content of sodium ions 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 the sections "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 patients, 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, but it does not matter whether this increase is due to congenital causes or effects of medications.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias such as pirouettes, which can be fatal. In all cases described above, more regular monitoring of the potassium ion content in the blood plasma is necessary. 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, it is necessary to cancel the intake of diuretic drugs.
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). In elderly patients, the clearance of creatinine is calculated taking into account age, body weight and sex.
At the beginning of treatment with diuretics in patients due to hypovolemia and hyponatremia, there may be a temporary decrease in the 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 kidney function, however, in patients with renal insufficiency, its severity can increase.
Athletes
Indapamide can give a positive reaction during doping control.