Symptoms: pronounced decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in BCC), possible violations of the water-electrolyte balance (low content of sodium and potassium in blood plasma).
Treatment: gastric lavage and / or administration of activated carbon, restoration of water-electrolyte balance in a hospital setting. With a pronounced decrease in blood pressure, it is necessary to transfer the patient to a lying position on his back with his legs raised upside down, then measures should be taken to increase the BCC (introduction of 0.9% sodium chloride solution in/in). Perindoprilat, the active metabolite of perindopril, it may be removed from the body by dialysis.
hypersensitivity to the active substance, any ACE inhibitor, sulfonamide derivatives, or any excipients of the drug,
angioedema (hereditary, idiopathic, or angioedema) with other ACE inhibitors (in the anamnesis),
severe renal failure,
bilateral renal artery stenosis, stenosis of the artery to a solitary kidney,
refractory hyperkalemia,
lactose intolerance, lactase deficiency, or glucose-galactose malabsorption,
simultaneous administration of drugs that prolong the QT interval on the ECG, simultaneous administration with antiarrhythmic drugs that can cause ventricular tachycardia of the "pirouette" type (see " Interaction»),
severe hepatic insufficiency (including encephalopathy),
pregnancy, breast-feeding, age under 18 (efficacy and safety have not been established),
given the lack of sufficient experience of use, the drug Co-Perineva® it should not be taken in patients on dialysis and in patients with untreated decompensated heart failure.
With caution: systemic diseases of the connective tissue (in t.tsch.
Simultaneous use is not recommended
Lithium preparations. With the simultaneous use of lithium preparations and ACE inhibitors, cases of a reversible increase in the concentration of lithium in the blood serum have been reported. Concomitant administration of thiazide diuretics may contribute to an increase in the concentration of lithium in the blood plasma and the risk of its toxic effect against the background of taking an ACE inhibitor.
Simultaneous use of the drug Co-Perineva® with lithium preparations, it is not recommended. If concomitant use is necessary, serum lithium concentrations should be carefully monitored.
Simultaneous use, requiring special care
Baclofen - potentiation of the hypotensive effect. It is necessary to monitor blood pressure, kidney function and, if necessary, adjust the dose of antihypertensive agents.
NSAIDs, including high doses of acetylsalicylic acid (more than 3 g/day). Concomitant use of ACE inhibitors with NSAIDs (including acetylsalicylic acid in doses that have an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) reduces the hypotensive effect of ACE inhibitors, increases the risk of developing renal impairment, up to the development of acute renal failure, increases the content of potassium in the blood serum, especially in patients with pre-existing renal impairment.
This combination is recommended to be used with caution, especially in elderly patients. Before starting treatment, patients need to compensate for fluid loss, as well as regularly monitor kidney function both at the beginning of therapy and during treatment.
Simultaneous use requiring caution
Tricyclic antidepressants, antipsychotics (neuroleptics). They increase the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).
GCS, tetracosactide. Reduction of the hypotensive effect (retention of fluid and sodium ions as a result of the action of GCS).
Other antihypertensive agents: it is possible to increase the hypotensive effect of the drug Co-Perineva®.
Perindopril
Simultaneous use is not recommended
Potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) and potassium preparations: ACE inhibitors reduce the loss of potassium by the kidneys caused by the diuretic. When used together with ACE inhibitors, it is possible to increase the content of potassium in the blood serum up to a fatal outcome. If the simultaneous use of an ACE inhibitor and the above drugs is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.
Simultaneous use, requiring special care
Hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin: the use of ACE inhibitors (described for captopril and enalapril) in very rare cases can increase the hypoglycemic effect of sulfonylureas and insulin derivatives in patients with diabetes mellitus, with their simultaneous use, it is possible to increase glucose tolerance and reduce the need for insulin, which may require correction of doses of hypoglycemic agents for oral administration and insulin.
Simultaneous use requiring caution
Allopurinol, cytostatic immunosuppressants, corticosteroids (with systemic use) and procainamide: concomitant use of these drugs with ACE inhibitors may increase the risk of developing leukopenia.
Means for general anesthesia: ACE inhibitors may increase the antihypertensive effect of some general anaesthetic agents.
Diuretics (thiazide and loop): the use of diuretics in high doses can lead to hypovolemia (due to a decrease in BCC), and the addition of perindopril to therapy - to a pronounced decrease in blood pressure.
Indapamide
Simultaneous use, requiring special care
Drugs that can cause ventricular polymorphic tachycardia of the "pirouette" type»: t.to.. Concomitant use with the above drugs should be avoided. It is necessary to monitor the content of potassium in the blood serum in order to avoid hypokalemia, with the development of which it is necessary to correct it, to monitor the QT interval on the ECG
Drugs that can cause hypokalemia: amphotericin B with intravenous administration, gluco - and mineralocorticoids (with systemic administration), laxatives that stimulate intestinal motility (laxatives that do not stimulate intestinal motility should be used), tetracosactide — an increase in the risk of hypokalemia (additive effect). It is necessary to control the content of potassium in the blood plasma, if necessary, its correction. Special attention should be paid to patients who are simultaneously receiving cardiac glycosides.
Cardiac glycosides: hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the content of potassium in the blood plasma, ECG indicators should be monitored and, if necessary, the dose of cardiac glycosides should be adjusted.
Simultaneous use requiring caution
Metformin: functional renal failure on the background of taking diuretics, especially loop, when used simultaneously with metformin increases the risk of lactic acidosis. Do not use metformin if the concentration of creatinine in the blood plasma exceeds 15 mg/l (135 mmol/l) - in men and 12 mg / l (110 mmol/l) - women.
Iodine-containing contrast agents: in patients with hypovolemia on the background of the use of diuretics, there is an increased risk of acute renal failure, especially when using contrast agents containing high doses of iodine. Before using iodine-containing contrast agents, the BCC should be replenished.
Preparations containing calcium salts: with simultaneous use, hypercalcemia may develop due to a decrease in the excretion of calcium by the kidneys.
Cyclosporine: it is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of cyclosporine in the blood plasma, even in the absence of pronounced loss of sodium ions and dehydration.
Perindopril has an inhibitory effect on the RAAS and reduces the excretion of potassium ions by the kidneys while taking indapamide. The risk of hypokalemia (potassium level in the blood serum of less than 3.4 mmol/l) in patients with the use of the drug Co-Perineva® the daily dose of 0.625 mg/2 mg is 2%, 1.25 mg/4 mg-4% and 2.5 mg/8 mg-6%.
WHO classification of the frequency of side effects: very often - ≥1/10, often-from ≥1/100 to <1/10, infrequently-from ≥1/1000 to <1/100, rarely-from ≥1/10000 to <1/1000, very rarely - from <1/10000, the frequency is unknown-cannot be estimated based on available data. In each group, undesirable effects are presented in order of decreasing severity.
From the side of the hematopoietic organs: very rarely — thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (there are reports of the use of ACE inhibitors). In certain clinical situations (conditions after kidney transplantation or in patients undergoing hemodialysis or peritoneal dialysis), ACE inhibitors can cause anemia.
From the central and peripheral nervous system: often-paresthesia, headache, dizziness, vertigo, infrequently-mood lability, sleep disorders, very rarely-confusion.
On the part of the senses: often-visual disturbances, tinnitus.
From the cardiovascular system: often marked reduction in blood pressure, including orthostatic hypotension, rarely — arrhythmia including bradycardia, ventricular tachycardia, atrial fibrillation, and angina, myocardial infarction, secondary, due to blood pressure lowering in patients at high risk, the frequency is unknown — ventricular tachycardia type "pirouette" (possibly fatal).
From the respiratory system: often-dry, long-lasting against the background of the use of ACE inhibitors and disappearing after their withdrawal cough, shortness of breath, infrequently — bronchospasm, very rarely — eosinophilic pneumonia, rhinitis.
From the digestive system: often-constipation, dryness of the oral mucosa, decreased appetite, nausea, epigastric pain, abdominal pain, impaired taste perception, vomiting, dyspepsia, diarrhea, very rarely-pancreatitis, angioedema of the intestine, jaundice, the frequency is not established — in the case of liver failure, there is a possibility of developing hepatic encephalopathy.
From the skin and subcutaneous fat: often — skin itching, skin rash, maculopapular rashes, infrequently — angioedema of the face, limbs, lips, oral mucosa, tongue, vocal folds and/or larynx, urticaria, hypersensitivity reactions, mainly dermatological, in patients with a burdened allergic history, worsening of SLE, very rarely — erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, isolated cases of photosensitivity reactions.
From the musculoskeletal system: often-muscle spasms.
From the urinary system: infrequently-renal failure, very rarely-acute renal failure.
On the part of the reproductive system: infrequently-impotence.
Other: often-asthenia, infrequently-increased sweating.
Laboratory parameters:
According to clinical studies, the side effects correspond to the previously established safety profile of the combination of perindopril and indapamide. In rare cases, the following serious adverse events have developed: hyperkalemia, acute renal failure, hypotension and cough, possibly the development of angioedema.
According to the recipe.
Lithium preparations. Simultaneous use of the drug Co-Perineva is not recommended® with lithium preparations.
Impaired renal function. Therapy with the drug Co-Perineva® It is contraindicated in patients with severe renal insufficiency (creatinine Cl less than 30 ml / min). In some patients with arterial hypertension without previous renal impairment on the background of Co-Perineva therapy® there may be signs of acute kidney failure. In this case, treatment with the drug Ko-Perineva® it should be stopped. In the future, you can resume combination therapy using low doses of the drug Co-Perineva®, or use the drugs perindopril and indapamide in monotherapy. Such patients need regular monitoring of the content of potassium and creatinine 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 is more common in patients with severe CHF or initial renal impairment, including with bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney. Taking the drug Ko-Perineva® it is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney.
Decrease in blood pressure and violation of the water-electrolyte balance. Hyponatremia is associated with the risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney). Therefore, when monitoring patients dynamically, you should pay attention 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 need regular monitoring of electrolytes in the blood plasma. With a pronounced decrease in blood pressure, an intravenous injection of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for further continuation of therapy. After the recovery of BCC and blood pressure, you can resume therapy with Ko-Perineva®, using low doses of the drug or using the drugs perindopril and indapamide in monotherapy.
The content of potassium. The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. As in the case of combined use of antihypertensive agents and diuretics, regular monitoring of the potassium content in the blood plasma is necessary.
Excipients. It should be borne in mind that the composition of the excipients of the drug Ko-Perineva® it contains lactose monohydrate, so the drug is contraindicated in patients with hereditary galactosemia, lactase deficiency, glucose-galactose malabsorption (see the section " Contraindications»)
Perindopril
Neutropenia/agranulocytosis. Patients taking ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves independently after the withdrawal 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. Such 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 white blood cells in the blood. The patient should be warned that in case of any signs of an infectious disease (sore throat, fever), it is necessary to immediately consult a doctor.
Hypersensitivity/angioedema (Quincke's edema). When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, lips, tongue, tongue of the upper palate and/or larynx may be observed. When these symptoms appear, the drug should be stopped immediately, the patient should be monitored until the signs of edema disappear completely.
If angioedema affects only the face and lips, then its manifestations usually go away on their own, or antihistamines can be used to treat its symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.
If such symptoms occur, you should immediately administer epinephrine (epinephrine) (in a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure the patency of the respiratory tract.
In patients with a history of Quincke's edema that is not associated with the use of ACE inhibitors, the risk of its development may be increased when taking drugs of this group.
In rare cases, angioedema of the intestine develops against the background of therapy with ACE inhibitors. At the same time, patients have 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 levels. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound or at the time of surgery. Symptoms disappear after stopping taking ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, when making a differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine
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 hymenopteran venom (bees, wasps). The administration of an ACE inhibitor to patients receiving immunotherapy with hymenopteran venom should be avoided. The development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis. In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes.
Hemodialysis. In patients receiving ACE inhibitors, during hemodialysis using high-flow membranes (for example, AN69® anaphylactoid reactions have been reported. Therefore, it is advisable to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group (see the section "With caution").
Potassium-sparing diuretics and potassium preparations. The combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes is not recommended.
Cough. Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of drugs of this group. If you have a dry cough, you should be aware of the possible connection of this symptom with the use of an ACE inhibitor. If the doctor believes that therapy with an ACE inhibitor is necessary for the patient, taking the drug Co-Perineva® can be continued.
Children and adolescents under 18 years of age. The drug Co-Perineva® it 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, impaired water-electrolyte balance, etc.). Cirrhosis of the liver accompanied by edema and ascites, hypotension, CHF may be a significant activation of the renin-angiotensin-aldosterone system (RAAS), especially in severe hypovolemia and decreased content of electrolytes in the blood plasma (compared to the salt-free diet or prolonged use of diuretics).
The use of ACE inhibitors causes a blockade of the RAAS, in this regard, perhaps a sharp decrease in blood pressure and/or increasing the concentration of creatinine in plasma, indicating the development of acute renal failure that often occurs when taking the first dose of the drug Co-Perineva® or during the first 2 weeks of therapy.
Elderly patients. Before taking the drug Ko-Perineva® It is necessary to evaluate the function of the kidneys and the content of potassium in the blood plasma. The initial dose of the drug Ko-Perineva® They are selected depending on the degree of reduction in blood pressure, especially with a decrease in BCC and CHF (IV functional class 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, but special care should be taken when using the drug Co-Perineva® in patients with ischemic heart disease and cerebral circulatory insufficiency. In such patients, treatment should begin with a dose of 0.625/2 mg of the drug Co-Perineva® (initial dose).
Patients with renovascular hypertension. Treatment with Ko-Perineva® patients with diagnosed or suspected renal artery stenosis should be started in a hospital setting with a dose of Co-Perineva® 0.625/2 mg, monitoring kidney function and blood plasma potassium content. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.
Other risk groups. In patients with CHF (NYHA functional class IV) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium content), treatment should be started with an initial dose of 0.625/2 mg of the drug Co-Perineva® and under medical supervision.
Patients with diabetes mellitus. When prescribing the drug Co-Perineva® patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood.
Ethnic characteristics. Perindopril (as well as other ACE inhibitors), has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races.
Surgical interventions/General anesthesia. The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a marked 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 outlet tract obstruction and aortic and / or mitral stenosis.
Liver failure. In rare cases, against the background of taking ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If there is jaundice or a significant increase in the activity of hepatic transaminases against the background of taking ACE inhibitors, take the drug Co-Perineva® it should be stopped.
Anemia. It can develop in patients after kidney transplantation or in patients on hemodialysis.
Hyperkalemia. May develop during treatment with ACE inhibitors, in t.tsch. and perindopril. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing substitutes for dietary salt, and the use of other drugs that increase the potassium content in the blood plasma (for example, heparin). Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal. The combined use of the above drugs should be carried out with caution
Indapamide
Photosensitivity. There are reports of cases of increased photosensitivity against the background of taking thiazide and thiazide-like diuretics. With the development of a photosensitivity reaction against the background of taking the drug Co-Perineva®treatment should be discontinued. If there is a need to resume the use of the drug Co-Perineva®, it is necessary to protect the exposed areas of the skin from direct exposure to sunlight and artificial UV rays.
Water-electrolyte balance. The content of sodium in the blood plasma. Before starting treatment with Ko-Perineva® it is necessary to determine the sodium content in the blood plasma and, against the background of taking the drug, conduct regular monitoring of electrolytes in the blood plasma. All diuretics can cause hyponatremia, leading to serious complications.
The content of potassium in the blood plasma. Treatment with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia (less than 3.4 mmol/l) in the following patients: elderly, emaciated patients, patients with cirrhosis of the liver, patients with peripheral edema, ascites, coronary heart disease, CHF. 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 extended QT interval on the ECG. Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disorders, especially arrhythmias of the "pirouette" type, which can be fatal. In all the described cases, 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 from the start of therapy with the drug Ko-Perineva®.
The content of 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 content of calcium in the blood plasma. Severe hypercalcemia may be a consequence of latent hyperparathyroidism. Before examining the function of the parathyroid glands, you should stop taking the drug Ko-Perineva®.
The concentration of glucose in the blood plasma. It is necessary to monitor the concentration of glucose in patients with diabetes mellitus.
Uric acid. In patients with an increased concentration of uric acid in the blood plasma during therapy with Co-Perineva® the frequency of gout exacerbation may increase.
Diuretics and renal function. Hypovolemia as a result of a decrease in BCC or hyponatremia caused by taking diuretics at the beginning of treatment with Ko-Perineva® it can lead to a decrease in the glomerular filtration rate and be accompanied by an increase in the concentration of creatinine and urea in the blood plasma.
Athletes. Indapamide may give a false positive reaction during doping control.
Influence on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. It is necessary to be careful when driving vehicles and working with technical devices that require increased attention and speed of psychomotor reactions.
Essential hypertension.
Ko-Perineva® - a combination drug containing an ACE inhibitor-perindopril and a thiazide-like diuretic-indapamide. The drug has antihypertensive, diuretic and vasodilating effects.
Ko-Perineva® It has a pronounced dose-dependent antihypertensive effect, which does not depend on the age and body position of the patient and is not accompanied by reflex tachycardia. It does not affect the metabolism of lipids (total cholesterol, LDL, VLDL, HDL, triglycerides (TG) and carbohydrates), including in patients with diabetes mellitus. Reduces the risk of hypokalemia due to diuretic monotherapy.
The antihypertensive effect persists for 24 hours.
A stable decrease in blood pressure is achieved within 1 month on the background of the use of the drug Ko-Perineva® without increasing the heart rate. Discontinuation of treatment does not lead to the development of the "withdrawal"syndrome.
Perindopril-an ACE inhibitor, the mechanism of action of which is associated with the 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, does not cause reflex tachycardia with 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 Ko-Perineva® results in:
- venous dilation (reduction of preload on the heart), due to changes in the metabolism of PG,
- reduction of OPSS (reduction of afterload on the heart).
In patients with heart failure, perindopril promotes:
- reducing the filling pressure of the left and right ventricles,
- increased cardiac output and cardiac index,
- increased regional blood flow in the muscles.
Perindopril is effective for hypertension of any severity: mild, moderate and severe. The maximum antihypertensive effect develops in 4-6 hours after a single oral administration and persists for a day. Discontinuation of therapy does not lead to the development of the "withdrawal"syndrome.
It has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances the antihypertensive effect of perindopril.
Indapamide belongs to the derivatives of sulfonamide, is a diuretic. It 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, it increases the excretion of potassium and magnesium. Having the ability to selectively block "slow" calcium channels, indapamide increases the elasticity of the arterial walls and reduces OPSS. 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 does not affect the metabolism of lipids: TG, LDL and HDL and carbohydrate metabolism, even in patients with diabetes mellitus and arterial hypertension.
The combined use of perindopril and indapamide does not change their pharmacokinetic parameters in comparison with the separate administration of these drugs.
Perindopril after oral administration, it is rapidly absorbed from the gastrointestinal tract. Bioavailability of about 65-70%. Food intake reduces the conversion of perindopril to perindoprilate. T1/2 perindopril from the blood plasma is 1 h.
Cmax in the blood plasma, it is reached in 3-4 hours after oral administration. Since food intake reduces the conversion of perindopril to perindoprilat and the bioavailability of the drug, perindopril should be taken 1 time a day in the morning, before breakfast. Taking perindopril 1 time a day, the equilibrium concentration is reached within 4 days.
In the liver metabolized with the formation of the active metabolite of perindoprilat. In addition to the active metabolite of perindoprilat, perindopril forms 5 more inactive metabolites. The binding to plasma proteins of perindoprilat is dose-dependent and is 20%. Perindoprilat easily passes through the histohematic barriers, excluding BBB, a small amount penetrates through the placenta and into breast milk. Excreted by the kidneys, T1/2 of perindoprilat is about 17 h It does not accumulate.
In elderly patients, in patients with renal and heart failure, the elimination of perindoprilat is slowed down.
In case of renal insufficiency, it is recommended to reduce the dose of perindopril depending on the severity of renal insufficiency (creatinine clearance). The dialysis Cl of perindoprilate is 70 ml/min.
The kinetics of perindopril is changed in patients with cirrhosis of the liver: hepatic clearance is reduced by half. However, the quantity of perindoprilat formed is not reduced, which does not require dose adjustment.
Indapamide. It is quickly and almost completely absorbed into the gastrointestinal tract. Food intake slows down the absorption somewhat, but does not significantly affect the amount of absorbed indapamide. Cmax in the blood plasma, it is reached 1 h after ingestion of a single dose. Is associated with blood plasma proteins is 79%. T1/2 it is from 14 to 24 hours (on average-18 hours). It does not accumulate.
It is 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 intestine with bile in the form of inactive metabolites (22%). In patients with renal insufficiency, the pharmacokinetic parameters of indapamide do not significantly change.
At a temperature not exceeding 30 °C, in the original packaging.
Keep out of reach of children.
Shelf life of the drug Ko-Perineva®3 года.Do not use after the expiration date indicated on the package.
| Pills | 1 table. |
| the composition is based on 1 table. specified in the table |
| Active ingredients | Dosage of tablets, mg | ||
| 0,625 2 | 1,25 4 | 2,5 8 | |
| Indapamide | 0,625 | 1,25 | 2,5 |
| perindopril erbumin K semi-finished pellets | 37,515 | 75.03 mg | 150,06 |
| The active substance of the semi-finished product-granules | |||
| Perindopril erbumin | 2 | 4 | 8 |
| Excipients of semi-finished pellets | |||
| calcium chloride hexahydrate | 0,6 | 1,2 | 2,4 |
| lactose monohydrate | 30,915 | 61,83 | 123,66 |
| crospovidon | 4 | 8 | 16 |
| Excipients | |||
| MCC | 11,25 | 22,5 | 45 |
| sodium bicarbonate | 0,25 | 0,5 | 1 |
| colloidal silicon dioxide | 0,135 | 0,27 | 0,54 |
| magnesium stearate | 0,225 | 0,45 | 0,9 |
The tablet of 0.625 mg, 2 mg, 4 mg and 1.25 mg, 2.5 mg 8 mg. According to 10 tables. in a contour cell package made of a combined OPA/Al/PVC material and aluminum foil. 3 contour cell packages (10 tables each).) put in a pack of cardboard..
Pregnancy. Taking the drug Ko-Perineva® contraindicated in pregnancy. When planning pregnancy or when it occurs against the background of taking the drug Ko-Perineva® you should immediately stop taking the drug and prescribe another antihypertensive therapy. Do not use the drug Ko-Perineva® in the first trimester of pregnancy. Controlled clinical studies on the use of ACE inhibitors in pregnant women have not been conducted. Limited data indicate that the use of ACE inhibitors in the first trimester did not lead to fetal malformations associated with fetotoxicity, but the fetotoxic effect of ACE inhibitors cannot be completely excluded. The drug Co-Perineva® contraindicated in the second and third trimesters of pregnancy. Prolonged use of ACE inhibitors in the second and third trimesters of pregnancy can lead to impaired fetal development (decreased kidney function, oligohydramnion, slowing of ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia).
Prolonged use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in utero-placental blood flow, which leads to fetoplacental ischemia and fetal development delay. In rare cases, while taking diuretics, the fetus/newborn may develop hypoglycemia and thrombocytopenia. If a woman took an ACE inhibitor in the second and third trimesters of pregnancy, it is recommended to perform ultrasound of the kidneys and skull of the fetus/newborn.
Newborns whose mothers have received ACE inhibitor therapy may experience hypotension, so newborns should be under close medical supervision.
The period of breastfeeding. The drug Co-Perineva® contraindicated during breastfeeding.
It is not known whether perindopril is excreted in breast milk.
Indapamide is excreted in breast milk. Causes a decrease or suppression of lactation. The newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia and "nuclear" jaundice.
It is necessary to assess the significance of therapy for the mother and make a decision about stopping breastfeeding or stopping taking the drug.
Inside, 1 time a day, preferably in the morning before breakfast, with a sufficient amount of liquid.
If possible, the drug should be started with the selection of doses of single-component drugs. In case of clinical necessity, 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 tab. of the drug Ko-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 control of blood pressure, the dose of the drug should be increased to 1 table of the drug Co-Perineva® (1.25 mg/4 mg) 1 time per day.
If necessary, to achieve a more pronounced antihypertensive effect, it is possible to increase the dose of the drug to the maximum daily dose of the drug Co-Perineva® — 1 tablet (2.5 mg/8 mg) 1 time per day.
Elderly patients. The initial dose is 1 tab. of the drug Ko-Perineva® 0.625 mg/2 mg once a day. It is necessary to prescribe treatment with the drug after monitoring kidney function and blood pressure.
Patients with impaired renal function. The drug Co-Perineva® in patients with severe renal insufficiency, it is contraindicated (creatinine Cl less than 30 ml / min) (see "Contraindications").
Patients with moderate renal insufficiency (creatinine Cl 30-60 ml / min) are recommended to start therapy with the necessary doses of drugs (in monotherapy) that are part of the drug Co-Perineva®, the maximum daily dose of the drug Co-Perineva® - 1.25 mg/4 mg.
In patients with a creatinine Cl equal to or greater than 60 ml/min, no dose adjustment is required. During therapy, it is necessary to regularly monitor the concentration of creatinine and the content of potassium in the blood serum.
Patients with impaired liver function. The drug is contraindicated in patients with severe hepatic insufficiency (see "Contraindications"). In moderate hepatic insufficiency, dose adjustment is not required.
Children and teenagers. The drug Co-Perineva® it should not be used in children and adolescents under 18 years of age, because data on efficacy and safety are insufficient.
C09BA04 Perindopril in combination with diuretics
