indapamide, Perindopril | Noliprel A tablets 2.5 + 0.625 mg 30 pcs.

Packing

30 pcs.

Pharmacological action

Noliprel A is a combined antihypertensive drug containing perindopril (an ACE inhibitor) and indapamide (a diuretic from the sulfonamide derivative group). The pharmacological effect of Noliprel is due to a combination of the individual properties of each of the components. The combination of perindopril and indapamide enhances the action of each of them.

Noliprel A has a pronounced dose-dependent hypotensive effect on both systolic and diastolic blood pressure in the supine and standing position. The effect 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.

Noliprel reduces the degree of left ventricular hypertrophy, improves arterial elasticity, reduces OPSS, does not affect lipid metabolism (total cholesterol, HDL, LDL, triglycerides) and does not affect carbohydrate metabolism (including in patients with diabetes mellitus).

Indications

Essential arterial hypertension.

Contraindications

Hypersensitivity to perindopril and other ACE inhibitors

Hypersensitivity to indapamide and sulfonamides

History of angioedema (including those treated with ACE inhibitors) mild mild / moderate )

Severe liver failure (including with encephalopathy)

Concomitant use of drugs prolonging the QT interval

Pregnancy, lactation (breastfeeding).

With caution, the drug should be used with bilateral renal artery stenosis or artery stenosis of the only functioning kidney, with renal failure, systemic diseases of the connective tissue (SLE, scleroderma), during therapy with immunosuppressants (risk of neutropenia, agranulocytosis), inhibition of bone marrow hematopoiesis, decreased BCC (taking diuretics, salt-free diet, vomiting, diarrhea, hemodialysis), in cerebrovascular diseases, renovascular hypertension, diabetes mellitus, severe heart failure (stage IV), with hyperuricemia and with concurrent hypoglycemia nephrolithiasis), while taking potassium-sparing diuretics, potassium and lithium preparations, with blood pressure lability, during hemodialysis using high-flow membranes, during desensitization and, after kidney transplantation, with aortic valve stenosis / hypertrophic cardiomyopathy, with lactose deficiency, galactosemia or glucose / galactose malabsorption syndrome, in elderly patients, in patients under the age of 18 (efficacy and safety have not been established).

Use during pregnancy and lactation

Contraindicated.

Special instructions

The use of Noliprel may cause a sharp decrease in blood pressure, especially at the first dose and during the first 2 weeks of therapy.

Composition

1 tablet contains:

active ingredients of perindopril arginine - 2.5 mg, which corresponds to 1.6975 mg of perindopril and indapamide 0.625 mg.

excipients: lactose monohydrate 74.455 mg, magnesium stearate 0.45 mg, maltodextrin 9 mg, colloidal silicon dioxide anhydrous 0.27 mg, sodium carboxymethyl starch (type A) 2.7 mg.

film sheath: macrogol 6000 0.087 mg, premix for white film sheath SEPIFILM 37781 RBC (glycerol 4.5%, hypromellose 74.8%, macrogol 6000 1.8%, magnesium stearate 4.5%, titanium dioxide (E 171 ) 14, 4%) 2.913 mg.

Dosage and administration of

Adults, including elderly patients, are prescribed 1 tablet per day, preferably in the morning.

Side effects of

Perindopril has an inhibitory effect on the renin-angiotensin-aldosterone (RAAS) system and reduces the excretion of potassium ions by the kidneys while taking indapamide. In 4% of patients with the use of Noliprel® A, hypokalemia develops (potassium level less than 3.4 mmol / L).

The frequency of adverse reactions that may occur during therapy is given in the form of the following gradation: very often (> 1/10) often (> 1/100, 1/1000, 1/10000, from the circulatory and lymphatic system

Very rarely : thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia

Anemia: in certain clinical situations (patients after kidney transplantation, patients on hemodialysis) ACE inhibitors can cause anemia (see the section “Special Instructions” p srd). From the central nervous system Topics

Common: paraesthesia, headache, dizziness, fatigue, vertigo Uncommon:. sleep disturbances, mood lability Very rarely. confusion. Unspecified frequency: fainting.

From the organ of vision

Often: visual impairment.

On the part of the hearing organ

Often: tinnitus.

From the cardiovascular system

Often: marked decrease in blood pressure, including orthostatic hypotension. Very rarely: cardiac arrhythmias, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in patients at high risk (see section "Special Instructions"). Unspecified frequency: pirouette type arrhythmias (possibly fatal) (see section “Interaction with other drugs”).

From the respiratory system, chest and mediastinal organs

Often: dry cough may occur with the use of ACE inhibitors, long lasting while taking drugs of this group and disappearing after their cancellation. Dyspnea. Infrequently: bronchospasm. Very rarely: eosinophilic pneumonia, rhinitis.

From the digestive system

Often: dry oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste, loss of appetite, dyspepsia, constipation, diarrhea. Very rarely: angioedema of the intestine, cholestatic jaundice, pancreatitis

Unspecified frequency: hepatic encephalopathy in patients with liver failure (see sections "Contraindications" and "Special instructions"), hepatitis.

From the skin and subcutaneous fat

Often: skin rash, itching, maculopapular rash. Infrequently: angioedema of the face, lips, limbs, mucous membrane of the tongue, vocal folds and / or larynx urticaria (see section "Special Instructions") hypersensitivity reactions in patients predisposed to bronchial obstruction and allergic reactions of purpura. In patients with acute systemic lupus erythematosus, the course of the disease may worsen. Very rarely: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Cases of photosensitivity reaction have been noted (see the section "Special Instructions").

From the musculoskeletal system and connective tissue

Often: muscle cramps.

Urinary system

Infrequently: renal failure. Very rare: acute renal failure.

From the reproductive system

Infrequently: impotence.

General disorders and symptoms of

Often: asthenia. Infrequently: increased sweating.

Laboratory findings

- Hyperkalemia, more often transient.

- A slight increase in the concentration of creatinine in the urine and in the blood plasma that occurs after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of hypertension with diuretics and in case of renal failure. Rarely: hypercalcemia. Unspecified frequency: An increase in the QT interval on the ECG (cf. the "Special Instructions" section).

- Increased levels of uric acid and blood glucose.

- Increased activity of "liver" enzymes.

- Hypokalemia, especially significant for patients at risk (see section "Special instructions").

- Hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension. Simultaneous hypochloremia can lead to compensatory metabolic alkalosis (the probability and severity of this effect is low).

Adverse events reported during clinical trials

Adverse events reported during the ADVANCE study are consistent with the previously established safety profile for the combination of perindopril and indapamide. Serious adverse events were observed in some patients in the study groups: hyperkalemia (0.1%), acute renal failure (0.1%), arterial hypotension (0.1%) and cough (0.1%).

Three patients in the perindopril / indapamide group had angioedema (versus 2 in the placebo group).

Drug Interactions

Combinations, not recommended for use

Lithium preparations

- with the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in blood plasma and the associated toxic effects may occur. The additional use of thiazide diuretics can further increase lithium concentration and increase the risk of toxicity. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. If necessary, such therapy should constantly monitor the lithium content in the blood plasma (see section "Special instructions").

Drugs, the combination of which requires special attention and caution

Baclofen: an increase in the hypotensive effect is possible. Blood pressure and kidney function should be monitored, if necessary, dose adjustment of antihypertensive drugs is required.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including high doses of acetylsalicylic acid (more than 3 g / day): NSAIDs may lead to a decrease in diuretic, natriuretic and antihypertensive effects. With significant fluid loss, acute renal failure may develop (due to a decrease in glomerular filtration rate). Before starting treatment with the drug, it is necessary to make up for fluid loss and regularly monitor kidney function at the beginning of treatment.

Combination of drugs requiring attention

Tricyclic antidepressants, antipsychotics (antipsychotics): drugs of these classes increase the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

Corticosteroids, tetracosactide: decrease in antihypertensive effect (fluid retention and sodium ions as a result of the action of corticosteroids).

Other antihypertensive drugs: antihypertensive effect may be enhanced.

Perindopril: Combinations not recommended for use

Potassium-sparing diuretics (amiloride, spironolactone, triamteren) and potassium preparations: ACE inhibitors reduce the loss of potassium caused by the diuretic in the kidneys. Potassium-sparing diuretics (for example, spironolactone, triamteren, amiloride), potassium preparations, and potassium-containing salt substitutes can lead to a significant increase in serum potassium up to death. If simultaneous use of an ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), care should be taken and regular monitoring of the potassium content in blood plasma and ECG parameters should be carried out.

Combination of drugs requiring special attention

Hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin: The following effects have been described for captopril and enalapril.

ACE inhibitors may enhance the hypoglycemic effect of insulin and sulfonylurea derivatives in patients with diabetes mellitus. The development of hypoglycemia is observed very rarely (due to an increase in glucose tolerance and a decrease in the need for insulin).

Combination of drugs requiring attention

Allopurinol, cytostatic and immunosuppressive drugs, corticosteroids (for systemic use) and procainamide: concomitant use of

with ACE inhibitors may be associated with an increased risk of leukopenia.

Means for general anesthesia: the simultaneous use of ACE inhibitors and means for general anesthesia can lead to an increase in the antihypertensive effect.

Diuretics (thiazide and "loopback"): the use of diuretics in high doses can lead to hypovolemia, and the addition of perindopril to therapy can lead to arterial hypotension.

Gold preparations: when using ACE inhibitors, including perindopril, for patients receiving an intravenous gold preparation (sodium aurothiomalate), a symptom complex was described, including: facial skin flushing, nausea, vomiting, arterial hypotension.

Indapamide: A combination of drugs that requires special attention

Drugs that can cause pirouette arrhythmias: due to the risk of hypokalemia, caution should be exercised while using indapamide with drugs that can cause pirouette arrhythmias, for example, antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretilium tosylate, sotalol) with some antipsychotics (chlorpromazine , cyamemazine, levomepromazine, thioridazine, trifluoperazin) with benzamides (amisulpride, sulpiride, sultopride, tiapride) butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide), other drugs riv, such as bepridil, cisapride, diphenyl methyl sulphate, iv erythromycin, halofantrine, misolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine iv, methadone, astemizole, terfenadine.

The simultaneous use of the above drugs with the risk of hypokalemia should be avoided, if necessary, carry out its correction to control the QT interval.

Drugs that can cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticosteroids (for systemic use), tetracosactides, laxatives that stimulate intestinal motility: increased risk of hypokalemia (additive effect). It is necessary to control the potassium content in the blood plasma, if necessary, its correction.

Particular attention should be given to patients who are simultaneously receiving cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used.

Cardiac glycosides: hypokalemia enhances the toxic effects of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the potassium content in the blood plasma and ECG indices should be monitored and, if necessary, adjust therapy.

A combination of drugs that requires attention

Metformin: functional renal failure that may occur with diuretics, especially loopback diuretics, while metformin is given, increases the risk of lactic acidosis. Metformin should not be used if the creatinine concentration in blood plasma exceeds 15 mg / l (135 μmol / l) in men and 12 mg / l (110 μmol / l) in women.

Iodine-containing contrast agents: dehydration of the body while taking diuretic drugs increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast agents, patients need to compensate for fluid loss.

Calcium Salts: with the simultaneous appointment, the development of hypercalcemia is possible due to a decrease in the excretion of calcium ions by the kidneys.

Cyclosporine: an increase in plasma creatinine concentration is possible without changing the concentration of cyclosporine in blood plasma, even with a normal content of water and sodium ions.

Overdose

Symptoms of

The most likely symptom of overdose is a pronounced decrease in blood pressure, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oligurium, and oliguria. Electrolyte disorders (hyponatremia, hypokalemia) can also occur.

Treatment

Emergency measures are reduced to removing the drug from the body: washing the stomach and / or the appointment of activated carbon with the subsequent restoration of the water-electrolyte balance.

With a significant decrease in blood pressure, the patient should be placed in a "lying" position with his legs elevated. If necessary, correct hypovolemia (eg, intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, the active metabolite of perindopril, can be removed by dialysis.

Storage Conditions

In a dark place at a temperature not exceeding 30 РC.

Shelf life

3 years.

Deystvuyushtee substance

Indapamide, perindopril

dosage form

tablets

Possible product names

NOLIPREL A 0.0025 + 0.000625 N30 TABLE P / O

NOLIPREL A 2.5MG. + 0.625MG. No. 30 TAB.

Noliprel A 2.5mg / 0.625 No. 30

Noliprel A 2.5mg No. 30 tab

Noliprel A 2.5mg + 0.625mg Tab. p / pl / rev X30

Servye, France