Co-Perineva tablets 0.625 mg+2 mg 30 pcs.

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.

Co-Perineva® (Co-Perineva®)

Co-Perineva®

Lithium preparations

The simultaneous use of Co-Perineva® with lithium preparations is not recommended (see section “Interaction with other drugs”).

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, laboratory signs of functional renal failure may appear during therapy with Co-Perineva®. In this case, treatment with Co-Perineva® should be discontinued. In the future, combination therapy can be resumed using low doses of Co-Perineva® or using perindopril and indapamide in monotherapy.

Such patients require regular monitoring of potassium levels and creatinine concentrations in the blood serum 2 weeks after the start of therapy and every subsequent 2 months of therapy with Co-Perineva®.

Renal failure often develops in patients with severe CHF or underlying renal impairment, including renal artery stenosis.

Arterial hypotension and water-electrolyte imbalance

In the case of initial hyponatremia, there is a risk of a sudden decrease in blood pressure (especially in patients with renal artery stenosis). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in plasma electrolytes, for example, after prolonged diarrhea or vomiting. Such patients require regular monitoring of plasma electrolytes.

With a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After restoration of blood volume and blood pressure, you can resume therapy with Co-Perineva®, using low doses of the drug or using 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 or renal failure. As with the combined use of other antihypertensive drugs and a diuretic, regular monitoring of potassium levels in the blood plasma is necessary.

Special information on 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 lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome (see section “Contraindications”).

Children and teenagers

Prescribing Co-Perineva® to children and adolescents under 18 years of age is contraindicated due to the lack of data on the effectiveness and safety of perindopril and indapamide. both in monotherapy and in combined use in patients of this age group.

Indapamide

Hepatic encephalopathy

In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking Co-Perineva®.

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 then regularly monitor it while taking the drug. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of plasma sodium levels is indicated in elderly patients and patients with liver cirrhosis. Treatment with any diuretics can cause hyponatremia, sometimes leading to serious complications. Hyponatremia accompanied by hypovolemia can lead to dehydration and orthostatic hypotension. A simultaneous decrease in the content of chloride ions can lead to the development of secondary compensatory metabolic alkalosis: the frequency of its occurrence and severity are insignificant.

Potassium content in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/L) should be avoided in the following high-risk patients: elderly patients, malnourished patients (both those receiving and not receiving concomitant drug therapy), patients with cirrhosis (with edema and ascites) , IHD, CHF. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.

A high-risk group includes patients with a prolonged QT interval on the ECG. both congenital and caused by the action of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias, which can be fatal. In all the described cases, regular monitoring of potassium levels in the blood plasma is necessary. The first determination of potassium content in the blood plasma should be carried out within the first week from the start of therapy with Co-Perineva®.

Calcium content in blood

Thiazide and thiazide-like diuretics may reduce renal excretion of calcium, leading to a slight and temporary increase in plasma calcium. Severe hypercalcemia may be a consequence of latent hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking diuretics.

Plasma glucose concentration

Glucose concentrations should be monitored in patients with diabetes, especially in the presence of hypokalemia.

Uric acid

In patients with elevated concentrations of uric acid in the blood plasma, the frequency of gout attacks may increase during therapy.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adult patients below 25 mg/l or 220 µmol/l). In elderly patients, the standard plasma creatinine concentration should be adjusted taking into account age, body weight and gender, in accordance with the Cockroft formula:

CC = (140 - age)

×
body weight/0.814
x
plasma creatinine concentration,
where: age is in years, body weight is in kg, creatinine concentration is in µmol/l.

For women, this formula should be adjusted by multiplying the result by a factor of 0.85.

At the beginning of treatment with diuretics, patients may experience a temporary decrease in GFR and an increase in plasma creatinine and urea concentrations due to hypovolemia and hyponatremia. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.

Athletes

Indapamide may give a positive reaction during doping control.

Choroidal effusion/acute myopia/acute angle-closure glaucoma

Sulfonamides and their derivatives can cause an idiosyncratic reaction, leading to the development of choroidal effusion with visual field impairment, acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug. If left untreated, acute angle-closure glaucoma can lead to permanent vision loss. First of all, it is necessary to stop taking the drug as quickly as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of an acute attack of angle-closure glaucoma are a history of allergic reactions to sulfonamide derivatives and penicillins.

Perindopril

Double blockade of the RAAS

There is evidence of an increased risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) with simultaneous use of ACE inhibitors and ARB II or aliskiren. Therefore, double blockade of the RAAS by combining an ACE inhibitor with ARA II or aliskiren is not recommended (see sections “Pharmacological properties. Pharmacodynamics” and “Interaction with other drugs”). If a double blockade is necessary, then this should be performed under the strict supervision of a specialist with regular monitoring of kidney function, potassium levels in the blood plasma and blood pressure. Concomitant use with aliskiren or drugs containing aliskiren in patients with diabetes and/or moderate or severe renal impairment (GFR < 60 ml/min/1.73 m2 body surface area) is contraindicated 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.

Potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes

Usually serum potassium levels remain within normal limits, but hyperkalemia may occur in some patients taking perindopril. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may cause significant increases in serum potassium levels. Caution should also be exercised when using perindopril concomitantly with other drugs that increase serum potassium levels, such as trimethoprim and co-trimoxazole (sulfamethoxazole + trimethoprim), since trimethoprim is known to act similarly to the potassium-sparing diuretic amiloride. Therefore, simultaneous use of perindopril with the above drugs is not recommended. If simultaneous use is necessary, caution should be exercised and plasma potassium levels should be regularly monitored.

Neutropenia/agranulocytosis/thrombocytopenia/anemia

There are reports of the development of neutropenia/agranulocytosis, thrombocytopenia and anemia during the use of ACE inhibitors. In patients with normal renal function and without concomitant risk factors, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors. Perindopril should be used with extreme caution in patients with systemic connective tissue diseases (including SLE, scleroderma), as well as while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function. 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.

Increased sensitivity/angioedema

When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may occur. This can happen at any time during therapy. If these symptoms occur, use of Co-Perineva® should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually goes away on its 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) at a dilution of 1:1000 (0.3 ml or 0.5 ml) should be immediately administered subcutaneously and/or the airway should be secured.

A higher risk of developing angioedema has been reported in black patients.

Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section "Contraindications").

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal C-1 esterase activity. 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. When making a differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

mTOR
inhibitors In patients concomitantly taking mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus), therapy may be accompanied by an increased risk of developing angioedema (eg, swelling of the upper respiratory tract or tongue with or without respiratory distress).

Tissue plasminogen activators:

Observational studies have shown an increased incidence of angioedema in patients taking ACE inhibitors after the use of alteplase for thrombolytic therapy of ischemic stroke.

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.

Anaphylactoid reactions during desensitization procedures

There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients with a history of allergies or those prone to allergic reactions undergoing desensitization procedures. The use 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 have developed in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each apheresis procedure.

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.

Primary aldosteronism

Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that inhibit the RAAS, so the use of perindopril is not recommended.

Cough

During therapy with an ACE inhibitor, a dry persistent cough may occur, which disappears after discontinuation of drugs from 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.

Risk of arterial hypotension and/or renal failure (in patients with CHF, fluid and electrolyte imbalance, etc.)

In some pathological conditions, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (due to a salt-free diet or long-term use of diuretics), arterial hypotension, renal artery stenosis, CHF or cirrhosis of the liver with edema and ascites.

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 functional renal failure, which is more often observed when taking the first dose of Co-Perineva® or during the first two weeks 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 blood pressure reduction, especially with a decrease in blood volume and loss of electrolytes. 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 Co-Perineva® in patients with coronary artery disease and cerebrovascular insufficiency. In such patients, treatment should begin with a dose of Co-Perineva® 0.625 mg + 2 mg (initial dose).

Renovascular hypertension

The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients both awaiting surgery and in cases where surgery is not possible.

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 functional renal failure, which is reversible after discontinuation of the drug.

When using ACE inhibitors in patients with bilateral renal artery stenosis or renal artery stenosis of a single functioning kidney, there is an increased risk of developing arterial hypotension and renal failure. Concomitant use of diuretics may be a contributing factor. Renal failure can develop with minor changes in serum creatinine concentration in patients even with unilateral renal artery stenosis.

CHF

In patients with CHF (functional class IV according to the NYHA classification) and in patients with type 1 diabetes (risk of a spontaneous increase in potassium in the blood plasma), treatment should begin with an initial dose of 0.625 mg + 2 mg of Co-Perineva® and under medical supervision.

Patients with arterial hypertension and coronary artery disease should not stop taking beta-blockers; the combination of perindopril and indapamide should be used together with beta-blockers.

Diabetes

In patients with type 1 diabetes (the risk of spontaneous increases in potassium levels in the blood plasma), treatment should begin with a low dose of the drug and under close medical supervision.

During the first month of therapy with ACE inhibitors, blood glucose concentrations should be carefully monitored in patients with diabetes treated with oral hypoglycemic agents or insulin.

Ethnic characteristics

Perindopril, like other ACE inhibitors. has a less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.

Surgical interventions/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 general anesthetic agents that have an antihypertensive effect.

It is recommended to stop taking ACE inhibitors, including perindopril, the day before surgery, warning the anesthesiologist about the use of ACE inhibitors.

Aortic stenosis/mitral stenosis/HOCM

ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction.

Liver failure

In rare cases, while taking ACE inhibitors, cholestatic jaundice occurs; as this syndrome progresses, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of “liver” transaminases in the blood plasma while taking ACE inhibitors, taking Co-Perineva® should be discontinued.

Anemia

Anemia may develop in patients after kidney transplantation or in patients undergoing hemodialysis. In this case, the decrease in hemoglobin is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.

Hyperkalemia

The use of ACE inhibitors may cause hyperkalemia due to inhibition of aldosterone release, which is usually mild in patients with normal renal function. Risk factors for hyperkalemia are renal failure, old age (over 70 years), diabetes, some concomitant conditions (dehydration, acute decompensation of CHF, 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 level of potassium in the blood plasma (for example, heparin, trimethoprim or co-trimoxazole (sulfamethoxazole + trimethoprim) and especially aldosterone antagonists or ARA II). Hyperkalemia can lead to severe heart rhythm disturbances, sometimes fatal. Caution should be exercised when using ACE inhibitors and potassium-sparing diuretics and ARB II simultaneously; it is necessary to monitor renal function and serum potassium levels.

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 (0.625/2 mg) per day. 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.

Compound

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 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.

Baclofen with extreme caution , as it 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.

Tetracosactide 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 with extreme caution. leukopenia increases when used with cytostatic immunosuppressants, Allopurinol , GCS 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 , chlorpromazine , etc.), antiarrhythmic drugs ( Amiodarone , hydroquinidine , ibutilide , tosylate etc.), benzamides ( sultopride , Tiapride , Sulpiride , Amisulpride ), butyrophenones ( 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.

Perineva

Use during pregnancy and breastfeeding

During pregnancy, the use of the drug is contraindicated.
If pregnancy is confirmed, Perineva® should be discontinued as soon as possible. Use in the 2nd and 3rd trimesters of pregnancy can cause fetotoxic effects (decreased renal function, oligohydramnios, delayed ossification of fetal skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If the drug is used in the second and third trimesters of pregnancy, it is necessary to conduct an ultrasound examination of the fetal kidneys and skull bones. The use of Perineva® during lactation is not recommended due to the lack of data on the possibility of perindopril passing into breast milk. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use for liver dysfunction

Patients with liver disease do not require dose adjustment. In patients with liver cirrhosis, the hepatic clearance of perindopril changes, while the total amount of perindoprilate formed does not change, and no adjustment of the dosage regimen is required.

Use for renal impairment

In patients with kidney disease, the dose of Perineva is determined depending on the degree of renal dysfunction. During treatment, the content of potassium ions and creatinine in the blood serum should be regularly monitored. Recommended doses are presented in the table.

*- Dialysis clearance of perindoprilate is 70 ml/min. Perineva should be taken after a dialysis session.

Use in children

Contraindicated: under 18 years of age (efficacy and safety have not been established).

Use in elderly patients

In elderly patients, the recommended starting dose is 2 mg/day. In the future, the dose can be gradually increased to 4 mg and, if necessary, to a maximum of 8 mg/day, provided that the lower dose is well tolerated.

special instructions

Stable ischemic heart disease

In patients with coronary artery disease who develop an episode of unstable angina (significant or not) during the first month of therapy with Perineva®, it is necessary to assess the benefit/risk ratio of therapy with this drug.

Arterial hypotension

When treating arterial hypertension, ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated hypertension, symptomatic hypotension rarely occurs after the first dose. The risk of excessive reduction in blood pressure is increased in patients with reduced blood volume during diuretic therapy, while following a strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or in those suffering from severe renin-dependent arterial hypertension. Severe arterial hypotension was observed in patients with severe chronic heart failure, both in the presence of concomitant renal failure and in its absence. The most common arterial hypotension can develop in patients with more severe chronic heart failure, taking high-dose loop diuretics, as well as in the presence of hyponatremia or renal failure. In such patients, careful medical monitoring is recommended during initiation of therapy and during dosage titration. The same applies to patients with coronary artery disease or cerebrovascular diseases, in which an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications.

If arterial hypotension develops, it is necessary to place the patient in a horizontal position with elevated legs, and, if necessary, administer an intravenous solution of sodium chloride to increase blood volume. Transient arterial hypotension is not a contraindication for further therapy. After restoration of blood volume and blood pressure, treatment can be continued subject to careful selection of the dose of the drug.

In some patients with chronic heart failure and normal or low blood pressure, an additional decrease in blood pressure may occur during therapy with Perineva®. This effect is expected and is usually not a reason to discontinue the drug. If arterial hypotension is accompanied by clinical manifestations, dose reduction or discontinuation of Perineva® may be required.

Aortic or mitral valve stenosis/hypertrophic cardiomyopathy

ACE inhibitors, incl. Perindopril should be prescribed with caution to patients with mitral valve stenosis and left ventricular outflow tract obstruction (aortic valve stenosis and hypertrophic cardiomyopathy).

Renal dysfunction

In patients with renal insufficiency (creatinine clearance less than 60 ml/min), the initial dose of Perineva should be adjusted according to the clinical clearance and then depending on the therapeutic response. For such patients, regular monitoring of the concentration of potassium ions and creatinine in the blood serum is necessary.

In patients with symptomatic heart failure, arterial hypotension that develops during the initial period of therapy with ACE inhibitors can lead to deterioration of renal function. Cases of acute renal failure, usually reversible, have sometimes been reported in such patients.

In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney (especially in the presence of renal failure), an increase in serum concentrations of urea and creatinine was observed during therapy with ACE inhibitors, which was reversible after discontinuation of therapy. In patients with renovascular hypertension during therapy with ACE inhibitors, there is an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients should begin under close medical supervision, with small doses of the drug and with further adequate dose selection. During the first weeks of therapy with Perineva®, it is necessary to discontinue diuretics and regularly monitor renal function. In some patients with arterial hypertension in the presence of previously undetected renal failure, especially with concomitant diuretic therapy, there was a slight and temporary increase in serum urea and creatinine concentrations. In this case, it is recommended to reduce the dose of Perineva® and/or discontinue the diuretic.

Hemodialysis patients

Several cases of persistent, life-threatening anaphylactic reactions have been reported in patients undergoing dialysis using high-flux membranes and concomitantly taking ACE inhibitors. If hemodialysis is necessary, a different type of membrane must be used.

Kidney transplantation

There is no experience with the use of perindopril in patients with recent kidney transplantation.

Hypersensitivity/angioedema

Rarely in patients taking ACE inhibitors, incl. perindopril, angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx developed. This condition can develop at any time during treatment. If angioedema develops, treatment should be stopped immediately, and the patient should be under medical supervision until symptoms disappear completely. Angioedema of the lips and face usually does not require treatment; Antihistamines can be used to reduce the severity of symptoms. Angioedema of the tongue, glottis, or larynx can be fatal. If angioedema develops, it is necessary to immediately administer epinephrine (adrenaline) subcutaneously and ensure airway patency.

Patients with a history of angioedema not related to the use of ACE inhibitors have a higher risk of developing angioedema while taking an ACE inhibitor.

Anaphylactoid reactions during LDL apheresis procedure

In patients prescribed ACE inhibitors during the procedure of LDL apheresis using dextran sulfate absorption, in rare cases, an anaphylactic reaction may develop. It is recommended to temporarily discontinue the ACE inhibitor before each apheresis procedure.

Anaphylactic reactions during desensitization

In patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera venom), in very rare cases, life-threatening anaphylactic reactions may develop. It is recommended to temporarily discontinue the ACE inhibitor before each desensitization procedure.

Liver failure

During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that begins with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or elevated liver enzymes occur while taking an ACE inhibitor, the ACE inhibitor should be discontinued immediately and the patient should be closely monitored. It is also necessary to conduct an appropriate examination.

Neutropenia, agranulocytosis, thrombocytopenia, anemia

Cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitor therapy. With normal renal function in the absence of other complications, neutropenia rarely develops. Perineva® should be used with great caution in patients with systemic connective tissue diseases (for example, SLE, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as when combining all of these factors, especially with existing renal impairment. Such patients may develop severe infections that do not respond to intensive antibiotic therapy. When carrying out therapy with Perineva® in patients with the above factors, it is recommended to periodically monitor the number of leukocytes in the blood and warn the patient about the need to inform the doctor about the appearance of any symptoms of infection.

In patients with congenital deficiency of glucose-6-phosphate dehydrogenase, isolated cases of hemolytic anemia have been reported.

Negroid race

The risk of developing angioedema in black patients is higher. Like other ACE inhibitors, perindopril is less effective in lowering blood pressure in black patients, possibly due to the higher prevalence of low-renin conditions in this population of patients with arterial hypertension.

Cough

During therapy with ACE inhibitors, a persistent, non-productive cough may develop, which stops after discontinuation of the drug. This should be taken into account in the differential diagnosis of cough.

Surgery/general anesthesia

In patients whose condition requires major surgery or anesthesia with drugs that cause hypotension, ACE inhibitors, including perindopril, may block the formation of angiotensin II with compensatory renin release. One day before surgery, therapy with ACE inhibitors must be discontinued. If the ACE inhibitor cannot be canceled, then arterial hypotension developing according to the described mechanism can be corrected by increasing the volume of blood volume.

Hyperkalemia

During therapy with ACE inhibitors, including perindopril, the concentration of potassium ions in the blood may increase in some patients. The risk of hyperkalemia is increased in patients with renal and/or heart failure, decompensated diabetes mellitus, and in patients using potassium-sparing diuretics, potassium supplements, or other drugs that cause hyperkalemia (eg, heparin). If it is necessary to prescribe these drugs simultaneously, it is recommended to regularly monitor the potassium content in the blood serum.

Diabetes

In patients with diabetes mellitus taking oral hypoglycemic agents or insulin, blood glucose concentrations should be carefully monitored during the first few months of ACE inhibitor therapy.

Lithium

Concomitant use of lithium and perindopril is not recommended.

Potassium-sparing diuretics, potassium-containing drugs, potassium-containing foods and nutritional supplements

It is not recommended to use in combination with ACE inhibitors.

Lactose

Perineva® tablets contain lactose. Therefore, patients with hereditary galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption syndrome should not take this drug.

Impact on the ability to drive vehicles and operate machinery

It is necessary to take into account the possibility of developing arterial hypotension or dizziness, which may affect driving and working with technical equipment.

Analogs

Level 4 ATX code matches:
Akkuzid

Enap-N

Iruzid

Co-Diroton

Enalozide

Enap NL

Enapril-N

Capozide

Tritace Plus

Enzix

Liprazid

Co-Renitec

Hartil N

Hartil D

Noliprel

Kaptopres

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 levels checked every two weeks.

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.

Use during pregnancy and breastfeeding

Pregnancy. Taking Co-Perineva® is contraindicated during pregnancy. If you are planning pregnancy or if it occurs while taking Co-Perineva®, you should immediately stop taking the drug and prescribe other antihypertensive therapy. You should not use Co-Perineva® in the first trimester of pregnancy. There have been no controlled clinical studies on the use of ACE inhibitors in pregnant women. Limited data indicate that taking ACE inhibitors in the first trimester did not lead to fetotoxicity-related fetal malformations, but the fetotoxic effect of ACE inhibitors cannot be completely excluded. The drug Co-Perineva® is contraindicated in the second and third trimesters of pregnancy. Long-term use of ACE inhibitors in the second and third trimesters of pregnancy can lead to impaired fetal development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal growth retardation. In rare cases, while taking diuretics, hypoglycemia and thrombocytopenia may develop in the fetus/newborn. If a woman took an ACE inhibitor in the second and third trimesters of pregnancy, it is recommended to conduct an ultrasound of the kidneys and skull of the fetus/newborn.

In newborns whose mothers received therapy with ACE inhibitors, hypotension may occur, so newborns should be under close medical supervision.

Breastfeeding period. The drug Co-Perineva® is 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 to stop breastfeeding or stop taking the drug.

Ko-Perineva price, where to buy

The cost of the drug in Russia on average is about 500 rubles per package of 1.25 mg + 4 mg 30 pcs. and 900 rubles for 1.25 mg + 4 mg 90 pcs. packaged.

• Online pharmacies in RussiaRussia

ZdravCity

• KO-Perineva tablets 4mg+1.25mg 30 pcs. Krka-Rus LLC
  502 rub. order
• KO-Perineva tablets 8mg+2.5mg 90 pcs. Krka-Rus LLC

  RUB 1,141 order

• KO-Perineva tablets 8mg+2.5mg 30 pcs. Krka-Rus LLC

  RUR 617 order

• KO-Perineva tablets 2mg+0.625mg 30 pcs. Krka-Rus LLC

  RUB 344 order

• KO-Perineva tablets 4mg+1.25mg 90 pcs. Krka-Rus LLC

  RUR 978 order

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.