Index of drugs

Table. powl. 2.5 mg + 0.625 mg: essential hypertension.Table. powl. 5 mg + 1.25 mg: essential hypertension in patients whose blood pressure is not adequately controlled after using Perindopril alone.

1 tabl contains 2.5 mg or 5 mg perindopril tosylate and 0.625 mg or 1.25 mg Indapamide, respectively. The preparation contains lactose.

Preparation consisting of the tosylate salt of perindopril - an ACE inhibitor and Indapamide - a chlorosulfamoyl diuretic. The preparation uses the additive synergism of the antihypertensive effect of both components. Perindopril is an inhibitor of angiotensin converting enzyme. This enzyme converts angiotensin I to angiotensin II and stimulates the secretion of aldosterone in the adrenal cortex and breakdown of bradykinin. Indapamide is a sulphonamide derivative with properties similar to thiazide diuretics. It inhibits the reabsorption of sodium in the cortex of the kidneys, resulting in increased excretion of sodium and chloride in the urine, and to a lesser extent the excretion of potassium and Magnesium, thus increasing urine production and acting antihypertensive. In patients with hypertension, regardless of age, the preparation induces a dose-dependent hypotensive effect on both systolic and diastolic blood pressure in a supine or standing position. The hypotensive effect is maintained for 24 hours. Perindopril after oral administration is rapidly absorbed from the gastrointestinal tract, and C_max reaches within 1 hour. T_0,5 perindopril is 1 hour. Perindopril is a prodrug. 27% of the perindopril administered reach the bloodstream as an active metabolite of perindoprilat. C_max Perindoprilat in plasma is achieved within 3-4 h. The degree of binding to plasma proteins is 20%, mainly with the angiotensin converting enzyme, but it is concentration-dependent. Perindoprilat is excreted in the urine, and T_0,5 its unbound fraction is about 17 h, which leads to steady state within 4 days. Indapamide is rapidly and completely absorbed from the gastrointestinal tract. C_max in plasma occurs approximately 1 hour after oral administration. Plasma protein binding is 79%. T_0,5 in the elimination phase, it is 14-24 h (average 18 h). Multiple administration does not lead to accumulation. The elimination occurs mainly in the urine (70% of the dose) and faeces (22% of the dose) in the form of inactive metabolites.

Hypersensitivity to perindopril or other ACE inhibitors, indapamide or other sulfonamides or to any of the excipients. Due to the lack of sufficient therapeutic experience, the preparation should not be used in patients undergoing dialysis or in patients with untreated decompensated heart failure. Peripheral edema (quincke edema) related to previous ACE inhibitor therapy, congenital or idiopathic angioedema, second and third trimester of pregnancy, concomitant use with aliskiren in patients with diabetes or renal dysfunction (glomerular filtration rate, GFR <60 ml / min / 1.73 m²). Associated with indapamide: severe renal impairment (creatinine clearance less than 30 ml / min), hepatic encephalopathy, severe hepatic failure, hypokalaemia, breastfeeding, concomitant use with antiarrhythmic drugs causingtorsade de pointes.

If the patient is exposed to two antihypertensive agents not previously used, an increased incidence of idiosyncrasies can not be ruled out - the patient should be under close medical care. Because of the risk of severe infections, perindopril should be used with particular caution in patients with vascular collagenosis who are receiving immunosuppressive therapy, Allopurinol or procainamide, or who have a combination of complicating factors, especially if there is pre-existing renal impairment, periodic monitoring of the number of white blood cells and patients should be informed about any symptoms of infection (eg sore throat, fever).In the event of angioedema, treatment should be stopped immediately and appropriate measures should be instituted; in black patients angioedema is more common. In patients with a history of angioneurotic edema, which is unrelated to treatment with an ACE inhibitor, there may be an increased risk of developing it. Angioedema of the gut should be taken into account when diagnosing patients with abdominal pain. ACE inhibitors should be used with caution in allergy patients during desensitisation, and should be avoided in patients undergoing insect venom immunotherapy. In patients requiring both the use of an ACE inhibitor and desensitisation therapy, these reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the de-sensitization treatment. In patients receiving ACE inhibitors, during low-density lipoprotein (LDL) apheresis with dextran sulphate, life-threatening anaphylactoid reactions have been observed; these reactions were avoided by temporarily discontinuing the ACE inhibitor before each apheresis. Due to the risk of anaphylactoid reactions in dialysis patients with high permeability membranes (eg AN 69) and those treated with an ACE inhibitor, consideration should be given to using other type of dialysis membranes or antihypertensive agents from another group. 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 cases of hepatic impairment, thiazide and thiazide diuretics may cause hepatic encephalopathy - if encephalopathy occurs, treatment with diuretics should be stopped immediately. 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. During treatment, some hypertensive patients without prior overt renal function whose blood tests for renal function have shown functional renal failure should be discontinued and, possibly, restarted with either a lower dose or just one component. In these patients, as part of basic medical monitoring, potassium and creatinine should be periodically evaluated after 2 weeks of treatment and then every 2 months during the entire treatment. Renal failure was reported mainly in patients with severe heart failure or with underlying kidney disease, including renal artery stenosis. In the case of bilateral renal artery stenosis, or the only active kidney, it is usually not recommended to use the medicine. Due to the risk of sudden hypotension, patients should be regularly monitored for dehydration and electrolyte depletion (eg in case of vomiting or diarrhea) - plasma electrolytes should be checked regularly. Significant hypotension may require intravenous infusion of isotonic saline. Transient hypotension is not a contraindication to continuation of treatment. After restoring adequate blood volume and blood pressure, you can restart treatment with a lower dose or just one of the ingredients. Due to the risk of hypokalaemia during the use of the preparation, regular monitoring of plasma potassium levels during therapy should be performed. In the case of a dry cough, iatrogenic etiology should be considered; if treatment with ACE inhibitors is still necessary, consideration should be given to continuing. Inhibition of the renin-angiotensin-aldosterone system by an ACE inhibitor can cause, especially after the first dose and during the first 2 weeks.treatment, sudden decreases in blood pressure, and / or an increase in serum creatinine, indicating functional renal failure; sometimes it may have a severe onset, although it is rare and at various times of treatment. In these cases, the treatment should start with a lower dose and increase it gradually. In elderly patients, renal function and potassium should be evaluated before starting treatment. The initial dose should then be adjusted depending on the blood pressure response, especially in cases of fluid and electrolyte deficiency to avoid sudden hypotension. There is a risk of hypotension in all patients, but caution should be exercised in patients with ischemic heart disease or cerebral circulation disorders, starting with low doses. The use of ACE inhibitors may be beneficial in patients with renovascular hypertension waiting for corrective surgery or when such surgery is not possible. If the preparation has been prescribed to patients with known or suspected renal artery stenosis, treatment should be started in the hospital at low doses. Renal function and potassium levels should be monitored as some patients develop functional renal failure that resolves after discontinuation of therapy. In patients with severe heart failure (Class IV) and in patients with insulin-dependent diabetes (who have a tendency to increase potassium levels), treatment should be started under close medical supervision from a lower initial dose. Do not interrupt beta-blocker therapy in patients with ischemic heart disease and hypertension: 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 carefully monitored, especially during the first month of treatment with an ACE inhibitor. Perindopril is less effective in lowering blood pressure in black patients than in non-black patients. Due to the risk of hypotension, it is recommended to discontinue perindopril treatment one day before the planned surgery. ACE inhibitors should be used with extreme caution in patients with narrowing of the left ventricle outflow pathway. In patients receiving ACE inhibitors who develop cholestatic jaundice or who have increased liver enzymes, treatment with ACE inhibitors should be discontinued and appropriate medical treatment instituted. In some patients, during the use of Perindopril, an increase in serum potassium was observed. The risk factors for hyperkalaemia are: renal failure, decreased renal function, age (> 70 years), diabetes, concomitant conditions, especially dehydration, acute heart decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics (eg spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium chloride substitutes, or patients who are taking other medicines that increase serum potassium (eg heparin). If concomitant use of the above-mentioned medicines is considered appropriate, caution and frequent monitoring of serum potassium is recommended. Before starting the use of indapamide, then at regular intervals should be tested for sodium; more often in elderly patients and cirrhotic patients. The risk of decreased potassium levels (<3.4 mmol / l) should be avoided in some risk groups, such as elderly patients and / or malnutrition, whether or not they are taking many medications, cirrhosis patients liver with edema and ascites, patients with coronary artery disease and patients with heart failure. In these cases, hypokalaemia increases the toxicity of digitalis and the risk of arrhythmias. Patients who have prolonged QT ECG intervals, regardless of iatrogenic or congenital origin, are also at risk. Hypokalemia, like bradycardia, may predispose to severe arrhythmias, especiallytorsade de pointesthat can lead to death. In all these cases, more frequent serum potassium determination is necessary.The first determination of potassium concentration should be made in the first week after the start of treatment. If deficiency of potassium is detected, the deficiency should be compensated. Thiazide and thiazide diuretics may reduce the excretion of Calcium in the urine, causing a slight and transient increase in plasma calcium. A significant increase in calcium concentration may be associated with unrecognized hyperparathyroidism. In such cases, treatment should be discontinued prior to testing for parathyroid function. Controlling blood glucose is important in patients with diabetes, especially in the case of low potassium levels. In patients with increased uric acid levels there is an increased risk of gout attacks. Thiazides and thiazine diuretics are fully effective only when the kidney function is normal or only slightly affected (creatinine less than or close to 25 mg / l, ie 220 μmol / l in adults). In elderly patients, creatinine should be adjusted for age, body weight and sex according to the Cockroft formula. A diuretic can cause transient functional renal failure at the beginning of treatment, which has no consequences in patients with normal renal function, but may exacerbate existing renal failure. It should not be used in children and adolescents, because the safety and efficacy of perindopril alone or in combination in children and adolescents has not been established. The product contains lactose - should not be used in patients with rare, hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose and galactose.

The preparation is not recommended during the first trimester of pregnancy; is contraindicated during the second and third trimester of pregnancy. The preparation is contraindicated during breast-feeding. In a high dose, perindopril can reduce the fertility of male rats. The effect of perindopril or indapamide on human fertility is unknown.

Common: paresthesia, headaches, weakness, dizziness, vertigo, blurred vision, tinnitus, orthostatic or nonostostatic hypotension, dry persistent cough (iatrogenic etiology should be considered in the presence of this symptom), dyspnea, constipation, dryness mouth, nausea, abdominal pain, anorexia, vomiting, taste disorder, indigestion, diarrhea, rash, pruritus, maculopapular eruptions, painful muscle spasms, asthenia. Uncommon: mood or sleep disorders, bronchospasm, angioneurotic edema (face, limbs, lips, mucous membranes, tongue, glottis and / or larynx), urticaria, hypersensitivity reactions (mainly cutaneous in patients predisposed to allergic and asthmatic reactions), purpura, exacerbation of symptoms of previously diagnosed acute systemic lupus erythematosus, renal failure, impotence, increased sweating. Rare: hypercalcemia. Very rare: thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, haemolytic anemia, anemia (seen with ACE inhibitors in kidney transplant patients, hemodialysis patients), confusion, arrhythmia (including bradycardia, ventricular tachycardia, atrial fibrillation, angina and myocardial infarction, probably secondary to marked hypotension in high-risk patients), eosinophilic pneumonia, rhinitis, pancreatitis, hepatitis (cytolytic or cholestatic), erythema multiforme, epidermal necrolysis, Stevens-Johnson syndrome, hypersensitivity to light, acute renal failure. Frequency unknown: fainting, type tachycardiatorsade de pointes (potentially fatal), in the case of hepatic failure there is a possibility of hepatic encephalopathy, prolongation of the QT interval in ECG, increase in blood glucose and uric acid, slight increase in urea and creatinine in plasma (transient after discontinuation of treatment, more common in cases of narrowing renal artery, hypertension treated with diuretics, renal failure), increased liver enzymes, potassium loss from hypokalaemia, particularly severe course in high-risk patients, increased potassium (usually transient), hyponatremia with hypovolaemia causing dehydration and orthostatic hypotension .

Orally. Adults.Table. powl. 2.5 mg + 0.625 mg: 1 tabl. powl. once a day, preferably in the morning before a meal. If you do not get blood pressure control after 1 month of treatment, the dose can be doubled. In elderly patients, treatment should be started with the usual dose (1 monthly table once a day).In patients with moderate renal impairment (creatinine clearance 30-60 ml / min) the maximum dose is 1 tablet. per day. In patients with a creatinine clearance greater than or equal to 60 ml / min and in patients with moderate hepatic insufficiency, no dose modification is required.Table. powl. 5 mg + 1.25 mg: 1 tabl. powl. once a day, preferably in the morning before a meal. If possible, individual dose adjustments are recommended using the individual components of the preparation. The product should be used when the blood pressure is not adequately controlled after using the tablet. powl. 2.5 mg + 0.625 mg. If clinically appropriate, a direct change of monotherapy to treatment with the preparation may be considered. In elderly patients, treatment should be started depending on the response of blood pressure and renal function. In patients with moderate renal impairment (creatinine clearance 30-60 ml / min), it is recommended to start treatment with the appropriate dose of one of the active substances of the combined preparation. In patients with a creatinine clearance greater than or equal to 60 ml / min and in patients with moderate hepatic impairment, no dose adjustment is required.