Buy Noliprel A Bi-forte film-coated tablets 10mg+2.5mg No. 30 in pharmacies
Instructions for use Noliprel A Bi-forte tab p.o 10mg+2.5mg No. 30
Dosage forms tablets 2.5 mg + 10 mg Synonyms Co-Perineva Noliprel Noliprel A Noliprel A forte Noliprel forte Perindide Perindopril Plus Indapamide Group Combination of angiotensin-converting enzyme inhibitors and diuretics International nonproprietary name Indapamide + Perindopril Composition Active substances: perindopril and indapamide. Manufacturers Laboratories Servier Industry (France), Serdix (Russia) Pharmacological action A combined drug containing perindopril (ACE inhibitor) and indapamide (a diuretic from the group of sulfonamide derivatives). The pharmacological action of Noliprel is due to the combination of the individual properties of each component. The combination of perindopril and indapamide enhances the effect of each of them. Noliprel has a pronounced dose-dependent hypotensive effect on both systolic and diastolic blood pressure in the supine and standing position. The effect of the drug lasts 24 hours. A persistent clinical effect occurs 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, does not affect the metabolism of lipids (total cholesterol, HDL, LDL, triglycerides) and does not affect the metabolism of carbohydrates (including in patients with diabetes). Side effects From the water-electrolyte balance: possible hypokalemia, decreased sodium levels, accompanied by hypovolemia, dehydration and orthostatic arterial hypotension. The simultaneous loss of chlorine ions can lead to compensatory metabolic alkalosis (the incidence of alkalosis and its severity is low). In some cases, an increase in calcium levels. From the cardiovascular system: excessive decrease in blood pressure, orthostatic hypotension; in some cases - myocardial infarction, angina, stroke, arrhythmia. From the urinary system: rarely - decreased renal function, proteinuria (in patients with glomerular nephropathy); in some cases - acute renal failure. A slight increase in the concentration of creatinine in urine and blood plasma (reversible after discontinuation of the drug) is most likely in case of renal artery stenosis, treatment of arterial hypertension with diuretics, or the presence of renal failure. From the central nervous system and peripheral nervous system: headache, increased fatigue, asthenia, dizziness, mood lability, visual disturbances, tinnitus, sleep disturbance, convulsions, paresthesia, anorexia, impaired taste perception; in some cases - confusion. From the respiratory system: dry cough; rarely - difficulty breathing, bronchospasm; in some cases - rhinorrhea. From the digestive system: abdominal pain, nausea, vomiting, constipation, diarrhea; rarely - dry mouth; in some cases - cholestatic jaundice, pancreatitis, increased activity of liver transaminases, hyperbilirubinemia; with liver failure, the development of hepatic encephalopathy is possible. From the hematopoietic system: anemia (in patients after kidney transplantation, hemodialysis); rarely - hypohemoglobinemia, thrombocytopenia, leukopenia, decreased hematocrit; in some cases - agranulocytosis, pancytopenia, aplastic anemia, hemolytic anemia. From the metabolic side: an increase in the content of urea and glucose in the blood plasma is possible. Allergic reactions: skin rashes, itching; rarely - urticaria, angioedema; in some cases - erythema multiforme, hemorrhagic vasculitis, exacerbation of SLE. Other: temporary hyperkalemia; rarely - increased sweating, decreased potency. Indications for use: Essential arterial hypertension. Contraindications: history of angioedema (including while taking ACE inhibitors); - hypokalemia; — severe renal failure (creatinine clearance less than 30 ml/min); - severe liver failure (including with encephalopathy); - simultaneous use of drugs that prolong the QT interval; - pregnancy; - lactation (breastfeeding); - hypersensitivity to perindopril and other ACE inhibitors; - hypersensitivity to indapamide and sulfonamides. Method of administration and dosage The drug is prescribed orally, 1 tablet 1 time per day, preferably in the morning, before meals. Overdose Symptoms: marked decrease in blood pressure, nausea, vomiting, convulsions, dizziness, insomnia, decreased mood, polyuria or oliguria, which can turn into anuria (as a result of hypovolemia), bradycardia, electrolyte disturbances. Treatment: gastric lavage, administration of adsorbents, correction of water and electrolyte balance. If there is a significant decrease in blood pressure, the patient should be transferred to a horizontal position with legs elevated. Perindoprilat can be removed from the body using dialysis. Interaction The simultaneous use of Noliprel and lithium preparations is not recommended. Increasing lithium concentrations may result in symptoms and signs of lithium overdose. (due to decreased excretion of lithium by the kidneys). The combination of perindopril with potassium-sparing diuretics and potassium supplements can lead to a significant increase in the concentration of potassium in the blood serum (especially against the background of renal failure) and even death. It should be taken into account that indapamide in combination with potassium-sparing diuretics or potassium supplements does not exclude the development of hypokalemia or hyperkalemia (especially in patients with diabetes mellitus and renal failure). With the simultaneous use of erythromycin (for intravenous administration), pentamidine, sultopride, vincamine, halofantrine, bepridil and indapamide, the development of arrhythmias is possible (provoking factors include hypokalemia, bradycardia or a prolonged QT interval). When using ACE inhibitors, the hypoglycemic effect of insulin and sulfonylurea derivatives may be enhanced. The development of hypoglycemia is extremely rare. With the simultaneous use of Noliprel and baclofen, the hypotensive effect is enhanced. With the simultaneous use of indapamide and NSAIDs in case of dehydration, acute renal failure may develop. It should also be taken into account that NSAIDs weaken the hypotensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have been found to have an additive effect on hyperkalemia, and a decrease in renal function is also possible. 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). GCS, tetracosactide reduce the hypotensive effect of Noliprel. With simultaneous use of indapamide with antiarrhythmic drugs IA (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, bretylium, sotalol), the development of arrhythmias is possible (provoking factors include hypokalemia, bradycardia or a prolonged QT interval). If arrhythmia develops, antiarrhythmic drugs should not be used (an artificial pacemaker must be used). With the simultaneous use of indapamide and drugs that reduce potassium levels (including intravenous amphotericin B, gluco- and mineralocorticoids for systemic use, tetracosactide, stimulant laxatives), the risk of developing hypokalemia increases. Potassium concentration should be monitored and adjusted if necessary. If it is necessary to prescribe laxatives, drugs without a stimulating effect on intestinal motility should be used. When using Noliprel simultaneously with cardiac glycosides, it should be taken into account that low potassium levels may enhance the toxic effect of cardiac glycosides. Potassium levels and ECG should be monitored and therapy adjusted if necessary. Lactic acidosis while taking metformin is apparently associated with functional renal failure, which is caused by the action of indapamide. Metformin should not be used if creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (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, it is possible to increase the calcium content in the blood plasma as a result of a decrease in its excretion in the urine. When Noliprel is used against the background of constant use of cyclosporine, the level of creatinine in plasma increases even with a normal state of water-electrolyte balance. Special instructions The use of the drug Noliprel can cause a sharp decrease in blood pressure, especially when first taking the drug and during the first 2 weeks of therapy. The risk of developing an excessive decrease in blood pressure is increased in patients with reduced blood volume (as a result of following a strict salt-free diet, hemodialysis, vomiting and diarrhea), with severe heart failure (both in the presence of concomitant renal failure and in its absence), with initially low blood pressure, with stenosis of the renal arteries or stenosis of the artery of the only functioning kidney, cirrhosis of the liver, accompanied by edema and ascites. It is necessary to systematically monitor the appearance of clinical signs of dehydration and salt loss, and regularly measure the concentration of electrolytes in the blood plasma. A pronounced decrease in blood pressure when taking the drug for the first time is not an obstacle to further prescription of the drug. After restoration of blood volume and blood pressure, treatment can be continued, using a lower dose of the drug or monotherapy with one of its components. Blocking the renin-angiotensin-aldosterone system with ACE inhibitors can lead, along with a sharp drop in blood pressure, to an increase in plasma creatinine, indicating functional kidney failure, sometimes acute. These conditions occur rarely. However, in all such cases, treatment should be started carefully and carried out gradually. When treating with Noliprel, it is necessary to systematically monitor the concentration of creatinine in the blood plasma. While taking Noliprel, it is necessary to regularly monitor the concentration of potassium in the blood plasma. In elderly or debilitated patients, it is necessary to take into account the risk of a decrease in potassium concentration below the permissible level (less than 3.4 mmol/l). This group should also include people taking several different medications, patients with liver cirrhosis, which is accompanied by the appearance of edema or ascites, patients with coronary artery disease or heart failure. A decrease in potassium levels increases the toxicity of cardiac glycosides and increases the risk of developing arrhythmias. Low potassium levels, bradycardia, and an increase in the QT interval are risk factors for the development of arrhythmias, which can be fatal. It should be borne in mind that the excipients of the drug Noliprel include lactose monohydrate. As a result, this drug is not recommended for use in persons with lactase deficiency, galactosemia, or glucose/galactose malabsorption syndrome. While taking Noliprel (especially at the beginning of the course of therapy), caution should be exercised when driving a car and performing work that requires increased attention and a high speed of psychomotor reactions. Storage conditions List B. The drug should be stored out of the reach of children at a temperature not exceeding 30°C.
Instructions for use NOLIPREL® BI-FORTE (NOLIPREL BI-FORTE)
The combination of lithium and the combination of perindopril with indapamide is generally not recommended.
Perindopril
Neutropenia, agranulocytosis, thrombocytopenia, anemia
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 non-black 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, abdominal pain is noted (with or without nausea and vomiting), in some cases, without previous angioedema of the face and with a normal level of C1-esterase. 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.
Potassium-sparing diuretics, potassium salts
Usually, the combined use of perindopril with potassium-sparing diuretics or potassium salts is not recommended.
Double blockade of the RAAS
There is evidence that the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure). In this regard, double blockade of the RAAS by combined use of an ACE inhibitor and an angiotensin II receptor antagonist or aliskiren is not recommended.
If dual blockade of the RAAS is considered absolutely necessary, it should be carried out under specialist supervision and with careful frequent monitoring of renal function, blood pressure and electrolytes.
Patients with diabetic nephropathy should not take ACE inhibitors and angiotensin II receptor antagonists concomitantly.
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.
Patients with an established diagnosis of renal artery stenosis or if it is suspected are not recommended to prescribe Noliprel® Bi-Forte, because in such cases, treatment with the perindopril/indapamide combination should be started in a hospital and lower doses should be used than a single dose of Noliprel® Bi-Forte.
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 the Negroid race compared to representatives of other races. Perhaps this difference is due to the fact that arterial hypertension in patients of the Negroid race 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
ACE inhibitors should be used 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
In some patients treated with ACE inhibitors, including perindopril, cases of increased serum potassium levels were observed. 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. Consideration of the risk of potassium levels falling below acceptable levels (<3.4 mmol/L) is necessary in persons at increased risk, such as elderly patients and/or patients with impaired or malnutrition, regardless of whether they are taking one or more medications drugs, in patients with liver cirrhosis, which is accompanied by edema and ascites, in patients with coronary artery disease and in patients with heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of developing arrhythmias. Patients with congenital or iatrogenic prolongation of the QT interval are also at risk. Hypokalemia, like bradycardia, is a risk factor for the development of serious cardiac arrhythmias, especially torsade de pointes (TdP), which can be fatal. In any case, potassium levels should be monitored as often as possible. The first determination of plasma potassium should be carried out within the first week after the start of treatment. If potassium levels decrease, dose adjustment is necessary.
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.
Blood glucose level
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:
- For men:
CC (ml/min) = (140 – age) × body weight (kg)/0.814 × serum creatinine (µmol/l)
For women:
the calculation result should be multiplied by 0.85.
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® Bi-forte
Kidney failure
For patients with moderate to severe renal failure (creatinine clearance <60 ml/min), Noliprel® Bi-forte is contraindicated.
Treatment should be discontinued if a blood test reveals renal failure in a patient suffering from arterial hypertension and without clinical symptoms of kidney damage. Treatment can be resumed with the drug at a lower dose, or with only one of the components.
Routine medical monitoring of these patients should include frequent monitoring of serum potassium and creatinine levels, initially after 2 weeks of treatment, then once every 2 months during the period of therapeutic stability. Renal failure was mainly observed in patients with acute heart failure or underlying renal impairment, including renal artery stenosis.
It is not recommended to use Noliprel® Bi-forte in patients with bilateral renal artery stenosis or in patients with a solitary kidney.
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® Bi-forte 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 is taken in addition to a beta blocker.
Arterial hypotension, deficiency of water and electrolytes in the body
With low sodium levels, especially in patients with renal artery stenosis, there is a risk of a sudden drop in blood pressure. Therefore, tests should be systematically carried out to identify clinical signs of deficiency in the body of water and electrolytes, which may occur against the background of attacks of diarrhea or vomiting. Plasma electrolyte levels should be regularly monitored.
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 satisfactory blood volume and blood pressure, treatment can be resumed either with the drug at a lower dose, or with only one of its components.
Potassium level
The combination of perindopril and indapamide does not prevent the onset of hypokalemia, especially in patients with diabetes mellitus or in patients with renal failure. As with any antihypertensive drug containing a diuretic, regular monitoring of plasma potassium levels should be carried out.
Excipients
Noliprel® Bi-forte should not be prescribed to patients with hereditary lactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption syndrome.
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® Bi-forte do not affect the ability to concentrate. 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.
Preclinical safety data
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.
Perindopril
In chronic oral toxicity studies (in rats and monkeys), the receptor organ is the kidney, and the damage is reversible.
No mutagenicity was observed in in vitro or in vivo studies.
Reproductive toxicity studies (in rats, mice, rabbits and monkeys) showed no evidence of embryotoxicity or teratogenicity. However, ACE inhibitors as a class have been shown to have adverse effects on late fetal development, leading to fetal death and congenital defects in rodents and rabbits:
- kidney damage and an increase in perinatal and postnatal mortality were observed.
No carcinogenicity was observed in studies with long-term administration in rats and mice.
Indapamide
When indapamide was administered orally in the highest doses to different types of animals (doses 40-8000 times higher than the therapeutic dose), an increase in the diuretic effect was observed. In acute toxicity studies of indapamide administered intravenously or intraperitoneally, the main symptoms of poisoning were related to the pharmacological effects of indapamide, such as bradypnea and peripheral vasodilation.
When indapamide was tested for mutagenicity and carcinogenicity, negative results were obtained.
