PERINDOPRIL PLUS INDAPAMIDE PILLS 0.625MG + 2MG

Active substance

Indapamide, Perindopril

Composition

Tablets, film coated from gray-green to green with a grayish shade of color, round, biconvex; on the cross-section, the core is white or almost white.
1 tab.

indapamide 0.625 mg

perindopril erbumin 2 mg

Excipients: microcrystalline cellulose - 70.375 mg, pregelatinized corn starch - 15 mg, crospovidone - 10 mg, Magnesium stearate - 1 mg, colloidal silicon dioxide - 1 mg.

The composition of the film shell: opadry II green (85F21738), including polyvinyl alcohol - 40%, titanium dioxide - 24.345%, macrogol-3350 - 20.2%, talc - 14.8%, indigo carmine aluminum lacquer - 0.54%, quinoline yellow - 0.115%.

Mechanism of action

Combined antihypertensive drug containing an angiotensin-converting enzyme (ACE) inhibitor - perindopril and thiazide-like diuretic - indapamide. The drug has antihypertensive, diuretic and vasodilating action.

Perindopril PLUS Indapamide has a pronounced dose-dependent antihypertensive effect that does not depend on the age and position of the patient’s body and is not accompanied by reflex tachycardia. Does not affect lipid metabolism (total cholesterol, low density lipoproteins (LDL), very low density lipoproteins (VLDL), high density lipoproteins (HDL), triglycerides (TG) and carbohydrates), includingin patients with diabetes. Reduces the risk of hypokalemia caused by diuretic monotherapy.

The antihypertensive effect persists for 24 hours.

A stable reduction in blood pressure (BP) is achieved within 1 month against the background of the use of the drug Perindopril PLUS Indapamide without an increase in heart rate (HR). Termination of treatment does not lead to the development of "withdrawal" syndrome.

Perindopril is an ACE inhibitor, the mechanism of action of which is associated with the inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictor effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to sodium retention and fluid, does not cause reflex tachycardia with prolonged treatment. The hypotensive effect of perindopril develops in patients with low or normal plasma renin activity. Perindopril acts through its main active metabolite, perindoprilat. His other metabolites are inactive.

The action of perindopril leads to the expansion of the veins (decrease in the preload on the heart), due to a change in the metabolism of prostaglandins; decrease in total peripheral vascular resistance (OPS) (decrease in heart load).

In patients with heart failure, perindopril helps reduce the filling pressure of the left and right ventricles; increase in cardiac output and cardiac index; increased regional blood flow in the muscles.

Perindopril is effective for hypertension of any severity: mild, moderate, and severe.

The maximum hypotensive effect develops 4-6 hours after a single ingestion and persists for a day.

Termination of therapy does not lead to the development of "withdrawal" syndrome.

It has vasodilating properties and restores the elasticity of large arteries. Adding a thiazide-like diuretic enhances the hypotensive (additive) effect of perindopril.

Indapamide refers to a sulfonamide derivative, is a diuretic. Inhibits sodium reabsorption in the cortical segment of the renal tubules, increasing the excretion of sodium and chlorine by the kidneys, thus leading to increased diuresis. To a lesser extent increases the excretion of potassium and magnesium. Possessing the ability to selectively block slow Calcium channels, indapamide increases the elasticity of the artery walls and reduces the CRIA. It has an antihypertensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not entail an increase in the hypotensive effect, but increases the risk of developing adverse events. Indapamide in patients with arterial hypertension has no effect on lipid metabolism - TG, LDL and HDL; on the metabolism of carbohydrates, even in patients with diabetes mellitus and arterial hypertension.

Pharmacokinetics:

Combined use of perindopril and indapamide does not change their pharmacokinetic parameters,compared to taking these drugs separately.

Perindopril

Suction

After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract (GIT). Bioavailability is 65-70%. The maximum concentration (Cmax) in the blood plasma is reached 3-4 hours after ingestion.

Eating reduces the conversion of perindopril to perindopril and the bioavailability of perindopril, so it should be taken 1 time per day in the morning before breakfast. When taking perindopril 1 time / day. Equilibrium concentration (Css) is achieved within 4 days.

Distribution

Plasma protein binding of perindoprilat is dose-dependent and is 20%. Perindoprilat easily passes through histohematogenous barriers, excluding the blood-brain barrier (BBB). Does not accumulate.

Metabolism

In the liver it is metabolized to form the active metabolite of perindoprilat. In addition, 5 more inactive metabolites are formed.

Removal

The half-life (T1 / 2) of perindopril from blood plasma is 1 h. T1 / 2 of perindoprilat is about 17 h. It is excreted by the kidneys.

Pharmacokinetics in Special Patient Groups

In elderly patients, in patients with renal and heart failure, the elimination of perindoprilat is delayed.

The dialysis clearance of perindoprilat is 70 ml / min.

Perindopril kinetics changed in patients with cirrhosis of the liver: the hepatic clearance is reduced by half. However, the amount of perindoprilat formed does not decrease, which does not require dose adjustment.

Indapamide

Suction

After ingestion quickly and almost completely absorbed from the gastrointestinal tract.Food intake slows down the absorption somewhat, but does not significantly affect the amount of indapamide absorbed. After ingestion in a single dose of C max in the blood plasma is achieved after 1 h.

Distribution

Plasma protein binding is 79%. Does not accumulate.

Metabolism

Metabolized in the liver.

Removal

T1 / 2 ranges from 14 to 24 hours (average 18 hours). Excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of unchanged drug is about 5%) and the intestine with bile in the form of inactive metabolites (22%).

Pharmacokinetics in special clinical situations

In patients with renal failure, the pharmacokinetic parameters of indapamide do not change significantly.

Indications

- arterial hypertension.

Contraindications

- hypersensitivity to excipients that are part of the drug;

- severe renal failure (CC <30 ml / min);

- simultaneous use with potassium-sparing diuretics, potassium and lithium preparations, and in patients with hyperkalemia;

- simultaneous administration of drugs that prolong the QT interval;

- due to the lack of sufficient clinical experience, Perindopril plus Indapamide should not be used in patients on hemodialysis, as well as in patients with untreated heart failure in the stage of decompensation;

- age up to 18 years (efficacy and safety have not been established).

Carefully: the drug should be used for systemic diseases of the connective tissue (includingsystemic lupus erythematosus, scleroderma); during therapy with immunosuppressants (risk of developing neutropenia, agranulocytosis); in the suppression of bone marrow hematopoiesis; decrease in circulating blood volume (BCC) (due to diuretic intake, diet with restricted salt, vomiting, diarrhea); coronary heart disease (CHD); cerebrovascular diseases; Renovascular hypertension; chronic heart failure (NYHA functional class IV); with hyperuricemia (especially accompanied by gout and urate nsfrolithiasis); lability of blood pressure; in hemodialysis using high-flow polyacrylonitrile membranes (risk of developing anaphylactoid reactions); before the procedure of LDL apheresis using dextrin sulphate; simultaneously with the conduct of desensitizing therapy with allergens (for example, hymenoptera poison); in the condition after kidney transplantation; stenosis of aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy; in elderly patients. In patients with a history of angioedema, not associated with taking ACE inhibitors, the risk of its development when taking drugs in this group may be increased. Patients of the Negroid race develop angioedema more often than patients of other races.

Side effects

The classification of the incidence of side effects (WHO): very often (> 1/10).often (from> 1/100 to <1/10), infrequently (from> 1/1000 to <1/100), rarely (from> 1/10 000 to <1/1000). very rarely (from <1/10 000), the frequency is unknown (the frequency cannot be calculated from the available data).

On the part of the hemopoietic system: infrequently - eosinophilia, hyponatremia, very rarely - thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (patients after kidney transplantation, patients on hemodialysis), ACE inhibitors can cause anemia.

From the side of the central nervous system: often - paresthesia, headache, dizziness, vertigo; infrequently - sleep disturbance, mood lability; very rarely confusion of consciousness; frequency unknown - syncope.

On the part of the organ of vision: often - visual impairment.

From the organ of hearing: often - tinnitus.

Since the cardiovascular system: infrequently - a pronounced decrease in blood pressure (including orthostatic hypotension), palpitations; very rarely - cardiac arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation), angina pectoris, and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients; frequency is unknown - arrhythmias of the "pirouette" type (possibly fatal), an increase in the QT interval on the ECG.

On the part of the respiratory system: often - against the background of the use of ACE inhibitors, a dry cough may persist, which persists for a long time while taking this group of drugs and disappears after their withdrawal, shortness of breath; infrequently - bronchospasm; very rarely - eosiophilic pneumonia, rhinitis.

On the part of the digestive system: often - dryness of the oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, disturbed taste perception, loss of appetite, dyspepsia, constipation, diarrhea: very rarely - pancreatitis, angioedema of the intestines, cholestatic jaundice; unknown frequency - hepatic encephalopathy in patients with hepatic insufficiency, increased activity of "hepatic" transaminases.

On the part of the skin: often - skin rash, itching, maculopapular rash; infrequently, angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and / or larynx, urticaria, hypersensitivity reactions in patients prone to broncho-obstructive and allergic reactions, hemorrhagic vasculitis. Patients with an acute form of systemic lupus erythematosus may worsen the course of the disease; very rarely - erythema multiforme, toxic epidermal necrolysis. Stevens-Johnson syndrome. Reported cases of photosensitivity reaction.

From the musculoskeletal system: often - muscle spasms.

From the urinary system: infrequently - renal failure; very rarely - acute renal failure, the frequency is unknown - hepatitis.

Reproductive system: Infrequently, erectile dysfunction.

Laboratory indicators: rarely - hypercalcemia; frequency is unknown - hypokatemia, especially significant for patientsat risk; hyponatremia and ginovolemia, leading to dehydration and orthostatic hypotension; increased uric acid and blood glucose levels while taking the drug: a slight increase in creatinine in the urine and in the blood plasma, taking place after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of arterial hypertension with diuretics and in the case of renal failure; hyperkalemia, often transient.

Other: often - asthenia; infrequently - increased sweating.

When using ACE inhibitors, the syndrome of impaired secretion of thyroid hormone was rarely observed.

Interaction

Simultaneous use is not recommended. Preparations of lithium: cases of a reversible increase in the concentration of lithium in blood serum have been reported. The risk of its toxic action increases while taking an ACE inhibitor. Simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of therapy, control of lithium concentration in the blood plasma is necessary. If used simultaneously, special caution is required. . The combination of ACE inhibitors with nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2) and neselk active NSAIDs, Acetylsalicylic acid in doseshave anti-inflammatory effect) reduces the antihypertensive effect of ACE inhibitors; increases the risk of impaired renal function, up to the development of acute renal failure; increases the content of potassium in the blood serum in patients with already existing renal dysfunction. This combination is recommended to be used with caution, especially in elderly patients. Patients need to compensate for BCC, as well as monitor kidney function before and after starting treatment with Perindopril PLUS with Indapamide. When used simultaneously, caution is required. Glucocorticosteroids (GCS), tetrakozaktid reduce the antihypertensive effect (fluid retention). If used concomitantly with other antihypertensive drugs, the antihypertensive effect of the drug may be enhanced. With the combined use of potassium-sparing diuretics (spironolactone, triamteren. Amiloride.eplerenone), potassium preparations or potassium-containing salt substitutes with ACE inhibitors, an increase in serum potassium up to a fatal outcome is possible.If combined use of an ACE inhibitor and the above drugs is necessary (in the case of confirmed hypokalemia), caution should be taken and regular monitoring of potassium in the blood plasma and ECG parameters should be used. patients with moderate renal failure (CC less than 60 ml / min). If used simultaneously with estramustine, the risk of angioedema increases. edema. When used simultaneously, special care is required. The use of ACE inhibitors may enhance the hypoglycemic effect of hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin in patients with diabetes mellitus; with their combined use, it is possible to increase glucose tolerance, which may require correction of doses of hypoglycemic