Lithium preparations
Simultaneous use of perindopril and indapamide with lithium preparations is not recommended (see section "Interaction with other drugs").
Impaired renal function
Therapy with Co-Parnavel is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min). In some patients with hypertension without a previous impairment of the function of the nosocles, there may be signs of acute renal failure in the area of therapy with Co-Parnavel, in which case treatment with the drug should be discontinued.In the future it is possible to resume combination therapy using low doses of the drug Ko-Parnavel, or use drugs perindopril and indapamide in monotherapy. Such patients need regular monitoring of serum potassium and serum creatinine levels every 2 weeks after initiation of therapy and every subsequent 2 months of therapy with Ko-Parnavel.
Acute renal failure in the bowl develops in patients with severe chronic heart failure or with an initial impairment of kidney function, incl. with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney. The drug is not recommended for patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney.
Arterial hypotension and disturbances of water-electrolyte balance
Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney). Therefore, when observing patients dynamically, attention should be paid to the possible symptoms of dehydration and a decrease in the electrolyte content in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients need regular monitoring of electrolytes in blood plasma. With a marked decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for further continuation of therapy.After recovering the volume of circulating blood pressure blood, you can resume therapy with Co-Pausing a low dose of the drug, or using drugs perindopril and indapamide in monotherapy.
The content of potassium
The simultaneous use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes or renal disease insufficiency. As with other antihypertensives in combination with a diuretic, regular monitoring of the potassium content in the blood plasma is necessary.
Excipients
It should be taken into account that lactose monohydrate is included in the auxiliary substances of the drug, therefore the drug is contraindicated in patients with hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
Perindopril
Neutropenia / agranulocytosis
In patients taking ACE inhibitors, there may be cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function, in the absence of other complications, neutropenia develops rarely and passes on its own after the withdrawal of ACE inhibitors.
Perindopril must be used with great care the patients with diseases of connective tissue and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing impairments of kidney function.
Such patients can develop severe infections that are not amenable to intensive antibiotic therapy. In the case of the appointment of perindopril it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that in case of any signs of an infectious disease (sore throat, fever), you should immediately consult a doctor.
Hypersensitivity / angioedema (angioedema)
When taking ACE inhibitors, incl. perindopril, in rare cases, development of an angioedema of the face, lips, tongue, tongue of the upper palate and / or larynx can be observed. If these symptoms appear, the drug should be stopped immediately, the patient should be observed until the signs of edema disappear completely.
If the angioedema affects only the face and lips, then its manifestations usually pass alone, or to treat its symptoms can be used antihistamines. Angioedema, accompanied by swelling of the tongue and larynx, can lead to airway obstruction and death. When such symptoms occur, immediately enter subcutaneously epinephrine (adrenaline) (at 1: 1000 dilution (0.3 or 0.5 mL) and / or provide airway patency.
Patients with a history of observed angioedema not associated with ACE inhibitors, the risk of its development when receiving the drugs in this group (see. The section "Contra ') can be raised.
In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. Thus, patients have a pain in the abdomen as an isolated symptom or in combination with nausea and vomiting in some cases without prior angioneurotic edema of the face and at normal enzyme activity C-1 esterase. The diagnosis is established by means of computed tomography of the abdominal cavity, ultrasound examination or at the time of surgical intervention. 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 of the intestine.
Anaphylactoid reactions during desensitization procedures
There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with Hepaticoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients with a history of allergic anamnesis or susceptibility to allergic reactions following desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving immunotherapy with venom of Hymenoptera. The development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.
Anaphylactoid reactions during apheresis of LDL
In rare cases in patients receiving ACE inhibitors, in the course of APH apheresis II I With the use of dextran sulfate, life-threatening anaphylactoid reactions can develop.To prevent the anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each procedure for LDL apheresis using high-flow membranes.
Hemodialysis
In patients receiving ACE inhibitors, when performing hemodialysis using high-flux membranes (for example, AN69®) anaphylactoid reactions were noted. Therefore, it is desirable to use a membrane of a different type or use an antihypertensive drug of another pharmacotherapeutic group.
Cough
Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of this group. When dry cough occurs, remember the possible association of this symptom with the administration of an ACE inhibitor. If the doctor believes that therapy with an ACE inhibitor is necessary for the patient, the use of Ko-Parnavel can be continued.
The risk of arterial hypotension and / or renal failure (in patients with chronic heart failure, water-electrolyte balance disorders, etc.)
In some pathological states, a significant activation of the renin-angiotensin-aldosterone system (RAAS) can be noted,especially in severe hypovolemia and a decrease in the electrolyte content in the blood plasma (against a background of diet with restriction of table salt or long-term diuretics), in patients with initially low blood pressure, stenosis of the renal artery (including bilateral), chronic heart failure or cirrhosis with edema and ascites. The use of ACE inhibitors causes blockade of the RAAS; in this regard, a sharp decrease in blood pressure and / or an increase in serum creatinine, indicating the development of acute renal failure, is more likely to occur with the first dose of the drug or during the first 2 weeks of therapy. Sometimes these conditions develop sharply. In such cases, when resuming therapy, it is recommended that a combination of perindopril and indapamide be used at a lower dose and then gradually increased the dose.
Elderly patients
Before the start of the drug, Co-Parnavel should evaluate the function of the kidneys and the content of potassium in the blood plasma. The initial dose is selected depending on the degree of decrease in blood pressure, especially with a decrease in the volume of circulating blood and chronic heart failure (IV functional class by classification NYHA). Such measures allow avoiding a sharp drop in blood pressure.
Atherosclerosis
The risk of arterial hypotension exists in all patients, but special care should be taken when applying preparation in patients with ischemic heart disease and cerebral circulatory insufficiency. In such patients, treatment should begin with a dose of 2 mg / 0.625 mg (initial dose).
Patients with Renovascular Hypertension
Treatment of the drug with patients diagnosed or suspected renal artery stenosis should begin in a hospital with a dose of 2 mg / 0.625 mg, controlling the function of the nights and the content of potassium in the blood plasma. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.
Other risk groups
In patients with chronic heart failure (IV functional class by classification NYHA) and patients with diabetes mellitus 1 (risk of spontaneous increase in potassium content) treatment should start with an initial dose of 2 mg / 0.625 mg of the drug Ko-Parnavel and under medical supervision.
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 it is necessary to regularly monitor the concentration of glucose in the blood. Surgery / General Anesthesia
The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetics, which have an antihypertensive effect.
It is recommended to stop taking ACE inhibitors. in t.ch. perindopril, 12 hours prior to surgery, warning the anesthetist about the use of ACE inhibitors.
Ethnic differences
Perindopril, like other ACE inhibitors, apparently has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races. Perhaps this difference is due to the fact that patients with Negroid races with arterial hypertension often have a low renin activity.
Aortic stenosis / mitral stenosis / Hypertrophic obstructive cardiomyopathy
ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract and in aortic and / or mitral stenosis.
Liver failure
In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes fatal. When jaundice or a significant increase in the activity of "hepatic" transaminases on the background of the administration of ACE inhibitors, the drug of Co-Parnavel should be discontinued.
Anemia
It can develop in patients after kidney transplantation or in patients on hemodialysis. In this case, the decrease in hemoglobin is greater, the higher was its initial value. This effect appears to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.
Hyperkalemia
Hyperkalemia can develop during treatment with ACE inhibitors, including. and perindopril. Risk factors for hyperkalemia are renal failure, elderly age, diabetes mellitus, some concomitant conditions (decreased circulating blood volume,chronic heart failure in the stage of decompensation, metabolic acidosis), simultaneous reception of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes for edible salt and the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. The simultaneous use of the above drugs should be done with caution (see section "Interaction with other drugs").
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, you should immediately stop taking Co-Parnavel.
Photosensitivity
There are reports of cases of the development of the photosensitivity reaction against the background of the use of thiazide and thiazide-like diuretics. With the development of the photosensitivity reaction on the background of taking the drug, treatment should be stopped.If there is a need to renew the use of Ko-Parnavel, protect open skin from direct exposure to sunlight and artificial ultraviolet rays.
Water-electrolyte balance. The sodium content in the blood plasma.
Before the start of treatment with the drug it is necessary to determine the sodium content in the blood plasma and on the background of taking the drug to conduct regular monitoring of electrolytes in the blood plasma. All diuretics are capable of causing hyponatremia, leading 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 the sodium content is indicated for patients with cirrhosis of the liver and elderly patients (see "Side effects" and "Overdose" sections).
The content of potassium in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia (less than 3.4 mmol / L) in the following patients: the elderly, depleted patients, patients with cirrhosis, patients with peripheral edema, ascites, coronary heart disease, insufficiency.Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.
The high-risk group includes patients with an increased interval QT on the ECG, it does not matter whether this increase is due to innate causes or effects of drugs.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias such as "pirouettes," which can be lethal. In all cases described, regular monitoring of the potassium content in the blood plasma is necessary. The first determination of the potassium content in the blood plasma should be carried out within the first week of the beginning of therapy with the drug Ko-Parnavel.
If hypokalemia is detected, appropriate treatment should be prescribed.
Calcium in the blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of latent hyperparathyroidism. Before the study of parathyroid gland function, it is necessary to cancel the use of Co-Parnavella.
The concentration of glucose in the blood plasma
It is necessary to monitor the concentration of glucose in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
In patients with a high concentration of uric acid in the blood plasma -tfa background therapy with the drug may increase the frequency of exacerbation of gout.
Diuretics 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, CC is calculated taking into account age, body weight and sex.
At the beginning of diuretic treatment in patients due to hypovolemia and hyponatremia, a temporary decrease in the glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma can be observed. This transient functional renal failure is not dangerous for patients with unchanged renal function, however, in patients with renal insufficiency all severity can be increased.
Athletes
Co-Parnavel can give a false positive reaction in the conduct of doping control.