Pharmacodynamics and pharmacokinetics
Co-Perineva is a combination drug containing perindopril and indapamide .
The drug has an antihypertensive effect, the effectiveness of which does not depend on the patient’s age, body position, and is not accompanied by tachycardia. Does not affect lipid metabolism, including in patients with diabetes . When taking the drug, the risk of hypokalemia .
The antihypertensive effect persists throughout the day.
After just a month of taking the drug, a decrease in blood pressure is achieved. If treatment is stopped, there is no risk of withdrawal syndrome .
Perindopril is extremely effective in the fight against arterial hypertension (all forms of severity). 4-6 hours after taking the medicine, the maximum antihypertensive effect develops, which lasts throughout the day.
Perindopril after administration is quickly absorbed from the gastrointestinal tract. Bioavailability is 65-70%. 3-4 hours after administration, the maximum level of the drug in the blood plasma is reached. It is metabolized in the liver, forming an active ( perindoprilat ) and five inactive metabolites. A small amount of perindoprilate passes into breast milk and through the placenta. Excreted through the kidneys.
The elimination of perindoprilate is slowed down in patients with heart and renal failure and patients over 65 years of age. In patients suffering from liver cirrhosis, hepatic clearance is reduced by half, however, the level of perindoprilate is not reduced.
Indapamide is almost completely absorbed from the gastrointestinal tract; simultaneous intake of food can slow down this process. After an hour, the maximum level in the blood is reached. Metabolized in the liver. Excreted through the kidneys and intestines.
Pharmacodynamics
Co-Perineva® is a combination drug containing an ACE inhibitor - perindopril and a thiazide-like diuretic - indapamide. The drug has antihypertensive, diuretic and vasodilating effects.
Co-Perineva® has a pronounced dose-dependent antihypertensive effect, independent of the patient’s age and body position and not accompanied by reflex tachycardia. Does not affect lipid metabolism (total cholesterol, LDL, VLDL, HDL, triglycerides (TG) and carbohydrates), incl. in patients with diabetes mellitus. Reduces the risk of hypokalemia caused by diuretic monotherapy.
The antihypertensive effect lasts for 24 hours.
A stable reduction in blood pressure is achieved within 1 month with the use of the drug Co-Perineva® without an increase in heart rate. Stopping treatment does not lead to the development of withdrawal syndrome.
Perindopril is an ACE inhibitor, the mechanism of action of which is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictor effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to sodium and fluid retention and does not cause reflex tachycardia during long-term treatment. The antihypertensive effect of perindopril develops in patients with low or normal plasma renin activity.
Perindopril acts through its main active metabolite, perindoprilate. Its other metabolites are inactive. The effect of the drug Co-Perineva® leads to:
- dilation of veins (reduction of preload on the heart), caused by changes in PG metabolism;
- reduction of peripheral vascular resistance (reduction of afterload on the heart).
In patients with heart failure, perindopril helps:
- decreased filling pressure of the left and right ventricles;
- increase in cardiac output and cardiac index;
- increasing regional blood flow in the muscles.
Perindopril is effective for arterial hypertension of any severity: mild, moderate and severe. The maximum antihypertensive effect develops 4–6 hours after a single oral dose and persists throughout the day. Discontinuation of therapy does not lead to the development of withdrawal syndrome.
It has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances (addition) the antihypertensive effect of perindopril.
Indapamide is a sulfonamide derivative and is a diuretic. Inhibits the reabsorption of sodium in the cortical segment of the renal tubules, increasing the excretion of sodium and chlorine by the kidneys, thus leading to increased diuresis. To a lesser extent increases the excretion of potassium and magnesium. Having the ability to selectively block “slow” calcium channels, indapamide increases the elasticity of arterial walls and reduces peripheral vascular resistance. It has a hypotensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not increase the antihypertensive effect, but increases the risk of adverse events.
Indapamide in patients with arterial hypertension has no effect on lipid metabolism: TG, LDL and HDL and carbohydrate metabolism, even in patients with diabetes mellitus and arterial hypertension.
Contraindications
The drug Co-Perineva is contraindicated in the following cases:
- sensitivity to any element of the drug;
- lactose intolerance;
- refractory hyperkalemia;
- angioedema;
- bilateral renal artery stenosis;
- lactase deficiency;
- liver failure;
- glucose-galactose malabsorption;
- renal failure;
- renal artery stenosis;
- pregnancy, lactation, children under 18 years of age.
You should take the drug with caution in the following cases:
- connective tissue diseases ( scleroderma , SLE );
- immunosuppressant therapy;
- inhibition of bone marrow hematopoiesis;
- angina pectoris;
- renovascular hypertension;
- decrease in blood volume;
- hyperuricemia;
- diabetes;
- cerebrovascular diseases.
Perineva®
IHD: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and/or coronary revascularization
If unstable angina develops during the first month of therapy with Perineva®, the benefits and risks should be assessed to decide whether to continue therapy.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of a pronounced decrease in blood pressure is increased in patients with reduced 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" and "Side effects"). In patients at increased risk of developing symptomatic hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored during therapy with Perineva®.
A similar approach is used in patients with coronary artery disease 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 supine position with legs elevated. If necessary, the blood volume should be replenished by intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of blood volume and blood pressure, treatment can be continued.
In some patients with CHF and normal or reduced blood pressure, Perineva® may cause an additional decrease in blood pressure. This effect is predictable and does not usually require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.
Mitral stenosis/aortic stenosis/HOCM
Perineva®, like other ACE inhibitors, should be administered with caution to patients with left ventricular outflow tract obstruction (aortic stenosis, HOCM), as well as to patients with mitral stenosis.
Renal dysfunction
For patients with renal failure (creatinine clearance < 60 ml/min), the initial dose of Perineva® is selected depending on the clearance value (see section “Method of administration and dosage”) and then depending on the therapeutic effect. For such patients, regular monitoring of creatinine concentration and potassium content in the blood serum is necessary (see section "Side effects").
Hypotension, which sometimes develops when starting ACE inhibitors in patients with symptomatic CHF, can lead to deterioration of renal function. It is possible to develop acute renal failure, which is usually reversible. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood serum, which usually resolves when therapy is discontinued. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients.
Treatment of such patients begins under close medical supervision using low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and serum potassium and creatinine concentrations regularly monitored during the first few weeks of therapy.
In some patients with arterial hypertension without indication of pre-existing renal vascular disease, serum urea and creatinine concentrations may increase, especially with simultaneous use of diuretics. These changes are usually mild and reversible. The likelihood of developing these disorders is higher in patients with a history of renal failure. In such cases, it may be necessary to discontinue or reduce the dose of Perineva® and/or the diuretic.
Hemodialysis
In patients undergoing hemodialysis using high-flux membranes (for example, AN69®), cases of anaphylactic reactions have been reported during therapy with ACE inhibitors. The use of ACE inhibitors should be avoided when using this type of membrane.
Kidney transplant
There are no data on the use of perindopril in patients after kidney transplantation.
Hypersensitivity, angioedema
When using ACE inhibitors, including perindopril, in rare cases and during any period of therapy, the development of angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may be observed (see section “Adverse reactions”). action"). If symptoms appear, Perineva® should be discontinued immediately and the patient should be observed until signs of edema have completely disappeared. 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 these symptoms occur, emergency treatment is required, including subcutaneous injection of epinephrine (adrenaline) and/or airway management. 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 using 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 C1-esterase activity. Diagnosis was made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after discontinuation of ACE inhibitor therapy. 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”).
Neutral endopeptidase inhibitors
When ACE inhibitors are used simultaneously with drugs containing sacubitril (neprilysin inhibitor), the risk of developing angioedema increases, and therefore the simultaneous use of these drugs is contraindicated. ACE inhibitors should be prescribed no earlier than 36 hours after discontinuation of drugs containing sacubitril. Prescription of drugs containing sacubitril is contraindicated in patients receiving ACE inhibitors, as well as within 36 hours after discontinuation of ACE inhibitors.
Tissue tasminogen activators
Observational studies have shown an increased incidence of angioedema in patients taking ACE inhibitors following the use of alteplase for thrombolytic therapy of ischemic stroke.
An increased risk of angioedema was observed in patients concomitantly taking ACE inhibitors and drugs such as mTOR inhibitors (temsirolimus, sirolimus, everolimus), DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin), estramustine, neutral endopeptidase inhibitors (racecadotril). , sacubitril) and tissue plasminogen activators.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during 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 therapy with ACE inhibitors during desensitization therapy, for example, hymenoptera venom. ACE inhibitors should be used with caution in patients susceptible to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily discontinuing the ACE inhibitor before starting the desensitization procedure.
Liver dysfunction
In rare cases, during the use of ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes in the blood plasma occurs during the use of ACE inhibitors, the drug should be stopped (see section “Side Effects”), the patient should be under appropriate medical supervision.
Neutropenia/ agranulocytosis/ thrombocytopenia/ anemia
Neutropenia/agranulocytosis, thrombocytopenia and anemia may occur during the use of ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Perineva® should be used with extreme caution in patients with systemic 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 using the drug Perineva®, such patients are 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.
Ethnic differences
It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, Perineva® is less effective in lowering blood pressure in black patients.
This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.
Cough
During therapy with ACE inhibitors, a persistent dry cough may occur, which stops after discontinuation of the drug. This should be taken into account when carrying out the differential diagnosis of cough.
Surgery, general anesthesia
The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using drugs for general anesthesia that have an antihypertensive effect. Taking Perineva® should be stopped one day before surgery. If arterial hypotension develops, blood pressure should be maintained by replenishing blood volume. It is necessary to warn the surgeon/anesthesiologist that the patient is taking ACE inhibitors.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalemia are impaired renal function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute heart failure, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), food potassium supplements/preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase serum potassium levels (for example, heparin trimethoprim or co-trimoxazole (trimethoprim + sulfamethoxazole) and especially aldosterone antagonists or angiotensin receptor blockers).
The use of potassium supplements/preparations, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in serum potassium levels, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If simultaneous use of Perineva® 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”).
Diabetes
When using perindopril in patients with diabetes mellitus who are receiving oral hypoglycemic agents or insulin, during the first month of therapy it is necessary to regularly monitor the concentration of glucose in the blood (see section “Interaction with other drugs”).
Lithium preparations
The simultaneous use of Perineva® and lithium preparations is not recommended (see section “Interaction with other drugs”).
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements
Although serum potassium levels usually remain within normal limits, hyperkalemia may occur in some patients receiving perindopril. Concomitant use of potassium-sparing diuretics (such as spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing supplements or salt substitutes may lead to hyperkalemia.
Caution should also be exercised when co-prescribing perindopril with other drugs that increase serum potassium, such as heparin, trimethoprim and co-trimoxazole (trimethoprim + sulfamethoxazole), since trimethoprim is known to act as a potassium-sparing diuretic (such as amiloride). Therefore, the combination of perindopril with the above drugs is not recommended.
If it is necessary to use perindopril and the drugs listed above simultaneously, caution should be exercised and the potassium level in the blood serum should be regularly monitored.
Double blockade of the RAAS
Cases of hypotension, syncope, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used concomitantly with drugs that affect this system.
Concomitant use of ACE inhibitors with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients .
Concomitant use of ACE inhibitors with ARB II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Primary aldosteronism
Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act by inhibiting the RAAS. Therefore, the use of Perineva® in this group of patients is not recommended.
Special information on excipients
The drug Perineva® contains lactose, therefore its use is contraindicated in patients with congenital galactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome.
Side effects
The use of the drug may cause the following side effects:
- thrombocytopenia , agranulocytosis , hemolytic anemia , leukopenia , aplastic anemia ;
- vertigo , paresthesia , dizziness, headache; unstable mood, sleep disturbance; in rare cases – confusion;
- tinnitus, blurred vision;
- orthostatic hypotension , arrhythmias ( bradycardia , atrial fibrillation , ventricular tachycardia ), myocardial infarction , angina pectoris ;
- dry cough , shortness of breath , bronchospasm, rhinitis , eosinophilic pneumonia ;
- dry mouth, constipation, nausea, abdominal pain, loss of appetite, epigastric pain, vomiting, diarrhea, dyspepsia, pancreatitis , jaundice ;
- angioedema (face, lips, limbs, here, tongue, larynx), rash, urticaria , itching;
- muscle spasms;
- renal failure;
- impotence;
- asthenia , increased sweating.
Instructions for use (Method and dosage)
The medicine Co-Perineva is taken 1 time per day, orally, in the morning before breakfast, with water.
Doses are listed in the indapamine/perindopril ratio.
To begin with, you should take one tablet per day (0.625/2 mg). If it is not possible to achieve blood pressure control within a month, the dose is increased to one tablet (1.25/4 mg). To achieve the most pronounced effect, you should increase the daily dose to the limit - one tablet (2.5/8 mg).
For elderly patients, the initial dose is one tablet (0.625/2 mg). Treatment with the drug can be prescribed in case of control of blood pressure and kidney function.
Patients with moderate renal impairment are started on the lowest dose, with the maximum allowed dose being 1.25/4 mg.
Pharmacokinetics
The combined use of perindopril and indapamide does not change their pharmacokinetic parameters compared to the separate administration of these drugs.
Perindopril after oral administration is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65–70%. Eating reduces the conversion of perindopril to perindoprilat. T1/2 of perindopril from blood plasma is 1 hour.
Cmax in blood plasma is achieved 3–4 hours after oral administration. Since taking with food reduces the conversion of perindopril to perindoprilat and the bioavailability of the drug, perindopril should be taken once a day in the morning, before breakfast. Taking perindopril once a day, equilibrium concentration is achieved within 4 days.
It is metabolized in the liver to form an active metabolite - perindoprilate. In addition to the active metabolite perindoprilate, perindopril forms 5 more inactive metabolites. The binding of perindoprilate to plasma proteins is dose-dependent and amounts to 20%. Perindoprilat easily passes through histohematic barriers, excluding the blood-brain barrier; a small amount penetrates the placenta and into breast milk. Excreted by the kidneys, T1/2 of perindoprilate is about 17 hours. It does not accumulate.
In elderly patients and in patients with renal and heart failure, the elimination of perindoprilate is slowed down.
In case of renal failure, it is recommended to reduce the dose of perindopril depending on the severity of renal failure (creatinine clearance). The dialysis Cl of perindoprilate is 70 ml/min.
The kinetics of perindopril is altered in patients with liver cirrhosis: hepatic clearance is reduced by half. However, the amount of perindoprilate formed does not decrease, which does not require dose adjustment.
Indapamide. Quickly and almost completely absorbed into the gastrointestinal tract. Eating slightly slows down absorption, but does not significantly affect the amount of indapamide absorbed. Cmax in blood plasma is achieved 1 hour after oral administration of a single dose. Binds to plasma proteins by 79%. T1/2 ranges from 14 to 24 hours (average 18 hours). Does not accumulate.
Metabolized in the liver. It is excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of the unchanged drug is about 5%) and by the intestines with bile in the form of inactive metabolites (22%). In patients with renal failure, the pharmacokinetic parameters of indapamide do not change significantly.
Overdose
Symptoms of overdose: vomiting , nausea, muscle cramps, drowsiness , dizziness, confusion, decreased water and electrolyte balance, oliguria , significant decrease in blood pressure.
If the above symptoms appear, you should rinse your stomach, then take activated charcoal to restore the water and electrolyte balance. If the pressure decreases significantly, the patient should lie on his back and raise his legs, then inject a 0.9% sodium chloride solution.
Interaction
You should not combine the drug Co-Perineva with ACE inhibitors and lithium preparations , as the level of lithium in the blood may increase. If co-administration is necessary, lithium levels should be monitored.
Use extreme caution when taking baclofen , which may increase the hypotensive effect. Blood pressure and kidney function should be monitored and the dose adjusted if necessary.
Neuroleptics and tricyclic antidepressants enhance the effect of hypotension and increase the likelihood of orthostatic hypotension.
Tetracosactitol and GCS help reduce the hypotensive effect.
When taken simultaneously with any other antihypertensive drugs, there is a possibility of a stronger manifestation of the hypotensive effect.
Perindopril
At the same time, it is not recommended to use it with potassium-sparing diuretics ( Spironolactone , amiloride , eplerenone , triamterene ) and potassium supplements . When used in parallel, the level of potassium in the blood may increase, which can lead to death. If joint therapy is necessary (for hypokalemia), it is necessary to monitor potassium levels and ECG parameters.
It is recommended to take Co-Perineva together with insulin and hypoglycemic agents . leukopenia increases when used with cytostatic immunosuppressants , allopurinol , corticosteroids and procainamide . When used with general anesthesia agents, their hypotensive effect may increase. When used in high doses, thiazide and loop diuretics can lead to hypovolemia .
Indapamide
Drugs that cause ari must be taken with caution, since there is a possibility of developing hypokalemia . It is recommended to take Indapamide with caution with medications such as antipsychotics ( cyamemazine , trifluoperazine , chlopromazine , etc.), antiarrhythmic drugs ( amiodarone , hydroquinidine , ibutilide , tosilade etc.), benzamides ( sultopride , tiapride , sulpiride , amisulpride ), buterophenones ( haloperidol , droperidol ), other drugs ( astemizole , mizolastine , sparfloxacin , methadone , bepridil , halofantrine , terfenadine , cisapride ).
Medicines that can cause hypokalemia : tetracosactide , laxatives that stimulate intestinal motility, amphotericin B , glucocorticoids , mineralocorticoids , cardiac glycosides .
lactic acidosis increases when used with Metformin . Patients taking high-dose iodine contrast agents are at risk of kidney failure. Hypercalcemia can develop when taking medications containing calcium salts.
KO-PERINEVA
special instructions
Co-Perineva®
Lithium preparations:
The simultaneous use of Co-Perineva® with lithium preparations is not recommended.
Renal dysfunction
| Therapy with Co-Perineva® is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with arterial hypertension without previous renal impairment, signs of acute renal failure may appear during therapy with Co-Perineva®. |In this case, treatment with Co-Perineva® should be discontinued. In the future, you can resume combination therapy using low doses of Co-Perineva®, or use 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-Perineva®.
Acute renal failure often develops in patients with severe CHF or underlying renal impairment, including bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.
Taking Co-Perineva® is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.
Decreased blood pressure and water-electrolyte imbalance
Hyponatremia is associated with a risk of a sudden decrease in blood pressure (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 the content of electrolytes in the blood plasma, 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 blood volume and blood pressure, you can resume therapy with Co-Perineva®, using low doses of the drug, or using the drugs perindopril and indapamide in monotherapy.
Potassium content
The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and 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 Co-Perineva® include lactose monohydrate, therefore the drug is contraindicated in patients with hereditary galactosemia, lactase deficiency, and glucose-galactose malabsorption. (see section "Contraindications")
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 should 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, including perindopril, in rare cases, the development of angioedema of the face, lips, tongue, uvula, and/or larynx may occur. If these symptoms appear, the drug should be stopped immediately, and the patient should be observed until the 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 or 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.
In rare cases, angioedema of the intestine develops during ACE inhibitor therapy. 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 a normal level of C1-esterase. 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 long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, 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 occur in patients receiving ACE inhibitors during LDL 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 reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group (see section “With caution”).
Potassium-sparing diuretics and potassium supplements
The combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended.
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-Perineva® can be continued.
Children and adolescents under 18 years of age
The drug Co-Perineva® is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of use.
Risk of arterial hypotension and/or renal failure in patients with CHF, water and electrolyte imbalance, etc.)
In liver cirrhosis, accompanied by edema and ascites, arterial hypotension, and CHF, 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-free diet or long-term use of diuretics).
The use of an ACE inhibitor 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 Co-Perineva® or during the first two weeks of therapy .
Elderly patients
Before starting to take Co-Perineva®, renal function and potassium levels in the blood plasma should be assessed. The initial dose of Co-Perineva® is selected depending on the degree of reduction in blood pressure, especially with a decrease in blood volume and 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 Co-Perineva® in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with a dose of 0.625 mg/2 mg of Co-Perineva® (initial dose).
Patients with renovascular hypertension
Treatment with Co-Perineva in patients with diagnosed or suspected renal artery stenosis should begin in a hospital setting with a dose of Co-Perineva® 0.625 mg/2 mg, monitoring renal 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 CHF (functional class IV according to the NYHA classification) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium levels), treatment should begin with an initial dose of 0.625 mg/2 mg of Co-Perineva® and under medical supervision.
Patients with diabetes mellitus
When prescribing Co-Perineva® to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy.
Ethnic characteristics
Perindopril (like other ACE inhibitors) has a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races.
Surgical interventions/General anesthesia
The use of ACE inhibitors in patients undergoing surgery using general anesthesia may lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.
It is recommended to stop taking ACE inhibitors, including perindopril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.
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, cholestatic jaundice occurs while taking ACE inhibitors, and as it progresses, fulminant liver necrosis develops, sometimes with death. If jaundice or a significant increase in the activity of “liver” transaminases occurs while taking ACE inhibitors, taking Co-Perineva® should be discontinued.
Anemia
Anemia can develop in patients after kidney transplantation or in patients on hemodialysis.
Hyperkalemia
May develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as drugs potassium or potassium-containing substitutes for table salt and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. The combined use of the drugs listed above must be carried out with caution.
Indapamide
Photosensitivity
There are reports of cases of increased photosensitivity while taking thiazide and thiazide-like diuretics. If a photosensitivity reaction develops while taking Co-Perineva®, treatment should be discontinued. If there is a need to resume use of the drug Co-Perineva®, 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 Co-Perineva®, 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.
Potassium content in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of developing hypokalemia (less than 3.4 mmol/l) in the following patients: elderly, malnourished patients, patients with liver cirrhosis, patients with peripheral edema, ascites, coronary heart disease, CHF. Hypokalemia in these patients enhances 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.
Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, 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 should be carried out within the first week from the start of therapy with Co-Perineva®.
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-Perineva®.
Plasma glucose concentration
Glucose concentrations should be monitored in patients with diabetes mellitus.
Uric acid
In patients with increased concentrations of uric acid in the blood plasma during therapy with Co-Perineva®, the frequency of exacerbations of gout may increase.
Diuretics and kidney function
Hypovolemia as a result of a decrease in blood volume or hyponatremia caused by taking diuretics at the beginning of treatment with Co-Perineva® can lead to a decrease in glomerular filtration rate I and be accompanied by an increase in concentration; creatinine and urea in blood plasma.
Athletes
Indapamide may give a false-positive reaction during doping control.
special instructions
It is not recommended to take it in parallel with lithium preparations .
Therapy is strictly contraindicated in patients with impaired renal function . Patients suffering from hypertension may experience symptoms of renal failure . In this case, you should stop treatment with Co-Perineva. Later, therapy can be repeated, prescribing minimal doses, or indapamide and perindopril can be used in monotherapy. These patients should have their blood creatinine and potassium
The combination of Indapamide and Perindopril cannot prevent the development of hypokalemia , especially in cases where the patient has diabetes mellitus or renal failure. In this case, the level of potassium in the blood must be monitored regularly.
Directions for use and doses
Orally, 1 time per day, preferably in the morning before breakfast, with a sufficient amount of liquid.
If possible, taking the drug should begin with selecting doses of single-component drugs. If clinically necessary, it is possible to prescribe combination therapy with Co-Perineva® immediately after monotherapy.
Doses are given for the indapamide/perindopril ratio.
The initial dose is 1 tablet. drug Co-Perineva® (0.625 mg/2 mg) 1 time per day. If after 1 month of taking the drug it is not possible to achieve adequate blood pressure control, the dose of the drug should be increased to 1 table. drug Co-Perineva® (1.25 mg/4 mg) 1 time per day.
If necessary, to achieve a more pronounced hypotensive effect, it is possible to increase the dose of the drug to the maximum daily dose of Co-Perineva® - 1 table. (2.5 mg/8 mg) 1 time per day.
Elderly patients. Initial dose - 1 tablet. Co-Perineva® drug 0.625 mg/2 mg 1 time per day. Treatment with the drug should be prescribed after monitoring renal function and blood pressure.
Patients with impaired renal function. The drug Co-Perineva® is contraindicated in patients with severe renal failure (Cl creatinine less than 30 ml/min) (see “Contraindications”).
Patients with moderately severe renal failure (creatinine clearance 30–60 ml/min) are recommended to begin therapy with the required doses of drugs (in monotherapy) included in the Co-Perineva® drug; The maximum daily dose of Co-Perineva® is 1.25 mg/4 mg.
Patients with creatinine Cl equal to or greater than 60 ml/min do not require dose adjustment. During therapy, it is necessary to regularly monitor the concentration of creatinine and potassium levels in the blood serum.
Patients with impaired liver function. The drug is contraindicated in patients with severe liver failure (see "Contraindications"). For moderately severe liver failure, no dose adjustment is required.
Children and teenagers. The drug Co-Perineva® should not be used by children and adolescents under 18 years of age, because Data on efficacy and safety are insufficient.
Ko-Perineva price, where to buy
The cost of the drug in Russia on average is about 350 rubles per package of 30 pieces. and 900 rubles for 90 pcs. packaged. Average price in Ukraine for a package of 30 pcs. – 205 UAH, per package 90 pcs. – 400 UAH.
- Online pharmacies in RussiaRussia
ZdravCity
- KO-Perineva tablets 2mg+0.625mg 30 pcs. Krka-Rus LLC
291 rub. order - KO-Perineva tablets 4mg+1.25mg 90 pcs. Krka-Rus LLC
RUR 851 order
- KO-Perineva tablets 4mg+1.25mg 30 pcs. Krka-Rus LLC
RUR 535 order
- KO-Perineva tablets 8mg+2.5mg 30 pcs. Krka-Rus LLC
RUR 515 order
- KO-Perineva tablets 8mg+2.5mg 90 pcs. Krka-Rus LLC
RUR 977 order
