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).
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). Perindoprilate, the active metabolite of perindopril, can be eliminated from the body by dialysis.
angioedema (hereditary, idiopathic, or angioedema) with other ACE inhibitors (in the anamnesis),
severe renal failure,
refractory hyperkalemia,
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:
Simultaneous use of the drug Co-Perineva®
- potentiation of the hypotensive effect. It is necessary to monitor blood pressure, kidney function and, if necessary, adjust the dose of antihypertensive drugs.
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
Other antihypertensive agents: it is possible to increase the hypotensive effect of the drug Co-Perineva®.
Simultaneous use is not recommended
Simultaneous use, requiring special care
(sulfonylurea derivatives)
: concomitant use of these drugs with ACE inhibitors may increase the risk of developing leukopenia.
Means for general anesthesia: ACE inhibitors may increase the hypotensive effect of some general anesthesia agents.
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.
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
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.
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.
Cyclosporine:
Tablets 0.625 mg 2 mg:
round, biconvex, white or almost white in color with a risk on one side and with a chamfer.
round, biconvex, white or almost white in color with a risk on one side.
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.
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:
On the part of the senses: often-visual disturbances, tinnitus.
often-a marked decrease in blood pressure, including orthostatic hypotension, very rarely-arrhythmias, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina, myocardial infarction, possibly secondary, due to a decrease in blood pressure in high — risk patients, the frequency is unknown-ventricular tachycardia of the "pirouette" type (possibly fatal).
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 urinary system: infrequently-renal failure, very rarely-acute renal failure.
infrequently-impotence.
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.
Lithium preparations.®
® 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®®, 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®.
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.
®, using low doses of the drug or using the drugs perindopril and indapamide in monotherapy.
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.
Perindopril
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.
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.
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 established by 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.
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.
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").
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. 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.
With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension, CHF, there may be a significant activation of the renin-angiotensin-aldosterone system (RAAS), 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).
®
Elderly patients. 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.
® (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®
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 Co-Perineva®
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.
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.
ACE inhibitors should be used with caution in patients with left ventricular outlet tract obstruction and aortic and / or mitral stenosis.
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
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, 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. 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 calcium in the blood plasma..
In patients with an increased concentration of uric acid in the blood plasma during therapy with Co-Perineva®
Essential hypertension.
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.
® without increasing the heart rate. Discontinuation of treatment does not lead to the development of the "withdrawal"syndrome.
Perindopril acts through its main active metabolite, perindoprilate. Its other metabolites are inactive. The effect of the drug Ko-Perineva®
- reducing the filling pressure of the left and right ventricles,
- 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.
after oral administration, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65-70%. Food intake reduces the conversion of perindopril to perindoprilate. T perindopril from the blood plasma is 1 h.
C in the blood plasma, it is reached in 3-4 hours after oral administration. Since food intake reduces the conversion of perindopril to perindoprilate 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, it is metabolized to form an active metabolite, perindoprilate. 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, T
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 amount of perindoprilate formed does not decrease, 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
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.| Pills | |
| Dosage of tablets, mg | |||
| 2,5 | |||
| 0,6 | 2,4 | ||
| 123,66 | |||
| 4 | |||
| 45 | |||
| sodium bicarbonate | 0,25 | ||
| 0,54 | |||
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..
Taking the drug Ko-Perineva contraindicated in pregnancy. When planning a pregnancy or when it occurs against the background of taking 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).
Newborns whose mothers have received ACE inhibitor therapy may experience hypotension, so newborns should be under close medical supervision.
The drug Co-Perineva® contraindicated during breastfeeding.
It is not known whether perindopril is excreted in breast milk.
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®
Elderly patients. 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").
®, the maximum daily dose of the drug Co-Perineva®
Patients with impaired liver function.
Children and teenagers.® it should not be used in children and adolescents under 18 years of age, because data on efficacy and safety are insufficient.
