KO-PARNAVEL
special instructions
Lithium preparations
The simultaneous use of perindopril and indapamide with lithium preparations is not recommended (see section “Interaction with other drugs”).
Renal dysfunction
Therapy with Co-Parnavel is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with arterial hypertension without previous impairment of nocturnal function, signs of acute renal failure may appear in the area of treatment with Co-Parnavel. In this case, treatment with the drug should be discontinued. In the future, combination therapy can be resumed using low doses of Co-Parnavel, or use the drugs perindopril and indapamide in monotherapy. Such patients require regular monitoring of potassium and creatinine levels in the blood serum every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Co-Parnavel.
Acute renal failure often develops in patients with severe chronic heart failure or underlying renal impairment, incl. with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney. The drug is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney.
Arterial hypotension and water-electrolyte imbalance
Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in plasma electrolytes, for example, after prolonged diarrhea or vomiting. Such patients require regular monitoring of plasma electrolytes. With a pronounced 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 restoration of circulating blood volume and blood pressure, you can resume therapy with Co-Parnavel, using low doses of the drug, or using the drugs perindopril and indapamide in monotherapy.
Potassium content
The simultaneous use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with the use of other antihypertensive drugs in combination with a diuretic, regular monitoring of potassium levels in the blood plasma is necessary.
Excipients
It should be taken into account that the excipients of the drug include lactose monohydrate, therefore the drug is contraindicated in patients with hereditary lactose intolerance, lactase deficiency, and glucose-galactose malabsorption.
Perindopril
Neutropenia/agranulocytosis
In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. In patients with normal renal function, in the absence of other complications, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors.
Perindopril must be used with great caution
in
patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing renal impairment.
These patients may develop severe infections that do not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.
Hypersensitivity/angioedema (Quincke's edema)
When taking ACE inhibitors, incl. perindopril, in rare cases, the development of angioedema of the face, lips, tongue, uvula of the upper palate and/or larynx may occur. If these symptoms occur, the drug should be stopped immediately and the patient should be observed until signs of edema disappear completely.
If angioedema affects only the face and lips, its symptoms usually resolve on their own, or antihistamines can be used to treat the symptoms. Angioedema, accompanied by swelling of the tongue and larynx, can lead to airway obstruction and death. If such symptoms appear, epinephrine (adrenaline) should be immediately administered subcutaneously (diluted 1:1000 (0.3 or 0.5 ml) and/or the airway should be secured.
Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section “Contraindications”).
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal activity of the C-1 esterase enzyme. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.
Anaphylactoid reactions during desensitization procedures
There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients with a history of allergies or a tendency to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. The development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may develop in patients receiving ACE inhibitors during LGI II I apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flux membranes.
Hemodialysis
Anaphylactoid reactions have been observed in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.
Cough
During therapy with an ACE inhibitor, a dry cough may occur, which disappears after discontinuation of drugs in this group. If a dry cough appears, you should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the doctor believes that ACE inhibitor therapy is necessary for the patient, taking Co-Parnavel can be continued.
Risk of arterial hypotension and/or renal failure (in patients with chronic heart failure, fluid and electrolyte imbalance, etc.)
In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system (RAAS) may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a salt-restricted diet or long-term use of diuretics), in patients with initially low blood pressure, renal artery stenosis (including bilateral), chronic heart failure or cirrhosis of the liver with edema and ascites. The use of ACE inhibitors causes blockade of the RAAS, and therefore a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose of the drug or during the first 2 weeks of therapy. Sometimes these conditions develop acutely. In such cases, when resuming therapy, it is recommended to use a combination of perindopril and indapamide at a lower dose and then gradually increase the dose.
Elderly patients
Before starting to take Co-Parnavel, kidney function and potassium levels in the blood plasma should be assessed. The initial dose is selected depending on the degree of reduction in blood pressure, especially with a decrease in circulating blood volume and chronic heart failure (functional class IV according to the NYHA classification). Such measures help to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of arterial hypotension exists in all patients, however, special caution should be observed when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with a dose of 2 mg/0.625 mg (initial dose).
Patients with renovascular hypertension
Treatment with the drug in patients with diagnosed or suspected renal artery stenosis should begin in a hospital setting with a dose of 2 mg/0.625 mg, monitoring night function and potassium levels 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 (functional class IV according to the NYHA classification) and patients with diabetes mellitus type 1 (risk of spontaneous increase in potassium levels), treatment should begin with an initial dose of 2 mg/0.625 mg of Co-Parnavel and under medical supervision.
Patients with diabetes mellitus
When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy. Surgery/General anesthesia
The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a marked decrease in blood pressure, especially when using general anesthetic agents that have an antihypertensive effect.
It is recommended to stop taking ACE inhibitors. incl. perindopril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.
Ethnic differences
Perindopril, like other ACE inhibitors, apparently has a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.
Aortic stenosis/Mitral stenosis/Hypertrophic obstructive
cardiomyopathy
ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and aortic and/or mitral stenosis.
Liver failure
In rare cases, while taking ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice or a significant increase in the activity of liver transaminases occurs while taking ACE inhibitors, the drug Co-Parnavel should be discontinued.
Anemia
May develop in patients after kidney transplantation or in patients on hemodialysis. In this case, the decrease in hemoglobin is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, incl. and perindopril. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, certain concomitant conditions (decreased circulating blood volume, chronic heart failure in the stage of decompensation, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), and also potassium preparations or potassium-containing substitutes for table salt and the use of other drugs that help increase the content of potassium in the blood plasma (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. The simultaneous use of the drugs listed above should be carried out with caution (see section “Interaction with other drugs”).
Indapamide
In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug Co-Parnavel.
Photosensitivity
There are reports of cases of the development of photosensitivity reactions while taking thiazide and thiazide-like diuretics. If a photosensitivity reaction develops while taking the drug, treatment should be stopped. If there is a need to resume use of the drug Co-Parnavel, you should protect exposed skin from direct exposure to sunlight and artificial ultraviolet rays.
Water and electrolyte balance. Sodium content in blood plasma.
Before starting treatment with the drug, it is necessary to determine the sodium content in the blood plasma and, while taking the drug, regularly monitor electrolytes in the blood plasma. All diuretics can cause 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 sodium levels is indicated in patients with liver cirrhosis and elderly patients (see sections "Side effects" and "Overdose").
Potassium content 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: elderly, malnourished patients, patients with liver cirrhosis, patients with peripheral edema, ascites, coronary artery disease, chronic heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.
The high-risk group includes patients with an increased QT interval on the ECG, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias, which can be fatal. In all the described cases, regular monitoring of potassium levels in the blood plasma is necessary. The first determination of potassium content in the blood plasma must be carried out within the first week from the start of therapy with Co-Parnavel.
If hypokalemia is detected, appropriate treatment should be prescribed.
Calcium content in blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in calcium levels in the blood plasma. Severe hypercalcemia may be a consequence of latent hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking Co-Parnavel.
Plasma glucose concentration
Glucose concentrations should be monitored in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
In patients with increased concentrations of uric acid in the blood plasma during drug therapy, the frequency of exacerbations of gout may increase.
Diuretics and kidney function
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adult patients below 25 mg/l or 220 µmol/l). In elderly patients, CC is calculated taking into account age, body weight and gender.
At the beginning of treatment with diuretics, patients may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma due to hypovolemia and hyponatremia. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.
Athletes
Ko-Parnavel may give a false positive reaction during doping control.
Parnavel Amlo, 5 mg+8 mg, tablets, combi-pack 1+1, 30 pcs.
Perindopril
Hypersensitivity/angioedema
When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may occur (see section “Side effects”). If symptoms appear, the drug should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms occur, epinephrine (adrenaline) should be immediately administered subcutaneously and/or the airway should be secured. The patient should be under medical supervision until symptoms disappear completely and permanently. Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section "Contraindications").
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases, without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine (see section “Side effects”).
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy (for example, hymenoptera venom). In these same patients, an anaphylactoid reaction was avoided by temporarily discontinuing ACE inhibitors, and if the drug was accidentally taken, the anaphylactoid reaction occurred again.
Neutropenia/agranulocytosis/thrombocytopenia/anemia
While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.
Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with reduced circulating blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see sections "Interaction with other drugs"). In patients at increased risk of developing symptomatic hypotension, blood pressure, renal function, and serum potassium levels should be carefully monitored during drug therapy.
Amlodipine+Perindopril
A similar approach is also used in patients with angina pectoris and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident. If arterial hypotension develops, the patient should be transferred to the “lying” position on his back with his legs elevated. If necessary, the volume of circulating blood should be replenished with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of circulating blood volume and blood pressure, treatment can be continued.
Mitral stenosis/aortic stenosis/hypertrophic cardiomyopathy
Parnavel Amlo, like other ACE inhibitors, should be administered with caution to patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.
Renal dysfunction
In patients with renal failure (creatinine clearance less than 60 ml/min.), individual selection of doses of perindopril and amlodipine is recommended. Such patients require regular monitoring of potassium and creatinine levels in the blood serum (see section “Side Effects”).
In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, an increase in the concentration of urea and creatinine in the blood serum is possible, which usually resolves when therapy is discontinued. This effect is most often observed in patients with renal failure. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients. In some patients with arterial hypertension without signs of renal vascular damage, an increase in the concentration of urea and creatinine in the blood serum is possible, especially when perindopril is co-administered with a diuretic, usually slight and transient. This effect is more often observed in patients with pre-existing renal impairment.
Liver failure
In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug and consult a doctor (see section “Side Effects”).
Ethnic differences
In patients of the Negroid race, angioedema develops more often than in representatives of other races while taking ACE inhibitors.
Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race more often have low renin activity. Cough
During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. When patients develop a dry cough, one should be aware of the possible iatrogenic nature of this symptom. Surgery/general anesthesia
The use of ACE inhibitors in patients undergoing major surgery and/or general anesthesia can lead to a significant decrease in blood pressure if general anesthesia agents with a hypotensive effect are used. This is due to blocking the formation of angiotensin II against the background of a compensatory increase in renin activity. If the development of arterial hypotension is associated with the described mechanism, the volume of circulating blood plasma should be increased.
It is recommended to stop taking the drug 24 hours before surgery.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, old age (over 70 years), diabetes mellitus, some concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride ), as well as potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that help increase the content of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics, and potassium-containing salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If simultaneous use of perindopril and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of potassium levels in the blood serum (see section “Interaction with other drugs”). Patients with diabetes mellitus
When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy it is necessary to carefully monitor the concentration of glucose in the blood (see section “Interaction with other drugs”). Amlodipine
The effectiveness and safety of amlodipine in hypertensive crisis has not been established.
Heart failure
Patients with heart failure should be treated with caution. When using amlodipine in patients with chronic heart failure of functional class III and IV according to the NYHA classification, pulmonary edema may develop. Slow calcium channel blockers, including amlodipine, should be used with caution in patients with chronic heart failure due to a possible increased risk of cardiovascular adverse events and mortality. Liver failure
In patients with impaired liver function, T1/2 and AUC of amlodipine are increased. Taking amlodipine should be started with the lowest doses and precautions should be taken both at the beginning of treatment and when increasing the dose. In patients with severe hepatic impairment, the dose should be increased gradually, ensuring careful monitoring of the clinical condition.
Elderly patients
In elderly patients, T1/2 may increase and amlodipine clearance may decrease. No dose changes are required, but more careful monitoring of patients in this category is necessary.
In patients with impaired renal function, monitoring of the condition is necessary.
Kidney failure
Patients with renal failure can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Amlodipine is not excreted from the body by dialysis.
Parnavel Amlo Excipients
Due to the presence of lactose in the drug, the drug should not be prescribed to patients with hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.
Impact on the ability to drive vehicles and operate machinery
Due to the possible development of weakness, dizziness, and drowsiness, caution should be exercised when driving vehicles and engaging in certain activities that require increased concentration and rapid motor response.
