Parnavel, 4 mg, capsules, combi-pack 1+1, 30 pcs.

Parnavel, 4 mg, capsules, 30 pcs.

The risk of developing hyperkalemia increases with simultaneous use of perindopril with other drugs that can cause hyperkalemia: aliskiren and aliskiren-containing drugs, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim.

When used concomitantly with aliskiren in patients with diabetes mellitus or impaired renal function (GFR <60 ml/min), the risk of hyperkalemia, deterioration of renal function and an increase in the incidence of cardiovascular morbidity and mortality increases (in patients of these groups this combination is contraindicated).

Concomitant use with aliskiren is not recommended in patients who do not have diabetes mellitus or impaired renal function, because there may be an increased risk of hyperkalemia, deterioration of renal function, and increased incidence of cardiovascular morbidity and mortality.

The literature has reported that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with end-organ damage, concomitant therapy with an ACE inhibitor and an angiotensin II receptor antagonist is associated with a higher incidence of hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared with the use of only one drug that affects the RAAS. Dual blockade (for example, when combining an ACE inhibitor with an angiotensin II receptor antagonist) should be limited to selected cases with careful monitoring of renal function, potassium and blood pressure.

Concomitant use with estramustine may lead to an increased risk of side effects such as angioedema.

With the simultaneous use of lithium and perindopril, a reversible increase in the concentration of lithium in the blood serum and associated toxic effects is possible (this combination is not recommended).

Simultaneous use with hypoglycemic drugs (insulin, hypoglycemic agents for oral administration) requires special caution, because ACE inhibitors, incl. perindopril, can enhance the hypoglycemic effect of these drugs up to the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function.

Baclofen enhances the antihypertensive effect of perindopril; with simultaneous use, dose adjustment of the latter may be required.

In patients receiving diuretics, especially those that remove fluid and/or salts, an excessive decrease in blood pressure may be observed at the beginning of perindopril therapy, the risk of which can be reduced by discontinuing the diuretic, replacing fluid or salt loss before starting perindopril therapy, as well as using perindopril at low doses. initial dose with further gradual increase.

In chronic heart failure, when using diuretics, perindopril should be used in a low dose, possibly after reducing the dose of a potassium-sparing diuretic used simultaneously. In all cases, renal function (creatinine concentration) should be monitored in the first weeks of using ACE inhibitors.

The use of eplerenone or spironolactone in doses from 12.5 mg to 50 mg/day and ACE inhibitors (including perindopril) in low doses: in the treatment of heart failure of functional class II-IV according to the NYHA classification with a left ventricular ejection fraction <40% and previously used ACE inhibitors and loop diuretics, there is a risk of developing hyperkalemia (possibly fatal), especially if the recommendations for this combination are not followed. Before using this combination, you must ensure that there is no hyperkalemia or impaired renal function. It is recommended to regularly monitor the concentration of creatinine and potassium in the blood - weekly in the first month of treatment and monthly thereafter.

The simultaneous use of perindopril with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) may lead to a decrease in the antihypertensive effect of ACE inhibitors. Concomitant use of ACE inhibitors and NSAIDs may lead to deterioration of renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced renal function. Use this combination with caution in elderly patients. Patients should receive adequate fluids; It is recommended to carefully monitor renal function, both at the beginning and during treatment.

The hypotensive effect of perindopril may be enhanced when used simultaneously with other antihypertensive drugs, vasodilators, including short- and long-acting nitrates.

Concomitant use of gliptins (linagliptin, saxagliptin, sitagliptin, vitagliptin) with ACE inhibitors (including perindopril) may increase the risk of angioedema due to inhibition of dipeptidyl peptidase IV activity by gliptin.

Concomitant use of perindopril with tricyclic antidepressants, antipsychotic drugs and general anesthesia may lead to increased antihypertensive effects.

Sympathomimetics may reduce the antihypertensive effect of perindopril.

When using ACE inhibitors, incl. perindopril, in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described in which facial skin flushing, nausea, vomiting, and arterial hypotension were observed.

Parnavel tablets 4 mg No. 30

Compound

1 tablet contains
the active substance: perindopril erbumine 4 mg.

Excipients: lactose (milk sugar) - 66.5 mg, microcrystalline cellulose - 19.0 mg, corn starch - 7.0 mg, povidone (polyvinylpyrrolidone) - 2.5 mg, magnesium stearate - 1.0 mg.

Pharmacokinetics

After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract and reaches maximum plasma concentrations within 1 hour.

Bioavailability is 65-70%.

During metabolism, 20% is transformed into the active metabolite perindoprilat. The half-life (T)/2) of perindopril from blood plasma is 1 hour. Maximum plasma concentrations of perindoprilate are achieved after 3-4 hours.

Taking the drug during meals is accompanied by a decrease in the conversion of perindopril to perindoprilat, and accordingly the bioavailability of the drug decreases. The volume of distribution of free perindoprilate is 0.2 l/kg. The association with plasma proteins is insignificant; the association of perindoprilate with ACE is less than 30%, but depends on its concentration. Perindoprilat is excreted by the kidneys. T1/2 of the free fraction is about 3-5 hours. The dissociation of perindoprilate bound to ACE is slow. As a result, the effective T1/2 is 25 hours. It does not accumulate. T1/2 of perindoprilat upon repeated administration corresponds to the period of its activity. In elderly patients, in patients with renal and chronic heart failure, the elimination of perindoprilate is slowed down. Perindoprilat is removed by hemodialysis (rate 70 ml/min, 1.17 ml/sec) and peritoneal dialysis.

In patients with liver cirrhosis, the hepatic clearance of perindopril changes, but the total amount of perindoprilate formed does not change and no dosage adjustment is required.

Indications for use

arterial hypertension,

chronic heart failure,

prevention of recurrent stroke (as part of complex therapy with indapamide) in patients with a history of cerebrovascular diseases (stroke or transient cerebral ischemic attack),

stable coronary heart disease (CHD): reduction

the risk of developing cardiovascular complications in patients who have previously suffered a myocardial infarction and/or hereditary lactose intolerance, lactase deficiency or impaired absorption of glucose and galactose.

Contraindications

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, water-electrolyte imbalance (hyperkalemia, hyponatremia), renal failure, hyperventilation, tachycardia, palpitations, dizziness, anxiety, cough. Treatment: emergency measures are limited to removing the drug from the body: gastric lavage and/or taking activated charcoal, followed by restoration of water and electrolyte balance.

If there is a pronounced decrease in blood pressure, place the patient in a horizontal position with raised legs and take measures to replenish the circulating blood volume (CBV). With the development of severe bradycardia that is not amenable to drug therapy (including atropine), placement of an artificial pacemaker is indicated. It is necessary to monitor vital signs and serum creatinine and electrolyte concentrations.

Perindoprilat, the active metabolite of perindopril, can be removed from the systemic circulation by hemodialysis. The use of high-flow polyacrylonitrile membranes should be avoided.

Directions for use and doses

Inside. It is recommended to take once a day, before meals, preferably in the morning, without chewing.

The dose of the drug is selected individually for each patient, depending on the severity of the disease and individual response to treatment.

Arterial hypertension

The drug Perindopril can be used in monotherapy and in combination with other antihypertensive drugs. The recommended starting dose is 4 mg once daily, in the morning.

For patients with pronounced activation of the renin-angiotensin-aldosterone system (for example, with renovascular hypertension, hypovolemia and/or hyponatremia, decompensated CHF or severe arterial hypertension), the recommended initial dose is 2 mg per day in one dose. If therapy is ineffective within a month, the dose can be increased to 8 mg 1 time / day and if the previous dose is well tolerated.

The addition of ACE inhibitors to patients taking diuretics may cause the development of arterial hypotension. In this regard, it is recommended to carry out therapy with caution, stop taking diuretics 2-3 before starting treatment with Perindopril, or start treatment with Perindopril with an initial dose of 2 mg per day, in one dose. Monitoring is necessary: ​​blood pressure, kidney function and potassium levels in the blood serum. In the future, the dose of the drug can be increased, depending on the dynamics of blood pressure. If necessary, diuretic therapy can be resumed.

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

Chronic heart failure

The recommended starting dose is 2 mg in the morning, under medical supervision. After 2 weeks, the dose can be increased to 4 mg per day in one dose, under blood pressure monitoring. Treatment of symptomatic CHF is usually combined with potassium-sparing diuretics, beta-blockers and/or digoxin.

In patients with CHF, with renal failure and with a tendency to water-electrolyte disturbances (hyponatremia), as well as in patients taking diuretics and/or vasodilators at the same time, treatment with the drug is started under strict medical supervision.

In patients at high risk of developing clinically significant arterial hypotension (for example, when taking high doses of diuretics), if possible, hypovolemia and electrolyte disturbances should be eliminated before starting Perindopril.

It is recommended to carefully monitor blood pressure, renal function and serum potassium levels before and during therapy.

Prevention of recurrent stroke in patients with a history of cerebrovascular diseases

Therapy with Perindopril should be started with 2 mg for the first 2 weeks before taking indapamide. Treatment should begin at any time (from 2 weeks to several years) after a stroke.

Stable coronary heart disease (CHD)

In patients with stable coronary artery disease, the recommended initial dose of Perindopril is 4 mg per day. After 2 weeks, the dose is increased to 8 mg per day, provided that the dose of 4 mg per day is well tolerated and renal function is monitored.

Treatment of elderly patients should begin with a dose of 2 mg, which after a week can be increased to 4 mg per day. In the future, if necessary, after another week you can increase the dose to 8 mg per day with mandatory preliminary monitoring of renal function. In elderly patients, the dose of the drug can be increased only if the previous, lower dose is well tolerated.

For renal failure: in patients with kidney disease, the dose of Perindopril is determined depending on the degree of renal dysfunction.

Monitoring the patient's condition usually includes regular determination of serum potassium and creatinine levels.

Recommended doses:

The dialysis clearance of perindoprilate is 70 ml/min.

The drug Perindopril must be taken after a dialysis session.

For liver diseases, no dose adjustment is required.

If you miss one or more doses, the next dose should be taken at the usual dose; a higher dose should not be taken.

Storage conditions

List B. Store in a dry place, protected from light, at a temperature not exceeding 25C. Keep out of the reach of children.

Best before date

3 years. Do not use after expiration date.

special instructions

Stable ischemic heart disease

If an episode of unstable angina (significant or not) develops during the first month of therapy with Perindopril, it is necessary to assess the benefit/risk ratio of therapy with this drug.

Arterial hypotension 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 circulating blood volume (CBV) during diuretic therapy, while following a strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or with severe renin-dependent arterial hypertension.

Severe arterial hypotension was observed in patients with severe CHF, both in the presence of concomitant renal failure and in its absence. The most common arterial hypotension can develop in patients with more severe CHF, taking loop diuretics in high doses, as well as against the background of hyponatremia or renal failure. Close medical monitoring is recommended for these patients during initiation of therapy and during dosage titration. The same applies to patients with coronary artery disease or cerebrovascular diseases, in whom 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 raised legs, and, if necessary, administer a 0.9% sodium chloride solution intravenously to increase the volume of 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 CHF and normal or low blood pressure, an additional decrease in blood pressure may occur during therapy with Perindopril. This effect is expected and is usually not a reason to discontinue the drug. If arterial hypotension is accompanied by clinical manifestations, it may be necessary to reduce the dose or discontinue the drug Perindopril. Impaired renal function In patients with renal failure (creatinine clearance less than 60 ml/min), the initial dose of Perindopril should be adjusted in accordance with the clinical clearance (see section Dosage and administration) and then depending on the therapeutic response. For such patients, regular monitoring of serum potassium and creatinine levels 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 Perindopril, diuretics should be discontinued and renal function should be regularly monitored.

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 Perindopril 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 transplant

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, tongue, vocal folds 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, vocal folds, or larynx can be fatal. If angioedema develops, it is necessary to immediately administer epinephrine (adrenaline) subcutaneously and ensure airway patency. ACE inhibitors are more likely to cause angioedema in black patients. Patients with a history of angioedema not associated with the use of ACE inhibitors may be at high risk of developing angioedema while taking an ACE inhibitor.

Anaphylactoid reactions during low-density lipoprotein apheresis (LDL apheresis)

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 fatal. 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 treated with ACE inhibitors. With normal renal function in the absence of other complications, neutropenia rarely develops. The drug Perindopril 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 Perindopril 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 and general anesthesia

In patients whose condition requires major surgery or general 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, potassium levels 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 (for example, 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.

Description

Tablets are white or almost white, flat-cylindrical in shape, scored on one side and chamfered on both sides.

Conditions for dispensing from pharmacies

On prescription

Dosage form

pills

Pharmacodynamics

Perindopril is an angiotensin-converting enzyme (ACE) inhibitor, or kininase II, an oxopeptidase. Converts angiotensin I into the vasoconstrictor angiotensin II and destroys the vasodilator bradykinin to an inactive hectapeptide. Suppression of ACE activity leads to a decrease in the level of angiotensin II and an increase in plasma renin activity (suppressing the negative feedback of renin release) and a decrease in aldosterone secretion.

Since ACE also destroys bradykinin, suppression of ACE also leads to an increase in the activity of the circulating and tissue kallikrein-kinin system, while the prostaglandin system is activated.

Perindopril has a therapeutic effect due to the active metabolite perindoprilat.

Perindopril reduces both systolic and diastolic blood pressure (BP) in the supine and standing positions. Perindopril reduces total peripheral vascular resistance (TPVR), which leads to a decrease in blood pressure. At the same time, peripheral blood flow accelerates. However, the heart rate (HR) does not increase. Renal blood flow usually increases, while the glomerular filtration rate does not change. The maximum antihypertensive effect is achieved 4-6 hours after a single oral dose of perindopril, the antihypertensive effect persists for 24 hours, and after 24 hours the drug still provides 87% to 100% of the maximum effect. The decrease in blood pressure develops quickly. Stabilization of the antihypertensive effect is observed after 1 month of therapy and persists for a long time. Discontinuation of therapy is not accompanied by the development of withdrawal syndrome. Perindopril reduces left ventricular myocardial hypertrophy. With long-term use, it reduces the severity of interstitial fibrosis and normalizes the myosin isoenzyme profile. Increases the concentration of high-density lipoproteins (HDL); in patients with hyperuricemia, reduces the concentration of uric acid. Perindopril improves the elasticity of large arteries and eliminates structural changes in small arteries.

Perindopril normalizes heart function, reducing pre- and afterload.

In patients with chronic heart failure (CHF) during therapy with perindopril, the following was noted:

- decrease in filling pressure in the left and right ventricles,

- decrease in OPSS,

- increase in cardiac output and cardiac index.

Taking an initial dose of perindopril 2 mg in patients with CHF functional class I-II according to the NYHA classification is not accompanied by a statistically significant decrease in blood pressure compared to placebo.

Side effects

The frequency of the adverse reactions listed below was determined according to the following (World Health Organization classification):

very often - at least 10%, often - at least 1%, but less than 10%, infrequently - at least 0.1%, but less than 1%, rarely - at least 0.01%, but less than 0.1%, very rarely - less than 0.01%, including individual messages.

From the central and peripheral nervous system:

often - headache, dizziness, paresthesia; infrequently - sleep or mood disturbances; very rarely - confusion.

From the side of the organ of vision: often - visual impairment.

On the part of the hearing organ: often - tinnitus.

From the cardiovascular system: often - a pronounced decrease in blood pressure, very rarely arrhythmias, angina pectoris, myocardial infarction or stroke, possibly secondary, due to severe arterial hypotension in high-risk patients, vasculitis (frequency unknown).

From the respiratory system: often - cough, shortness of breath, infrequently bronchospasm, very rarely eosinophilic pneumonia, rhinitis.

From the digestive tract: often - nausea, vomiting, abdominal pain, dysgeusia, dyspepsia, diarrhea, constipation, infrequently - dry oral mucosa, rarely - pancreatitis, very rarely - cytolytic or cholestatic hepatitis (see section Special instructions), angioedema of the intestine.

From the skin: often - skin rash, itching, infrequently - angioedema of the face, extremities, urticaria, very rarely - erythema multiforme.

From the musculoskeletal system: often - muscle cramps.

From the genitourinary system: impotence, very rarely - acute renal failure.

General disorders: often - asthenia, infrequently - increased sweating.

From the hematopoietic organs and lymphatic system: very rarely - with long-term use in high doses, a decrease in hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, agranulocytosis, pancytopenia is possible, very rarely - hemolytic anemia (in patients with congenital deficiency of glucose-6-phosphate dehydrogenase) .

Laboratory indicators: increased concentrations of urea in the blood serum and plasma creatinine, and hyperkalemia, reversible after discontinuation of the drug (especially in patients with renal failure, severe CHF and renovascular hypertension), rarely - increased activity of hepatic transaminases and bilirubin in the blood serum, hypoglycemia.

Use during pregnancy and breastfeeding

During pregnancy, the use of Perindopril is contraindicated. The drug should not be used in the first trimester of pregnancy, therefore, when planning pregnancy or diagnosing it, Perindopril should be discontinued as early as possible and other antihypertensive therapy should be administered. There have been no adequate controlled studies of the use of ACE inhibitors in pregnant women. The limited available data on the effects of the drug in the first trimester of pregnancy indicate that the use of ACE inhibitors does not lead to fetal malformations associated with fetotoxicity. The drug Perindopril is contraindicated in the II-III trimesters of pregnancy, as it can cause fetotoxic effects in the fetus (decreased renal function, oligohydramnios, delayed ossification of the fetal skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If, nevertheless, the drug was used in the II-III trimesters of pregnancy, then it is necessary to conduct an ultrasound examination of the kidneys and bones of the fetal skull.

The use of Perindopril during breastfeeding is not recommended due to the lack of data on the possibility of its excretion into breast milk. If it is necessary to use the drug during this period, you must stop breastfeeding.

Interaction

Diuretics

In patients taking diuretics, especially with excessive fluid and/or sodium excretion, severe arterial hypotension may develop when initiating therapy with ACE inhibitors. The risk of developing excessive arterial hypotension can be reduced by discontinuing the diuretic, intravenous administration of 0.9% sodium chloride solution, and by prescribing an ACE inhibitor in lower doses. Further increases in the dose of Perindopril should be carried out with caution.

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

Typically, during therapy with ACE inhibitors, serum potassium levels remain within normal limits, but some patients may develop hyperkalemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid in doses of 3 g/day and above. NSAID therapy may weaken the antihypertensive effect of ACE inhibitors. In addition, NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium levels, which may precipitate deterioration of renal function. This effect is usually reversible. In rare cases, acute renal failure may occur, especially in patients with pre-existing renal impairment, such as the elderly or those who are dehydrated.

Other antihypertensives and vasodilators

Concomitant use of Perindopril with other antihypertensive drugs may enhance the antihypertensive effect of perindopril. Concomitant use of nitroglycerin, other nitrates or vasodilators may lead to an additional hypotensive effect. Hypoglycemic agents The simultaneous use of ACE inhibitors and hypoglycemic agents (insulin or oral hypoglycemic agents) can enhance the hypoglycemic effect, even leading to the development of hypoglycemia. As a rule, this phenomenon occurs in the first weeks of combination therapy in patients with renal failure.

Acetylsalicylic acid, thrombolytic agents, beta-blockers and nitrates Perindopril can be combined with acetylsalicylic acid (as an antiplatelet agent), thrombolytic agents and beta-blockers and/or nitrates.

Tricyclic antidepressants/antipsychotics (neuroleptics)/general anesthetics (general anesthetics)

Combined use with ACE inhibitors may lead to increased antihypertensive effect.

Sympathomimetics Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. When prescribing such a combination, the effectiveness of ACE inhibitors should be regularly assessed.

Myelotoxic drugs - increased myelotoxic effect.

Overdose

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, water-electrolyte imbalance (hyperkalemia, hyponatremia), renal failure, hyperventilation, tachycardia, palpitations, dizziness, anxiety, cough. Treatment: emergency measures are limited to removing the drug from the body: gastric lavage and/or taking activated charcoal, followed by restoration of water and electrolyte balance.

If there is a pronounced decrease in blood pressure, place the patient in a horizontal position with raised legs and take measures to replenish the circulating blood volume (CBV). With the development of severe bradycardia that is not amenable to drug therapy (including atropine), placement of an artificial pacemaker is indicated. It is necessary to monitor vital signs and serum creatinine and electrolyte concentrations.

Perindoprilat, the active metabolite of perindopril, can be removed from the systemic circulation by hemodialysis. The use of high-flow polyacrylonitrile membranes should be avoided.

Impact on the ability to drive vehicles and operate machinery

It should be used with caution in patients driving vehicles and engaging in activities that require increased concentration and quick reaction, due to the risk of developing arterial hypotension and dizziness.