Perindopril Plus tabs 2.5mg + 8mg #30

Instruction for Perindopril Plus

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Perindopril Plus is a combined antihypertensive drug that includes an ACE (angiotensin-converting enzyme) inhibitor and a thiazide-like diuretic.

Release form and composition

Dosage form - film-coated tablets: round biconvex, almost white or white core; the color of the film coat of the tablets depends on the composition: dosage 0.625 mg + 2 mg - from green with a gray tint to gray-green; dosage 1.25 mg + 4 mg - from light yellow with a pink tint to deep yellow with a pinkish tint; dosage 2.5 mg + 8 mg - white or almost white (10 pcs. in blister packs made of PVC film / lacquered aluminum foil; in a cardboard box 1, 3, 6 or 9 packs and instructions for use Perindopril Plus ).
1 tablet contains:
    active ingredients: indapamide + perindopril erbumin - 0.625 mg + 2 mg; 1.25 mg + 4 mg or 2.5 mg + 8 mg;
    auxiliary components: pregelatinized corn starch, crospovidone, magnesium stearate, microcrystalline cellulose, colloidal silicon dioxide;
    film shell: tablets at a dose of 0.625 mg + 2 mg - green Opadry II (85F21738), including polyvinyl alcohol, titanium dioxide, macrogol-3350, quinoline yellow, indigo carmine aluminum varnish, talc; tablets at a dose of 1.25 mg + 4 mg - yellow Opadry II (85F38201), including polyvinyl alcohol, titanium dioxide, macrogol-3350, iron oxide red, iron oxide yellow, talc; tablets at a dose of 2.5 mg + 8 mg - white Opadry II (85F48105), including polyvinyl alcohol, macrogol-3350, titanium dioxide, talc.

Pharmacodynamics

Perindopril Plus is a combined antihypertensive drug, which, along with the antihypertensive drug, has diuretic and vasodilating efficacy. The therapeutic effect of the drug is due to the content of two active components: perindopril - an ACE inhibitor and indapamide - a thiazide-like diuretic.
The pronounced dose-dependent antihypertensive effect of the drug is not affected by factors such as body position or age of the patient, in addition, therapy is not accompanied by reflex tachycardia. There is no effect on lipid metabolism, including in patients with diabetes mellitus, therefore, during treatment, the indicators of total cholesterol, LDL (low density lipoproteins), VLDL (very low density lipoproteins), HDL (high density lipoproteins), triglycerides and carbohydrates are not disturbed. The drug helps to reduce the risk of hypokalemia, which is characteristic of diuretic monotherapy.
After taking the pill, the hypotensive effect lasts for 24 hours.
A steady decrease in blood pressure (blood pressure) is achieved after 30 days of regular use of Perindopril Plus and is not accompanied by an increase in heart rate (HR). After discontinuation of treatment, the development of withdrawal syndrome was not noted.

Perindopril

The mechanism of action of perindopril is associated with the elimination of the vasoconstrictor action of angiotensin II and a decrease in the secretion of aldosterone, which arise as a result of inhibition of ACE activity and a decrease in the formation of angiotensin II. Perindopril has a pronounced vasodilator property, promotes the regeneration of the elasticity of large arteries, does not cause sodium and fluid retention, and with long-term treatment - reflex tachycardia. The antihypertensive effect of perindopril develops in patients with low / normal blood plasma renin activity and is mediated by the influence of perindoprilat, which is its main active metabolite. Perindopril reduces cardiac preload and total peripheral vascular resistance (OPSR) against the background of varicose veins caused by changes in prostaglandin metabolism.
In heart failure, perindopril provides a decrease in the filling pressure of both the left and right ventricles, an increase in the cardiac index, cardiac output and regional blood flow in the muscles.
The use of perindopril is equally effective in mild, moderate or severe hypertension.
As a result of a single oral administration of the substance, the maximum hypotensive effect is observed after 4-6 hours and continues to persist for 24 hours.
The combination of perindopril with a thiazide-like diuretic causes an additive effect and enhances the hypotensive effect of the drug Perindopril Plus.

Indapamide

Being a sulfonamide derivative, a diuretic, indapamide inhibits sodium reabsorption in the cortical segment of the renal tubules, increases the excretion of sodium and chlorine by the kidneys. It causes an increase in diuresis, while the degree of its effect on an increase in the excretion of potassium and magnesium is insignificant.
The consequence of the ability to selectively block slow calcium channels is an increase in the elasticity of the arterial walls and a decrease in systemic vascular resistance. The antihypertensive effect of indapamide is achieved by taking doses that do not have a pronounced diuretic effect. With an increase in the dose, the risk of developing undesirable reactions of indapamide also increases, while the hypotensive effect does not increase.

Pharmacokinetics

Compared with the separate administration of perindopril and indapamide, with a combination of substances in one tablet form, their pharmacokinetic parameters do not change.

Perindopril

After oral administration, absorption of perindopril from the gastrointestinal tract (GIT) occurs rapidly. Bioavailability is 65–70%. TCmax - the time to reach the maximum concentration of a substance in the blood plasma reaches 1 hour. Its half-life (T1 / 2) is also 1 hour.
Since perindopril is a prodrug, up to 27% of its total amount adsorbed in the gastrointestinal tract is determined in the blood as an active metabolite - perindoprilat, in addition to which 5 more inactive metabolites are formed.
Perindoprilat reaches Cmax in blood plasma 3-4 hours after oral administration of the drug. Concomitant food intake reduces the bioavailability of perindopril due to a slowdown in its biotransformation to perindoprilat. Therefore, the drug is recommended to be taken in the morning, before breakfast. The equilibrium concentration (Css) of perindopril when taken once a day is reached within 4 days.
There is a linear dependence of the concentration of perindopril in the blood plasma from the dose taken. The apparent volume of distribution (Vd) for unbound perindoprilat is approximately 0.2 L / kg. The substance binds to blood plasma proteins at a level of about 20% (depending on the concentration), mainly with ACE.
Perindoprilat is excreted from the body mainly by the kidneys. The endpoint T1 / 2 is several hours, the stage of equilibrium plasma concentration in the blood is reached 4 days after the start of therapy.
In elderly patients, as in patients with cardiac and renal failure, the excretion of perindoprilat is slowed down.
Patients with impaired renal function require dose adjustment of perindopril, depending on the severity of renal failure, determined by CC (creatinine clearance). The dialysis clearance rate of perindoprilat is 70 ml / min.
In patients with cirrhosis of the liver, the hepatic clearance of perindopril is halved. Despite this, the amount of perindoprilat formed during the metabolism of perindopril does not decrease, therefore, such patients do not need to adjust the dose.

Indapamide

Indapamide is absorbed from the gastrointestinal tract quickly and completely. After 1 hour after taking the drug inside, the blood plasma reaches Cmax.
Plasma protein binding - 79%.
T1 / 2 varies from 14 to 24 hours, with an average of 18 hours.
Repeated administration of the drug does not cause the accumulation of indapamide in the body.
The substance is excreted in the form of inactive metabolites, mainly by the kidneys - 70%, up to 22% is excreted through the intestines.
In case of impaired renal function, the pharmacokinetics of indapamide does not change.

Indications for use

The use of Perindopril Plus is indicated for essential arterial hypertension in patients who need combination therapy.

Contraindications

Absolute:
    hereditary / idiopathic angioedema;
    bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, severe renal failure with CC less than 30 ml / min, including patients on hemodialysis;
    concomitant therapy with aliskiren or aliskiren-containing agents in patients with diabetes mellitus and patients with renal insufficiency with CC less than 60 ml / min;
    severe liver failure, including encephalopathy;
    hypo- or hyperkalemia;
    simultaneous treatment with potassium and lithium preparations, potassium-sparing diuretics, drugs that can cause ventricular tachycardia of the "pirouette" type or prolongation of the QT interval;
    untreated / chronic heart failure (NYHA classification - IV functional class) in the stage of decompensation;
    pregnancy;
    lactation period;
    children and adolescents under 18 years of age;
    lactase deficiency, lactose intolerance, galactosemia / glucose-galactose malabsorption syndrome (the tablets contain lactose);
    the presence of indications in the history of the development of angioedema (angioedema) caused by the intake of an ACE inhibitor;
    established hypersensitivity to perindopril and other ACE inhibitors, to indapamide and other sulfonamide derivatives; individual intolerance to other components of the drug.
With caution, Perindopril Plus should be prescribed for systemic lupus erythematosus, scleroderma and other diseases of the connective tissue of a systemic nature, for patients with a reduced volume of circulating blood (including vomiting, diarrhea, diuretics, adherence to a diet with limited salt), and cerebrovascular diseases , inhibition of bone marrow hematopoiesis, renovascular hypertension, lability of blood pressure (BP), ischemic heart disease (ischemic heart disease), hypertrophic obstructive cardiomyopathy, stenosis of the aortic / mitral valve, hyperuricemia (especially in patients with gout and urate nephrolithiasis of kidney transplantation), after in old age, patients of the Negroid race, with a history of Quincke's edema, which is not a consequence of taking ACE inhibitors.
It is necessary to use Perindopril Plus with caution while taking immunosuppressants, before the LDL apheresis procedure performed with dextran sulfate, as well as during hemodialysis using high-flow polyacrylonitrile membranes and during desensitizing therapy with allergens (including insect venom).

Perindopril Plus, instructions for use: method and dosage

Perindopril Plus tablets are taken orally with a sufficient amount of liquid, 1 time per day, preferably in the morning, before breakfast.
Recommended dosage (in the ratio of indapamide + perindopril): initial dose - 1 tablet 0.625 mg + 2 mg. If, after 30 days of therapy, adequate control of blood pressure is not observed, the dose is increased, starting with taking 1.25 mg + 4 mg tablets, 1 pc. 1 per day.
With moderate violations of liver function and renal failure with a CC of 60 ml / min and above, dose adjustment is not performed. In patients with CC 30-60 ml / min, the dose of perindopril and indapamide is selected during preliminary monotherapy with each of the drugs. The maximum daily dose of Perindopril Plus for this category of patients should not exceed 0.625 mg + 2 mg.
Prescribing the drug to patients in old age requires an assessment of renal function and the level of potassium in the patient's blood plasma. The initial dose of Perindopril Plus for elderly patients is 0.625 mg + 2 mg.
In case of suspected or diagnosed renal artery stenosis, it is required to start using the drug in a hospital under the control of renal function and potassium content in blood plasma with a dose of 0.625 mg + 2 mg. With the development of acute renal failure, taking Perindopril Plus is canceled until the renal function is fully restored.
In chronic heart failure (NYHA functional class III), drug treatment should be started under medical supervision.

Side effects

    on the part of the heart and blood vessels: infrequently - a marked decrease in blood pressure (including orthostatic hypotension), palpitations; very rarely - cardiac arrhythmias (including atrial fibrillation, bradycardia, ventricular tachycardia), angina pectoris, myocardial infarction (including due to a significant decrease in blood pressure in patients at risk); the frequency has not been established - an increase in the QT interval, arrhythmias of the "pirouette" type (including those with a fatal outcome);
    from the hematopoietic system: infrequently - hyponatremia, eosinophilia; very rarely - leukopenia or neutropenia, thrombocytopenia, agranulocytosis, hemolytic anemia, aplastic anemia; in patients after kidney transplantation or on hemodialysis - anemia may develop;
    on the part of the auditory analyzer: often - tinnitus;
    on the part of the visual system: often - visual impairment;
    from the central and peripheral nervous system: often - vertigo, headache, paresthesia, dizziness; infrequently - mood lability, sleep disturbance; very rarely - confusion of consciousness; frequency not established - syncope;
    from the digestive system: often - a violation of taste, dryness of the oral mucosa, nausea, loss of appetite, abdominal pain, vomiting, epigastric pain, constipation / diarrhea, dyspepsia; very rarely - angioedema of the intestine, pancreatitis, cholestatic jaundice; frequency not established - increased activity of hepatic transaminases, hepatitis, with hepatic failure - hepatic encephalopathy;
    from the respiratory system: often - shortness of breath, dry cough (disappears after discontinuation of the drug); infrequently - bronchospasm; very rarely - rhinitis, eosinophilic pneumonia;
    dermatological reactions: often - itchy skin, rash, maculopapular rash; infrequently - urticaria, angioedema (including the face, lips, mucous membrane of the tongue, vocal folds and / or larynx, extremities), hemorrhagic vasculitis, with a predisposition to broncho-obstructive and allergic reactions - hypersensitivity reactions, in the acute form of systemic lupus erythematosus, the course of the disease may worsen ; very rarely - Stevens-Johnson syndrome, erythema multiforme, photosensitivity reactions, toxic epidermal necrolysis;
    from the urinary system: infrequently - renal failure; very rarely - acute renal failure;
    from the reproductive organs: infrequently - erectile dysfunction;
    on the part of the musculoskeletal system: often - muscle spasms;
    laboratory data: rarely - hypercalcemia; frequency not established - hypokalemia, hyponatremia, hypovolemia, increased blood levels of glucose, uric acid, hyperkalemia, a slight increase in the concentration of creatinine in blood plasma and urine (more often with renal artery stenosis, renal failure);
    other reactions: often - asthenia; infrequently - increased sweating; rarely - syndrome of impaired secretion of antidiuretic hormone.

Overdose

Symptoms of an overdose of Perindopril Plus are nausea, vomiting, marked decrease in blood pressure, dizziness, drowsiness, confusion, muscle cramps, decreased circulating blood volume (BCC), oliguria, anuria. A decrease in the content of sodium and potassium in the blood plasma is possible.
For the purpose of treating the condition, it is recommended to immediately wash the stomach, take activated charcoal, with a significant decrease in blood pressure, the patient must be transferred to the supine position and his legs raised. To increase the BCC, intravenous administration of 0.9% sodium chloride solution is indicated. In a hospital setting - carrying out activities aimed at restoring the water and electrolyte balance.
With the help of dialysis, perindoprilat can be removed from the body.

Special instructions

When symptoms of acute renal failure appear during therapy with Perindopril Plus, the drug is discontinued. When resuming combination therapy, perindopril and indapamide should be used as monotherapy or low doses of the drug should be used. Specialists are obliged to accompany treatment in this category of patients with regular monitoring of potassium content and serum creatinine concentration (2 weeks after the start of therapy, then every 8 weeks).
The risk of developing acute renal failure is increased in patients with underlying renal impairment or severe chronic heart failure.
The likelihood of a sudden decrease in blood pressure increases with hyponatremia, therefore, it is recommended, after prolonged diarrhea or severe vomiting, to take into account the possible dehydration of the body and a decrease in the content of electrolytes in the blood plasma. With a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution is indicated.
In patients with transient arterial hypotension, after the restoration of blood pressure and BCC, therapy with low doses of Perindopril Plus can be resumed or perindopril and indapamide can be taken as separate drugs.
The use of a combined antihypertensive drug is carried out under regular monitoring of the potassium content in the blood plasma, especially in diabetes mellitus or renal failure.
When planning a major surgical intervention, it is important to warn the anesthesiologist about the use of Perindopril Plus. When using drugs with hypotensive effect as general anesthesia, it is recommended to stop taking the drug 24 hours before the start of general anesthesia. In cases of emergency use of general anesthetics, arterial hypotension, which develops as a result of blocking the formation of angiotensin II by perindopril during compensatory release of renin, is corrected by increasing the BCC.
Caution should be exercised in patients with connective tissue diseases who are on concomitant immunosuppressive therapy with allopurinol or procainamide, especially with impaired renal function. Patients should be informed about the possible development of a severe infection, the requirement for periodic monitoring of the number of leukocytes in the blood and immediate medical attention if the temperature rises or the appearance of a sore throat.
When symptoms of the development of angioedema of the face and / or lips appear, the administration of Perindopril Plus is immediately stopped and the patient's condition is carefully monitored until the signs of edema disappear completely. Angioedema of the tongue or larynx can obstruct the airways and be fatal. Therefore, to relieve the symptoms of angioedema, it is necessary to immediately inject epinephrine (adrenaline) subcutaneously and ensure airway patency.
In patients of the Negroid race, the antihypertensive effect of perindopril is less pronounced, they are at increased risk of developing angioedema.
In rare cases, the development of angioedema of the intestine is possible. Therefore, when a patient complains of abdominal pain (including in combination with nausea and vomiting) in patients taking ACE inhibitors, the possible presence of angioedema of the intestine is taken into account and, if necessary, appropriate research methods are used.
It is recommended to stop taking Perindopril Plus no later than 24 hours before the start of the desensitization procedure with hymenoptera venom.
To prevent the development of life-threatening anaphylactoid reactions, before each procedure of LDL apheresis using high-flow membranes, the drug is interrupted, and during hemodialysis, high-flow membranes of the AN69 type are not used.
It should be borne in mind that the use of an ACE inhibitor causes a blockade of the renin-angiotensin-aldosterone system (RAAS), which can cause a sharp decrease in blood pressure and / or an increase in serum creatinine, indicating the development of acute renal failure. Most often this occurs after taking the first dose of Perindopril Plus or during the first 2 weeks of therapy.
With a significant increase in the activity of hepatic transaminases or the appearance of jaundice, the pills are stopped.
Hyperkalemia can cause serious, sometimes fatal, heart rhythm disturbances. Risk factors for the development of hyperkalemia against the background of the use of an ACE inhibitor include old age, the presence of renal failure, diabetes mellitus, some concomitant conditions in the patient (including acute heart failure in the stage of decompensation, decreased BCC, metabolic acidosis), intake of potassium-sparing diuretics, potassium preparations, heparin and other agents that increase the level of potassium in the blood plasma.
During the treatment period, patients are required to avoid direct exposure to sunlight or artificial ultraviolet rays on exposed skin. If a photosensitivity reaction develops, taking Perindopril Plus is interrupted for a while or stopped.
Before prescribing the drug, especially for elderly patients, a study is carried out to determine the sodium content in the blood plasma. Due to the fact that hyponatremia can lead to serious complications, treatment should be accompanied by regular monitoring of plasma electrolytes.
Hypokalemia in malnourished patients, elderly patients, with cirrhosis of the liver, peripheral edema, ascites, chronic heart failure or ischemic heart disease increases the toxic effect of cardiac glycosides, contributes to the development of severe cardiac arrhythmias, including ventricular arrhythmias of the "pirouette" type. Therefore, during the first week of drug therapy, they determine the level of potassium in the blood plasma and then regularly monitor its plasma concentration.
With an increased content of uric acid in the blood plasma, taking a combined antihypertensive drug may increase the frequency of exacerbations of the course of gout.
At the beginning of the use of the drug in patients with hypovolemia caused by a decrease in BCC, or hyponatremia caused by taking diuretics, a decrease in the glomerular filtration rate is possible, accompanied by an increase in the level of creatinine and urea in the blood plasma.
During doping control, a false positive reaction is possible due to the presence of indapamide in the drug.
During the planning of the examination of the function of the parathyroid glands, the drug is interrupted before the start of the procedure.

Influence on the ability to drive vehicles and complex mechanisms

During the period of application of Perindopril Plus, care must be taken when driving vehicles and complex mechanisms, due to the risk of developing such undesirable phenomena as dizziness, fainting.

Application during pregnancy and lactation

The use of Perindopril Plus during gestation and breastfeeding is contraindicated.
Stop taking the drug and switch to another antihypertensive therapy when planning pregnancy or in case of conception during therapy.
It has been established that with prolonged exposure to ACE inhibitors on the fetus in the II and III trimesters of pregnancy, such disorders in its development as a decrease in renal function, oligohydramnios, and a slowdown in ossification of the skull bones can occur. In addition, in newborns, intrauterine complications can be manifested by renal failure, arterial hypotension, and hyperkalemia.
Long-term use of thiazide diuretics in the third trimester of gestation in the mother leads to hypovolemia, and in the fetus it causes placental ischemia and developmental delay as a result of a decrease in uteroplacental blood flow. In rare cases, shortly before delivery, newborns may develop hypoglycemia and thrombocytopenia.
Given the existing risks, if the mother received the drug in the II or III trimester of pregnancy, it is recommended to assess the condition of the skull bones and the function of the fetal kidneys by ultrasound. The condition of the newborn is carefully monitored for the occurrence of arterial hypotension.
Indapamide is excreted in breast milk, therefore, if it is necessary to use Perindopril Plus during lactation, breastfeeding should be discontinued.

Childhood use

Perindopril Plus is contraindicated in patients under the age of 18 years due to the lack of sufficient information on the safety and efficacy of the drug in pediatrics.

With impaired renal function

The use of Perindopril Plus is contraindicated in severe renal failure (CC less than 30 ml / min), including patients on hemodialysis, with bilateral renal artery stenosis or stenosis of an artery of a single kidney.
In renal failure with a CC of 60 ml / min and above, dose adjustment is not required. With a CC of 30-60 ml / min, the dose of Perindopril Plus is determined individually during preliminary monotherapy with perindopril and indapamide.

For violations of liver function

The use of Perindopril Plus is contraindicated in severe hepatic failure, including accompanied by hepatic encephalopathy.
With moderate impairment of liver function, dose adjustment is not required.

Use in the elderly

Care must be taken when prescribing Perindopril Plus to elderly patients.

Drug interactions

If it is necessary to take other medicines simultaneously with the drug, the attending physician makes an appointment taking into account their interaction with perindopril and indapamide.
Combinations not recommended for use:
    Perindopril Plus with lithium preparations: concomitant therapy with lithium preparations should be avoided, this is associated with a high risk of a reversible increase in the concentration of lithium in the blood serum and its toxic effect. If it is necessary to conduct joint therapy, treatment is accompanied by careful monitoring of the level of lithium concentration in the blood plasma;
    perindopril with potassium-sparing diuretics (amiloride, eplerenone, spironolactone, triamterene), potassium preparations, potassium-containing salt substitutes: while taking these drugs, an increase in the level of potassium concentration in the blood serum, up to death, is possible. With confirmed hypokalemia, combination therapy with potassium-sparing diuretics, potassium preparations or potassium-containing salt substitutes with an ACE inhibitor should be accompanied by regular monitoring of plasma potassium levels and electrocardiogram (ECG) parameters. Estramustine: when taken in combination with perindopril, the risk of developing angioedema significantly increases;
    indapamide with sultopride: due to the possible development of hypokalemia, there is a risk of ventricular arrhythmia, mainly of the "pirouette" type.
Combinations with perindopril and indapamide, which require special care and increased attention:
    baclofen: in connection with the potentiation of the antihypertensive effect with this combination, exercise caution, control blood pressure and renal function for timely dose adjustment;
    hypoglycemic agents for oral administration (sulfonylurea derivatives), insulin: in patients with diabetes mellitus, an increase in glucose tolerance is possible, which leads to an increase in the effect of hypoglycemic agents and it may be necessary to reduce the doses of hypoglycemic agents for oral administration and insulin;
    non-steroidal anti-inflammatory drugs (NSAIDs), including non-selective NSAIDs, selective inhibitors of cyclooxygenase-2, acetylsalicylic acid in high anti-inflammatory doses: concomitant therapy causes a decrease in the antihypertensive effect of the drug, an increased risk of functional renal impairment (including the development of acute renal failure) in patients with initial impairment renal function - an increase in serum potassium levels. Therefore, it is recommended to be careful, especially when using this combination in elderly patients. It is necessary to compensate for the volume of circulating blood (BCC) and control renal function.
Combinations with indapamide, which require special care and increased attention:
    class IA antiarrhythmic drugs - quinidine, disopyramide; class III antiarrhythmic drugs - sotalol, hydroquinidine, dofetilide, ibutilide, amiodarone, bretylium tosylate; antipsychotics - pimozide, levomepromazine, thioridazine, chlorpromazine, cyamemazine, trifluoperazine; benzamides - amisulpride, tiapride, sulpiride, sultopride; derivatives of butyrophenone - haloperidol, droperidol; other drugs - erythromycin (intravenous), bepridil, cisapride, halofantrine, diphemanil methyl sulfate, mizolastine, moxifloxacin, vincamine (intravenous), pentamidine, sparfloxacin, methadone, terfenadine, astemizole: provoke the development of their combination of ventricular arrhythmias, the risk of hypokalemia, therefore, treatment must be accompanied by monitoring the level of potassium in the blood;
    amphotericin B (c), gluco- and mineralocorticoids for systemic use, tetracosactide, laxatives that stimulate gastrointestinal motility: these substances / drugs help to reduce the potassium content, causing an increased risk of hypokalemia;
    cardiac glycosides: aggravation of hypokalemia while taking indapamide can increase the toxic effect of cardiac glycosides, therefore, their dose must be adjusted in accordance with the parameters of potassium in the blood plasma and ECG;
    iodine-containing contrast media: high doses of iodine-containing contrast media can increase the risk of acute renal failure, therefore, it is necessary to compensate for the BCC before using them;
    metformin: promotes the development of renal failure, lactic acidosis; if the concentration of serum creatinine in men exceeds 15 mg / l, and in women 12 mg / l, metformin should not be used in combination with indapamide;
    calcium supplements: taking calcium supplements increases the risk of developing hypercalcemia;
    tricyclic (imipramino-like) antidepressants, antipsychotics (antipsychotic drugs): taking these drugs causes an additive effect, the antihypertensive effect increases, the risk of orthostatic hypotension increases significantly;
    tetracosactide, glucocorticosteroids (GCS): combination therapy causes fluid retention and a decrease in the antihypertensive effect;
    cyclosporine: taking cyclosporine increases the likelihood of developing hypercreatininemia;
    antihypertensive drugs: taking other antihypertensive drugs can enhance the antihypertensive effect of the drug.
Combinations with perindopril, which require special care and increased attention:
    angiotensin receptor antagonists (ARA) II: taking AT1 receptor blockers in patients with heart failure, atherosclerotic disease or diabetes mellitus with target organ damage causes a double blockade of the RAAS, which often leads to the development of arterial hypotension, hyperkalemia, and deterioration of renal function (including acute kidney failure), may cause fainting; with double blockade (for example, a combination of an ACE inhibitor with ARAII), close monitoring of renal function, blood pressure and potassium content is carried out; combined therapy should be limited to individual cases;
    sympathomimetics: it is possible to increase the hypotensive effect of the drug when combined with perindopril;
    allopurinol, cytostatics, procainamide, immunosuppressants, systemic corticosteroids: these drugs can increase the risk of developing leukopenia;
    diuretics: high doses of diuretics cause a decrease in BCC, which can lead to hypovolemia; additional intake of perindopril contributes to a pronounced decrease in blood pressure;
    gold preparations: intravenous administration of sodium aurothiomalate can cause nitrate-like reactions such as flushing of the skin of the face, nausea / vomiting, a marked drop in blood pressure;
    potassium-sparing diuretics, gliptins (sitagliptin, vildagliptin, linagliptin, saxagliptin): these agents inhibit the activity of dipeptidyl peptidase IV, causing an increased risk of angioedema;
    anesthetics that cause hypotension: in case of need for extensive surgery or general anesthesia, ACE inhibitors, including perindopril, with compensatory release of renin, can block the formation of angiotensin II.

Terms and conditions of storage

Keep out of the reach of children.
Store at temperatures up to 25 ° C in a dark place.
Shelf life is 2 years.

Reviews about Perindopril Plus

Many patients in reviews of Perindopril Plus indicate the effectiveness of the drug, good tolerance and long-term antihypertensive effect. But along with this, there are responses in which patients report the lack of a sufficient clinical effect or a short-term effect of the drug.

Terms of sell

You can buy Perindopril Plus without a prescription.