Buy Perindopril-Indapamide pills 2.5 mg + 8 mg 30 pcs packaging

Indapamide, Perindopril

Brand Izvarino Pharma

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Available since: 2019-09-19

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Clinical Pharmacology

Pharmacological group: Antihypertensive drug.
Pharmacological action: Combined preparation containing perindopril (ACE inhibitor) and indapamide (diuretic from the sulfonamide group). The pharmacological action of the drug is due to a combination of the individual properties of each of the components, the combination of which enhances the action of each other. The drug has antihypertensive, diuretic, vasodilator, cardioprotective effect.
Perindopril PLUS Indapamide has a pronounced dose-dependent hypotensive effect on systolic and diastolic blood pressure in the prone position and standing, independent of the age and body position of the patient. The effect of the drug lasts 24 hours. Persistent clinical effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. Termination of treatment is not accompanied by the development of withdrawal syndrome.
Perindopril PLUS Indapamide reduces the degree of left ventricular hypertrophy, improves the elasticity of the arteries, reduces OPSS, does not affect the metabolism of lipids (total cholesterol, HDL, LDL, triglycerides) and does not affect the metabolism of carbohydrates (including in diabetic patients).
Perindopril belongs to the group of ACE inhibitors, has a hypotensive, vasodilator, cardioprotective, natriuretic effect. Inactivates ACE in plasma, vascular wall endothelium, possibly in the cells of the renal glomeruli and tubules, lung tissue, heart, adrenal glands and brain. Lowers the level of angiotensin II in the blood and tissues, reduces the production and release of aldosterone from the adrenal glands, inhibits the release of norepinephrine from the endings of sympathetic nerve fibers and the formation of endothelin in the vascular wall, increases the concentration of bradykinin, vasodilator prostaglandins. Increases the activity of the kallikrein-kinin system, stabilizes the level of atrial natriuretic peptide.
The reduction in the formation of angiotensin II is accompanied by an increase in the activity of plasma renin.
Reduces the OPSS, blood pressure (without developing tachycardia), filling pressure of the left ventricle. Arterial and venous vasodilation is accompanied by a weakening of the post- and preload on the myocardium, a decrease in the final diastolic pressure in the ventricles of the heart, a moderate decrease in heart rate, an increase in cardiac output. It improves regional (coronary, cerebral, renal, muscle) blood circulation, reduces the need for myocardial oxygen in IHD. By inhibiting tissue renin-angiotensin systems, it has a cardioprotective effect (reduces left ventricular hypertrophy) and an angioprotective effect (prevents hyperplasia and proliferation of vascular smooth muscle cells, induces the reverse development of vascular wall hypertrophy, restores the imbalance of the large vessels and the endothelium, and induces the respiratory chyroidism, and induces imbalance. nitric oxide, endothelial relaxing factor).
It inhibits the development of tolerance to nitrates and enhances their vasodilating action.
In patients with chronic heart failure, statistically reliably reduces the severity of clinical symptoms and increases exercise tolerance. Does not cause fluctuations in blood pressure after the first dose and during long-term therapy.
Pharmacological properties of indapamide are close to thiazide diuretics (violates the reabsorption of sodium ions in the cortical segment of the loop of Henle); It has a hypotensive, diuretic, vasodilating effect. Increases urinary excretion of sodium ions, chlorine and to a lesser extent potassium and magnesium ions. Possessing the ability to selectively block slow calcium channels, it increases the elasticity of the artery walls and lowers the round fist. Helps to reduce left ventricular hypertrophy. Reduces the sensitivity of the vascular wall to norepinephrine and angiotensin II, stimulates the synthesis of prostaglandin PgE2 and prostacyclin PgI2, reduces the production of free and stable oxygen radicals.
The hypotensive effect of indapamide is manifested in doses that do not practically cause a diuretic effect.
Pharmacokinetics: The pharmacokinetic parameters of perindopril and indapamide do not change when combined with their separate use.
1. Perindopril
When taken inside, perindopril is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65-95%, reduced by 35% with a simultaneous meal. Cmax is reached after 1 h and decreases to 33-44% by the end of the day.
In the process of metabolism, perindopril biotransformed with the formation of the active metabolite of perindoprilat (about 20%) and 5 inactive compounds. Cmax perindoprilata is reached in 3-4 hours.
Plasma protein binding is low, less than 30%, and depends on the concentration of the drug. Vd free perindoprilat - 0.2 l / kg.
Re-appointment of perindopril does not lead to its cumulation, and T1 / 2 perindoprilat after repeated administration corresponds to the period of its activity. Css at repeated use is reached in 4 days.
Perindoprilat is excreted by the kidneys. T1 / 2 of the free fraction of the metabolite is 3-5 hours. Slowly dissociates from the association with ACE, as a result, T1 / 2, corresponding to the activity of the preparation, is 25-30 hours.
Pharmacokinetics in special clinical situations:
In elderly patients, as well as in patients with renal and heart failure, the elimination of perindopril is slowed down (correction of the dosage regimen is necessary). The dialysis clearance of perindopril is 70 ml / min.
In patients with cirrhosis of the liver, hepatic clearance of perindopril is reduced by 2 times, while the total amount of perindoprilat formed does not change and correction of the dosage regimen is not required.
2. Indapamide
After oral administration, indapamide is rapidly and completely absorbed from the gastrointestinal tract; bioavailability is high. Meal somewhat slows down the rate of absorption, but does not affect the final amount of the absorbed drug. TCmax in blood plasma - 1-2 hours after ingestion. With repeated administration, fluctuations in the concentration of the drug in plasma in the interval between doses of 2 doses are reduced. Css is set after 7 days of regular use.
Plasma protein binding - 71-79%. Indapamide also binds to the elastin of the smooth muscles of the vascular wall. Has a high Vd. Penetrates histohematogenous barriers (including placental). Not cumulated.
Metabolized in the liver. T1 / 2 - 14-24 hours (on average 19 hours). By the kidneys, 60-70% is excreted as metabolites (about 5-7% is excreted unchanged), through the intestine - 20-23%.
Pharmacokinetics in special clinical situations:
In patients with renal insufficiency, the pharmacokinetics of indapamide does not change.

Indications

- arterial hypertension.

Indapamide, Perindopril is marketed under different brands and generic names, and comes in different dosage forms:

Brand name	Manufacturer	Country	Dosage form
Perindopril-Indapamide	Izvarino Pharma	Russia	pills
Perindopril-Indapamide	Teva	Israel	pills
Co-perineva	Krka dd Novo mesto AO	Slovenia	pills
Noliprel A Bi-forte	Servier	France	pills
Noliprel A forte	Servier	France	pills
Noliprel a	Servier	France	pills

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Dosage and Administration

Perindopril PLUS Indapamide is ingested 1 time / day. at the same time (preferably in the morning), before eating.
Adults, including elderly patients, the drug is prescribed for 1 tab. 1 time / day
The maintenance dose is selected individually, depending on the tolerance of the drug, the therapeutic effect and the patient's condition.
The pill is taken whole without chewing.

Adverse reactions

In recommended doses, the drug is usually well tolerated.
Determination of the frequency of side effects: often (1-10%), rarely (0.1-1%), very rarely (less than 0.1%).
Effects caused by the action of Perindopril Plus
From the side of water and electrolyte balance: hypokalemia is possible. Part of the drug perindopril, which has the ability to increase the concentration of potassium by inhibiting the RAAS, leads to a decrease in the loss of potassium caused by indapamide.
1. Effects caused by the action of perindopril:
Since the cardiovascular system: often - an excessive decrease in blood pressure and related symptoms; very rarely - arrhythmia, angina, myocardial infarction, stroke.
On the part of the urinary system: rarely - reduced kidney function; very rarely, acute renal failure. An insignificant increase in the creatinine content in urine and serum (reversible after discontinuation of the drug) is most likely in cases of renal artery stenosis, diuretic treatment of hypertension, renal failure, transient hyperkalemia, proteinuria (in patients with glomerular nephropathy).
On the part of the respiratory system: often - dry cough, difficulty breathing; rarely - bronchospasm; very rarely - rhinorrhea.
On the part of the digestive system: often - nausea, vomiting, abdominal pain, diarrhea, constipation, taste disturbance; rarely, dry mouth; very rarely - cholestatic jaundice, pancreatitis.
From the side of the central nervous system and peripheral nervous system: often - headache, asthenia, dizziness, tinnitus, blurred vision, muscle cramps, paresthesia, taste disorder; rarely - lower mood, sleep disturbance; very rarely - confusion.
From the hematopoietic system: rarely - thrombocytopenia, decrease in hemoglobin, hematocrit; very rarely - agranulocytosis, pancytopenia; against the background of a deficiency of glucose-6-phosphate dehydrogenase, hemolytic anemia may develop. While receiving ACE inhibitors in patients after kidney transplantation and hemodialysis, anemia may develop.
Allergic reactions: often - skin rash, itching; rarely - urticaria, angioedema; very rarely - erythema multiforme.
Other: rarely - increased sweating, impaired sexual function.
2. Effects due to the action of indapamide:
On the part of the central nervous system and peripheral nervous system: rarely - dizziness, headache, asthenia, paresthesias (usually disappear with a decrease in the dose of the drug).
On the part of the digestive system: rarely - nausea, constipation, dry mouth, in some cases - pancreatitis; in case of liver failure, hepatic encephalopathy may develop.
From the side of water and electrolyte balance: possible hypokalemia (especially in patients at risk), a decrease in sodium levels, accompanied by dehydration of the body and orthostatic hypotension. The simultaneous loss of chlorine ions can lead to a compensatory metabolic alkalosis (its frequency and severity are small). In some cases, increased calcium levels.
On the part of metabolism: it is possible to increase the content of urea and glucose in the blood plasma.
From the hematopoietic system: in some cases - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
Dermatological reactions: possible skin rash, hemorrhagic vasculitis, exacerbation of SLE.
Allergic reactions: in predisposed patients - skin manifestations.

Contraindications

- angioedema in history;
- hypokalemia;
- renal failure severe (CC <30 ml="" min="" br="">- severe liver failure (including with encephalopathy);
- simultaneous administration of drugs that prolong the QT interval;
- II and III trimesters of pregnancy;
- breast-feeding;
- children's and teenage age up to 18 years;
- Hypersensitivity to the components of the drug Perindopril PLUS Indapamide;
- hypersensitivity to other ACE inhibitors;
- hypersensitivity to sulfonamides.

Drug interactions

Perindopril PLUS Indapamide increases the severity of the hypoglycemic effect of insulin and sulfonylurea drugs (by increasing glucose tolerance and reducing the need for insulin).
Baclofen, tricyclic antidepressants, antipsychotic drugs (antipsychotics), beta-blockers (including with significant systemic absorption from ophthalmic dosage forms), saluretics, alcohol, and other antihypertensive drugs increase the hypotensive effect and increase the risk of orthostatic hypotension (addititis), and increase the risk of developing orthostatic hypotension (addititis), and other antihypertensive drugs increase the hypotensive effect and increase the risk of orthostatic hypotension (addititis), and increase the risk of orthostatic hypotension (addititis), and other antihypertensive drugs increase the hypotensive effect and increase the risk of orthostatic hypotension (addititis), and increase the risk of orthostatic hypotension. ). It is necessary to control blood pressure and adjust the dose of the drug.
When combined use of Perindopril Plus and muscle relaxants or agents used for anesthesia may increase the hypotensive effect. The risk of severe arterial hypotension can be reduced by stopping diuretic administration several days before starting treatment with Perindopril Plus.
When combined with sympathomimetics, GCS, NSAIDs, estrogens, it is possible to reduce the hypotensive effect of Perindopril Plus.
With simultaneous use with NSAIDs increases the risk of renal dysfunction.
Cyclosporine, potassium-sparing diuretics, potassium preparations increase the risk of hyperkalemia. The simultaneous use of drugs that can cause hyperkalemia and ACE inhibitors is not recommended, except in cases of severe hypokalemia.
With simultaneous use of Perindopril Plus with myelodepressants, interferon increases the risk of neutropenia and / or agranulocytosis with a fatal outcome.
With simultaneous use with lithium preparations, perindopril increases the concentration of lithium and its toxic effect.
Antacids and tetracyclines reduce the rate and completeness of absorption of the drug from the gastrointestinal tract.
Cyclosporine increases the risk of kidney dysfunction (hypercreatininemia).
With the simultaneous use of erythromycin (for iv administration), pentamidine, sulfopride, vincamine, halofantrine, bepridil and indapamide, as well as antiarrhythmic drugs of class I A and class III, pirouette-type arrhythmia may develop.
With simultaneous use of Perindopril Plus and NSAIDs in the case of dehydration, the development of acute renal failure is possible (due to a decrease in glomerular filtration). In such cases, before starting treatment, it is necessary to ensure sufficient hydration of the body and evaluate the functional activity of the kidneys.
Before using iodine-containing contrast agents, rehydration is necessary to reduce the risk of developing renal failure while taking diuretics.
With simultaneous use of calcium salts may increase the calcium content in the blood plasma as a result of reducing its excretion in the urine.

Pregnancy and Lactation

The use of perindopril is not recommended in the first trimester of pregnancy. The use of perindopril is contraindicated in the II and III trimesters of pregnancy.
Do not start therapy with ACE inhibitors during pregnancy. Epidemiological data on the risk of teratogenicity when taking ACE inhibitors in the first trimester of pregnancy do not allow a final conclusion, but there is a possibility of some increase in risk.With the exception of cases when it is not possible to replace an ACE inhibitor with an alternative therapy, patients planning pregnancy should be transferred to antihypertensive therapy with drugs whose safety profile for pregnant women is well studied. In the event of pregnancy, the use of ACE inhibitors should be immediately stopped and, if necessary, another antihypertensive therapy should be prescribed.
When using ACE inhibitors in the II and III trimesters of pregnancy, a manifestation of the fetotoxic action (renal dysfunction, oligohydramnios, delayed ossification of the cranial bones) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia) is established. In the case of taking an ACE inhibitor from the second trimester of pregnancy, ultrasound of the kidney function and cranial bones is recommended. In newborns whose mothers took ACE inhibitors, blood pressure should be carefully monitored to prevent possible development of arterial hypotension.
Since information on the use of Perindopril PLUS Indapamide during breastfeeding is not available, it is not recommended to prescribe the drug to nursing women. Consideration should be given to the prescription of antihypertensive therapy with drugs whose safety profile for nursing women has been well studied.

Special instructions

Perindopril PLUS Indapamide:
The treatment is carried out under the supervision of a physician.
Use of the drug Perindopril PLUS Indapamide may cause a sharp decrease in blood pressure, especially when you first take the drug and during the first 2 weeks of therapy. The risk of developing an excessive reduction in blood pressure is increased in patients with reduced BCC (as a result of following a strict salt-free diet, hemodialysis, vomiting and diarrhea), with severe heart failure (both with and without concomitant renal insufficiency), in case of bilateral stenosis of the renal arteries or stenosis of the artery of the single kidney, cirrhosis of the liver, accompanied by edema and ascites. A pronounced decrease in blood pressure at the first dose of the drug is not an obstacle to its further appointment. After the restoration of BCC and blood pressure treatment can be continued, with the use of a lower dose of the drug or monotherapy with one of its components.
During treatment, it is necessary to systematically monitor the concentration of electrolytes (potassium, sodium, magnesium), glucose, uric acid, plasma creatinine and pH. Elderly patients, debilitated patients taking several different medications, patients with cirrhosis of the liver, in the presence of edema or ascites, patients with coronary artery disease or heart failure, should take into account the risk of reducing the potassium concentration below the permissible level (less than 3.4 mmol / l). Reducing potassium levels increases the toxicity of cardiac glycosides and increases the risk of arrhythmias.
It should be borne in mind that the composition of the excipients of the drug Perindopril PLUS Indapamide includes lactose. As a consequence, this drug is not recommended for people with lactase deficiency, galactosemia or malabsorption of glucose-galactose.
It should stop taking the drug before the upcoming surgical treatment (for 12 hours).
During treatment, it is recommended to eliminate the use of alcohol.
1. Perindopril:
Before and during therapy, it is recommended to determine the concentration of creatinine, electrolytes and urea (for 1 month). In patients treated with diuretics, they should be canceled 3 days before the start of treatment with perindopril, and against the background of chronic heart failure - reduce the dose (to reduce the risk of orthostatic hypotension).During therapy, it is necessary to monitor blood pressure, monitor the pattern of peripheral blood (before starting treatment, in the first 3-6 months of treatment and later at periodic intervals for 1 year, especially in patients with an increased risk of neutropenia), protein levels, potassium plasma, urea nitrogen, creatinine, kidney function, body weight, diet.
In patients at risk, especially with decompensated chronic heart failure, elderly patients, as well as patients with initially low blood pressure, impaired renal function or receiving large doses of diuretics, the drug should be started under medical supervision.
It should be borne in mind that in patients with renal artery stenosis, as well as with hyponatremia, the first admission may be accompanied by severe arterial hypotension and the development of acute renal failure.
During treatment with perindopril, especially in the presence of renal and / or heart failure, hyperkalemia may develop.
In patients on hemodialysis, the use of polyacrylonitrile membranes should be avoided (anaphylactoid reactions may develop).
Caution should be given in case of renovascular hypertension, severe autoimmune diseases, aortic or mitral stenosis, constrictive pericarditis, hypertrophic cardiomyopathy with hemodynamic disorders, obstructive changes that impede the outflow of blood from the heart, bilateral renal artery symphysis, or the renal artery symphysis lesion, as a result of which the renal artery leaks and the renal artery systhesis, complicates the outflow of blood from the heart, bilateral renal artery stenosis, or the renal artery symphysis lesion, as a result of which the renal artery leaks out of theusterium syringe. , obliterating atherosclerosis of the arteries of the lower extremities, common atherosclerosis with lesions of the coronary and carotid ap terium, in case of moderate renal failure, hyperkalemia (from 5 to 5.5 mmol / l), hyponatremia or sodium restriction in the diet, dehydration, leukopenia, thrombocytopenia.
Care must be taken when carrying out any surgical interventions (including dental) during the treatment period.
2. Indapamide:
In patients taking cardiac glycosides, laxatives, on the background of hyper aldosteronism, as well as in elderly people, careful monitoring of the content of potassium and creatinine is shown.
The most careful control is shown in patients with cirrhosis of the liver (especially with edema or ascites - the risk of developing metabolic alkalosis, enhancing manifestations of hepatic encephalopathy), coronary artery disease, and chronic heart failure. Patients with an increased QT interval on an ECG are also at increased risk. The first determination of the concentration of potassium in the blood should be carried out within 1 week. treatment.
Hypercalcemia with indapamide may be due to previously undiagnosed hyperparathyroidism.
In patients with diabetes, it is extremely important to control blood glucose, especially in the presence of hypokalemia.
Significant dehydration can lead to the development of acute renal failure (reduced glomerular filtration).
Patients need to compensate for the loss of water and at the beginning of treatment carefully monitor kidney function.
Indapamide can give a positive result during the doping control.
Influence on ability to drive motor transport and control mechanisms:
Due to the danger of arterial hypotension and dizziness when taking the drug (especially at the beginning of the course of therapy), patients should be careful when driving and doing work that requires increased concentration and psychomotor speed.

Overdosage

Symptoms: pronounced decrease in blood pressure, nausea, vomiting, convulsions, dizziness, insomnia, low mood, polyuria or oliguria, which can go into anuria (as a result of hypovolemia), impaired water and electrolyte balance, bradycardia.
Treatment: dose reduction or complete drug withdrawal; gastric lavage, the adoption of measures aimed at increasing the BCC (the introduction of saline and other blood-substituting liquids). With the development of severe hypotension should give the patient a horizontal position, lifting the legs up. Symptomatic therapy - epinephrine (s / c or v / v), antihistamines, hydrocortisone (w / v), dialysis procedures (do not use highly permeable polyacrylonitrile membranes).
With the development of bradycardia, atropine is used, it may be necessary to install an artificial pacemaker.