Noliprel A Bi-Forte tabs 10mg + 2.5mg #30

Instruction for use of Noliprel A Bi-Forte

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Noliprel A Bi-forte is a combined antihypertensive drug.

Release form and composition

The drug is produced in the form of film-coated tablets: biconvex, round, white (29 or 30 pcs. In a polypropylene bottle equipped with a dispenser and a stopper containing a moisture-absorbing gel; 1 bottle in a cardboard box with first opening control; for hospitals - 30 pcs. in a polypropylene bottle with a dispenser, 3 bottles in a cardboard box with first opening control; 30 bottles each in a cardboard pallet, in a cardboard box with first opening control, 1 pallet and instructions for use of Noliprel A Bi-forte).
Composition of 1 tablet:
    active ingredients: perindopril arginine - 10 mg (equivalent to perindopril in the amount of 6.79 mg); indapamide - 2.5 mg;
    additional components: anhydrous colloidal silicon dioxide, magnesium stearate, lactose monohydrate, maltodextrin, sodium carboxymethyl starch (type A);
    film shell: magnesium stearate, macrogol 6000, titanium dioxide (E171), hypromellose, glycerol.

Pharmacodynamics

Noliprel A Bi-forte is a combined agent that includes an angiotensin-converting enzyme (ACE) inhibitor and a sulfonamide diuretic. The drug is characterized by pharmacological properties that combine the action of each of its active components. The antihypertensive properties of which are enhanced by their additive synergism.
Perindopril belongs to ACE inhibitors, the so-called. kininase II is an exopeptidase involved in the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, as well as in the breakdown of bradykinin, which has a vasodilating effect, to the formation of an inactive heptapeptide. This substance provides a decrease in the production of aldosterone, in the blood plasma it helps to increase the activity of renin according to the principle of negative feedback, with prolonged use it weakens the total peripheral vascular resistance (OPSR), which is largely associated with the effect on the vessels of the muscles and kidneys. These events do not increase the risk of developing tachycardia and do not lead to fluid and sodium retention.
By helping to reduce preload and afterload, perindopril normalizes and supports the work of the heart muscle. In patients with chronic heart failure (CHF), due to its action (according to hemodynamic parameters), filling pressure in the right and left ventricles of the heart decreases, systemic vascular resistance decreases, cardiac output and cardiac index increase, and muscle peripheral blood flow increases.
Indapamide belongs to the group of sulfonamides and exhibits pharmacological properties similar to those of thiazide diuretics. By inhibiting sodium reabsorption in the cortical segment of Henle's loop, the substance provides an increase in the excretion of sodium and chlorine ions by the kidneys, and, to a lesser extent, magnesium and potassium ions, which causes an increase in diuresis and a decrease in blood pressure.
Noliprel A Bi-forte demonstrates a dose-dependent hypotensive effect on diastolic and systolic blood pressure, both in the standing and lying position. The antihypertensive effect of the drug is observed for 24 hours. Less than one month after the start of the course, a stable therapeutic effect is achieved, in which the occurrence of tachyphylaxis is not observed. Completion of therapy does not lead to withdrawal symptoms. The antihypertensive agent helps to reduce the level of left ventricular hypertrophy (LVH), improve the elasticity of the arteries, reduce the systemic vascular resistance, does not interfere with the metabolism of lipids - triglycerides, total cholesterol, low and high density lipoprotein cholesterol (LDL and HDL).
The effect of the combined use of perindopril and indapamide on LVOT has been proven when compared with enalapril. In patients with arterial hypertension and LVOTH who took perindopril erbumine at a dose of 2 mg (which corresponds to perindopril arginine in an amount of 2.5 mg) + indapamide at a dose of 0.625 mg / enalapril at a dose of 10 mg once a day, after increasing the dose of perindopril erbumine to 8 mg (which corresponds to perindopril arginine in an amount of 10 mg) + indapamide - up to 2.5 mg / enalapril - up to 40 mg, with the same frequency of administration in the perindopril / indapamide group, when compared with the enalapril group, a greater decrease in the left ventricular mass index was observed ( LVMI). The most significant effect on LVMI was observed with perindopril erbumine 8 mg + indapamide 2.5 mg.
A stronger antihypertensive effect has also been reported with combined treatment with perindopril and indapamide compared with enalapril.
The effectiveness of perindopril has been noted in the treatment of arterial hypertension of any severity, both with low and normal renin activity in the blood plasma. The maximum antihypertensive effect of this substance is observed 4-6 hours after oral administration and persists for more than 24 hours. After this period, a high level (about 80%) of residual ACE inhibition is noted.
The complex use of thiazide diuretics leads to an increase in the severity of the antihypertensive effect. Also, the combination of an ACE inhibitor and a thiazide diuretic helps to reduce the risk of hypokalemia with concomitant use of diuretics.
The combination of an ACE inhibitor and an angiotensin II receptor antagonist (ARA II) [double blockade of the renin-angiotensin-aldosterone system (RAAS)] is not recommended for use in patients with diabetic nephropathy. This conclusion was reached in the course of clinical studies, in which patients with a history of cardiovascular or cerebrovascular diseases, or type 2 diabetes mellitus, occurring with confirmed target organ damage, as well as patients with type 2 diabetes mellitus, took part. type and diabetic nephropathy. According to the results of the conducted studies, in patients receiving this combination therapy, there was no significant positive effect on the development of renal and / or cardiovascular events and on mortality rates. At the same time, the threat of hyperkalemia, arterial hypotension and / or acute renal failure in this case was aggravated when compared with the group of patients receiving monotherapy.
The antihypertensive effect of indapamide is observed during treatment with this drug in doses that provide a minimal diuretic effect. This property of the active substance is due to an increase in the elasticity of large arteries and a decrease in systemic vascular resistance. Indapamide reduces LVOT, does not affect the level of lipids in the blood (LDL, HDL, total cholesterol, triglycerides) and carbohydrate metabolism, even in the presence of diabetes mellitus.

Pharmacokinetics

The pharmacokinetic characteristics of the active substances of Noliprel A Bi-forte with combined use do not differ from those when these drugs are used in monotherapy.

Perindopril

When taken orally, perindopril is rapidly absorbed. The maximum concentration of the substance (Cmax) in the blood plasma is noted 1 hour after ingestion. The drug is not characterized by pharmacological activity. The half-life (T1 / 2) is 1 hour. Approximately 27% of the oral dose of perindopril is in the bloodstream in the form of its active metabolite, perindoprilat. In the process of biotransformation of the active substance, in addition to perindoprilat, 5 more inactive metabolites are formed. After oral administration in blood plasma Cmax of perindoprilat is achieved after 3-4 hours, food intake slows down the conversion of perindopril to perindoprilat, thus affecting the bioavailability of the drug.
A linear dependence of the level of perindopril in plasma from its dose was established. The volume of distribution (Vd) of unbound perindoprilat can be about 0.2 L / kg. With blood plasma proteins, mainly with ACE, perindoprilat (depending on the concentration) binds by about 20%.
The active metabolite is excreted from the body by the kidneys, the effective T1 / 2 of the unbound fraction is approximately 17 hours, the equilibrium state is reached within 4 days.
In the presence of heart and renal failure, as well as in elderly patients, the excretion of perindoprilat is slowed down. The dialysis substance clearance is 70 ml / min.

Indapamide

The active substance is rapidly and completely absorbed from the gastrointestinal tract (GIT). After 1 hour after oral administration, Cmax of indapamide in blood plasma is achieved. When taken again, there is no accumulation of the substance. The connection with blood plasma proteins is 79%, T1 / 2 varies in the range from 14 to 24 hours (on average 18 hours).
Indapamide is excreted mainly by the kidneys (about 70% of the dose taken) and in the form of inactive metabolites through the intestines (about 22%).
Pharmacokinetic parameters in patients with renal insufficiency do not change.

Indications for use

Noliprel A Bi-Forte is recommended for use for the treatment of hypertension in patients who require combined administration of perindopril and indapamide at a dose of 10 and 2.5 mg, respectively.

Contraindications

Absolute contraindications for perindopril:
    the presence of one functioning kidney or bilateral stenosis of the renal arteries (since, against the background of initial hyponatremia, there is a possibility of sudden arterial hypotension);
    hereditary / idiopathic angioedema;
    a history of indications of angioedema (Quincke's edema) caused by taking an ACE inhibitor;
    combined use with aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function [glomerular filtration rate (GFR) less than 60 ml / min / 1.73 m2 of body surface area]; due to the aggravation of the risk of hyperkalemia, deterioration of renal function, cardiovascular morbidity and mortality;
    hypersensitivity to perindopril and other ACE inhibitors.
Absolute contraindications for indapamide:
    hypokalemia;
    severe hepatic failure (including with the development of encephalopathy);
    renal failure of moderate and severe degree [creatinine clearance (CC) less than 60 ml / min];
    combined use with drugs that can lead to the appearance of pirouette-type arrhythmias;
    hypersensitivity to indapamide and other sulfonamides.
Absolute contraindications for Noliprel A Bi-forte:
    lactase deficiency, glucose-galactose malabsorption syndrome or galactosemia, lactose intolerance;
    simultaneous use with potassium and lithium preparations, potassium-sparing diuretics, drugs that prolong the QT interval; the presence in the blood plasma of an increased content of potassium ions;
    the presence of untreated heart failure in the stage of decompensation, hemodialysis therapy (due to the lack of sufficient clinical experience with the use of Noliprel A Bi-forte);
    pregnancy and breastfeeding period;
    age under 18;
    hypersensitivity to additional ingredients included in the composition of the drug.
Noliprel A Bi-forte should be taken with caution in the following conditions / diseases:
    systemic lesions of connective tissue (including systemic lupus erythematosus, scleroderma);
    immunosuppressive therapy (the threat of neutropenia, agranulocytosis is aggravated);
    cerebrovascular diseases, coronary heart disease (CHD), CHF functional class IV according to the NYHA classification (it is recommended to start therapy with the lowest effective doses);
    aortic valve stenosis / hypertrophic obstructive cardiomyopathy;
    oppression of bone marrow hematopoiesis;
    lability of blood pressure, renovascular hypertension;
    disorders of the liver and / or kidneys;
    condition after kidney transplantation;
    reduced BCC (diarrhea, vomiting, diuretic therapy, salt-free diet);
    hyperuricemia (especially with gout and urate nephrolithiasis);
    performing hemodialysis using high-flow membranes (such as AN69) or desensitization, LDL apheresis;
    diabetes;
    upcoming anesthesia;
    belonging to the Negroid race;
    elderly age;
    combined administration with non-steroidal anti-inflammatory drugs (NSAIDs), gold preparations, lithium, corticosteroids, baclofen, drugs that can provoke pirouette-type arrhythmias.

Noliprel A Bi-forte, instructions for use: method and dosage

Noliprel A Bi-forte 10 mg + 2.5 mg tablets are taken orally.
The recommended dosage regimen is 1 tablet 1 time per day, preferably in the morning, before meals.

Side effects

    nervous system: often - headache, vertigo, dizziness, paresthesia; infrequently - mood lability, sleep disturbance; extremely rarely - confusion of consciousness; with an unknown frequency - fainting;
    sense organs: often - tinnitus, visual impairment;
    lymphatic and circulatory systems: extremely rarely - leukopenia / neutropenia, hemolytic / aplastic anemia, thrombocytopenia, agranulocytosis;
    the respiratory system, organs of the chest and mediastinum: often - shortness of breath (when using ACE inhibitors, a dry cough is possible, which persists for a long time against the background of therapy with drugs of this group and passes after its completion); infrequently - bronchospasm; extremely rare - eosinophilic pneumonia, rhinitis;
    cardiovascular system: often - a significant decrease in blood pressure, including orthostatic hypotension; extremely rare - cardiac arrhythmias (atrial fibrillation, ventricular tachycardia, bradycardia), angina pectoris and myocardial infarction, presumably as a result of an excessive decrease in blood pressure in high-risk patients; with an unknown frequency - pirouette-type arrhythmia, in some cases fatal;
    musculoskeletal system and connective tissue: often - muscle spasms;
    digestive system: often - dry mouth, impaired appetite, epigastric / abdominal pain, vomiting, nausea, impaired taste, diarrhea, dyspepsia, constipation; extremely rare - cholestatic jaundice, pancreatitis, cytolytic / cholestatic hepatitis, angioedema of the intestine; with an unknown frequency - hepatic encephalopathy against the background of hepatic failure;
    urinary system: infrequently - renal failure; extremely rare - acute renal failure;
    reproductive system: infrequently - impotence;
    skin and subcutaneous fat: often - skin rashes, rash, itching, maculopapular rash; infrequently - hypersensitivity reactions in the presence of a predisposition to allergic and broncho-obstructive responses; urticaria, angioedema of the extremities, lips, face, mucous membrane of the tongue, larynx and / or vocal folds, hemorrhagic vasculitis; worsening of the course of systemic lupus erythematosus in patients with an acute form of the disease; extremely rare - toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, photosensitivity reactions;
    general disorders and symptoms: often - asthenia; infrequently - increased sweating;
    laboratory parameters: rarely - hypercalcemia; with an unknown frequency - an increase in the QT interval on the electrocardiogram (ECG); an increase in the level of glucose and uric acid in the blood, an increase in the activity of liver enzymes; a slight increase in the level of creatinine in the blood plasma and urine, which occurs when therapy is discontinued and occurs mainly in patients with renal artery stenosis, during the treatment of arterial hypertension with diuretics and in renal failure; hyperkalemia (usually transient), hypokalemia, especially significant for patients at risk, hypovolemia and hyponatremia, causing dehydration and orthostatic hypotension.

Overdose

The most common symptom of an overdose of Noliprel A Bi-forte is a pronounced decrease in blood pressure, against the background of which dizziness, drowsiness, nausea, vomiting, confusion, convulsions and oliguria (in combination with hypovolemia, can turn into anuria) can sometimes be observed. The appearance of electrolyte disturbances is also possible, including hyponatremia and hypokalemia.
If an overdose is suspected, the intake of activated charcoal and / or gastric lavage is prescribed with further measures to restore the water-electrolyte balance. If necessary, with a pronounced decrease in blood pressure, the patient is transferred to the supine position with raised legs, and hypovolemia is corrected by intravenous (iv) infusion of 0.9% sodium chloride solution. Perindoprilat can be eliminated from the body by dialysis.

Special instructions

During the period of therapy, possible clinical signs of dehydration and a decrease in the plasma level of electrolytes should be taken into account, including with diarrhea and / or vomiting, since in the case of initial hyponatremia, the threat of a sharp development of arterial hypotension increases. In such cases, regular monitoring of the concentration of electrolytes in the blood plasma is required.
If marked arterial hypotension is noted, intravenous administration of 0.9% sodium chloride solution may be prescribed.
Transient arterial hypotension is not a contraindication for further treatment with Noliprel A Bi-Forte. With the subsequent normalization of blood pressure and BCC, you can resume using the drug in lower doses, or use only one of the active substances.
During treatment, cases of severe infectious lesions, sometimes resistant to intensive antibiotic therapy, were recorded. When using perindopril in such patients, the number of leukocytes in the blood should be monitored periodically. Patients should inform their doctor if they experience any symptoms of an infectious disease (including fever and sore throat).
During treatment with Noliprel A Bi-forte, rare cases of angioedema of the tongue, lips, vocal folds and / or larynx, face, and extremities were recorded. These complications could occur during any period of therapy. If symptoms of angioedema appear, the drug should be stopped immediately and the patient should be monitored until the signs of this lesion are completely removed. If the swelling has spread to the face and lips, then in most cases the symptoms go away on their own, although antihistamines may also be prescribed if necessary. Angioneurotic edema, accompanied by laryngeal edema, can be fatal. Swelling of the vocal folds, tongue, or larynx increases the risk of airway obstruction. With the development of these symptoms, it is recommended to immediately subcutaneously inject epinephrine (adrenaline) at a dilution of 1: 1000 (0.3-0.5 ml) or take measures to ensure airway patency.
There are reports of a higher risk of angioedema in black patients.
In very rare cases, during the period of therapy with ACE inhibitors, the development of angioedema of the intestine was observed, accompanied by abdominal pain (with or without vomiting / nausea); sometimes with normal concentration of C1-esterase and without the previous appearance of angioedema of the face. The diagnosis of this adverse reaction is made by performing computed tomography (CT) of the abdomen, ultrasound (ultrasound), or during surgery. Symptoms of the lesion are relieved after the withdrawal of ACE inhibitors.
In patients with allergies during desensitization, ACE inhibitors should be used with extreme caution. Patients receiving immunotherapy with drugs containing hymenoptera venom (including bees and wasps) should avoid the use of ACE inhibitors, as this increases the risk of developing long-term and life-threatening anaphylactic reactions. However, these side effects can be avoided by temporarily discontinuing ACE inhibitors at least 24 hours before starting the desensitization procedure.
In the presence of arterial hypertension and ischemic heart disease during the period of therapy, patients should not stop using beta-blockers.
Perindopril, like other ACE inhibitors, shows a weaker antihypertensive effect in black patients when compared with representatives of other races. It is assumed that this difference is associated with the often observed low renin activity in patients of this race with arterial hypertension.
During treatment with thiazide diuretics, there have been cases of photosensitivity reactions, the development of which requires discontinuation of the drug. If diuretic therapy is to be continued, it is recommended to protect the skin from exposure to sunlight and artificial ultraviolet rays.
Indapamide can provoke a positive reaction in athletes during doping control.

Influence on the ability to drive vehicles and complex mechanisms

The active ingredients of Noliprel A Bi-forte do not lead to disturbances in psychomotor reactions. But it should be borne in mind that some patients may develop individual reactions in response to a decrease in blood pressure, especially at the beginning of treatment or when used simultaneously with other antihypertensive drugs. In this case, the ability to drive vehicles or work with other potentially dangerous mechanisms may deteriorate.

Application during pregnancy and lactation

Pregnant women, as well as women planning a pregnancy, are contraindicated to take Noliprel A Bi-forte. Strictly controlled studies of therapy with ACE inhibitors in pregnant women have not been conducted. The available data on the effect of the drug in the first trimester of pregnancy indicate the absence of drug-related malformations associated with fetotoxicity. Despite this, a slight increase in the threat of fetal development disorders cannot be completely ruled out when taking ACE inhibitors.
If pregnancy occurs against the background of drug therapy, you must immediately stop using Noliprel A Bi-forte and prescribe another antihypertensive treatment with drugs approved for use during pregnancy. In the II-III trimesters, with prolonged exposure to ACE inhibitors on the fetus, the risk of violations of its development, such as oligohydramnios, deterioration of renal function, and slowing of ossification of the skull bones, may be aggravated. A newborn may experience arterial hypotension, renal failure, hyperkalemia.
If a woman received treatment with ACE inhibitors in the II-III trimesters of pregnancy, an ultrasound of the fetus should be performed in order to assess the activity of the kidneys and the state of the skull. Newborns whose mothers took these drugs during pregnancy need careful medical supervision for the timely detection and correction of possible arterial hypotension.
In the third trimester of pregnancy, long-term therapy with thiazide diuretics can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, causing placental ischemia and fetal growth retardation. Thrombocytopenia and hypoglycemia were observed in newborns during treatment with diuretics shortly before delivery.
The use of Noliprel A Bi-forte during breastfeeding is contraindicated. It is not known whether perindopril penetrates into breast milk, but it has been established that indapamide is excreted in breast milk and can lead to the development of hypokalemia, kernicterus and hypersensitivity to sulfonamide derivatives in a newborn. Taking thiazide diuretics can cause suppression of lactation or a decrease in the amount of breast milk.

Childhood use

Patients under 18 years of age should not take Noliprel A Bi-forte, since there is no data that would confirm the efficacy and safety of its use in children and adolescents.

With impaired renal function

Patients with CC ≥60 ml / min during the treatment period require regular monitoring of the concentration of potassium and creatinine in the blood plasma.
In the presence of moderate and severe renal failure (CC less than 60 ml / min), taking Noliprel A Bi-forte is contraindicated. In some patients with arterial hypertension without prior obvious signs of impaired renal function, laboratory results may show signs of functional renal failure. In such cases, drug therapy must be discontinued. Treatment can be resumed by taking low doses of a combination of active substances, or using only one of the drugs. In patients of this risk group, monitoring of the content of creatinine and potassium ions in the blood serum is required 2 weeks after the start of taking Noliprel A Bi-forte and then every 2 months. Most of the renal failure occurs in patients with initial functional impairment of the kidneys (including renal artery stenosis) or with severe CHF.

For violations of liver function

In the presence of severe hepatic impairment, the use of Noliprel A Bi-forte is contraindicated. No dose adjustment is required in patients with moderate hepatic impairment.
In some cases, during the use of ACE inhibitors, the appearance of cholestatic jaundice was noted. Against the background of the progression of this side effect, the development of fulminant necrosis of the liver, sometimes with a fatal outcome, is possible. The mechanism for the development of this complication is unclear. If during the period of taking Noliprel A Bi-forte jaundice occurs or the activity of liver enzymes is significantly increased, therapy should be discontinued and an urgent doctor should be consulted.
Taking thiazide / thiazide-like diuretics with existing liver dysfunctions can cause the development of hepatic encephalopathy. In this case, it is necessary to immediately stop treatment with Noliprel A Bi-forte.

Use in the elderly

Before starting treatment in elderly patients, it is required to assess the functional activity of the kidneys and the plasma concentration of potassium in the blood. In this category of patients, the level of plasma creatinine should be determined taking into account age, body weight and sex. At the beginning of the course of therapy for the elderly, the dose of perindopril is set depending on the level of decrease in blood pressure, especially with a decrease in BCC and loss of electrolytes. These measures allow you to avoid a sharp drop in blood pressure.
Elderly patients with normal renal function are recommended to take Noliprel A Bi-forte as usual, 1 tablet 1 time per day.

Drug interactions

Not recommended combinations of Noliprel A Bi-forte, or its active ingredients with other substances / preparations:
    lithium preparations: the risk of a reversible increase in the concentration of lithium in the blood plasma and the resulting toxic effects while taking ACE inhibitors increases; additional use of thiazide diuretics can cause a further increase in the plasma level of lithium and an aggravation of the risk of toxicity; if necessary, the implementation of such a combination should regularly monitor the level of lithium in the plasma;
    estramustine: the threat of an increase in the frequency of undesirable effects, including angioedema, increases when taken together with perindopril;
    potassium preparations, potassium-sparing diuretics (spironolactone, amiloride, triamterene, eplerenone), potassium-containing substitutes for table salt: serum potassium levels are within normal limits, hyperkalemia may rarely develop when combined with ACE inhibitors; the simultaneous administration of all these agents in combination with the drug can cause a significant increase in the content of potassium in the blood serum, up to a lethal outcome; with confirmed hypokalemia, caution is required and regular monitoring of plasma potassium concentration and ECG parameters.
Possible interaction reactions requiring special attention and caution with the combined use of Noliprel A Bi-forte or its active ingredients with the following drugs / substances:
    baclofen: the antihypertensive effect is enhanced, it is required to control blood pressure and kidney function, if necessary, the dose of antihypertensive drugs should be adjusted;
    NSAIDs (including acetylsalicylic acid in doses exceeding 3000 mg per day, non-selective NSAIDs and COX-2 inhibitors): it is possible to reduce the antihypertensive effect when combined with ACE inhibitors; the risk of deterioration in renal function increases, including the appearance of acute renal failure, and an increase in the level of potassium in the blood serum, mainly in patients with initially reduced renal function; patients should restore fluid balance and regularly monitor kidney function at the beginning of joint treatment and during its course;
    hypoglycemic oral drugs, sulfonylurea derivatives: the hypoglycemic effect of these drugs and insulin increases in patients with diabetes mellitus while taking ACE inhibitors; there was extremely rare occurrence of hypoglycemia, due to an increase in glucose tolerance and a decrease in insulin requirements; requires regular monitoring of plasma glucose levels during the first month of this combination;
    antiarrhythmics of class IA (quinidine, disopyramide, hydroquinidine) and class III (bretylium tosylate, dofetilide, amiodarone, ibutilide), sotalol, benzamides (sultopride, amisulpride, tiapride, sulpiride); antipsychotics (levomepromazine, chlorpromazine, cyamemazine, trifluoperazine, thioridazine); butyrophenones (droperidol, haloperidol); pimozide, diphemanil methyl sulfate, sparfloxacin, bepridil, halofantrine, cisapride, moxifloxacin, erythromycin (i.v.), pentamidine, mizolastine, vincamine (i.v.), terfenadine, astemizole, methadone (drugs capable of initiating arrhythmias) the occurrence of hypokalemia while taking indapamide; control of the QT interval, plasma potassium, and, if necessary, correction of hypokalemia is required;
    gluco- and mineralocorticoids (having a systemic effect), amphotericin B (i / v), tetracosactide; laxatives that activate intestinal motility (drugs that can provoke hypokalemia): due to the additive effect, when combined with indapamide, the threat of hypokalemia increases; monitoring of the concentration of potassium in the plasma is required, and, if necessary, also its correction; patients receiving cardiac glycosides require careful monitoring; it is recommended to use laxatives that do not stimulate peristalsis;
    cardiac glycosides: the toxic effect of these drugs is enhanced with hypokalemia, as a result of which, when combined with indapamide, the plasma potassium content and ECG parameters should be monitored; correction of therapy may be required.
    Interaction reactions requiring attention in the combined use of Noliprel A Bi-forte or its active ingredients with the following drugs / substances:
    tetracosactide, corticosteroids: the antihypertensive effect is weakened, due to the retention of fluid and sodium ions due to the influence of corticosteroids;
    antipsychotics (neuroleptics), tricyclic antidepressants: the antihypertensive effect increases and the threat of orthostatic hypotension is aggravated (additive effect);
    other antihypertensive drugs; vasodilators: it is possible to increase the hypotensive effect;
    ARA II inhibitors, aliskiren: when these drugs are taken simultaneously with an ACE inhibitor, the incidence of undesirable effects, such as hyperkalemia, arterial hypotension, renal impairment (including acute renal failure), increases when compared with the use of a single drug that affects on the RAAS; as a result, double blockade of RAAS by the combined use of an ACE inhibitor with ARA II or aliskiren is not recommended; if this combination is necessary, the drugs should be taken under strict medical supervision, with regular monitoring of plasma potassium concentration, renal function and blood pressure;
    thiazide and loop diuretics (in high doses): hypovolemia may develop; when these drugs are added to the treatment with perindopril, the risk of arterial hypotension increases;
    cytostatic and immunosuppressive drugs, allopurinol, corticosteroids (with systemic use), procainamide: the threat of leukopenia increases when taken simultaneously with ACE inhibitors;
    drugs for general anesthesia: the antihypertensive effect is enhanced when combined with perindopril; it is recommended, if possible, to stop taking Noliprel A Bi-forte 24 hours before the surgery using general anesthesia;
    gliptins (sitagliptin, saxagliptin, linagliptin, vildagliptin): the risk of angioedema in combination with ACE inhibitors increases due to the inhibition of dipeptidylpeptidase-4 activity by gliptin;
    sympathomimetics: the antihypertensive effect decreases;
    gold preparations (i / v), including sodium aurothiomalate: against the background of the use of ACE inhibitors, nitrate-like reactions may develop, such as nausea, vomiting, arterial hypotension, flushing of the skin of the face;
    iodine-containing contrast agents (especially in large doses): the risk of developing acute renal failure as a result of dehydration of the body while taking diuretic drugs increases; before carrying out this combination, it is necessary to restore the water balance;
    metformin: the threat of lactic acidosis is increased due to functional renal failure associated with the intake of diuretics (especially loop diuretics); with a plasma creatinine level in men - 15 mg / l (135 μmol / l), and in women - 12 mg / l (110 μmol / l), you should not use metformin;
    calcium salts: hypercalcemia may develop as a result of a decrease in the excretion of calcium ions by the kidneys;
    cyclosporine: the concentration of creatinine in plasma increases in the absence of a change in its level, even with normal levels of water and sodium ions.

Terms and conditions of storage

Store at a temperature not exceeding 30 ° C, out of the reach of children.
Shelf life is 2 years.

Reviews about Noliprel A Bi-Fort

Reviews of Noliprel A Bi-forte are positive in most cases. Patients note that the combined antihypertensive drug effectively and stably normalizes blood pressure, improves the elasticity of the vascular walls, and helps to reduce LVOT. In patients with diabetes mellitus, Noliprel A Bi-forte does not affect blood glucose levels, unlike some of its analogues. Many physicians believe it is well suited for the treatment of primary hypotension, with possible further dosage adjustments.
The disadvantages of the remedy include the presence of a large number of contraindications and possible side effects.

Terms of sell

You can buy Noliprel A Bi-Forte without a prescription from a doctor.