Perindopril PLUS Indapamide pills 1.25mg + 4mg 30pcs

Pharmacological action

Pharmaceutical group:

Antihypertensive drug.

Pharmaceutical action:

A combination drug containing perindopril (an ACE inhibitor) and indapamide (a sulfonamide diuretic). The pharmacological effect of the drug is due to the combination of individual properties of each of the components, the combination of which enhances the effect of each other. The drug has antihypertensive, diuretic, vasodilator, cardioprotective effects.

Perindopril PLUS Indapamide has a pronounced dose-dependent hypotensive effect on systolic and diastolic blood pressure in the supine and standing positions, regardless of the patient’s age and body position. The action of the drug lasts 24 hours. A persistent clinical effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. Discontinuation 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 patients with diabetes mellitus).

Perindopril belongs to the group of ACE inhibitors, has a hypotensive, vasodilating, 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, suppresses 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.

A decrease in angiotensin II production is accompanied by an increase in plasma renin activity. Reduces OPSS, blood pressure (without tachycardia), left ventricular filling pressure. Arterial and venous vasodilation is accompanied by a weakening of 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, and an increase in cardiac output. Improves regional (coronary, cerebral, renal, muscular) blood circulation, reduces the need for myocardial oxygen in CHD.

Inhibiting tissue renin-angiotensin systems, it has a cardioprotective effect (reduces left ventricular hypertrophy) and angioprotective effect (prevents hyperplasia and proliferation of vascular smooth muscle cells, induces the reverse development of vascular wall hypertrophy, restores the elasticity of large vessels and endothelial functions, including the ability to release nitric oxide, endothelial relaxing factor).

Inhibits the development of tolerance to nitrates and enhances their vasodilating effect. In patients with chronic heart failure, it significantly reduces the severity of clinical symptoms and increases exercise tolerance. It does not cause blood pressure fluctuations after the first dose and during long-term therapy.

Indapamide has pharmacological properties similar to thiazide diuretics (it violates the reabsorption of sodium ions in the cortical segment of the Henle loop); it has a hypotensive, diuretic, vasodilating effect. Increases urinary excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions. Having the ability to selectively block slow calcium channels, it increases the elasticity of arterial walls and reduces OPSS. Helps to reduce hypertrophy of the left ventricle of the heart. 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 practically do not cause a diuretic effect.

Pharmacokinetics:  

The pharmacokinetic parameters of perindopril and indapamide in combination do not change in comparison with their separate use.

1. Perindopril When taken orally, perindopril is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65-95%, decreases by 35% with simultaneous food intake. Cmax is reached after 1 h and decreases by the end of the day to 33-44%. During metabolism, perindopril is biotransformed to form the active metabolite of perindoprilate (about 20%) and 5 inactive compounds. Cmax of perindoprilat is reached in 3-4 hours.

Binding to plasma proteins is insignificant, is less than 30% and depends on the concentration of the drug. Vd of free perindoprilat is 0.2 l / kg.

Repeated use of perindopril does not lead to its accumulation and T 1/2 of perindoprilat at repeated use corresponds to the period of its activity. Css when applied again is reached after 4 days.

Perindoprilat is excreted by the kidneys. T 1/2 of the free fraction of the metabolite is 3-5 hours. Slowly dissociates from the connection with ACE, as a result of which T 1/2, corresponding to the activity of the drug, is 25-30 h

. Pharmacokinetics in special clinical cases:

In elderly patients, as well as in patients with renal and heart failure, the elimination of perindopril slows down (dosage adjustment is necessary). The dialysis clearance of perindopril is 70 ml/min. In patients with cirrhosis of the liver, the hepatic clearance of perindopril decreases by 2 times, while the total amount of perindoprilate formed does not change and no dosage adjustment is required.

2. Indapamide

After oral use, indapamide is rapidly and completely absorbed from the gastrointestinal tract; bioavailability is high. Food intake slightly slows down the rate of absorption, but does not affect the total amount of absorbed drug. TSmax in blood plasma-1-2 hours after oral use. With repeated doses, fluctuations in the concentration of the drug in plasma in the interval between 2 doses are reduced. Css is set after 7 days of regular admission.

Binding to plasma proteins is 71-79%. Indapamide also binds to vascular wall smooth muscle elastin. It has a high Vd. Penetrates through histohematic barriers (including placental). It doesn’t accumulate.

It is metabolized in the liver. T1 / 2 – 14-24 hours (average 19 hours).60-70% is excreted by the kidneys in the form of metabolites (about 5-7% is excreted unchanged), and 20-23% is excreted through the intestine.

Pharmacokinetics in special clinical cases: In patients with renal insufficiency, the pharmacokinetics of indapamide do not change.

Indications

-arterial hypertension.

Contraindications

-a history of angioedema— – hypokalemia; – severe renal failure (CC;- severe hepatic insufficiency (including encephalopathy);- simultaneous use of drugs that prolong the QT interval— – II and III trimesters of pregnancy;- breastfeeding; – children and adolescents under 18 years of age;- hypersensitivity to the components of the drug Perindopril PLUS Indapamide;- hypersensitivity to other ACE inhibitors;- hypersensitivity to sulfonamides.

Side effects

At the recommended doses, the drug is usually well tolerated. Determination of the frequency of side effects: common (1-10%), rare (0.1-1%), very rare (less than 0.1%). Effects due to the action of Perindopril PLUS from the water-electrolyte balance: hypokalemia is possible. Perindopril, which is part of the drug and has the ability to increase the potassium concentration by inhibiting RAAS, reduces the potassium loss caused by indapamide. 1. Effects due to the action of perindopril: From the cardiovascular system: often-excessive decrease in blood pressure and associated symptoms; very rarely-arrhythmia, angina pectoris, myocardial infarction, stroke. From the urinary system: rarely-decreased renal function; very rarely-acute renal failure. There may be a slight increase in creatinine in the urine and serum (reversible after discontinuation of the drug) – most likely with renal artery stenosis, treatment of arterial hypertension with diuretics, with renal failure, temporary hyperkalemia, proteinuria (in patients with glomerular nephropathy). From the respiratory system: often-dry cough, difficulty breathing; rarely-bronchospasm; very rarely-rhinorrhea. From the digestive system: often – nausea, vomiting, abdominal pain, diarrhea, constipation, taste disorders; rarely-dry mouth; very rarely-cholestatic jaundice, pancreatitis. From the central nervous system and peripheral nervous system: often-headache, asthenia, dizziness, ringing in the ears, visual disturbances, muscle cramps, paresthesia, taste disorders; rarely-decreased mood, sleep disorders; very rarely-confusion. From the hematopoietic system: rarely-thrombocytopenia, decreased hemoglobin, hematocrit; very rarely-agranulocytosis, pancytopenia; against the background of glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia may develop. Against the background of taking ACE inhibitors in patients after kidney transplantation, hemodialysis, anemia may develop. Allergic reactions: often-skin rash, pruritus; rarely-urticaria, angioedema; very rarely-erythema multiforme. Other: rarely-increased sweating, impaired sexual function. 2. Effects due to the action of indapamide: From the central nervous system and peripheral nervous system: rarely-dizziness, headache, asthenia, paresthesia (usually disappear with a decrease in the dose of the drug). From the digestive system: rarely-nausea, constipation, dry mouth, in some cases – pancreatitis; with liver failure, hepatic encephalopathy may develop.From the side of the water-electrolyte balance: hypokalemia is possible (especially in patients at risk), a decrease in sodium levels, accompanied by dehydration of the body and orthostatic hypotension. Simultaneous loss of chlorine ions can lead to compensatory metabolic alkalosis (its frequency and severity are low). In some cases – an increase in the level of calcium. From the side of metabolism: an increase in the content of urea and glucose in blood plasma is possible. From the hematopoietic system: in some cases – thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia. Dermatological reactions: possible skin rashes, hemorrhagic vasculitis, exacerbation of SLE. Allergic reactions: in predisposed patients – skin manifestations.

Interaction

Perindopril PLUS Indapamide increases the severity of the hypoglycemic effect of insulin and sulfonylureas (by increasing glucose tolerance and reducing the need for insulin).

Baclofen, tricyclic antidepressants, antipsychotic drugs (neuroleptics), beta-blockers (including those with significant systemic absorption from ophthalmic dosage forms), saluretics, alcohol, and other antihypertensive agents enhance the hypotensive effect and increase the risk of orthostatic hypotension (additive effect). It is necessary to monitor blood pressure and adjust the dose of the drug.

With the combined use of Perindopril Plus and muscle relaxants or drugs used for anesthesia, it is possible to increase the hypotensive effect. The risk of developing severe hypotension can be reduced by stopping diuretics a few days before starting treatment with Perindopril plus.

When combined with sympathomimetics, corticosteroids, NSAIDs, estrogens, it is possible to reduce the hypotensive effect of Perindopril Plus. Concomitant use with NSAIDs increases the risk of impaired renal function.

Cyclosporine, potassium-sparing diuretics, and potassium supplements increase the risk of hyperkalemia. Concomitant use of drugs that can cause hyperkalemia and ACE inhibitors is not recommended, except in cases of severe hypokalemia. Concomitant use of Perindopril Plus with myelodepressants, interferon increases the risk of neutropenia and / or agranulocytosis with a fatal outcome.

When used concomitantly 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 developing impaired renal function (hypercreatininemia). With the simultaneous use of erythromycin (for intravenous use), pentamidine, sulfopride, vincamine, halofantrine, bepridil and indapamide, as well as antiarrhythmic drugs of class I and III, it is possible to develop arrhythmia of the “pirouette” type.

With the simultaneous use of Perindopril Plus and NSAIDs in case of dehydration, acute renal failure may develop (due to a decrease in glomerular filtration). In such cases, sufficient hydration of the body should be ensured before starting treatment and the functional activity of the kidneys should be evaluated.

Before using iodine-containing contrast agents, rehydration should be performed to reduce the risk of developing renal failure while taking diuretics.

When used concomitantly with calcium salts, it is possible to increase the content of calcium in the blood plasma as a result of a decrease in its excretion in the urine.

How to take, course of use and dosage

Perindopril PLUS Indapamide is taken orally 1 time/day. at the same time (preferably in the morning), before meals. Adults, including elderly patients, the drug is prescribed for 1 tab. 1 time/day.

The maintenance dose is selected individually, depending on the tolerability of the drug, the therapeutic effect and the patient’s condition. Tablets are taken whole, without chewing.

Overdose

Symptoms: a marked decrease in blood pressure, nausea, vomiting, convulsions, dizziness, insomnia, decreased mood, polyuria or oliguria, which can turn into anuria (as a result of hypovolemia), impaired water and electrolyte balance, bradycardia.

Treatment: reduction of the dose or complete withdrawal of the drug; gastric lavage, taking measures aimed at increasing the BCC (use of saline solution and other blood-substituting fluids). With the development of severe arterial hypotension, the patient should be given a horizontal position, lifting his legs up. Symptomatic therapy – epinephrine (subcutaneous or intravenous), antihistamines, hydrocortisone (intravenous), dialysis procedures (do not use highly permeable polyacrylonitrile membranes). With the development of bradycardia, atropine is used, and an artificial pacemaker may need to be installed.

Special instructions

Perindopril PLUS Indapamide:Treatment is carried out under the supervision of a doctor.

The use of Perindopril PLUS Indapamide can cause a sharp decrease in blood pressure, especially at the first dose of the drug and during the first 2 weeks of therapy. The risk of excessive blood pressure reduction is increased in patients with reduced BCC (due to a strict salt-free diet, hemodialysis, vomiting and diarrhea), with severe heart failure (both in the presence of concomitant renal failure and in the absence of it), with initially low blood pressure, with bilateral renal artery stenosis or stenosis of the artery of a single kidney, cirrhosis of the liver accompanied by edema and ascites. A marked decrease in blood pressure at the first dose of the drug is not an obstacle to its further use. After recovery of BCC and blood pressure, treatment can be continued, using 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. In elderly patients, debilitated patients taking several different medications, patients with cirrhosis of the liver, in the presence of edema or ascites, patients with CHD or heart failure, the risk of a decrease in potassium concentration below the permissible level (less than 3.4 mmol/l) should be taken into account. Lowering potassium levels increases the toxicity of cardiac glycosides and increases the risk of arrhythmias.

It should be borne in mind that the excipients of the drug Perindopril PLUS Indapamide include lactose. As a result, this drug is not recommended for people with lactase deficiency, galactosemia, or glucose-galactose malabsorption syndrome.

You should stop taking the drug before the upcoming surgical treatment (12 hours in advance).

During treatment, it is recommended to exclude alcohol consumption. 1. Perindopril:Before starting and during therapy, it is recommended to determine the concentration of creatinine, electrolytes and urea (within 1 month). In patients receiving diuretics, they should be discontinued 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, constantly monitor the peripheral blood picture (before starting treatment, during the first 3-6 months of treatment, and then at periodic intervals for 1 year, especially in patients with an increased risk of neutropenia), protein levels, plasma potassium, urea nitrogen, creatinine, kidney function, body weight, and diet.

In patients at risk, especially those with decompensated chronic heart failure, elderly patients, as well as patients with initially low blood pressure, impaired renal function, or receiving high doses of diuretics, the drug should be initiated under medical supervision.

It should be borne in mind that in patients with renal artery stenosis, as well as with hyponatremia, the first dose may be accompanied by severe hypotension and the development of acute renal failure.

Hyperkalemia may occur during treatment with perindopril, especially in the presence of renal and / or heart failure.

In patients undergoing hemodialysis, the use of polyacrylonitrile membranes should be avoided (anaphylactoid reactions may occur).

Use with caution in patients with renovascular hypertension, severe autoimmune diseases, aortic or mitral stenosis, constrictive pericarditis, hypertrophic cardiomyopathy with hemodynamic disorders, obstructive changes that hinder the outflow of blood from the heart, bilateral renal artery stenosis or stenosis of the renal artery of a single kidney, the presence of a transplanted kidney, obliterating atherosclerosis of the lower extremities, advanced atherosclerosis with damage to the coronary and carotid arteries, with moderate renal failure, hyperkalemia (from 5 to 5.5 mmol/l), hyponatremia or sodium restriction in the diet, dehydration, leukopenia, thrombocytopenia.

Care should be taken when performing any surgical procedures (including dental ones) during the treatment period. 2. Indapamide:In patients taking cardiac glycosides, laxatives, on the background of hyperaldosteronism, as well as in the elderly, careful monitoring of potassium and creatinine levels is indicated.

The most careful monitoring is indicated in patients with cirrhosis of the liver (especially with edema or ascites – the risk of developing metabolic alkalosis, which increases the manifestations of hepatic encephalopathy), coronary heart disease, and chronic heart failure. An increased risk group also includes patients with an extended QT interval on the ECG. The first determination of the potassium concentration in the blood should be carried out within 1 week. treatment options.

Hypercalcemia with indapamide may be a consequence of previously undiagnosed hyperparathyroidism. In patients with diabetes, it is extremely important to monitor the blood glucose level, especially in the presence of hypokalemia. Significant dehydration can lead to acute renal failure (decreased glomerular filtration rate). Patients should be compensated for water loss and renal function should be carefully monitored at the beginning of treatment. Indapamide can give a positive result during doping control.

Influence on the ability to drive motor vehicles and manage mechanisms:

Due to the risk of developing arterial hypotension and dizziness when taking the drug (especially at the beginning of the course of therapy), patients should exercise caution when driving vehicles and performing work that requires increased concentration of attention and speed of psychomotor reactions.

Active ingredient

Indapamide, Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart failure, Hypertension, Angina, Prevention of heart attacks and strokes