Simultaneous use of Enalapril and Indapamide leads to an increase in the antihypertensive effect of Enalapril.
Enalapril
Symptomatic arterial hypotension
Symptomatic arterial hypotension is rarely observed in patients with uncomplicated arterial hypertension. In patients with hypertension taking enalapril, arterial hypotension develops more often on the background of dehydration, which occurs, for example, as a result of diuretic therapy, restriction of consumption of table salt, in patients who are on dialysis, and also in patients with diarrhea or vomiting (see "Side effect", "Interaction with other drugs ").
Symptomatic arterial hypotension was also observed in patients with heart failure with or without renal failure. Arterial hypotension develops more often in patients with severe chronic heart failure with hyponatraemia or impaired renal function, which have higher doses of loop diuretics. In these patients, treatment with enalapril should be started under medical supervision, which should be particularly careful when changing the dose of enalapril and / or diuretic. Similarly, patients with ischemic heart disease or cerebrovascular disease should be monitored, in whom excessive BP reduction can lead to myocardial infarction or stroke.
With the development of arterial hypotension, the patient should be laid and, if necessary, to enter a 0.9% solution of sodium chloride. Transient arterial hypotension with enalapril is not a contraindication to further use and increase in the dose of the drug, which can be continued after replenishing the volume of fluid and normalizing blood pressure.
In some patients with heart failure and with normal or low blood pressure enalapril may cause an additional decrease in blood pressure. This reaction to taking the drug is expected and is not a basis for discontinuing treatment. In those cases when arterial hypotension assumes a stable character, it is necessary to lower the dose and / or stop treatment with a diuretic and / or enalapril,
Renovascular hypertension
The use of ACE inhibitors has a beneficial effect in patients with renovascular hypertension, both awaiting surgery and when surgery is not possible. Treatment should begin with low doses of the drug, in a hospital setting, while evaluating the functional activity of the kidneys and the content of potassium in the blood plasma. Some patients may develop functional kidney failure, which quickly disappears after drug withdrawal.
Aortic or mitral stenosis / hypertrophic obstructive cardiomyopathy
Like all drugs that have a vasodilating effect, ACE inhibitors should be administered with caution to patients with obstruction of the outflow path from the left ventricle.
Impaired renal function
In some patients, arterial hypotension, which develops after the initiation of treatment with ACE inhibitors, may lead to further deterioration in kidney function. In some cases, the development of acute renal failure, usually reversible, has been reported.
Patients with renal insufficiency may need to reduce the dose and / or frequency of the drug. In some patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, there was an increase in the concentration of urea in the blood and creatinine in the serum. Changes were usually reversible. This type of change is most likely in patients with impaired renal function.
In some patients who did not have any kidney disease before treatment, enalapril in combination with diuretics caused a usually minor and transient increase in the concentration of urea in the blood and creatinine in the blood serum. In such cases, a dose reduction and / or cancellation of the diuretic and / or enalapril may be required.
Kidney Transplantation
There is no experience of using the drug in patients after kidney transplantation, so treatment with enalapril is not recommended in patients after kidney transplantation.
Liver failure
The use of ACE inhibitors has rarely been associated with the development of a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant liver necrosis, sometimes with a fatal outcome. When jaundice or a significant increase in the activity of "liver" transaminases against the background of the use of ACE inhibitors, the drug should be discontinued and appropriate adjuvant therapy should be prescribed, the patient should be under appropriate supervision.
Neutropenia / Agranulocytosis
Neutropenia / agranulocytosis, thrombocytopenia, and anemia have been observed in patients receiving ACE inhibitors. Neutropenia occurs rarely in patients with normal renal function and without other complicating factors. Enalapril should be used with extreme caution in patients with systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.) taking immunosuppressive therapy, allopurinol or procainamide, or a combination of these complicating factors, especially if there are violations of kidney function. Some of these patients developed serious infectious diseases, which in some cases did not respond to intensive antibiotic therapy. If such patients are used enalapril, it is recommended that the number of leukocytes and lymphocytes in the blood be monitored regularly and patients should be warned about the need to report any signs of an infectious disease.
Hypersensitivity reactions / angioedema
With the use of ACE inhibitors, including enalapril, rare cases of angioneurotic edema of the face, limbs, lips, tongue, vocal folds and / or larynx that occurred during different periods of treatment were observed. In very rare cases, development was reportedintestinal edema. In such cases should immediately stop taking enalapril and carefully monitor the patient's condition in order to monitor and correct clinical symptoms. Even in cases where there is only swelling of the tongue without the development of respiratory distress syndrome, patients may need long-term follow-up, since therapy with antihistamines and corticosteroids may not be sufficient.
Very rarely reported a lethal outcome due to angioedema, associated with laryngeal edema or edema of the tongue. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction, especially in patients undergoing surgical procedures on the respiratory organs.In cases where edema is localized in the area of the tongue, vocal folds or larynx and can cause airway obstruction, immediate treatment should be prescribed, which may include subcutaneous administration of 0.1% epinephrine (adrenaline) solution (0.3-0.5 ml) and / or provide airway patency.
In patients of the Negroid race who took ACE inhibitors, angioedema was observed more often than in patients of other races. Patients who have a history of angioedema, not associated with the administration of ACE inhibitors, may be more at risk of developing angioedema along with therapy with ACE inhibitors (see section "Contraindications").
Anaphylactoid reactions during desensitization by venomnoMr.chickens
In rare cases, patients with ACE inhibitors developed life-threatening anaphylactoid reactions during desensitizing therapy with the poison of Hymenoptera insects (bees, wasps).
Undesirable reactions can be avoided if the ACE inhibitor is temporarily discontinued before desensitization begins.
Anaphylactoid reactions during of LDL-apheresis
In patients taking ACE inhibitors during LDL-apheresis using dextran sulfate, there were rarely any life-threatening anaphylactoid reactions. The development of these reactions can be avoided if the ACE inhibitor is temporarily discontinued before the beginning of each LDL-apheresis procedure.
Patients on hemodialysis
Anaphylactoid reactions have been observed in patients on dialysis using high-flux membranes (such as AN69®) and simultaneously receiving therapy with ACE inhibitors. In such patients, dialysis membranes of a different type or hypotensive agents of other classes should be used.
Cough
There were cases of coughing on the background of therapy with ACE inhibitors. As a rule, cough is unproductive, permanent and stops after the abolition of therapy. Cough associated with the use of ACE inhibitors should be taken into account in the differential diagnosis of cough.
Surgical interventions / general anesthesia
During major surgical interventions or general anesthesia with the use of funds,causing an antihypertensive effect, enalaprilate blocks the formation of angiotensin II, caused by compensatory release of renin. If this results in a pronounced decrease in blood pressure, explained by such a mechanism, it can be corrected by increasing the volume of circulating blood.
Hyperkalemia (see section "Interaction with other drugs")
The risk of developing hyperkalemia is observed in the elderly, with renal insufficiency, diabetes mellitus, certain concomitant conditions (heart failure in the stage of decompensation, metabolic acidosis), and also with the simultaneous use of potassium-sparing diuretics (eg spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salts.
The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with impaired renal function, can lead to a significant increase in potassium in the blood serum, hyperkalemia can lead to serious, sometimes fatal, arrhythmias.
If it is necessary to simultaneously use enalapril and the above medicinal productsmeans should be careful and regularly monitor the potassium content in the blood serum.
Hypoglycaemia
Patients with diabetes who take hypoglycemic agents for ingestion or insulin should be informed before starting the use of ACE inhibitors on the need for regular monitoring of blood glucose concentrations, especially during the first month of concurrent use of these medicines (see "Interaction with Other Drug Users" means ").
Lithium preparations
It is not recommended simultaneous use of drugs of lithium and enalapril (see the section "Interaction with other drugs").
Double blockade of RAAS
The development of arterial hypotension, fainting, stroke, hyperkalemia, and renal dysfunction (including acute renal failure) in susceptible patients has been reported, especially if combined therapy with drugs affecting the RAAS is used (see "Interactions with Other Drugs"). . It is not recommended to perform a double blockade of RAAS by the combined use of ACE inhibitors with receptor antagonists for angiotensin II or aliskiren.
Contraindicated simultaneous use of enalapril with aliskiren or aliskirenoderzhaschimi drugs in patients with diabetes mellitus and / or with impaired renal function (GFR less than 60 ml / min / 1.73 m2) (see the section "Contraindications").
It is not recommended simultaneous use of an ACE inhibitor with receptor antagonists for angiotensin II in patients with diabetic nephropathy.
Application in elderly patients
In elderly patients, the function of the kidneys and the potassium content in the body should be evaluated before taking the drug.
Ethnic differences
As with other ACE inhibitors, enalapril, apparently, less effectively reduces blood pressure in patients of the Negroid race than in patients of other races, which may be explained by the higher prevalence of conditions with low renin activity of blood plasma in the population of patients of negroid race with hypertension.
Indapamide
In the appointment of thiazide and thiazide-like diuretics in patients with impaired hepatic function, it is possible to develop hepatic encephalopathy, especially in the case of disturbance of the water-electrolyte balance. 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 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.
Water-electrolyte balance
Content of sodium ions in blood plasma
Before the start of treatment it is necessary to determine the sodium content in the blood plasma. Against the background of taking the drug should regularly monitor this figure. All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences.
It is necessary to regularly monitor the sodium content, since initially the decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most careful control of the sodium content is necessary for patients with cirrhosis of the liver and elderly patients.
The content of potassium ions in the blood plasma
With thiazide and thiazide-like diuretics, the main risk is a sharp decrease in potassium in the blood plasma and development of hypokalemia.It is necessary to avoid the risk of developing hypokalemia (potassium content less than 3.4 mmol / L) in the following patient groups: elderly patients, weakened patients or patients receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the QT interval, patients with cirrhosis liver, peripheral edema or ascites, ischemic heart disease, heart failure. Hypokalemia in patients of these groups increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.
In addition, patients with an increased QT interval are at increased risk, but it does not matter whether this increase is due to congenital causes or effects of drugs. Hypokalemia, as well as bradycardia, is a condition that promotes the development of severe arrhythmias and, especially, pirouette-type arrhythmias, which can lead to death. In all the cases described above, it is necessary to regularly monitor the potassium content in the blood plasma. The first measurement of the potassium content in the blood should be carried out within the first week after the start of treatment.When hypokalemia occurs, appropriate treatment should be prescribed.
The content of calcium ions in the blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, thereby causing mild and transient hypercalcemia. Hypercalcemia on the background of taking indapamide may be a consequence of previously undiagnosed hyperparathyroidism.
It is necessary to stop taking diuretic drugs before examining the function of parathyroid glands.
The concentration of glucose in the blood plasma
In patients with diabetes it is extremely important to control the concentration of glucose in the blood, especially in the presence of hypokalemia.
Uric acid
Patients with gout may increase the incidence of attacks or exacerbate the course of gout.
Diuretic drugs and kidney function
Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentration in adult patients is below 25 mg / L or 220 μmol / L). In elderly patients, the concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.
It should be borne in mind that at the beginning of treatment, patients may experience a decrease in GFR caused by hypovolemia, which in turn is caused by loss of fluid and sodium on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the function of the kidneys is not impaired, such temporary functional renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen. Derivatives of sulfonamides can exacerbate the course of systemic lupus erythematosus (should be borne in mind when administering indapamide).
Athletes
Indapamide can give a positive result in the conduct of doping control.