Index of drugs

Treatment of essential hypertension in patients who have achieved adequate pressure control with Perindopril and Indapamide administered in separate formulations at doses such as in Noliprel Bi-Forte.

1 tabl powl. contains 10 mg perindopril with arginine and 2.5 mg indapamide. The tablets contain lactose.

A preparation with synergistic action of two active substances. Perindopril is an inhibitor of an angiotensin converting enzyme that converts angiotensin I to angiotensin II, a substance that shrinks the blood vessels. The converting enzyme also stimulates the secretion of aldosterone in the adrenal cortex and the distribution of bradykinin, a vasodilator, to inactive heptapeptides. ACE inhibition results in a decrease in plasma angiotensin II, which leads to an increase in plasma renin activity (by inhibiting the negative feedback regulating renin secretion), aldosterone secretion reduction, reduction in peripheral resistance, especially in the vascular bed of the muscles and kidneys, without accompanying sodium retention and water and reflex tachycardia (in chronic treatment). The hypotensive effect of perindopril also occurs in patients with low or normal renin concentration. Perindopril reduces the preload and afterload. Studies in patients with heart failure have shown: reduced left and right ventricular filling pressure, decreased peripheral resistance, increased cardiac output and improved cardiac index, and increased local muscle flux. Perindopril is effective in all degrees of hypertension. Perindopril dilates vessels, restores the elasticity of large arteries, corrects structural changes in small arteries and reduces left ventricular hypertrophy. Indapamide is a sulfonamide derivative with an indole ring with pharmacological properties similar to thiazide diuretics. Indapamide inhibits the reabsorption of sodium in the cortical part of the kidneys. This increases the excretion of sodium and chlorides and to a lesser extent, potassium and Magnesium, thus increasing the volume of urine output and acting antihypertensive. Indapamide reduces the hypertrophy of the left ventricle. It does not affect carbohydrate metabolism (also in patients with diabetes mellitus and hypertension) and lipid metabolism. The hypotensive effect is proportional to the improvement of arterial compliance and reduction of total and arterial peripheral vascular resistance. The hypotensive effect persists for 24 h after drug administration. Food reduces the bioavailability of perindopril. The maximum antihypertensive effect is achieved 4-6 hours after a single dose. After 24 h, 80% of the converting enzyme activity is blocked. Perindopril is hydrolysed to perindoprilat, which is its active metabolite. The maximum concentration of perindoprilat is achieved after 3-4 hours, and indapamide after about 1 hour. T_0.5 perindoprilat is approximately 17 h. T_0,5 the elimination phase of indapamide is 14-24 h (average 18 h). Perindoprilat is mainly excreted in the urine and indapamide in the urine (70%) and faeces (22%) in the form of inactive metabolites. Elimination of perindoprilat is slower in elderly patients and in patients with heart failure or renal failure.

Hypersensitivity to perindopril or other ACE inhibitors; angioneurotic edema related to previous treatment with ACE inhibitors; congenital or idiopathic angioedema; II and III trimester of pregnancy; concomitant use with aliskiren in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate, GFR <60 ml / min / 1.73 m²). Hypersensitivity to indapamide or other sulfonamides; hepatic encephalopathy; severe liver failure; hypokalaemia; simultaneous use of anti-arrhythmic drugs that cause tachycardiatorsade de pointes; breastfeeding period. Hypersensitivity to any of the excipients. Severe and moderate renal insufficiency (creatinine clearance <60 ml / min). Patients on dialysis.Untreated and decompensated heart failure.

It is not recommended for patients with bilateral renal artery stenosis or one active kidney. Perindopril should be used with extreme caution in patients with vascular collagen, treated with immunosuppressive drugs, Allopurinol or procainamide or who have a combination of complicating factors, especially if a previous renal dysfunction has occurred (check the number of white blood cells and inform patients and report any symptoms infection). Anaphylactoid reactions may occur in patients receiving ACE inhibitors and co-dialyzed with high permeability membrane dialyzers (other types of membrane or antihypertensive drug from another group should be used) during LDL apheresis with dextran sulphate (discontinuation of treatment with ACE inhibitor prior to each apheresis ) or patients undergoing Hymenoptera desensitisation therapy (ACE inhibitors should be avoided in these patients if ACE inhibitors are required, ACE inhibitor should be discontinued at least 24 hours before treatment). If a hypersensitivity reaction occurs during treatment, discontinue therapy. If re-administration of the diuretic is considered necessary, it is recommended to protect surfaces exposed to the sun or artificial UVA rays. The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. In hypertensive patients without prior overt renal function, in whom renal function blood tests have demonstrated functional renal failure, therapy should be discontinued and therapy should be restarted with a lower dose or only one component - potassium and creatinine levels should be frequently assessed weeks and then every 2 months during the entire treatment. There is a risk of sudden hypotension with pre-existing sodium deficiency (especially in patients with renal artery stenosis) - the clinical symptoms of water and electrolyte deficiency should be monitored. Once sufficient blood volume and blood pressure have stabilized, you can restart treatment with a lower dose or just one of the ingredients. Because of the risk of hypotension and / or kidney failure, use caution in patients with significant loss of water and electrolytes (e.g., those who are on a strictly low-fat diet or long-term diuretic therapy) with initially low blood pressure with renal artery stenosis, with congestive heart failure or liver cirrhosis with edema and ascites (in such cases, treatment should start with a lower dose and increase it gradually). Particularly cautiously used in patients with ischemic heart disease or cerebral insufficiency, treatment should be started with a low dose. Treatment with the preparation is not suitable for patients with known or suspected renal artery stenosis, as treatment should be started in a hospital with a lower dose than the medicine it contains. In patients with severe heart failure (Class IV) or in patients with insulin-dependent diabetes mellitus, treatment with the preparation is not appropriate because therapy should start under close medical supervision from a lower initial dose. Do not interrupt beta-blocker therapy in patients with hypertension and coronary insufficiency: the ACE inhibitor should be added to the β-blocker.In diabetic patients previously treated with oral antidiabetic agents or insulin, blood Glucose levels should be closely monitored, especially during the first month of treatment with an ACE inhibitor. It is recommended to discontinue the treatment the day before the planned surgery. ACE inhibitors should be used with particular caution in patients with narrowing of the left ventricle outflow pathway. Caution for patients with risk factors for hyperkalemia, i.e. kidney failure, renal dysfunction, over 70 years, diabetes mellitus, dehydration, acute cardiac decomposition, metabolic acidosis, concomitant use of potassium sparing diuretics, potassium supplements or potassium chloride replacements or taking other medicines that increase serum potassium (eg heparin). Caution in patients with risk factors for hypokalemia, i.e. elderly and / or malnourished patients, liver cirrhosis with edema and ascites, coronary artery disease, and patients with heart failure or with prolonged QT interval (more frequent concentration determination is required) The first determination of potassium in the plasma should be done the first week after the start of treatment). Black patients have been reported to have lower efficacy of perindopril in lowering blood pressure and higher incidence of angioneurotic edema than in patients of other breeds. Sodium, potassium and creatinine must be checked periodically before and during treatment. The preparation should not be used in children and adolescents due to unsteady efficacy and safety of use. It should not be used in patients with rare, hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

The preparation is not recommended during the first trimester of pregnancy (there is a risk of teratogenic effects). The preparation is contraindicated in the second and third trimester of pregnancy and during breastfeeding. Administration of the preparation in the second and third trimester of pregnancy results in renal dysfunction, oligohydramnios and delayed bone ossification of the skull; in the newborn, renal failure, hypotension and hyperkalemia may occur. In the case of exposure to ACE inhibitors, starting from the second trimester of pregnancy, ultrasound examination of the kidneys and skull is recommended. Infants whose mothers have taken ACE inhibitors should be monitored for hypotension. Prolonged exposure to thiazide during the third trimester of pregnancy may reduce maternal plasma volume as well as uterine-placental flow, which may cause placental ischemia and growth retardation. In addition, rare cases of hypoglycaemia and thrombocytopenia have been reported in newborns who have been exposed to indapamide in the perinatal period.

Common: paraesthesia, headache and dizziness (including labyrinthine origin), blurred vision, tinnitus, hypotension, cough, shortness of breath, constipation, dry mouth, nausea, vomiting, abdominal pain, taste disturbances, indigestion, diarrhea, rash, pruritus, maculopapular eruptions, muscle spasms, asthenia. Uncommon: mood disorders, sleep disorders, bronchospasm, angioneurotic edema of the face, limbs, lips, tongue, glottis and / or larynx, urticaria, hypersensitivity reactions, purpura, exacerbation of systemic lupus erythematosus, renal failure, impotence, hyperhidrosis. Rare: hypercalcemia. Very rare: thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic or haemolytic anemia, confusion, arrhythmia, including bradycardia, ventricular tachycardia, atrial fibrillation, angina pectoris and myocardial infarction, eosinophilic pneumonia, rhinitis, pancreatitis, cytolytic or cholestatic hepatitis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, hypersensitivity to light, acute renal failure. Frequency unknown: fainting,torsade de pointes (potentially fatal), hepatic encephalopathy, prolonged QT interval in the eletrocardiogram, increased uric acid, Glucose, urea and creatinine in the blood (elevated levels of urea and creatinine are reduced after discontinuation of treatment, more often in the case of renal artery stenosis, hypertension treated with drugs diuretic, renal failure), increased liver enzymes, potassium loss with hypokalemia (with a particularly severe course in patients at high risk), hyperkalemia, hyponatremia with hypovolaemia. After the use of ACE inhibitors, the onset of syndrome starting with cholestasis jaundice developing into fulminant hepatic necrosis, sometimes leading to death, has been reported.

Orally, adults 1 tabl.once a day, preferably in the morning, before a meal. In elderly patients, serum creatinine must be corrected by age, weight and sex. Elderly patients can be treated if their kidneys are normal and after taking into account their response to blood pressure. No dosage adjustment is necessary for patients with moderate hepatic impairment.