Noliprel A FORTE

Active material: Indapamid, Perindopril
When ATH: C09BA04
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.03
Manufacturer: Servier Laboratories (France)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white, oblong.

Excipients: sodium carboxymethyl starch (Type A), Colloidal anhydrous silica, lactose monohydrate, magnesium stearate, maltodextrin.

The composition of the coating film: macrogol 6000, SEPIFILM 37781 RBC (glycerol, gipromelloza, macrogol 6000, magnesium stearate, Titanium dioxide (E171)).

30 PC. – vials made of polypropylene (1) – packs cardboard.

Pharmacological action

Combined preparation, containing perindopril (ACE inhibitor) and indapamide (tiazidopodobnый diuretic). The pharmacological action of the drug due to a combination of the individual properties of each component. The combined use of perindopril and indapamide provides a synergy of the antihypertensive effect compared with each of the components separately.

The drug has a pronounced dose-dependent antihypertensive effect on systolic, and the diastolic blood pressure in the supine position and standing. Effect of the drug continues 24 no. Persistent clinical effect is less than 1 months from the initiation of therapy and is not accompanied by tachycardia. Discontinuation of treatment is not accompanied by the development of withdrawal.

Noliprel^® A forte reduces the degree of left ventricular hypertrophy, It improves the elasticity of the arteries, reduces peripheral vascular resistance, It does not affect lipid metabolism (total cholesterol / XC /, Hs-HDL, LDL-C, trigliceridy).

Perindopril – antizymotic, prevrashtayushtego angiotensin I to angiotensin II. Angiotensin-converting enzyme (ACE), or kinase, It is an exopeptidase, which performs as the conversion of angiotensin I to angiotensin II, vasoconstrictor activity, and the destruction of bradykinin, having a vasodilating action, to inactive heptapeptyda. As a result, it reduces the secretion of aldosterone perindopril, by a negative feedback loop increases plasma renin activity in blood, long-term use reduces round, due, primarily, action on the blood vessels in the muscle and kidney. These effects were not accompanied by a delay of salt and water or the development of reflex tachycardia with prolonged use.

Perindopril has an antihypertensive effect in patients with both low, and with normal activity of renin in blood plasma.

Against the background of perindopril a decline in both systolic, and diastolic blood pressure in the supine position and standing. Cancel the drug does not increase blood pressure.

Perindopril has vasodilatory effect, It helps to restore the elasticity of the large arteries and the structure of the vascular wall of small arteries, and reduces left ventricular hypertrophy.

The combined use of thiazide diuretics increases the antihypertensive effect. Besides, combining an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia in patients receiving diuretics.

Perindopril normalizes heart function, reducing preload and afterload.

Patients with heart failure perindopril causes reduction of the filling pressure in the right and left ventricle, reduction in systemic vascular resistance, increased cardiac output and improved cardiac index, increase in regional blood flow in muscles.

Indapamid – derivative of sulfanilamide, for pharmacologically similar to thiazide diuretics. It inhibits the reabsorption of sodium in the cortical segment of the loop of Henle, which leads to increased urinary excretion of sodium ions, chlorine and, to a lesser extent magnesium and potassium ions, thereby increasing urine output. The antihypertensive effect is manifested in doses, cause essentially no diuretic effect.

Indapamide reduces vascular hyperreactivity in relation to adrenaline.

Indapamide does not affect the content of lipids in the blood plasma (triglycerides, cholesterol, LDL and HDL), carbohydrate metabolism (incl. in patients with concomitant diabetes).

Indapamide reduces left ventricular hypertrophy.

Pharmacokinetics

Farmakokineticheskie perindopril and indapamide options for combinations not menyayutsya in sravneniyu with gee razdelynыm primeneniem.

Perindopril

Absorption and metabolism

After oral administration, perindopril is rapidly absorbed. Bioavailability is 65-70%. C_max perindoprilat plasma levels achieved through 3-4 no. About 20% the total amount of perindopril absorbed is converted into an active metabolite perindoprilat. While taking the drug during meals reduced the conversion of perindopril perindoprilat (This effect has no significant clinical relevance).

Distribution and excretion

Plasma protein binding is less than 30% and it depends on the concentration in the blood plasma of perindopril. Dissociation of perindoprilat, associated with ACE, slowed. Consequently, T_1/2 is 25 no. Reappointment of perindopril does not lead to its accumulation, a T_1/2 perindoprilat Repeated dose corresponds to the period of its activity, thus, equilibrium state is achieved through 4 d. Perindopril crosses the placental barrier.

Perindoprilat excreted in the urine. T_1/2 perindoprilat is 3-5 no.

Pharmacokinetics in special clinical situations

Withdrawal perindoprilat slowing elderly patients, and in patients with renal failure and heart failure.

The clearance of perindoprilat dialysis 70 ml / min.

The pharmacokinetics of perindopril is altered in patients with liver cirrhosis: perindopril reduced hepatic clearance in 2 times. However, the concentration of perindoprilat formed is not changed, therefore, dose adjustment is not required.

Indapamid

Absorption

Indapamide is rapidly and completely absorbed from the gastrointestinal tract. C_max plasma levels achieved after 1 hours after ingestion.

Distribution

The binding to plasma proteins – 79%.

Re-taking the drug does not lead to its accumulation in the body.

Deduction

T_1/2 is 14-24 no (average 19 no). Write mainly in the urine (70% of the administered dose) and faeces (22%) in the form of inactive metabolites.

Pharmacokinetics in special clinical situations

Pharmacokinetics of indapamide is not changed in patients with renal insufficiency.

Testimony

- Essential hypertension.

Dosage regimen

Assign inside of 1 tab. 1 time / day, preferably in the morning, before meals.

Whenever possible, the drug starts with the selection of doses of single-component products. In the case of clinical need, you can consider the appointment of a combined therapy with Noliprel^® A fort immediately after monotherapy.

Elderly patients should be prescribed after control of renal function and blood pressure.

The drug is contraindicated patients with severe renal insufficiency (CC <30 ml / min). To Patients with renal insufficiency moderately (CC 30-60 ml / min) recommended to start therapy with the required doses of drugs (monotherapy), members of the Noliprel^® A fort. Patients with KK≥ 60 ml / min, dose adjustment is required. The therapy requires regular monitoring of serum creatinine and potassium in the blood plasma.

The drug is contraindicated Patients with severe hepatic insufficiency. At moderate hepatic insufficiency dose adjustment is required.

Noliprel^® A fort should not be given children and adolescents due to lack of data on efficacy and safety in patients in this age group.

Side effect

Perindopril exerts an inhibitory effect on the renin-angiotensin-aldosterone system, and reduces the excretion of potassium by the kidneys in patients receiving indapamide. In 2% patients during treatment with the drug Noliprel^® A fort develops hypokalemia (potassium levels <3.4 mmol / l).

The frequency of adverse reactions, that may occur during therapy, shown in the following gradation: Often (>1/10), often (> 1/100, <1/10), infrequently (>1/1000, <1/100), rarely (>1/10 000, <1/1000), rarely (<1/10 000), neutochnennoy chastotы (frequency can not be calculated on available data), including isolated reports.

From the digestive system: often – dry mouth, nausea, decreased appetite, abdominal pain, epigastric pain, taste disturbances, constipation; rarely – intestinal angioedema, cholestatic jaundice; rarely – pancreatitis. Patients with hepatic insufficiency may develop hepatic encephalopathy.

The respiratory system: often – during treatment with an ACE inhibitor a dry cough may occur, long-lasting while receiving drugs in this group, and disappearing after their withdrawal. When the patient has dry cough should be aware of the possible iatrogenic character of this symptom.

Cardio-vascular system: infrequently – decrease in blood pressure (incl. orthostatic hypotension).

Dermatological reactions: infrequently – hypersensitivity reactions, primarily, a dermatological reactions in patients, predisposed to allergic and asthmatic reactions, Hemorrhagic rash, skin rash, maculo-papular rash, exacerbation of systemic lupus erythematosus; rarely – angioedema (angioedema), photosensitivity reaction.

From the nervous system: infrequently – paresthesia, headache, asthenia, sleep disturbance, mood lability, dizziness.

On the part of the musculoskeletal system: infrequently – muscle spasms.

From the hematopoietic system: rarely – thrombocytopenia, leukopenia, agranulocytosis, aplasticheskaya anemia, gemoliticheskaya anemia. In certain clinical situations (patients after kidney transplantation, Patients on hemodialysis) ACE inhibitors can cause anemia.

Laboratory findings: kaliopenia (especially significant for patients, at risk), hyponatremia and hypovolemia, leading to dehydration and orthostatic hypotension, increased uric acid and glucose levels during treatment (slight increase in urea and creatinine in plasma, passing after discontinuation, more frequently in patients with renal artery stenosis, in the treatment of hypertension and in the case of diuretics, renal insufficiency), hyperkalemia (often transient); rarely – hypercalcemia.

Contraindications

- A history of angioedema (incl. in patients receiving other ACE inhibitors);

- Hereditary / idiopathic angioedema;

- Severe renal insufficiency (CC < 30 ml / min);

- Hypokalemia;

- Bilateral renal artery stenosis or stenosis of the artery to a solitary kidney;

- Severe hepatic impairment (incl. encephalopathy);

- Concomitant use of drugs, prolonging the QT interval;

- Concomitant use of antiarrhythmic agents, which can cause ventricular arrhythmias such as "pirouette";

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to perindopril or other ACE inhibitors, to indapamide and sulphonamides, as well as other ancillary components of the drug.

Not recommended simultaneous drug with potassium-sparing diuretics, drugs lithium and potassium and hyperkalemia.

Due to the lack of sufficient clinical experience, drug should not be used in patients with untreated decompensated heart failure and in patients, hemodialysis.

FROM caution It should be prescribed the drug for systemic connective tissue diseases (incl. systemic lupus erythematosus, scleroderma), immunosuppressive therapy (the risk of neutropenia, agranulocytosis), suppression of bone marrow hematopoiesis, snizhennom OCK (diuretics, salt-free diet, vomiting, diarrhea, hemodialysis), angina, cerebrovascular diseases, renovascular hypertension, diabetes, chronic heart failure (IV functional class NYHA classification), hyperuricemia (especially accompanied by gout and urate nephrolithiasis), labile blood pressure; hemodialysis using membranes vysokoprotochnyh, Desensitization, before apheresis procedure LDL (LDL); if condition after kidney transplantation; aortic valve stenosis / hypertrophic cardiomyopathy; the presence of lactase deficiency, galactosemia or glucose-galactose syndrome malabsorption; and elderly patients or patients aged 18 years (efficacy and safety have not been established).

Pregnancy and lactation

The drug should not be used in the I trimester of pregnancy.

When planning a pregnancy or its occurrence in patients receiving the drug Noliprel^® A fort, stop taking the drug and to appoint another antihypertensive therapy.

Relevant controlled trials of ACE inhibitors in pregnancy has not been. The limited data available on the effects of the drug in the I trimester of pregnancy show, that the drug did not lead to malformations, related fetotoxic.

Noliprel^® A fort is contraindicated in II and III trimester of pregnancy.

Known, that prolonged exposure to ACE inhibitors on the fetus in the II and III trimester of pregnancy may lead to a breach of its development (decreased kidney function, oligogidramnion, slowing ossification of skull) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia).

Long-term use of thiazide diuretics in the III trimester of pregnancy can cause maternal hypovolemia and decreased blood flow Uteroplacental, which leads to a twin-placental ischemia and growth retardation. In rare cases, patients receiving diuretics just before birth in the newborn develops hypoglycemia and thrombocytopenia.

If the patient received the drug Noliprel^® A fort during the II and III trimester of pregnancy, It recommended to fetal ultrasound for the assessment of the skull and renal function.

Noliprel^® A fort is contraindicated during lactation.

Cautions

Noliprel^® A fort

Use of the drug Noliprel^® A fort is not accompanied by a significant reduction in the incidence of side effects, except hypokalemia, compared with perindopril and indapamide in the smallest doses approved for use. At the beginning of therapy with two antihypertensive drugs, that the patient has not previously received, we can not exclude high-risk idiosyncrasy. To minimize this risk,, should closely monitor the patient's condition.

Renal failure

Patients with severe renal insufficiency (CC < 30 ml / min) dannaya combination contraindicated.

Some hypertensive patients without previous renal dysfunction during therapy Noliprel^® A fort may appear laboratory signs of functional renal failure. In this case, the treatment should be discontinued. You can then resume the combination therapy, using low doses, any drugs used in monotherapy. Such patients need regular monitoring of potassium and creatinine serum – through 2 weeks after initiation of therapy and then every 2 Months. Kidney failure is more common in patients with severe chronic heart failure or renal dysfunction source, incl. Renal artery stenosis.

Hypotension and disruption of water and electrolyte balance

Hyponatremia associated with risk of sudden hypotension (especially in patients with stenosis of the artery to a solitary kidney, and bilateral renal artery stenosis). Therefore, in the follow-up of patients should pay attention to possible symptoms of dehydration and reduce the level of electrolytes in the blood plasma, eg, after diarrhea or vomiting. These patients required regular monitoring of plasma electrolytes. In severe hypotension may be required in / introduction 0.9 % sodium chloride solution.

Transient hypotension is not a contraindication to continue therapy. After the restoration of the bcc and blood pressure can resume therapy, using low doses, any drugs used in monotherapy.

Potassium content

The combination of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes or renal failure. As with any antihypertensive agent, receiving in combination with a diuretic, in the treatment of this combination should be monitored content of potassium in the blood plasma.

Excipients

It should be taken into account, that in the preparation of auxiliary substances include lactose monohydrate. It should appoint Noliprel^® A fort in patients with hereditary galactose intolerance, lactase deficiency of glucose-galactose and malabsorption.

Perindopril

Neutropenia / agranulocytosis

The risk of neutropenia in patients receiving ACE inhibitors is dose-dependent and depends on the medication and the presence of comorbidities. Neutropenia occurs rarely in patients without comorbidities, but the risk is increased in patients with impaired renal function, especially against the background of systemic diseases of connective tissue (incl. systemic lupus erythematosus, scleroderma). After the cancellation of ACE inhibitors are themselves signs of neutropenia. To avoid the development of these reactions, it is recommended to strictly follow the recommended dose. In the appointment of ACE inhibitors of this group of patients should be closely correlated factor of benefit / risk.

Angioedema (angioedema)

In rare cases during therapy with ACE inhibitors develop angioedema face, limbs, mouth, language, pharynx and / or larynx. In this situation, you should immediately stop taking perindopril and monitor the patient's condition until the complete disappearance of edema. If swelling affects only the face and mouth, the manifestations usually disappear without treatment, however, for a more rapid relief of symptoms can be used antihistamines.

Angioedema, accompanied by edema of the larynx, may be fatal. Swelling of the tongue, pharynx or larynx may cause airway obstruction. In this case, you should immediately enter epinephrine (adrenaline) p / dose 1:1000 (from 0.3 to 0.5 ml) and take other measures emergency. Patients, a history marked angioedema, not associated with ACE inhibitors, there is an increased risk of angioedema while taking these drugs.

In rare cases during therapy with ACE inhibitors develop angioedema of the intestine.

Anaphylactic reactions during desensitization

There are some reports about the development of life-threatening anaphylactic reactions in patients, receiving ACE inhibitors during desensitizing treatment poison Hymenoptera (incl. bee, hornet). ACE inhibitors must be used with caution in patients, prone to allergic reactions and undergoing desensitization treatments. Avoid prescribing for patients, receiving immunotherapy Hymenoptera venom. Nonetheless, anaphylactic reactions can be avoided by temporary withdrawal of the drug at least 24 hours before the course desensitizing therapy.

Anaphylactic reactions during LDL apheresis

In rare cases, patients, receiving ACE inhibitors, during LDL apheresis using a dextran sulfate, in patients during hemodialysis using membranes vysokoprotochnyh may develop life-threatening anaphylactic reactions. To prevent an anaphylactic reaction should temporarily discontinue therapy with an ACE inhibitor for at least 24 hours before apheresis procedure.

Cough

The therapy with an ACE inhibitor a dry cough may occur. Cough long preserved in patients receiving drugs in this group and disappears after their withdrawal. When the patient has dry cough should be aware of the possible iatrogenic character of this symptom. If the doctor says, that the ACE inhibitor needed patient, the drug can be extended.

The risk of hypotension and / or renal failure (incl. in the case of heart failure, deficiency of water and electrolytes)

Under certain pathological conditions there may be a significant activation of the renin-angiotensin-aldosterone system, especially in severe hypovolemia and decrease in plasma levels of electrolytes (against the backdrop of a salt-free diet or prolonged use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, chronic heart failure or cirrhosis with edema and ascites. ACE inhibitors cause a blockade of the system and, therefore, may be accompanied by a sharp decrease in blood pressure and / or increased levels of creatinine in the blood plasma, shows the development of functional renal failure. These phenomena often observed when receiving the first dose of the drug or during the first two weeks of treatment. Sometimes these states are developing sharply in other periods of therapy. In such cases, the resumption of therapy is recommended to use the drug at a lower dose and then gradually increase the dose.

Elderly patients

Before the drug is necessary to evaluate the functional activity of the kidneys and the potassium concentration in blood plasma. At the beginning of therapy, the dose is selected, taking into account the degree of decrease in blood pressure, especially in the case of dehydration and electrolyte loss. Such measures help to avoid a sharp decline in blood pressure.

Patients with established atherosclerosis

The risk of hypotension exists in all patients, but with caution drug should be used in patients with coronary heart disease or cerebrovascular insufficiency. In such cases, the treatment should be started with a low dose.

Renovascular hypertension

Methods of treatment of renovascular hypertension is revascularisation. Nonetheless, the use of ACE inhibitors has a beneficial effect in these patients, As expected surgery, and in the case, when surgery can not be made. Treatment with Noliprel^® A fort of patients with diagnosed or suspected bilateral renal artery stenosis or stenosis of the artery to a solitary kidney should start with a low dose of the drug in a hospital, monitoring renal function and potassium concentration in blood plasma. Some patients may develop a functional renal insufficiency, which disappears when canceling the drug.

Other risk groups

In patients with severe heart failure (Stage IV) and patients with insulin dependent diabetes mellitus (risk of spontaneous increase potassium levels) drug treatment should start with a low dose and be under the constant supervision of a doctor.

In patients with hypertension and congestive heart failure should not be lifted beta-blockers: ACE inhibitors should be used in conjunction with beta-blockers.

Anemia

Anemia may occur in patients, Kidney transplant, or in patients, on hemodialysis. The higher the baseline hemoglobin, the more pronounced its decline. This effect, apparently, is not dose dependent, but it may be related to the mechanism of action of ACE inhibitors. Reduction in hemoglobin slightly, it occurs within the first 1-6 months of treatment, and then stabilized. If you cancel the treatment of hemoglobin levels completely restored. Treatment can be continued under the control of peripheral blood picture.

Surgery / general anesthesia

The use of ACE inhibitors in patients, undergoing surgery with general anesthesia, It can lead to a marked decrease in blood pressure, particularly when using tools for general anesthesia, hypotensive effect. It is recommended to stop taking ACE inhibitors long-acting, incl. perindopril, one day prior to surgery. It is necessary to warn the anesthesiologist about, that the patient is taking ACE inhibitors.

Aortalnыy stenosis / hypertrophic kardyomyopatyya

ACE inhibitors should be administered with caution to patients with obstruction of the left ventricular outflow tract.

Hepatic failure

In rare cases, patients receiving ACE inhibitors occurs cholestatic jaundice. With the progression of the syndrome of possible rapid development of liver necrosis, sometimes with fatal consequences. The mechanism of this syndrome is unclear. When jaundice or significant increase in liver enzymes in patients receiving ACE inhibitors, patients should stop taking the drug and seek medical advice.

Indapamid

In the presence of impaired liver function receiving thiazide diuretics and thiazide may lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.

Disorders of water and electrolyte balance

Before treatment is necessary to determine the content of sodium ions in plasma. In patients receiving the drug should regularly monitor this indicator. All diuretic drugs can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia initially may not be accompanied by clinical symptoms, therefore requires regular laboratory monitoring. More frequent monitoring of the content of sodium ions is indicated for patients with cirrhosis of the liver and the elderly.

Therapy thiazide diuretics and thiazide related to the risk of hypokalemia. You should avoid hypokalemia (less 3.4 mmol / l) in the following categories of patients at high risk: the elderly, or malnourished patients receiving concomitant medication, patients with liver cirrhosis, ascites, or peripheral edema, CHD, Heart Failure. Hypokalemia in these patients increases the toxic effects of cardiac glycosides and increased risk of arrhythmias. High risk include patients with an increased QT interval, it does not matter, caused by this increase in congenital causes or action of drugs.

Kaliopenia, how and bradycardia, It contributes to the development of severe heart rhythm disorders, especially, the type of arrhythmia “pirouette”, which can be fatal. In all the above cases, a more regular monitoring of potassium ions in the blood plasma. The first measurement of potassium ion concentration must be held during the first week of therapy.

In identifying hypokalemia should be assigned the appropriate treatment.

Thiazide and thiazide diuretics reduce the excretion of calcium by the kidneys, resulting in a slight and transient increase in calcium concentration in blood plasma. Marked hypercalcemia may be due to previously undiagnosed hyperparathyroidism. Before examining parathyroid function should stop taking diuretics.

Blood glucose

It is necessary to control blood glucose levels in diabetic patients, especially in the presence of hypokalemia.

Uric acid

In patients with high levels of uric acid in the blood during therapy Noliprel^® A fort increases the risk of gout.

Renal function and diuretics

Thiazide diuretics and thiazide fully effective only in patients with normal or mildly impaired renal function (creatinine in blood plasma of adult individuals <2.5 mg / dL or 220 mmol / l). At the beginning of treatment with diuretics in patients due to hypovolemia and hyponatremia may be a temporary reduction in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transitory functional renal insufficiency is not dangerous for patients with intact renal function, however, in patients with renal insufficiency may increase its severity.

Photosensitivity

On FoNet accepts tiazidnыh and tiazidopodobnыh diuretikov soobshtalosy o sluchayah developments reactions fotochuvstvitelynosti. In the case of photosensitivity reactions in patients receiving the drug should be discontinued treatment. If necessary, continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial UV rays.

Athletes

Indapamide may give a positive reaction in doping control.

Use in Pediatrics

It should appoint Noliprel^® A fort children and adolescents under the age of 18 years, tk. efficacy and safety in these patients have not been established.

Effects on ability to drive vehicles and management mechanisms

Action substances, members of the drug Noliprel^® A fort, It does not lead to a breach of psychomotor reactions. However, some people in response to the decrease in blood pressure may develop different individual reactions, especially at the beginning of therapy, or when added to the therapy of other antihypertensive drugs. In this case, the ability to drive a car or other mechanisms may be reduced.

Overdose

Symptoms: marked reduction in blood pressure, nausea, vomiting, convulsions, dizziness, drowsiness, confusion, oligurija, which can go to anuria (as a result of hypovolemia), violations of water-electrolyte balance (giponatriemiya, kaliopenia).

Treatment: gastric lavage, administration of activated charcoal, Correction fluid and electrolyte balance in the hospital. With a significant decrease in blood pressure should be transferred to the patient in a horizontal position with raised legs. If necessary, – I / saline infusion, measures, to restore the BCC.

Perindoprilat can be removed from the body by dialysis.

Drug Interactions

Noliprel^® A fort

Combinations, It is not recommended for use

With simultaneous use of drugs lithium and ACE inhibitors can occur reversible increase in the concentration of lithium in blood plasma and related toxic effects. Additional administration of thiazide diuretics may further increase the concentration of lithium and increase the risk of toxicity. Simultaneous use of the combination of perindopril and indapamide with lithium is not recommended. When the need for such therapy should be continuously monitored, the lithium content in the blood plasma.

Combinations, the application of which requires special care

Baclofen enhances the hypotensive effect Noliprel^® A fort. In an application should be carefully monitored blood pressure and renal function and the need to adjust the dose Noliprel^® A fort.

In an application with NSAIDs, including aspirin in high doses (more 3 g / day) may reduce the diuretic, natriuretic and hypotensive effect. With a significant loss of fluid may develop acute renal failure (due to a decrease in glomerular filtration). Before the start of treatment is necessary to make up the loss of fluids and at the beginning of treatment carefully monitor renal function.

Combinations, the application of which requires careful

In an application Noliprel^® A fort and tricyclic antidepressants, neuroleptics may increase the hypotensive action and increased risk of orthostatic hypotension (additive effect).

GCS, tetrakozaktid reduce the hypotensive effect Noliprel^® A fort (electrolytes and water retention as a result of GCS).

Other antihypertensive drugs enhance the effect Noliprel^® A fort.

Perindopril

Combinations, It is not recommended for use

ACE inhibitors reduce the renal excretion of potassium, caused by diuretic. Potassium-sparing diuretics (eg, spironolactone, triamterene, amilorid), potassium supplements and food substitutes kalisodergaszczye salts can lead to a significant increase in the concentration of potassium in blood serum or death. If necessary the combined use of an ACE inhibitor and the above preparations (If confirmed, hypokalemia), care should be taken to carry out regular monitoring of the concentration of potassium in the blood plasma, and ECG parameters.

Combinations, the application of which requires special care

When using ACE inhibitors (captopril, Enalapril) patients with diabetes may increase the hypoglycemic effect of insulin and sulfonylureas. The states of hypoglycemia are rare (by increasing glucose tolerance and reduce insulin requirements).

Combinations, the application of which requires careful

In patients receiving ACE inhibitors, allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids or procainamide increase the risk of leucopenia.

ACE inhibitors may increase the hypotensive effect of funds for general anesthesia.

Previous treatment with diuretics (and thiazide “loop”) in high doses can cause a decrease in the bcc and hypotension in the appointment of perindopril.

Indapamid

Combinations, the application of which requires special care

Because of the risk of hypokalemia should be taken when used together with drugs indapamide, able to cause a type of arrhythmia “pirouette”, eg, antiarrhythmic drugs (quinidine, sotalol, gidroxinidin), some neuroleptics (pimozid, tioridazin), other drugs, such as cisapride. Avoid development of hypokalemia and, if necessary, conduct its correction. QT interval should be monitored.

Amphotericin B (I /), glitches- and mineralokortikosteroidy (when the appointment system), tetracosactide, laxatives, stimulate intestinal motility, increase the risk of hypokalemia (additive effect). Necessary to control the level of potassium in the blood plasma, if necessary – its correction. Particular attention should be paid to patients, while receiving cardiac glycosides. Use laxatives, does not stimulate intestinal motility.

Hypokalemia increases the toxic effects of cardiac glycosides. With simultaneous use of indapamide and cardiac glycosides should monitor the level of potassium in the blood plasma, and ECG and, if necessary, adjust therapy.

Combinations, the application of which requires careful

Diuretic (incl. indapamid) can cause functional renal failure, which increases the risk of lactic acidosis while taking metformin. It should appoint metformin, if the content of serum creatinine exceeds 1.5 mg / dL (135 mmol / l) in men and 1.2 mg / dL (110 mmol / l) female.

At considerable dehydration, which is caused by taking diuretics, It increases the risk of developing renal failure during treatment with iodine-containing contrast agents in high doses. Before use of iodine-containing contrast media is necessary to rehydrate.

In an application with calcium salts may develop hypercalcemia by lowering its excretion in the urine.

When use of indapamide with the constant use of cyclosporine increased the level of creatinine in the plasma even at normal water and electrolyte balance.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

No special storage conditions requires. Shelf life – 3 year.