Active substanceIndapamideIndapamide
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  • Dosage form: & nbspcapsules
    Composition:

    1 capsule contains:

    active substance - indapamide 2.5 mg;

    Excipients: cellulose microcrystalline 108.4 mg, magnesium stearate 1.1 mg;

    Capsule body composition: dye azorubin 0.0199%, color of diamond blue 0.0110%, titanium dioxide 2.2075%, gelatin up to 100%;

    composition of the cap capsule: dye diamond black 0.1401%, iron dye oxide black 0,6367%, titanium dioxide 0,9006%, gelatin up to 100%.

    Description:

    Capsules № 2: the body is gray-lilac opaque, The lid is dark blue opaque.

    The contents of the capsules are powder or a mixture of powder and granules from white to white with a creamy shade of color. It is allowed to compact the contents of the capsule according to the shape of the capsule, disintegrating when it is lightly pressed with a glass rod.

    Pharmacotherapeutic group:diuretic
    ATX: & nbsp

    C.03.B.A.11   Indapamide

    Pharmacodynamics:

    A hypotensive agent, a thiazide-like diuretic with a moderate in strength and long duration of action, a benzamide derivative. Has moderate saluretic and diuretic effects, which are associated with the blockade of the reabsorption of sodium, chlorine, hydrogen ions and, to a lesser extent, potassium ions in the proximal tubules and the cortical segment of the distal tubule of the nephron. The vasodilator effects and the reduction of the overall peripheral vascular resistance are based on the following mechanisms: a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandins with vasodilating activity; oppression of calcium current in the smooth-muscle walls of blood vessels.

    Reduces the tone of the smooth muscles of the arteries, reduces the overall peripheral resistance of the vessels. Helps reduce hypertrophy of the left ventricle of the heart. In therapeutic doses does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

    Antihypertensive effect develops at the end of the first / beginning of the second week with a constant intake of the drug and persists for 24 hours against a background of a single dose.

    Pharmacokinetics:

    After oral administration, it is quickly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Eating somewhat slows the rate of absorption, but does not affect the completeness of absorption.

    The maximum concentration in blood plasma is 12 hours after ingestion. With repeated administration of fluctuations in the concentration of indapamide in blood plasma in the interval between doses of two doses decrease. The equilibrium concentration is established after 7 days of regular intake. The half-life is 18 hours, the connection with plasma proteins is 79%. It also binds to the elastin of the smooth muscles of the vascular wall. Has a high volume of distribution, passes through the histohematological barriers (including placental), penetrates into breast milk.

    Metabolised in the liver. The kidneys excrete 60-80% in the form of metabolites (in unchanged form, about 5% is excreted), through the intestine - 20%.

    In patients with renal insufficiency, pharmacokinetics does not change.

    Do not cumulate.

    Indications:Arterial hypertension.
    Contraindications:

    Hypersensitivity to indapamide and other components of the drug, as well as to other derivatives of sulfonamide, severe renal failure (creatinine clearance less than 30 ml / min), hypokalemia, hepatic encephalopathy or severe liver dysfunction, pregnancy, lactation, age under 18 (efficacy and security is not established); simultaneous reception of drugs that extend the QT interval.

    Carefully:

    In case of violations of the liver and / or kidney function, violations of water-electrolyte balance, hyperparathyroidism, in weakened patients or in patients receiving combined therapy with other antiarrhythmics, while taking medications that extend the QT interval (see "Interaction with other drugs" "), diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis).

    Pregnancy and lactation:

    During pregnancy, do not prescribe diuretic drugs. Do not use these drugs to treat physiological swelling in pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development (hypotrophy). Application of the drug Indapamide not recommended during pregnancy.

    Indapamide excreted in breast milk. Given the potential for adverse events in infants, breastfeeding during treatment with the drug Indapamide Not recommended.

    Dosing and Administration:

    Capsules are taken orally, without chewing.

    Daily dose - 1 capsule Indapamide 1 time a day (in the morning), with plenty of liquid.

    When treating patients with hypertension, the dose of the drug should not exceed 2,5 mg (increased risk of actions without amplification antihypertensive effect).

    Elderly patients

    Elderly patients should monitor the plasma the concentration of creatinine taking into account age, body weight and sex.

    A drug Indapamide in a dose 2,5 mg / day (1 capsule) can be administered to elderly patients with normal or slightly impaired renal function (see "Contraindications").

    Side effects:

    Most adverse reactions (laboratory and clinical indicators) are dose-dependent.

    The incidence of adverse reactions that may be caused by thiazide-like diuretics, including indapamide, is given in the form of the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); frequency (frequency can not be calculated from available data).

    From the side of the blood and lymphatic system

    Very rarely: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

    From the central nervous system

    Rarely: dizziness, fatigue, headache, paresthesia.

    From the side of the cardiovascular system

    Very rarely: arrhythmia, lowering blood pressure.

    From the digestive system

    Infrequently: vomiting.

    Rarely: nausea, constipation, dryness of the oral mucosa.

    Very rarely: pancreatitis.

    From the urinary system

    Very rarely: renal failure.

    From the liver and biliary tract

    Very rarely: a violation of the liver.

    Unspecified frequency: the possibility of development. hepatic encephalopathy in case of hepatic insufficiency (see the sections "Contraindications", "Special instructions").

    From the skin

    Hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions:

    - Often: maculopapular rash.

    - Infrequently: hemorrhagic vasculitis.

    - Very rarely: angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome.

    - Unspecified frequency: deterioration in the presence of an acute form of disseminated lupus erythematosus is possible.

    Cases of photosensitivity reactions are described.

    Laboratory indicators:

    Very rarely: hypercalcemia.

    Unspecified frequency:

    - reduction of potassium content and development of hypokalemia, especially significant for patients at risk (see section "Special instructions");

    - hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous loss of chloride ions can lead to compensatory metabolic alkalosis, however, the frequency of development of alkalosis and its severity is negligible;

    - Increase in the concentration of uric acid and glucose in the blood plasma.

    Thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes.

    Overdose:

    Indapamide even in very high doses (up to 40 mg, i.e. 27 times more than the therapeutic dose) does not have a toxic effect.

    Symptoms: signs of acute drug poisoning are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). From clinical symptoms of overdose, nausea, vomiting, lowering of blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia) may occur.

    Treatment: emergency measures are reduced to removing the drug from the body: gastric lavage and / or the appointment of activated carbon, followed by the restoration of the water-electrolyte balance.

    Interaction:

    Unwanted combination of drugs

    - Lithium preparations:

    With simultaneous use of indapamide and lithium preparations, an increase in the concentration of lithium in blood plasma can be observed due to a decrease in its excretion, accompanied by the appearance of signs of an overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while carefully selecting the dose of drugs, constantly monitoring the lithium content in blood plasma.

    A combination of drugs that requires special attention

    Preparations that can cause arrhythmia of the "pirouette" type:

    - antiarrhythmic drugs IA class (quinidine, hydroquinidine, disopyramide);

    - antiarrhythmic drugs of III class (amiodarone, sotalol, dofetilide, ibutilide);

    - Some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

    - others: beprideil, cisapride, difemannil, erythromycin (iv), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (w / w).

    Increased risk of ventricular arrhythmias, especially arrhythmias such as pirouettes (risk factor - hypokalemia).

    It is necessary to determine the content of potassium in the blood plasma and, if necessary, adjust it before starting the combination therapy with indapamide and the above drugs. It is necessary to monitor the clinical condition of the patient, control of plasma electrolytes, ECG parameters.

    Patients with hypokalemia should use drugs that do not cause arrhythmia such as "pirouette".

    - Non-steroidal anti-inflammatory drugs (for systemic administration), including selective inhibitors of COX-2, high doses of salicylates (≥3 g / day):

    It is possible to reduce the antihypertensive effect of indapamide.

    With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration rate).

    Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

    - Angiotensin-converting enzyme (ACE) inhibitors:

    The administration of ACE inhibitors to patients with a reduced concentration of sodium ions in the blood (especially patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure.

    Patients with hypertension and possibly reduced, due to the use of diuretics, the content of sodium ions in blood plasma should:

    - 3 days before the start of treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, the reception of diuretics can be resumed;

    - or initiate therapy with an ACE inhibitor from low doses, followed by a gradual increase in dose if necessary.

    In chronic heart failure, treatment with ACE inhibitors should begin with low doses with the possible preliminary reduction of doses of diuretics.

    In all cases, in the first week of taking ACE inhibitors in patients, it is necessary to monitor renal function (creatinine concentration in the blood plasma).

    - Other drugs that can cause hypokalemia: amphotericin B (IV), gluco- and mineralocorticosteroids (for systemic administration), tetracosactide, laxatives, stimulating intestinal motility:

    Increased risk of hypokalemia (additive effect).

    Regular monitoring of the potassium content in the blood plasma is necessary; if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.

    - Baclofen:

    There is an increase in antihypertensive effect.

    Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

    - Cardiac glycosides:

    Hypokalemia increases the toxic effect of cardiac glycosides.

    With simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium content in the blood plasma, the ECG parameters and, if necessary, adjust the therapy.

    A combination of drugs that requires attention

    - Potassium-sparing diuretics (amiloride, spironolactone, triamterene):

    Combination therapy with indapamide and potassium-sparing diuretics is suitable in some patients, but the possibility of hypokalemia (especially in patients with diabetes mellitus and patients with renal insufficiency) or hyperkalemia is not ruled out.

    It is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

    - Metformin:

    Functional renal failure, which can occur against the background of diuretics, especially "loop", with the simultaneous appointment of metformin increases the risk of lactic acidosis.

    Do not use metformin, if the creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

    - Iodine-containing contrast agents:

    Dehydration of the body against the background of taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

    Before using iodine-containing contrast agents, patients needcompensate for fluid loss.

    - Tricyclic antidepressants, antipsychotics (antipsychotics):

    Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

    - Salts of calcium:

    With simultaneous administration, it is possible to develop hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

    - Cyclosporin, tacrolimus:

    It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even with a normal content of liquid and sodium ions.

    - Corticosteroids, tetracosactide (with system assignment):

    Reduction of antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

    Special instructions:

    Dysfunction of the liver

    In the appointment of thiazide and thiazide-like diuretics in patients with impaired hepatic function, it is possible to develop "hepatic encephalopathy, especially in the case of violations of the water-electrolyte balance, in which case diuretics should be discontinued immediately.

    Photosensitivity

    In patients receiving thiazide and thiazide diuretics reactions reported cases of photosensitivity (see. Section "Side effects"). In the case of the development of reactions photosensitivity against the background of taking the drug should stop treatment. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

    Water-electrolyte balance:

    - Content of sodium ions in blood plasma:

    Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug should regularly monitor this figure. All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. It is necessary to regularly monitor the content of sodium ions, since initially a decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most thorough control of the sodium ion content is indicated for patients with cirrhosis of the liver and elderly people (see "Side effect" and "Overdose" sections).

    - The content of potassium ions in blood plasma:

    With thiazide and thiazide-like diuretics, the main risk is a sharp decrease in potassium in the blood plasma and development of hypokalemia. It is necessary to avoid the risk of developing hypokalemia (<3.4 mmol / l) in elderly patients who are weakened or are receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the QT interval, patients with cirrhosis, peripheral edema or ascites, ischemic disease heart, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias.

    In addition, patients with an increased QT interval are at increased risk, but it does not matter whether this increase is due to congenital causes or effects of drugs.

    Hypokalemia, as well as bradycardia, is a condition that promotes the development of severe arrhythmias and, especially, pirouette-type arrhythmias, which can lead to death. In all the cases described above, it is necessary to regularly monitor the potassium content in the blood plasma.The first measurement of the potassium content in the blood should be carried out within the first week after the start of treatment.

    When hypokalemia occurs, appropriate treatment should be prescribed.

    - Calcium in the blood plasma:

    It should be borne in mind that thiazide and thiazide-like diuretics can reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in calcium in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism.

    It is necessary to cancel the reception of diuretic drugs before the study of the function of parathyroid glands.

    Concentration of glucose in blood plasma:

    It is necessary to monitor the concentration of glucose in the blood in patients with diabetes mellitus, especially in the presence of hypokalemia.

    Uric acid:

    In patients with gout, the frequency of seizures may increase or the course of gout may worsen.

    Diuretic drugs and kidney function:

    Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentrations in adults below 25 mg / L or 220 μmol / L in adults).In elderly patients, the normal concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.

    It should be borne in mind that at the beginning of treatment in patients may decrease the glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions against the background of taking diuretics. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the kidney function is not impaired, such temporary functional renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen.

    Application in athletes

    The active substance, which is a part of the preparation Indapamide, can give a positive result in the conduct of doping control in athletes.

    Effect on the ability to drive transp. cf. and fur:

    During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Capsules, 2.5 mg.

    Packaging:

    For 10, 30 capsules in a contour cell packaging of polyvinylchloride film and aluminum foil printed lacquered.

    For 10, 20, 30, 40, 50 or 100 capsules in cans of polyethylene terephthalate or cans of polymeric for medicines.

    One jar or 1, 2, 3, 4 or 5 contour squares, together with the instruction for use, is placed in a cardboard package (bundle).

    Storage conditions:

    Store in a dry, dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-000115
    Date of registration:28.12.2010
    Date of cancellation:2015-12-28
    The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspOZONE LLC OZONE LLC Russia
    Information update date: & nbsp16.10.2015
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