Description
Pharmacological action
Co-Parnawel is a combined preparation containing an ACE inhibitor – perindopril and a thiazide-like diuretic – indapamide. The synergistic effect of perindopril and indapamide determines the pharmacological properties of the drug.
Perindopril – 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, which has a vasoconstrictor effect, and also destroys bradykinin, which has a vasodilating effect, to an inactive heptapeptide.
As a result, perindopril reduces the secretion of aldosterone, increases the activity of renin in blood plasma by the principle of feedback with prolonged use, reduces the total peripheral vascular resistance (OPSS), which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by the retention of salts and fluids or the development of reflex tachycardia.
Perindopril has a therapeutic effect due to the active metabolite, perindoprilat. Other metabolites are pharmacologically inactive.
Perindopril normalizes heart function, contributing to the expansion of veins (reduction of preload) due to changes in the metabolism of prostaglandins and a decrease in OPSS (decrease in afterload).
In chronic heart failure (CHF), perindopril reduces filling pressure in the left and right ventricles of the heart, reduces OPSS, increases cardiac output and increases cardiac index, increases peripheral blood flow in the muscles.
Indapamide belongs to the group of sulfonamides and is close to thiazide diuretics in pharmacological properties. Indapamide inhibits sodium reabsorption in the cortical segment of the renal tubules, increasing the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium by the kidneys, increasing diuresis and lowering blood pressure (BP). The antihypertensive effect of
Co-Parnawel has a dose-dependent antihypertensive effect, as on diastolic, and systolic blood pressure in the “standing” and “lying” positions. Antihypertensive effect persists for 24 hours. The therapeutic effect occurs less than 1 month after the start of treatment and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal syndrome.
Synergistic effect of perindopril and indapamide was noted compared with monotherapy with these drugs. Perindopril is effective in the treatment of arterial hypertension of any severity. Antihypertensive effect is achieved a maximum of 4-6 hours after a single dose and lasts for 24 hours. 24 hours after taking perindopril, there is a pronounced (about 80%) residual inhibition of ACE.
Perindopril exhibits an antihypertensive effect in both patients with low and normal plasma renin activity.
Perindopril has a vasodilating effect, helps restore the elasticity of large vessels and the structure of the vascular wall of small arteries. It also reduces left ventricular hypertrophy.
Concomitant use of thiazide diuretics enhances the antihypertensive effect.
Indapamide in monotherapy has an antihypertensive effect for 24 hours in doses that have a minimal diuretic effect. Indapamide improves the elasticity of large arteries, reduces OPSS, reduces left ventricular hypertrophy. An increase in the dose of indapamide does not entail an increase in the antihypertensive effect, but increases the risk of developing adverse events.
Indapamide does not affect lipid metabolism (total cholesterol, high lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL), triglycerides) and carbohydrate metabolism.
Pharmacokinetics
The combined use of perindopril and indapamide does not change their pharmacokinetic characteristics compared with the separate use of these drugs. After oral administration, perindopril is rapidly absorbed in the gastrointestinal tract (GIT) and reaches its maximum plasma concentration (Cmax) within 1 hour. Perindopril does not have pharmacokinetic activity.
Approximately 27% of the total intake of perindopril enters the bloodstream as an active metabolite of perindopril. In addition to perindoprilat, 5 more metabolites are formed that do not have pharmacological activity. Cmax of perindoprilat is achieved after 3-4 hours.
Taking perindopril during meals is accompanied by a decrease in the conversion of perindopril to perindoprilat, accordingly, its bioavailability decreases. Therefore, perindopril should be taken 1 time per day, before meals.
There is a linear dependence of the concentration of perindopril in blood plasma on its dose. The distribution volume of free perindoprilat is 0.2 l / kg. The connection with blood plasma proteins is insignificant, the connection of perindoprilat, mainly with ACE, is less than 20% and depends on its concentration.
Perindopril is excreted by the kidneys. The ² Ñeffective ² Ñ half-life (T1 / 2) of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days.
Excretion of perindopril slows down in the elderly and in patients with heart and kidney failure.
The dialysis clearance of perindopril is 70 ml / min.
In patients with cirrhosis of the liver, ² Ñhepatic ² Ñ clearance of perindopril is reduced by 2 times, while the total amount of perindoprilat formed does not decrease and correction of the dosage regimen is not required.
Indapamide is rapidly and completely absorbed from the digestive tract. Cmax indapamide is reached in blood plasma after 1 hour. Communication with blood plasma proteins 79%. T1 / 2 is 14-24 hours (an average of 18 hours). Repeated intake of indapamide does not lead to its cumulation in the body. It is excreted mainly by the kidneys (70%) and through the intestines (22%) in the form of inactive metabolites. The pharmacokinetics of indapamide does not change in patients with renal failure.
Indications
Essential hypertension (for patients who are shown combination therapy).
Contraindications
Perindopril
– Hypersensitivity to perindopril and other ACE inhibitors.
– Concomitant use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) less than 60 ml / min / 1.73 m2).
– A history of angioedema (Quincke edema) associated with taking an ACE inhibitor.
– Hereditary / idiopathic angioedema.
– Pregnancy.
– The period of breastfeeding.
– Age under 18 years of age (efficacy and safety not established). Indapamide
– Hypersensitivity to indapamide, other sulfonamide derivatives, severe renal failure (creatinine clearance (CC) less than 30 ml / min), severe liver dysfunction or hepatic encephalopathy, hypokalemia, pregnancy, the period of breastfeeding, age up to 18 years (insufficient data on safety and effectiveness). The simultaneous use of drugs that can cause arrhythmias such as pirouette .
Co-Parnawel
– Hypersensitivity to the excipients that make up the drug.
– Concomitant use with potassium-sparing diuretics, potassium and lithium preparations, and in patients with high plasma potassium
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
– Concomitant use of drugs that extend the QT interval.
– Bilateral renal artery stenosis or artery stenosis of a single functioning kidney.
– Due to the lack of sufficient clinical experience, Co-Parnawel should not be used in patients undergoing hemodialysis, as well as in patients with untreated heart failure in the stage of decompensation.
– Age under 18 years of age (efficacy and safety not established).
Special instructions
Lithium preparations
The simultaneous use of perindopril and indapamide with lithium preparations is not recommended.
Impaired renal function
Co-Parnawel therapy is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml / min). Some patients with arterial hypertension without a previous renal impairment may experience signs of acute renal failure during therapy with Co-Parnawel. In this case, treatment with the drug should be discontinued.
In the future, you can resume combination therapy using low doses of Co-Parnawel, or use perindopril and indapamide in monotherapy. Such patients need regular monitoring of serum potassium and creatinine levels every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Co-Parnawel.
Acute renal failure often develops in patients with severe chronic heart failure or an initial impaired renal function, including with bilateral renal artery stenosis or artery stenosis of the only functioning kidney. Taking the drug is not recommended for patients with bilateral renal artery stenosis or artery stenosis of a single functioning kidney. Arterial hypotension and water-electrolyte imbalance
Hyponatremia is associated with the risk of sudden development of arterial hypotension (especially in patients with bilateral renal artery stenosis or artery stenosis of a single functioning kidney).
Therefore, when monitoring patients dynamically, attention should be paid to possible symptoms of dehydration and a decrease in electrolyte levels in blood plasma, for example, after prolonged diarrhea or vomiting. Such patients need regular monitoring of electrolytes in blood plasma. With a pronounced decrease in blood pressure, intravenous administration of a 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for further continuation of therapy. After restoration of the circulating blood volume and blood pressure, Co-Parnawel therapy can be resumed using low doses of the drug, or using perindopril and indapamide in monotherapy.
Potassium content
The simultaneous use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with other antihypertensive drugs in combination with a diuretic, regular monitoring of potassium in the blood plasma is necessary.
Excipients
It should be borne in mind that the excipients of the drug include lactose monohydrate, therefore the drug is contraindicated in patients with hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
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 disappears on its own 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.
These patients may develop severe infections that are not amenable to intensive antibiotic therapy. In the case of the appointment of perindopril, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that that in case of any signs of an infectious disease (sore throat, fever), you should immediately consult a doctor.
Hypersensitivity / angioedema (Quincke’s edema)
When taking ACE inhibitors, incl. perindopril, in rare cases, the development of angioedema of the face, lips, tongue, tongue of the upper palate and / or larynx can be observed. When these symptoms appear, the drug should be stopped immediately, the patient should be observed until the signs of edema disappear completely.
If angioneurotic edema affects only the face and lips, then its manifestations usually go away on their own, or antihistamines can be used to treat its symptoms. Angioneurotic edema, accompanied by swelling of the tongue and larynx, can lead to airway obstruction and death. If such symptoms appear, epinephrine (adrenaline) should be administered subcutaneously immediately (at a dilution of 1: 1000 (0.3 or 0.5 ml) and / or airway should be ensured.
In patients with a history of Quincke’s edema not associated with taking ACE inhibitors may increase the risk of its development when taking drugs of this group (see section “Contraindications”).
In rare cases, therapy with ACE inhibitors develop angioedema of the intestine. In this case, patients have abdominal pain as an isolated symptom and whether combined with nausea and vomiting, in some cases without prior angioedema of the face and with normal activity of the enzyme C-1 esterase.
Diagnosis is by CT scan of the abdomen, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, a differential diagnosis must take into account the possibility of developing angioedema of the intestine.
Anaphylactoid reactions during desensitization procedures
There are some 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 burdened allergic history or a tendency to allergic reactions, undergoing desensitization procedures. The administration of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. The development of anaphylactoid reactions can be avoided by temporarily canceling an 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 when performing 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, hemodialysis using high-flow membranes (e.g. AN69 ®) showed anaphylactoid reactions. Therefore, it is desirable to use a membrane of a different type or to use a hypotensive drug of another pharmacotherapeutic group.
Cough
Dry cough may occur during therapy with an ACE inhibitor, which disappears after discontinuation of this group of drugs. When a dry cough appears, one should remember the possible connection of this symptom with the use of an ACE inhibitor. If the doctor believes that the patient needs ACE inhibitor therapy, Co-Parnawel may be continued.
Risk of arterial hypotension and / or renal failure (in patients with chronic heart failure, impaired water-electrolyte balance, etc. ) In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system (RAAS) can be noted, especially with severe hypovolemia and a decrease in the electrolyte content in blood plasma (against a background of a diet with limited sodium chloride or long-term use of diuretics), in patients with initially low blood pressure , renal artery stenosis (including bilateral), chronic heart failure, or cirrhosis of the liver with edema and ascites.
The use of ACE inhibitors causes blockade of RAAS, in connection with this, a sharp decrease in blood pressure and / or an increase in the concentration of creatinine in blood plasma is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose of the drug or during the first 2 weeks of therapy. Sometimes these conditions develop acutely. In such cases, when resuming therapy, it is recommended to use a combination of perindopril and indapamide in a lower dose and then gradually increase the dose.
Elderly patients
Prior to taking Co-Parnawel, the renal function and plasma potassium should be evaluated. The initial dose is selected depending on the degree of lowering blood pressure, especially with a decrease in the volume of circulating blood and chronic heart failure (IV functional class according to NYHA classification). Such measures can 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 in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should be started with a dose of 2 mg / 0.625 mg (initial dose).
Patients with Renovascular Hypertension
Treatment with patients with diagnosed or suspected renal artery stenosis should be started in a hospital setting with a dose of 2 mg / 0.625 mg, monitoring renal function and plasma potassium. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.
Other risk groups
In patients with chronic heart failure (NYHA class IV functional class) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium), treatment should be started with an initial dose of 2 mg / 0.625 mg of Co-Parnawel and under medical supervision .
Patients with diabetes mellitus
When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, it is necessary to regularly monitor the blood glucose concentration during the first month of therapy.
Surgical intervention / General anesthesia
The use of ACE inhibitors in patients undergoing surgical intervention using general anesthesia can lead to a marked decrease in blood pressure, especially when using general anesthesia drugs that have antihypertensive effects.
It is recommended that you stop taking ACE inhibitors, including perindopril, 12 hours before surgery, warning the anesthetist about the use of ACE inhibitors.
Ethnic differences
Perindopril, like other ACE inhibitors, obviously has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races. Perhaps this difference is due to the fact that patients of the Negroid race with arterial hypertension are more likely to have low renin activity.
Aortic stenosis / Mitral stenosis / Hypertrophic obstructive cardiomyopathy
ACE inhibitors should be used with caution in patients with left ventricular outflow obstruction and in aortic and / or mitral stenosis.
Hepatic insufficiency
In rare cases, while taking ACE inhibitors, cholestatic jaundice occurs, with progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. When jaundice or a significant increase in the activity of hepatic transaminases occurs while taking ACE inhibitors, Co-Parnawel should be discontinued.
Anemia
May develop in patients after kidney transplantation or in patients undergoing hemodialysis. In this case, the decrease in hemoglobin is greater, the higher was its initial indicator. This effect, apparently, is not dose-dependent, but may be associated with the mechanism of action of ACE inhibitors.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, including and perindopril. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decreased blood volume, chronic heart failure in the decompensation stage, metabolic acidosis), simultaneous administration of potassium-sparing diuretics (such as spironolactone, eplerenone, triamteren, amiloride), as well as potassium preparations or potassium-containing substitutes for edible salt and the use of other drugs that increase the potassium content in blood plasma (for example, heparin).
Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal. The simultaneous use of the above drugs must be carried out with caution.
Indapamide
In the presence of impaired liver function, the use of thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking Co-Parnawel.
Photosensitivity
There are reports of cases of the development of the photosensitivity reaction while taking thiazide and thiazide-like diuretics. With the development of the photosensitivity reaction while taking the drug, treatment should be stopped. If there is a need to resume the use of Co-Parnawel, protect exposed skin from direct exposure to sunlight and artificial ultraviolet rays.
Water-electrolyte balance.
Plasma sodium.
Before starting treatment with the drug, it is necessary to determine the sodium content in the blood plasma and, while taking the drug, conduct regular monitoring of electrolytes in the blood plasma. All diuretics can cause hyponatremia, leading to serious complications.
Hyponatremia at the initial stage may not be accompanied by clinical symptoms, therefore, regular laboratory monitoring is necessary. More frequent monitoring of sodium is indicated in patients with cirrhosis and elderly patients.
Plasma potassium content
Thiazide and thiazide-like diuretics are associated with a risk of hypokalemia (less than 3.4 mmol / L) in the following patients: elderly patients, malnourished patients, patients with cirrhosis, patients with peripheral edema, ascites, coronary artery disease heart, chronic heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of arrhythmias.
An increased risk group includes patients with an increased QT interval on the ECG, it does not matter this increase is caused by congenital causes or the action of drugs.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially pirouette arrhythmias, which can be fatal. In all the cases described, regular monitoring of the potassium content in the blood plasma is necessary. The first determination of the potassium content in blood plasma must be carried out during the first week from the start of therapy with Co-Parnawel.
If hypokalemia is detected, appropriate treatment should be prescribed.
Plasma calcium content
Thiazide and thiazide-like diuretics reduce kidney excretion of calcium, resulting in a slight and temporary increase in plasma calcium. Severe hypercalcemia may be due to latent hyperparathyroidism. Before examining the function of the parathyroid glands, Co-Parnawel should be discontinued.
Plasma glucose concentration
The glucose concentration in patients with diabetes should be monitored, especially in the presence of hypokalemia.
Uric acid
In patients with an increased concentration of uric acid in the blood plasma during treatment with the drug, the frequency of exacerbation of the course of gout may increase.
Diuretics and renal function
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adult patients is below 25 mg / L or 220 μmol / L). In elderly patients, QC is calculated taking into account age, body weight and gender.
At the beginning of treatment with diuretics, patients due to hypovolemia and hyponatremia may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, however, in patients with renal failure, its severity may increase.
Athletes Co-Parnawel may give a false positive reaction during the doping control.
Influence on the ability to drive vehicles and other complex mechanisms
Care must be taken when driving vehicles and working with technical devices that require increased attention and speed of psychomotor reactions.
Composition of
Per tablet:
Active ingredients:
indapamide – 1,250 mg,
perindopril erbumin – 4,000 mg.
Excipients:
lactose monohydrate (milk sugar) – 135,750 mg,
microcrystalline cellulose – 38,000 mg,
corn starch – 14,000 mg,
povidone-K25 – 5,000 mg,
magnesium 2 mg –
Dosage and administration
Inside, once a day, preferably in the morning before breakfast, without chewing, drinking plenty of fluids. The dose of the drug is selected individually for each patient, depending on the patient’s condition and individual response to treatment.
Dosages are given for the perindopril / indapamide ratio. The recommended starting dose is 1 tablet. Co-Parnawel (2 mg / 0, 625 mg) 1 time per day. If after 1 month. taking the drug can not achieve adequate control of blood pressure, the dose should be increased to 1 table. Co-Parnawel (4 mg / 1.25 mg) once a day.
Elderly patients
The recommended starting dose is 1 tablet of the drug, 2 mg / 0.625 mg once daily.
In the absence of the desired antihypertensive effect after examining renal function, you can proceed to the use of a dose of 1 tablet at a dosage of 4 mg / 1.25 mg.
Patients with impaired renal function
In severe renal impairment (creatinine clearance less than 30 ml / min), the use of the drug is contraindicated.
Patients with moderate renal failure (creatinine clearance 30-60 ml / min) are recommended to start therapy with the necessary doses of drugs (in monotherapy), included in the preparation of Co-Parnawel.
For patients with impaired renal function (creatinine clearance is 60 ml / min or more), dose adjustment is not required.
Serum potassium and serum creatinine should be monitored regularly.
Patients with impaired liver function
Dose adjustment is not required in patients with moderate hepatic impairment.
In severe cases of impaired liver function, the use of the drug is contraindicated.
Children and adolescents
The drug should not be used in children and adolescents under 18 years of age, because efficacy and safety not established.
If you skip taking one or more doses at the next dose, Co-Parnawel should be taken in the usual dose, you cannot take a higher dose.
Side effects
The frequency of adverse reactions was determined in accordance with the recommendations of the World Health Organization: very often (> 1/10) often (> 1/100, <1/10) infrequently (> 1/1000, <1/100) rarely (> 1/10000, <1/1000) is very rare (<1/10000), including individual messages of unspecified frequency (the frequency cannot be calculated from the available data). From the circulatory and lymphatic systems Very rarely: thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (patients after kidney transplantation, patients on hemodialysis) ACE inhibitors can cause anemia. From the central nervous system Often: paresthesia, headache, dizziness, vertigo. Infrequently: sleep disturbance, mood lability. Very rare: confusion. Unspecified frequency: fainting. From the organ of vision Often: visual impairment. On the part of the hearing organ Often: tinnitus. From the cardiovascular system Infrequently: marked decrease in blood pressure, including orthostatic hypotension. Very rarely: heart rhythm disturbances, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in patients at high risk. Unspecified frequency: Pirouette type arrhythmias (possibly fatal). On the part of the respiratory system, chest organs and mediastinum Often: with the use of ACE inhibitors, a dry cough may occur, which persists for a long time while taking this group of drugs and disappears after they are canceled. Dyspnea. Infrequently: bronchospasm. Very rarely: eosinophilic pneumonia, rhinitis. From the digestive system Often: dry oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste, loss of appetite, dyspepsia, constipation, diarrhea. Very rare: pancreatitis, angioedema of the intestines, cholestatic jaundice. Unspecified frequency: hepatic encephalopathy in patients with liver failure. From the skin and subcutaneous fat Often: skin rash, itching, maculopapular rash. Infrequently: angioedema of the face, lips, mucous membrane of the tongue, vocal folds and / or larynx, urticaria, hypersensitivity reactions in patients predisposed to asthmatic and allergic reactions hemorrhagic vasculitis. In patients with an acute form of systemic lupus erythematosus, an exacerbation of the course of the disease is possible. Very rare: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. There have been cases of photosensitivity reaction (see section “Special instructions”). From the musculoskeletal system and connective tissue Often: muscle cramps. Urinary system Infrequently: renal failure. Very rare: acute renal failure. From the reproductive system Infrequently: impotence. General disorders and symptoms of Infrequently: increased sweating. Laboratory findings Rarely: hypercalcemia. Unspecified frequency: – Increased QT interval on the ECG. – An increase in the concentration of uric acid and glucose in the blood during administration of the drug. – Increased activity of hepatic transaminases. – A slight increase in the concentration of creatinine in the urine and in the blood plasma that occurs after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of hypertension with diuretics and in case of renal failure. – Hypokalemia, especially significant for patients at risk. – Hyperkalemia, more transient. – Hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension. Overdose Symptoms: marked decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in circulating blood volume), water-electrolyte balance disturbances (low sodium and potassium in plasma blood). Treatment: gastric lavage and / or administration of activated carbon, restoration of water-electrolyte balance in a hospital. With a marked decrease in blood pressure, it is necessary to transfer the patient to the “lying” position on the back with raised legs, then measures should be taken to increase the volume of circulating blood (introducing a 0.9% solution of sodium chloride intravenously). Perindoprilat, an active metabolite of perindopril, can be excreted by dialysis. Storage conditions In a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children. Expiration 3 years. Do not use after expiration date. Prescription conditions from pharmacies Prescription sachets Dosage form tablets
