Noliprel forte: a double blow to hypertension. Instructions for use Noliprel ® forte a (noliprel forte a) Noliprel a forte doses
- Instructions for use Noliprel ® forte a
- Composition of the drug Noliprel ® forte a
- Indications of the drug Noliprel ® forte a
- Storage conditions for the drug Noliprel ® forte a
- Shelf life of the drug Noliprel ® forte a
ATX Code: Cardiovascular system (C) > Drugs affecting the renin-angiotensin system (C09) > ACE inhibitors in combination with other drugs (C09B) > ACE inhibitors in combination with diuretics (C09BA) > Perindopril in combination with diuretics (C09BA04)
Release form, composition and packaging
tab., cover film-coated, 5 mg+1.25 mg: 14 or 30 pcs.Reg. No.: 8649/08/10/13/18 dated 08/30/2018 - Registration period. beat is not limited
Film-coated tablets, white, elongated shape.
Excipients: lactose monohydrate - 71.33 mg, magnesium stearate (E470B), maltodextrin, colloidal anhydrous silicon dioxide (E551), sodium starch glycolate (type A).
Film shell composition: glycerol (E422), hypromellose (E464), macrogol 6000, magnesium stearate (E470B), titanium dioxide (E171).
14 pcs. - polypropylene tubes with dispenser (1) - cardboard packs.
30 pcs. - polypropylene tubes with dispenser (1) - cardboard packs.
Description of the drug NOLIPREL ® FORTE A based on officially approved instructions for use of the drug and made in 2013. Update date: 02/22/2013
A combination drug containing perindopril (ACE inhibitor) and indapamide (thiazide-like diuretic). The pharmacological effect of the drug Noliprel ® forte A is due to the combination of the properties of each component. The combined use of perindopril and indapamide provides a synergistic antihypertensive effect compared to each component separately.
Perindopril
Perindopril is an ACE inhibitor, the enzyme that converts angiotensin I to angiotensin II. In addition, ACE stimulates the secretion of aldosterone by the adrenal glands and enhances the breakdown of bradykinin, which has a vasodilator effect, to an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone, according to the principle of negative feedback, increases the activity of renin in the blood plasma, and with long-term use reduces the peripheral vascular resistance, which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by salt and water retention or the development of reflex tachycardia with prolonged use.
The action of perindopril is carried out through the active metabolite perindoprilat. Other metabolites are inactive.
Perindopril also has a hypotensive effect in patients with low or normal renin levels.
Perindopril facilitates the work of the heart due to a vasodilatory effect on the veins (reduced preload), probably due to changes in the metabolism of prostaglandins, as well as due to a decrease in peripheral vascular resistance (reduced afterload).
When studying hemodynamic parameters in patients with heart failure, the following was revealed:
- decreased filling pressure in the left and right ventricles of the heart;
- decrease in OPSS;
- increased cardiac output and increased cardiac index;
- increased peripheral blood flow in muscles.
Exercise tests also showed improved results.
Perindopril acts for arterial hypertension of any degree:
- from mild to moderate to severe. A decrease in diastolic and systolic blood pressure occurs both in the supine and standing positions. The maximum hypotensive effect is observed 4-6 hours after taking a single dose and persists for at least 24 hours. There is a high degree of residual inhibition of ACE activity 24 hours after taking the drug - about 80%. In patients amenable to treatment, normalization of blood pressure is achieved after one month and is maintained without the development of tachyphylaxis. Discontinuation of treatment does not lead to the restoration of arterial hypertension. Perindopril has vasodilatory properties and restores the elasticity of the main arterial vessels, corrects histomorphometric changes in resistant arteries and reduces left ventricular hypertrophy.
If necessary, the addition of a thiazide diuretic results in additive effects.
The combined administration of an ACE inhibitor with a thiazide diuretic reduces the risk of hypokalemia that occurs when taking only one diuretic.
Indapamide
Indapamide belongs to the group of sulfonamides and is a chlorsulfamoyl diuretic. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the loop of Henle, which leads to an increase in the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys, thereby increasing diuresis and having a hypotensive effect.
Indapamide, when used alone, has a hypotensive effect that lasts for 24 hours. This effect occurs at doses at which the diuretic effect of indapamide is minimal. The effectiveness of the hypotensive effect of indapamide is proportional to its ability to improve arterial elasticity, reduce peripheral vascular resistance and arteriolar resistance. Indapamide helps reduce left ventricular hypertrophy.
When doses of thiazide and thiazide-like diuretics are exceeded, their antihypertensive effectiveness reaches a plateau, and undesirable effects become more pronounced. If treatment is ineffective, then the dose should not be increased.
In addition, it has been shown that in short-, medium- and long-term treatment of patients suffering from arterial hypertension, indapamide does not affect lipid metabolism, i.e. for the content of triglycerides, LDL cholesterol, HDL cholesterol; does not affect carbohydrate metabolism, even in patients with diabetes mellitus and arterial hypertension.
Noliprel ® forte A
Noliprel ® forte A, regardless of the patient's age, has a dose-dependent hypotensive effect on both diastolic and systolic blood pressure in the standing and lying position.
The multicenter, randomized, double-blind PICXEL study assessed the effect of perindopril/indapamide on left ventricular hypertrophy compared with enalapril monotherapy using echocardiography.
In the PICXEL study, patients with hypertension and left ventricular hypertrophy (defined as a left ventricular mass index (LVMI) > 120 g/m2 in men and > 100 g/m2 in women) were randomized to either receive perindopril tert. butylamine 2 mg (equivalent to 2.5 mg perindopril arginine)/indapamide 0.625 mg or in the group receiving enalapril 10 mg, taken once a day for one year. The dose was adapted depending on changes in blood pressure towards an increase:
- up to perindopril tert-butylamine 8 mg (equivalent to 10 mg perindopril arginine)/indapamide 2.5 mg, or up to 40 mg enalapril 1 time/day. Only 34% of patients continued taking perindopril tert-butylamine 2 mg (equivalent to 2.5 mg perindopril arginine)/indapamide 0.625 mg;
- only 20% continued taking enalapril 10 mg.
At the end of treatment, LVMI decreased statistically significantly more in the perindopril/indapamide group (-10.1 g/m2) than in the enalapril group (-1.1 g/m2) in all populations of randomized patients. The difference in these changes between groups was -8.3 (CI 95% (-11.5; -5.0), p< 0.0001).
The most pronounced effect on LVMI was achieved with a dose of perindopril 8 mg (equivalent to 10 mg perindopril arginine)/indapamide 2.5 mg.
When assessing blood pressure, the mean difference between groups in the randomized population was -5.8 mm. rt. Art. (CI 95% (-7.9; -3.7), p< 0.0001) по систолическому АД и -2.3 мм. рт. ст. (ДИ 95% (-3.6;-0.9), р = 0.0004) по диастолическому АД, в пользу группы, получавшей периндоприл/индапамид.
The pharmacokinetic parameters of perindopril and indapamide when combined do not change compared to their separate use.
Perindopril
Absorption and Metabolism
After oral administration, perindopril is rapidly absorbed. Cmax of perindopril in blood plasma is achieved within 1 hour. T1/2 of perindopril from plasma is 1 hour. Bioavailability of perindopril is 65-70%. Perindopril is a prodrug. 27% of the administered dose of perindopril enters the systemic circulation in the form of the active metabolite perindoprilate. In addition, 5 more inactive metabolites are formed in the body. Cmax of perindoprilate in blood plasma is achieved 3-4 hours after oral administration of perindopril.
When taken with food, the conversion of perindopril to perindoprilat decreases, and therefore its bioavailability, therefore it is recommended to take perindopril arginine on an empty stomach. The correlation between the dose of perindopril and its plasma concentration has been shown to be linear.
Distribution
The binding of perindoprilate to plasma proteins is 20% (mainly with ACE) and depends on its concentration in the blood plasma.
V d of unbound perindoprilate is about 0.2 l/kg. C ss is achieved on average after 4 days.
Removal
Perindoprilat is excreted from the body in the urine. The final half-life of unbound perindoprilate is 17 hours.
The elimination of perindoprilate is slowed down in elderly patients, as well as in patients with renal failure and heart failure.
The clearance of perindoprilate during dialysis is 70 ml/min.
The pharmacokinetics of perindopril changes in patients with liver cirrhosis:
- hepatic clearance of perindopril is reduced by 2 times. However, the concentration of the resulting perindoprilate does not change, so dose adjustment of the drug is not required.
Indapamide
Suction
Indapamide is quickly and completely absorbed from the gastrointestinal tract. Cmax in blood plasma is achieved 1 hour after oral administration.
Distribution
Plasma protein binding - 79%.
Repeated administration of the drug does not lead to its accumulation in the body.
Removal
T1/2 is 14-24 hours (average 18 hours). It is excreted mainly in urine (70% of the administered dose) and in feces (22%) in the form of inactive metabolites.
Pharmacokinetics in special clinical situations
The pharmacokinetics of indapamide do not change in patients with renal failure.
The drug should be taken orally, in the morning, preferably before meals.
For adults the drug is prescribed 1 tablet. 1 time/day
A switch to Noliprel ® forte A should be carried out if the effectiveness of the drug Noliprel ® A 2.5 mg/0.625 mg is insufficient. In a stable clinical situation, you can transfer the patient from monotherapy directly to taking Noliprel ® forte A.
U elderly patients Treatment should be started after assessing blood pressure response and renal function.
At severe renal failure (SC< 30 мл/мин) At CC > 60 ml/min
The use of the drug is contraindicated.
Perindopril inhibits the activity of the RAAS and tends to reduce the excretion of potassium ions caused by indapamide. In 4% of patients while using the drug Noliprel ® forte A, hypokalemia was observed (potassium level<3.4 ммоль/л).
Determination of the frequency of adverse reactions:
- very often (≥1/10);
- often (≥1/100,<1/10);
- uncommon (≥1/1000,<1/100);
- rare (≥ 1/10,000,<1/1000);
- very rarely (< 1/10 000);
- unknown (impossible to estimate from available data).
From the hematopoietic system: very rarely - thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (patients after kidney transplantation, patients on hemodialysis), anemia has been observed when taking ACE inhibitors.
From the side of the central nervous system: uncommon - paresthesia, headache, dizziness, asthenia;
From the side of the organ of vision: often - visual impairment.
On the part of the hearing organ: often - tinnitus.
From the cardiovascular system: often - orthostatic or non-orthostatic hypotension;
From the respiratory system: often - during the use of ACE inhibitors, a dry cough may occur, which persists for a long time while taking drugs of this group and disappears after their withdrawal (the possibility of iatrogenic etiology should be taken into account), shortness of breath;
From the digestive system: often - dryness of the oral mucosa, nausea, vomiting, pain in the epigastric region, abdominal pain, change in taste, dyspepsia, constipation, diarrhea;
From the skin: often - rash, itching, maculopapular rash;
Allergic reactions: uncommon - angioedema of the face, lips, extremities, mucous membrane of the tongue, glottis and/or larynx;
From the immune system: infrequently - worsening of the course of acute disseminated lupus erythematosus.
From the musculoskeletal system: often - muscle cramps.
From the urinary system: infrequently - renal failure;
From the reproductive system: infrequently - impotence.
From the side of metabolism: rarely - hypercalcemia;
Laboratory indicators: unknown - prolongation of the QT interval on the ECG, increased concentrations of uric acid and glucose in the blood during treatment, increased activity of liver enzymes, a slight increase in plasma urea and creatinine, reversible after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of arterial hypertension with diuretics and in case of renal failure.
Others: often - asthenia;
Perindopril
- hereditary/idiopathic angioedema;
- history of angioedema (Quincke's edema) associated with treatment with an ACE inhibitor;
- II and III trimesters of pregnancy;
- hypersensitivity to perindopril and other ACE inhibitors.
- < 30 мл/мин);
- hepatic encephalopathy;
- severe liver failure;
- hypokalemia;
- lactation (breastfeeding);
- hypersensitivity to indapamide and sulfonamides;
- It is not recommended to prescribe in combination with non-antiarrhythmic drugs that cause paroxysmal ventricular tachycardia of the “pirouette” type.
- severe renal failure (CK<30 мл/мин);
- dialysis (due to lack of therapeutic experience);
- untreated decompensated heart failure (due to insufficient therapeutic experience);
- hypersensitivity to the components of the drug.
Indapamide
Noliprel ® forte A
Use during pregnancy and breastfeeding
Pregnancy
The use of Noliprel ® forte A in the first trimester of pregnancy is not recommended; in the second and third trimesters of pregnancy it is contraindicated.
Perindopril
The use of ACE inhibitors in the first trimester of pregnancy is not recommended; in the second and third trimesters of pregnancy it is contraindicated.
Epidemiological data regarding the risk of teratogenicity when taking ACE inhibitors in the first trimester of pregnancy do not allow definite conclusions to be drawn, however, some risk cannot be excluded. Unless continued ACE inhibitor therapy is considered absolutely necessary, patients planning pregnancy should switch to an alternative antihypertensive drug that has been established to have a safe profile in pregnancy. If pregnancy is confirmed, treatment with ACE inhibitors should be stopped immediately and, if necessary, switched to an alternative treatment.
It is known that taking ACE inhibitors in the second and third trimesters of pregnancy in humans has a toxic effect on the fetus (reduced renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, arterial hypotension, hyperkalemia). If you are taking ACE inhibitors, starting from the second trimester of pregnancy, it is recommended to conduct an ultrasound examination of kidney and skull function.
If the mother took ACE inhibitors during pregnancy, the infant should be closely monitored for the development of arterial hypotension.
Indapamide
Long-term use of a thiazide diuretic in the third trimester of pregnancy can lead to a decrease in blood volume in the mother's body, as well as a decrease in uteroplacental blood flow, which can cause fetoplacental ischemia and fetal growth retardation. In addition, rare cases of hypoglycemia and thrombocytopenia have been reported in newborns.
Breast-feeding
Noliprel ® forte A is contraindicated during breastfeeding. If it is necessary to prescribe Noliprel ® forte A during lactation, the issue of stopping breastfeeding should be decided.
Perindopril
Since there is no data on the use of perindopril during breastfeeding, the use of perindopril is not recommended. During breastfeeding, especially in newborns and premature infants, it is preferable to prescribe alternative treatments whose safety profile is better studied.
Indapamide
Indapamide is excreted in breast milk. Taking thiazide diuretics causes a decrease in the amount of breast milk or suppression of lactation. The newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia and kernicterus.
At moderate liver dysfunction no dose adjustment is required. At severe liver dysfunction the use of the drug is contraindicated.
At severe renal failure (creatinine clearance less than 30 ml/min) moderate renal failure (creatinine clearance 30-60 ml/min) It is recommended to begin treatment with an adequate dose of the free combination. At CC ≥ 60 ml/min no dose adjustment is required. During treatment, serum creatinine and potassium levels should be monitored frequently.
Perindopril
Neutropenia, agranulocytosis
Neutropenia/agranulocytosis, thrombocytopenia and anemia were observed while taking ACE inhibitors. In patients with normal liver function and in the absence of other complicating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with pre-existing liver dysfunction. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Hypersensitivity/angioedema
When taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and/or larynx may occur. These reactions may occur at any time during therapy. In such cases, the drug should be stopped immediately and the necessary monitoring should be carried out until the symptoms disappear completely. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used to treat symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. If these symptoms appear, you should immediately administer epinephrine solution 1:
- 1000 (0.3-0.5 ml) subcutaneously and/or ensure airway patency.
There are reports that black patients are more likely to experience angioedema when taking ACE inhibitors than white patients.
Patients who have had angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain (with or without nausea and vomiting), in some cases, without previous angioedema of the face and with normal C1-esterase levels. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of persistent, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteric venom (including bee and aspen). ACE inhibitors should be prescribed with extreme caution to patients prone to allergic reactions and undergoing desensitization; their use should be avoided in patients undergoing immunotherapy with insect venom allergens. However, if the patient requires both treatment with ACE inhibitors and desensitization, then the onset of such reactions can be prevented by temporarily stopping the use of ACE inhibitors at least 24 hours before starting the course of desensitization therapy.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Patients on hemodialysis
Anaphylactoid reactions have been reported in some patients undergoing hemodialysis using high-flux membranes (eg, AN69®) and concomitantly receiving one of the ACE inhibitors. For such patients, the use of a different type of membrane or a different class of antihypertensive drug should be considered.
Cough
Taking an ACE inhibitor may cause a dry cough. The cough persists for a long time while taking the drug, but disappears when the drug is discontinued. This symptom may have an iatrogenic etiology. If the need to take an ACE inhibitor remains, then continued treatment should be considered.
Risk of arterial hypotension and/or renal failure (in case of heart failure, water and electrolyte deficiency)
With significant loss of water and electrolytes (strict salt-free diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with renal artery stenosis, congestive heart failure or cirrhosis of the liver, accompanied by edema and ascites, pronounced stimulation of the RAAS occurs. Therefore, inhibition of RAAS activity when taking an ACE inhibitor may lead to a sudden decrease in blood pressure and/or an increase in serum creatinine, indicating functional renal failure. This is most likely when you first take the drug and during the first 2 weeks of treatment. In some, albeit very rare cases, such a disorder develops acutely, and the onset of the process is difficult to predict. In such cases, treatment should be resumed with a lower dose, gradually increasing it.
Elderly patients
Before starting treatment, kidney function and potassium levels should be monitored. To avoid sudden arterial hypotension, the initial dose of the drug is adjusted depending on the degree of decrease in blood pressure, especially in the case of dehydration and loss of electrolytes.
Patients with established atherosclerosis
The risk of arterial hypotension exists in all patients, but the drug should be used with extreme caution in patients with coronary artery disease or cerebrovascular insufficiency. In such cases, treatment should be started with a low dose.
Renovascular hypertension
Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension awaiting surgery or when surgery is not available.
In patients with an established diagnosis of renal artery stenosis or if it is suspected, treatment with Noliprel ® forte A should begin in the hospital with a small dose under monitoring of renal function and potassium levels, because Some patients developed renal failure, which was reversible when treatment was discontinued.
Other risk groups
In patients with severe acute heart failure (grade IV) and in patients with insulin-dependent diabetes mellitus (a tendency to spontaneously increase potassium levels), treatment with Noliprel ® forte A should be started with low doses and carried out under constant medical supervision.
Patients with arterial hypertension and coronary insufficiency should not stop taking beta-blockers:
- An ACE inhibitor should be used in addition to a beta blocker.
Diabetes
In diabetic patients already taking oral hypoglycemic agents or insulin, glycemic levels should be carefully monitored, especially during the first month of taking an ACE inhibitor.
Ethnic differences
Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of black race compared to representatives of other races. Perhaps this difference is due to the fact that arterial hypertension in black patients very often occurs against the background of low renin activity.
Surgery/anesthesia
ACE inhibitors can cause a drop in blood pressure during anesthesia, especially if the anesthetic used has a hypotensive effect. Therefore, long-acting ACE inhibitors such as perindopril should, if possible, be discontinued 24 hours before surgery.
Aortic or mitral valve stenosis/hypertrophic cardiomyopathy
Use ACE inhibitors with caution in patients with left ventricular outflow tract obstruction.
Liver dysfunction
In rare cases, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not yet clear. In patients receiving ACE inhibitors, if jaundice or a marked increase in liver enzyme activity develops, the ACE inhibitor should be discontinued and a thorough medical examination should be performed.
Hyperkalemia
Elevated serum potassium levels have been reported in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalemia include renal failure, deterioration of renal function, age (> 70 years), diabetes mellitus, intercurrent events such as dehydration, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or taking other drugs that cause increases in serum potassium (eg, heparin). Taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes, especially in patients with impaired renal function, may result in significant increases in serum potassium levels. Hyperkalemia can cause serious arrhythmias, sometimes fatal. If concomitant administration of perindopril or the above drugs is considered necessary, they should be taken with caution and with regular monitoring of serum potassium levels.
Indapamide
In patients with impaired liver function, taking thiazide and thiazide-like diuretics can cause hepatic encephalopathy. In this case, the diuretic should be stopped immediately.
Photosensitivity
Cases of photosensitivity have been reported with the use of thiazide and thiazide-like diuretics. If photosensitivity is noted during treatment, it is recommended to stop taking the drug. If re-administration of a diuretic is considered necessary, it is recommended to protect the skin from the sun and artificial UV radiation.
Water and electrolyte balance
Sodium level. Before starting treatment, it is necessary to evaluate the sodium content, and further such studies should be carried out regularly. Taking any diuretic medication can cause a decrease in sodium levels, which sometimes leads to a number of serious complications. Initially, a decrease in sodium levels may be asymptomatic, which is why it is necessary to regularly monitor its content. In elderly patients and patients with liver cirrhosis, monitoring should be carried out even more often.
Potassium level. The main danger when taking thiazide and thiazide-like diuretics is potassium deficiency and, accordingly, hypokalemia. Consider the risk of potassium falling below the permissible level (< 3.4 ммоль/л) необходимо у лиц, входящих в группы повышенного риска, таких как пациенты пожилого возраста или и/или пациенты с нарушенным или недостаточным питанием, независимо от того, принимают они один или несколько лекарственных препаратов, у пациентов с циррозом печени, который сопровождается отеками и асцитом, у пациентов с ИБС и у пациентов с сердечной недостаточностью. В таких случаях гипокалиемия усиливает токсичность сердечных гликозидов и повышает риск развития аритмий. Пациенты с врожденным или ятрогенным увеличением интервала QT также представляют собой группу риска. Гипокалиемия, как и брадикардия, является фактором риска для развития серьезных нарушений сердечного ритма, особенно пароксизмальной желудочковой тахикардии типа "пируэт", которые могут привести к летальному исходу. В любом случае следует как можно чаще контролировать уровень содержания калия. Первое определение содержания калия в плазме следует провести в течение первой недели после начала лечения. В случае снижения уровня калия, необходимо провести коррекцию дозы.
Calcium level. Thiazide and thiazide-like diuretics can reduce the excretion of calcium in the urine, which leads to a temporary and slight increase in the concentration of calcium in the blood. A marked increase in calcium levels may be associated with undiagnosed hyperparathyroidism. In this case, treatment should be stopped until the function of the parathyroid gland is examined.
In patients with diabetes mellitus, it is necessary to constantly monitor blood glucose levels, especially if potassium levels are simultaneously low.
Uric acid
Patients with high levels of uric acid in the blood may be predisposed to developing gout.
Effect on kidney function
Thiazide and thiazide-like diuretics are most effective when renal function is normal or only slightly impaired (serum creatinine is below approximately 2.5 mg/dL, i.e. 220 µmol/L for an adult patient). In elderly patients, plasma creatinine levels should be adjusted for age, weight and gender using the Cockcroft formula:
- the calculation result should be multiplied by 0.85.
For men: CC (ml/min) = (140 – age) x body weight (kg)/0.814 x serum creatinine (µmol/l)
For women:
At the beginning of treatment, taking diuretics can lead to loss of water and sodium, which in turn leads to hypovolemia. Hypovolemia causes a decrease in glomerular filtration rate. It may be accompanied by an increase in creatinine and urea in the blood. This renal failure is temporary and does not cause undesirable consequences in patients with normal renal function, but in cases of existing impairment, renal failure may worsen.
Athletes
Please note that indapamide may cause a positive reaction during doping control.
Noliprel ® forte A
The combination of lithium and the combination of perindopril with indapamide is generally not recommended.
Kidney failure. In patients with severe renal failure (SC< 30 мл/мин) данная комбинация противопоказана. Лечение следует прекратить, если у пациента, страдающего артериальной гипертензией без видимых поражений почек, но у которого в ходе анализа крови (почечный комплекс) была обнаружена почечная недостаточность. Лечение может быть возобновлено либо данной комбинацией в более низких дозах, либо только с одним компонентов. Таким пациентам обычно следует проводить частый контроль содержания сывороточного креатинина и калия в первый раз – через 2 недели лечения, затем – 1 раз в 2 месяца в период терапевтической стабильности.
Renal failure was mainly observed in patients with acute heart failure and was also observed in renal artery stenosis. This drug is generally not recommended for patients with bilateral renal artery stenosis or for patients with only one kidney.
Arterial hypotension, deficiency of water and electrolytes. The risk of a sudden drop in blood pressure increases with low sodium levels (especially in patients with renal artery stenosis). Therefore, during treatment, the state of water and electrolyte balance should be periodically monitored, which may be disturbed due to diarrhea or vomiting. In case of severe arterial hypotension, intravenous infusion of an isotonic solution may be necessary.
Transient arterial hypotension is not a contraindication for continued treatment. After restoration of adequate blood volume and blood pressure, treatment can be resumed either with this combination at lower doses, or with only one component.
Potassium content. The combination of perindopril and indapamide does not prevent the onset of hypokalemia, especially in patients with diabetes mellitus and in patients with renal failure. As with any antihypertensive drug taken in combination with a diuretic, plasma potassium levels should be regularly monitored during treatment with this combination.
Excipients. Noliprel ® forte A should not be prescribed to patients with lactose intolerance, lapp lactase deficiency or impaired absorption of glucose-galactose.
Use in pediatrics
The effectiveness and tolerability of perindopril in children and adolescents as mono- or as part of combination therapy has not been sufficiently studied.
Impact on the ability to drive vehicles and operate machinery
Perindopril and indapamide in the form of monotherapy or in combination as part of the drug Noliprel ® forte A do not affect the ability to concentrate and the speed of psychomotor reactions. However, in some patients, especially at the beginning of treatment or when combined with another antihypertensive drug, individual reactions may develop with a decrease in blood pressure. This leads to impaired ability to drive vehicles or other mechanisms.
Results of preclinical safety studies
The toxicity of the perindopril/indapamide combination is slightly higher than the toxicity of each component. No renal toxicity was detected in rats. However, this combination causes gastrointestinal toxicity in dogs; in rats, the toxic effect on the maternal body increases (compared to perindopril). These undesirable effects occurred at doses with a very high safety margin compared to the therapeutic doses used.
Preclinical studies conducted separately with perindopril and indapamide revealed neither genotoxic nor teratogenic potential.
Symptoms: most likely - arterial hypotension, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oliguria, which can develop into anuria (as a result of hypovolemia). Electrolyte disturbances (hyponatremia, hypokalemia) may also occur.
Treatment: Emergency measures are limited to removing the active substances of the drug from the body - gastric lavage and/or taking activated charcoal with subsequent restoration of water and electrolyte balance. Treatment should be carried out in a specialized hospital. If there is a pronounced decrease in blood pressure, the patient should be placed in a supine position with legs elevated, and, if necessary, correct hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis.
Noliprel ® forte A
With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma and associated toxic effects is possible. Concomitant use of thiazide diuretics may further increase the risk of lithium toxicity. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. If this combination is necessary, the concentration of lithium in the blood plasma should be regularly monitored.
When used simultaneously with baclofen, the hypotensive effect may be enhanced. Blood pressure and renal function should be monitored and the dose of Noliprel ® forte A adjusted if necessary.
When used simultaneously with NSAIDs, including acetylsalicylic acid in high doses (at which an anti-inflammatory effect develops), COX-2 inhibitors and non-selective NSAIDs, the hypotensive effect may be reduced. When combining ACE inhibitors and NSAIDs, there may be an increased risk of deterioration of renal function with the possible development of acute renal failure, and an increase in serum potassium levels, especially in
patients with already impaired renal function. Combinations of these drugs should be prescribed with caution, especially in elderly patients. Adequate hydration of the body should be maintained. At the beginning of combination therapy, as well as periodically during therapy, renal function should be monitored.
Tricyclic antidepressants, antipsychotics (neuroleptics) enhance the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).
Corticosteroids, tetracosactide reduce the antihypertensive effect (fluid and sodium ion retention caused by the action of corticosteroids).
Other antihypertensive drugs enhance the antihypertensive effect of the drug.
Perindopril
ACE inhibitors reduce potassium loss caused by diuretics. Concomitant use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium supplements and potassium-containing table salt substitutes can lead to a significant increase in serum potassium levels, including death. If the combined use of an ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), special care should be taken and regular monitoring of the content of potassium ions in the blood plasma and ECG parameters should be carried out.
Combinations that require special care
ACE inhibitors (data confirmed for captopril and enalapril) may enhance the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. The development of hypoglycemia is very rare (improved glucose tolerance leads to a decrease in the need for insulin).
Combinations that require caution
Allopurinol, cytostatic and immunosuppressive drugs, corticosteroids (when used systemically) and procainamide when used simultaneously with ACE inhibitors increase the risk of developing leukopenia.
The combined use of ACE inhibitors and general anesthesia may lead to an enhanced antihypertensive effect.
In patients receiving thiazide and loop diuretics, at the beginning of therapy with an ACE inhibitor, a decrease in blood volume may be observed, which leads to the risk of developing arterial hypotension.
When prescribing ACE inhibitors, incl. perindopril, patients receiving injectable gold preparations (sodium aurothiomalate) in rare cases, nitrate-like reactions (facial skin flushing, nausea, vomiting, arterial hypotension) were observed.
Indapamide
Combinations that require special care
Due to the risk of hypokalemia, caution should be exercised when co-administering indapamide with drugs that can cause torsades de pointes, such as class I A antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide), class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol), some antipsychotics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenone derivatives (droperidol, haloperidol), other antipsychotics (pimozide), other drugs, incl. h. bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine IV, methadone, astemizole, terfenadine. The development of hypokalemia should be avoided and, if necessary, corrected; monitor the QT interval.
Amphotericin B (iv), gluco- and mineralocorticoids (when administered systemically), tetracosactide, laxatives, stimulant laxatives increase the risk of hypokalemia (additive effect). The content of potassium ions in the blood plasma should be monitored and, if necessary, its correction. Particular attention should be paid to patients simultaneously receiving cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.
Hypokalemia enhances the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the content of potassium ions in the blood plasma and ECG readings should be monitored and, if necessary, therapy should be adjusted.
Combinations that require caution
Functional renal failure, which can occur while taking diuretics (especially loop diuretics), with simultaneous use of metformin increases the risk of developing lactic acidosis. Metformin should not be used if the plasma creatinine concentration exceeds 1.5 mg/dL (135 µmol/L) in men and 1.2 mg/dL (110 µmol/L) in women.
With significant dehydration of the body caused by taking diuretics, the risk of developing acute renal failure increases, especially when using iodine-containing contrast agents in high doses. Before using iodine-containing drugs, rehydration should be carried out.
It is possible that calcium levels may increase as a result of decreased urinary excretion.
When used simultaneously with cyclosporine, it is possible to increase the creatinine level in the blood serum without changing the concentration of circulating cyclosporine, even with normal water and electrolyte levels.
Le Laboratoire SERVIER, representative office, (France)
Representative office in the Republic of Belarus
Les Laboratoires Servier Belarus
Detailed instructions for use are published on this page. Noliprel. The available dosage forms of the drug are listed (tablets - A, Forte, Bi-Forte 2.5 mg, 5 mg and 10 mg), as well as its analogues. Information is provided on the side effects that Noliprel can cause and on interactions with other medications. In addition to information about the diseases for the treatment and prevention of which the drug is prescribed (arterial hypertension - to reduce blood pressure), administration algorithms, possible dosages for adults and children are described in detail, the possibility of use during pregnancy and breastfeeding is clarified. The abstract for Noliprel is supplemented with reviews from patients and doctors. Composition of the drug.
Instructions for use and dosage
Prescribed orally, preferably in the morning, before meals, 1 tablet 1 time per day. If, 1 month after the start of therapy, the desired hypotensive effect has not been achieved, the dose of the drug can be increased to a dose of 5 mg (manufactured by the company under the trade name Noliprel A forte).
Elderly patients should start therapy with 1 tablet once a day.
Noliprel should not be prescribed to children and adolescents due to the lack of data on efficacy and safety in patients in this age group.
Compound
Perindopril arginine + Indapamide + excipients.
Release forms
Tablets 2.5 mg (Noliprel A).
Tablets 5 mg (Noliprel A Forte).
Tablets 10 mg (Noliprel A Bi-Forte).
Noliprel- a combination drug containing perindopril (ACE inhibitor) and indapamide (thiazide-like diuretic). The pharmacological effect of the drug is due to the combination of the individual properties of each component. The combined use of perindopril and indapamide provides a synergistic antihypertensive effect compared to each component separately.
The drug has a pronounced dose-dependent antihypertensive effect on both systolic and diastolic blood pressure in the supine and standing positions. The effect of the drug lasts 24 hours. A persistent clinical effect occurs in less than 1 month from 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 peripheral vascular resistance, and does not affect lipid metabolism (total cholesterol, HDL-C, LDL-C, triglycerides).
Perindopril is an inhibitor of the enzyme that converts angiotensin 1 into angiotensin 2. Angiotensin-converting enzyme (ACE), or kinase, is an exopeptidase that carries out both the conversion of angiotensin 1 to angiotensin 2, which has a vasoconstrictor effect, and the destruction of bradykinin, which has a vasodilator effect, to an inactive heptapeptide . As a result, perindopril reduces the secretion of aldosterone, according to the principle of negative feedback, increases the activity of renin in the blood plasma, and with long-term use reduces the peripheral vascular resistance, which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by salt and water retention or the development of reflex tachycardia with prolonged use.
Perindopril has an antihypertensive effect in patients with both low and normal plasma renin activity.
With the use of perindopril, there is a decrease in both systolic and diastolic blood pressure in the supine and standing positions. Discontinuation of the drug does not lead to an increase in blood pressure.
Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.
Perindopril normalizes heart function by reducing preload and afterload.
The combined use of thiazide diuretics enhances the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia while taking diuretics.
In patients with heart failure, perindopril causes a decrease in filling pressure in the right and left ventricle, a decrease in peripheral vascular resistance, an increase in cardiac output and an improvement in the cardiac index, and an increase in regional blood flow in the muscles.
Indapamide is a sulfonamide derivative whose pharmacological properties are close to thiazide diuretics. Inhibits the reabsorption of sodium ions in the cortical segment of the loop of Henle, which leads to increased urinary excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, thereby increasing diuresis. The hypotensive effect occurs in doses that practically do not cause a diuretic effect.
Indapamide reduces vascular hyperreactivity to adrenaline.
Indapamide does not affect the content of lipids in the blood plasma (triglycerides, cholesterol, LDL and HDL), or carbohydrate metabolism (including in patients with concomitant diabetes mellitus).
Indapamide helps reduce left ventricular hypertrophy.
Pharmacokinetics
The pharmacokinetic parameters of perindopril and indapamide when combined do not change compared to their separate use.
Perindopril
After oral administration, perindopril is rapidly absorbed. Approximately 20% of the total amount of absorbed perindopril is converted to the active metabolite perindoprilat. When taking the drug with food, the conversion of perindopril to perindoprilat is reduced (this effect does not have significant clinical significance). Perindoprilat is excreted from the body in the urine. T1/2 of perindoprilate is 3-5 hours. The elimination of perindoprilate slows down in elderly patients, as well as in patients with renal failure and heart failure.
Indapamide
Indapamide is quickly and completely absorbed from the gastrointestinal tract. Repeated administration of the drug does not lead to its accumulation in the body. It is excreted mainly in urine (70% of the administered dose) and in feces (22%) in the form of inactive metabolites.
Indications
- essential arterial hypertension.
Contraindications
- history of angioedema (including while taking other ACE inhibitors);
- hereditary/idiopathic angioedema;
- severe renal failure (CK< 30 мл/мин);
- hypokalemia;
- bilateral renal artery stenosis or stenosis of the artery of a single kidney;
- severe liver failure (including with encephalopathy);
- simultaneous use of drugs that prolong the QT interval;
- simultaneous use of antiarrhythmic drugs that can cause ventricular arrhythmia of the “pirouette” type;
- pregnancy;
- lactation period (breastfeeding);
- hypersensitivity to perindopril and other ACE inhibitors, to indapamide and sulfonamides, as well as to other auxiliary components of the drug.
special instructions
The use of Noliprel is not accompanied by a significant reduction in the incidence of side effects, with the exception of hypokalemia, compared with perindopril and indapamide at the lowest approved doses. When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. To minimize this risk, careful monitoring of the patient's condition should be carried out.
Kidney failure
In patients with severe renal failure (SC< 30 мл/мин) данная комбинация противопоказана.
In some patients with arterial hypertension without previous renal impairment, laboratory signs of functional renal failure may appear during Noliprel therapy. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of drugs, or use drugs in monotherapy. Such patients require regular monitoring of potassium and creatinine levels in the blood serum - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, incl. with renal artery stenosis.
Arterial hypotension and water-electrolyte imbalance
Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with arterial stenosis of a solitary kidney and bilateral renal artery stenosis). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased levels of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of plasma electrolyte levels. In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, therapy can be resumed using low doses of drugs, or drugs can be used as monotherapy.
The combination of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with any antihypertensive drug taken in combination with a diuretic, plasma potassium levels should be regularly monitored during treatment with this combination.
Excipients
It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.
Neutropenia/agranulocytosis
The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma). After discontinuation of ACE inhibitors, signs of neutropenia disappear on their own. To avoid the development of such reactions, it is recommended to strictly follow the recommended dose. When prescribing ACE inhibitors to this group of patients, the benefit/risk factor should be carefully weighed.
Angioedema (Quincke's edema)
In rare cases, during therapy with ACE inhibitors, angioedema of the face, extremities, mouth, tongue, pharynx and/or larynx develops. In such a situation, you should immediately stop taking perindopril and monitor the patient's condition until the swelling completely disappears. If the swelling affects only the face and mouth, the symptoms usually go away without special treatment, but antihistamines can be used to more quickly relieve symptoms.
Angioedema, which is accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, pharynx, or larynx can lead to airway obstruction. In this case, you should immediately administer epinephrine (adrenaline) subcutaneously at a dose of 1:1000 (0.3 to 0.5 ml) and take other emergency measures. Patients with a history of angioedema not associated with taking ACE inhibitors have an increased risk of developing angioedema while taking these drugs.
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors.
Anaphylactic reactions during desensitization
There are isolated reports of the development of life-threatening anaphylactic reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera insect venom (including bee and aspen). ACE inhibitors should be prescribed with caution to patients prone to allergic reactions and undergoing desensitization procedures. Prescribing the drug to patients receiving immunotherapy with hymenoptera venom should be avoided. However, anaphylactic reactions can be avoided by temporarily discontinuing the drug at least 24 hours before starting a course of desensitizing therapy.
Cough
During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible iatrogenic nature of this symptom. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.
Risk of arterial hypotension and/or renal failure (including in case of heart failure, water and electrolyte deficiency)
In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system may be observed, especially with severe hypovolemia and a decrease in the level of plasma electrolytes (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, chronic heart failure or cirrhosis of the liver with edema and ascites. The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.
Elderly patients
Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.
Patients with established atherosclerosis
The risk of arterial hypotension exists in all patients, but the drug should be used with extreme caution in patients with coronary artery disease or cerebrovascular insufficiency. In such cases, treatment should be started with a low dose.
Renovascular hypertension
The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in this category of patients, both awaiting surgery and in cases where surgery is not possible. Treatment with Noliprel in patients with diagnosed or suspected bilateral renal artery stenosis or stenosis of the artery of a single kidney should begin with a low dose of the drug in a hospital setting, monitoring renal function and potassium concentration in the blood plasma. Some patients may develop functional renal failure, which disappears when the drug is discontinued.
Other risk groups
In patients with severe heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium levels), treatment with the drug should be started with low doses and carried out under constant medical supervision.
In patients with arterial hypertension and heart failure, beta-blockers should not be discontinued: ACE inhibitors should be used together with beta-blockers.
Anemia
Anemia may develop in patients who have undergone a kidney transplant or in patients undergoing hemodialysis. The higher the initial hemoglobin level, the more pronounced its decrease. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors. The decrease in hemoglobin content is insignificant; it occurs during the first 1-6 months of treatment, and then stabilizes. When treatment is discontinued, hemoglobin levels are completely restored. Treatment can be continued under monitoring of the peripheral blood picture.
Surgery/General anesthesia
The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect. It is recommended to stop taking long-acting ACE inhibitors, incl. perindopril, the day before surgery. It is necessary to warn the anesthesiologist that the patient is taking ACE inhibitors.
Aortic stenosis/Hypertrophic cardiomyopathy
ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.
Liver failure
In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, liver necrosis may rapidly develop, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, the patient should stop taking the drug and consult a doctor.
Indapamide
In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.
Water-electrolyte imbalance
Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following categories of high-risk patients: elderly patients, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias. The high-risk group also includes patients with an increased QT interval, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially pirouette-type arrhythmias, which can be fatal. In all the cases described above, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion concentration should be carried out within the first week from the start of therapy.
If hypokalemia is detected, appropriate treatment should be prescribed.
Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretics.
It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
In patients with high levels of uric acid in the blood during treatment with Noliprel, the risk of developing gout increases.
Kidney function and diuretics
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 2.5 mg/dL or 220 µmol/L). At the beginning of diuretic treatment in patients, due to hypovolemia and hyponatremia, a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.
Photosensitivity
Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics. If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.
Athletes
Indapamide may give a positive reaction during doping control.
Impact on the ability to drive vehicles and operate machinery
The action of the substances included in the drug Noliprel does not lead to impairment of psychomotor reactions. However, some people may develop different individual reactions in response to lowering blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to therapy. In this case, the ability to drive a car or operate other machinery may be reduced.
Side effect
- dry mouth;
- nausea;
- decreased appetite;
- abdominal pain;
- taste disturbances;
- constipation;
- dry cough that persists for a long time while taking drugs of this group and disappears after their withdrawal;
- orthostatic hypotension;
- hemorrhagic rash;
- skin rashes;
- exacerbation of systemic lupus erythematosus;
- angioedema (Quincke's edema);
- photosensitivity reactions;
- paresthesia;
- headache;
- asthenia;
- sleep disturbance;
- mood lability;
- dizziness;
- muscle spasms;
- thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia;
- hypokalemia (especially significant for patients at risk), hyponatremia, hypovolemia, leading to dehydration and orthostatic hypotension, hypercalcemia.
Drug interactions
Noliprel
With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma and associated toxic effects may occur. Additional administration of thiazide diuretics may further increase lithium concentrations and increase the risk of toxicity. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. If such therapy is necessary, the lithium content in the blood plasma should be constantly monitored.
Baclofen enhances the hypotensive effect of Noliprel. With simultaneous use, blood pressure and renal function should be carefully monitored and the dose of Noliprel should be adjusted.
When used simultaneously with nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid in high doses (more than 3 g per day), the diuretic, natriuretic and hypotensive effect may be reduced. With significant fluid loss, acute renal failure may develop (due to decreased glomerular filtration). Before starting treatment with the drug, it is necessary to replace fluid loss and carefully monitor kidney function at the beginning of treatment.
With the simultaneous use of Noliprel and tricyclic antidepressants, antipsychotics, it is possible to enhance the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).
Glucocorticosteroids (GCS), tetracosactide reduce the hypotensive effect of Noliprel (retention of water and electrolytes as a result of the action of GCS).
Other antihypertensive drugs enhance the effect of Noliprel.
Perindopril
ACE inhibitors reduce diuretic-induced renal excretion of potassium. Potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, and potassium-containing table salt substitutes can lead to significant increases in serum potassium concentrations, including death. If combined use of an ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), caution should be exercised and regular monitoring of plasma potassium concentrations and ECG parameters should be carried out.
Combinations that require special caution when using
When using ACE inhibitors (captopril, enalapril) in patients with diabetes mellitus, the hypoglycemic effect of insulin and sulfonylurea derivatives may be enhanced. Conditions of hypoglycemia occur extremely rarely (due to an increase in glucose tolerance and a decrease in the need for insulin).
Combinations that require caution when using
While taking ACE inhibitors, allopurinol, cytostatic or immunosuppressive drugs, systemic corticosteroids or procainamide increase the risk of developing leukopenia.
ACE inhibitors may enhance the hypotensive effect of general anesthesia.
Previous treatment with diuretics (thiazide and loop diuretics) in high doses can cause a decrease in blood volume and arterial hypotension when perindopril is prescribed.
Indapamide
Combinations that require special caution when using
Due to the risk of hypokalemia, caution should be exercised when using indapamide together with drugs that can cause torsades de pointes, for example, antiarrhythmic drugs (quinidine, sotalol, hydroquinidine), some antipsychotics (pimozide, thioridazine), other drugs such as cisapride . The development of hypokalemia should be avoided and, if necessary, corrected. The QT interval should be monitored.
Amphotericin B (iv), gluco- and mineralocorticosteroids (when administered systemically), tetracosactide, laxatives that stimulate intestinal motility, increase the risk of hypokalemia (additive effect). It is necessary to monitor the level of potassium in the blood plasma and, if necessary, correct it. Particular attention should be paid to patients simultaneously receiving cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used.
Hypokalemia enhances the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the level of potassium in the blood plasma and ECG readings should be monitored and, if necessary, therapy should be adjusted.
Combinations that require caution when using
Diuretics (including indapamide) can cause functional renal failure, which increases the risk of developing lactic acidosis while taking metformin. Metformin should not be prescribed if serum creatinine exceeds 1.5 mg/dL (135 µmol/L) in men and 1.2 mg/dL (110 µmol/L) in women.
With significant dehydration of the body, which is caused by taking diuretic drugs, the risk of developing renal failure increases due to the use of iodine-containing contrast agents in high doses. Rehydration is necessary before using iodinated contrast agents.
When used simultaneously with calcium salts, hypercalcemia may develop as a result of decreased excretion in the urine.
When using indapamide against the background of constant use of cyclosporine, the level of creatinine in plasma increases even with a normal state of water-electrolyte balance.
Analogues of the drug Noliprel
Structural analogues of the active substance:
- Ko Perineva;
- Noliprel A;
- Noliprel A Bi-forte;
- Noliprel A forte;
- Noliprel forte;
- Perindid;
- Perindopril Indapamide Richter.
Use during pregnancy and breastfeeding
The drug should not be used in the 1st trimester of pregnancy.
If you are planning pregnancy or if it occurs while taking Noliprel, you should immediately stop taking the drug and prescribe other antihypertensive therapy.
There have been no adequate controlled studies of ACE inhibitors in pregnant women. The limited available data on the effects of the drug in the 1st trimester of pregnancy indicate that the drug did not lead to malformations associated with fetotoxicity.
Noliprel is contraindicated in the 2nd and 3rd trimesters of pregnancy.
It is known that long-term exposure of the fetus to ACE inhibitors in the 2nd and 3rd trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, slow formation of bone tissue of the skull) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).
Long-term use of thiazide diuretics in the 3rd trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal growth retardation. In rare cases, while taking diuretics shortly before birth, newborns develop hypoglycemia and thrombocytopenia.
If the patient received the drug Noliprel in the 2nd or 3rd trimesters of pregnancy, it is recommended to conduct an ultrasound examination of the fetus to assess the condition of the skull and kidney function.
Noliprel is contraindicated during lactation.
Pharmacists offer a wide selection of antihypertensive drugs. One of the most effective and safe is Noliprel.
The drug quickly reduces and stabilizes blood pressure. How Noliprel works, dosage, how to take this medicine (before or after meals) - the article will tell you about all this.
The tablets contain Perindopril and. Both substances have a pronounced antihypertensive effect, but lower blood pressure readings in different ways.
Perindopril is and Indapamide belongs to the class of sulfonamide diuretics. When combined, these components enhance each other's effects.
Medicine is prescribed to lower blood pressure symptomatically. Doctors often include Noliprel in complex therapy for chronic hypertension.
The maximum hypotensive effect develops after a month of administration and persists for a long time. This drug is effective even when other antihypertensive drugs do not help.
At the same time, the cost of the tablets is relatively low. Many people buy Noliprel, but don’t know how to take it. Because of this, complaints often arise that the product does not work or reduces the tonometer readings too much.
It is better to start taking Noliprel as prescribed by your doctor. After all, only a specialist will be able to select the optimal dosage and draw up the correct treatment regimen.t
Noliprel dosages
Noliprel is produced in several forms. It is useful for patients and doctors to understand this range.
Noliprel A Bi-Forte
The following types of combination tablets are distinguished:
- Noliprel (contains 2 mg of perindopril and 0.625 mg of diuretic);
- Noliprel Forte (the dosage of indapamide is 1.25 mg, and perindopril is 4 mg);
- Noliprel A Forte (indapamide – 1.25 mg, perindopril – 5 mg);
- Noliprel A Bi-Forte (perindopril is contained in a dose of 10 mg, and the diuretic is 2.5 mg);
- Noliprel A (2.5 mg perindopril and 0.625 mg indapamide).
Noliprel A Bi-forte is most often prescribed due to its high dosage. If this dose turns out to be too much, the doctor selects tablets with a lower content of perindopril and indapamide.
The preparation Noliprel A, A Bi-Forte and A Forte contains the amino acid arginine, which has a beneficial effect on the cardiovascular system.
Therefore, if you have heart problems, you should use the drugs listed above. For each patient, the dosage is selected individually, taking into account concomitant pathologies and age. Elderly hypertensive patients are recommended to start treatment with one tablet.
If the maximum daily dosage is exceeded, the hypotensive effect does not increase. But at the same time, the incidence of side effects increases. Therefore, if there is no decrease in blood pressure when taking the tablets, you should contact your doctor to adjust the treatment regimen.
How to take Noliprel tablets?
The combination medicine is taken once a day. This is very convenient, especially for busy and distracted people.
If the doctor has prescribed Noliprel, how to take this drug before or after meals is a pressing question for many patients.
The official instructions do not provide an answer. It is only indicated that the medicine should be taken in the morning.
As for the dose, the doctor first prescribes one tablet per day. But, if a month after the start of treatment the desired result is not obtained, Noliprel Forte is prescribed at a dosage of 4 mg of perindopril and 1.25 indapamide. Sometimes doctors prescribe other medications. For example, calcium antagonists are added. In this case, the dosage of the antihypertensive drug is slightly reduced.
If the dose is too high, the following symptoms are observed:
- nausea and vomiting;
- drowsiness;
- apathy;
- dizziness;
- weakness;
- bradycardia;
- convulsions;
- fainting;
- cold sweat;
- severe decrease in blood pressure;
- cessation of urine output or frequent urge to go to the toilet.
If such signs appear, you should immediately call an ambulance. And when you feel better, you need to make an appointment with your doctor to adjust the dosage.
You cannot select the dose of the drug yourself. After all, excessively reducing the dosage causes poor health. An overdose can lead to heart attack and death.
Use during pregnancy
When planning pregnancy or bearing a child, it is not recommended to take Noliprel.
If a woman has previously used such pills, the course should be completed and contact the doctor so that he can prescribe another drug.
There have been no studies of the effects of ACE inhibitors on the body of pregnant women. It is still not known exactly how the drug affects fetal development.
Therefore, you need to be careful. After all, there is a risk that the active ingredients of the medication may negatively affect the formation of the skull bones and the functioning of the newborn’s kidneys. The likelihood of arterial hypotension also increases.
This medicine is also contraindicated during breastfeeding, as it suppresses lactation and reduces the amount of breast milk in a young mother. While taking this medication, the baby may develop hypokalemia and jaundice.
Even if Noliprel is well suited for a woman, it is better to stop taking such an antihypertensive drug while pregnant and breastfeeding.
Duration of treatment
Typically, Noliprel is the main drug used to treat hypertension.
Taking pills for a long time is allowed, but it is advisable to take short breaks. Otherwise, the drug may negatively affect the functioning of the kidneys and liver.
How long to take Noliprel, the dose - all this should be decided by the doctor, taking into account the patient’s condition.
The drug is contraindicated in patients with severe renal failure. For moderately severe renal failure, the dosage should not be more than one tablet per day.
In some patients with impaired renal function while taking the drug, laboratory signs of failure of this organ appear. In this case, treatment is stopped. In the future, it is allowed to resume combination therapy, but in the lowest possible dosage and for a short course.
Long-term treatment with Noliprel is not recommended for the following diseases:
- angina pectoris;;
- scleroderma;
- hyperuricemia;
- diabetes;
- systemic lupus erythematosus;
- hypertrophic cardiomyopathy;
- aortic valve stenosis;
- chronic heart failure.
