Indapamid

General characteristics. Structure:

Active ingredient: 2,5 mg of an indapamid in 1 tablet.

Excipients: lactoses monohydrate, cellulose microcrystallic, starch corn, magnesium stearate, polyvinylpirrolidone, talc.

Structure of a cover: gipromelloza, polysorbate 80, titanium dioxide, castor oil, talc, macrogoal-4000.

Pharmacological properties:

Pharmacodynamics. An antihypertensive, tiazidopodobny diuretic with moderated on force and action, long on duration, derivative benzamides. Has moderate saluretichesky and diuretic effects which are connected with blockade of a reabsorption of ions of sodium, chlorine, hydrogen, and to a lesser extent potassium ions in proximal tubules and a cortical segment of a distal tubule of nephron. Vasodilating effects and decrease in the general peripheric resistance of vessels have the following mechanisms in the basis: decrease in reactivity of a vascular wall to noradrenaline and angiotensin II; increase in synthesis of prostaglandins having vasodilating activity; oppression of current of calcium in smooth muscle walls of vessels.

Reduces a tone of smooth muscles of arteries, reduces the general peripheric resistance of vessels. Promotes reduction of a hypertrophy of a left ventricle of heart. In therapeutic doses does not influence lipidic and carbohydrate metabolism (including at patients with the accompanying diabetes mellitus). The anti-hypertensive effect develops at the end of the first / the beginning of the second week at constant administration of drug and remains up to eight weeks; against the background of a single dose the maximum effect is noted in 24 hours.

Pharmacokinetics. Absorption. After intake it is quickly and completely soaked up from the digestive tract (DT); bioavailability - high (93%). Meal slows down absorption speed a little, but does not influence completeness of absorption. Time of achievement of the maximum concentration in a blood plasma (TCmax) – 1-2 h after intake. At repeated methods of fluctuation of concentration of an indapamid in a blood plasma in an interval between receptions of two doses decrease. Equilibrium concentration is established in 7 days of regular reception.

Distribution. Communication with proteins of a blood plasma – 71-79%. Contacts also elastin of unstriated muscles of a vascular wall. Has the high volume of distribution, passes through gistogematichesky barriers (including placental), gets into breast milk.

Metabolism. It is metabolized in a liver.

Removal. An elimination half-life (T1/2) - 18 h. Kidneys remove 60 - 80% in the form of metabolites (in not changed look about 5% are removed), through intestines - 20%. At patients with a renal failure the pharmacokinetics does not change. Does not kumulirut.

Indications to use:

Arterial hypertension.

Route of administration and doses:

Pill is taken inside, without chewing. A daily dose - 1 tablet of drug INDAPAMID once a day (morning), washing down with enough liquid.

At therapy of patients with arterial hypertension the dose of drug should not exceed 2,5 mg (increase in risk of side effect without strengthening of anti-hypertensive effect).

Elderly patients. At elderly patients it is necessary to control plasma concentration of creatinine taking into account age, body weight and a floor.

Elderly patients can appoint drug INDAPAMID in a dose of 2,5 mg/days (1 tablet) with normal or insignificantly an impaired renal function (see the section "Contraindications").

Heavy renal failure: Administration of drug is contraindicated (see the section "Contraindications").

Features of use:

Use during pregnancy and during breastfeeding. During pregnancy it is not necessary to appoint diuretic drugs. It is impossible to use these drugs for treatment of physiological hypostases at pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to disturbance of fetation (hypotrophy). Use of drug INDAPAMID is not recommended during pregnancy. Indapamid is allocated with breast milk. Considering a possibility of emergence of the undesirable phenomena in babies, feeding by a breast during treatment by drug INDAPAMID it is not recommended.

Abnormal liver functions. At purpose of thiazide and tiazidopodobny diuretics at patients with abnormal liver functions development of hepatic encephalopathy, especially in case of disturbances of water and electrolytic balance is possible. In this case reception of diuretics should be stopped immediately.

Photosensitivity. Against the background of reception of thiazide and tiazidopodobny diuretics it was reported about cases of development of reactions of photosensitivity (see the section "Side effect"). In case of development of reactions of photosensitivity against the background of administration of drug it is necessary to stop treatment. In need of therapy continuation by diuretics, it is recommended to protect integuments from influence of sunshine or artificial ultraviolet rays.

Water and electrolytic balance. The maintenance of ions of sodium in a blood plasma: prior to treatment it is necessary to define the maintenance of ions of sodium in a blood plasma. Against the background of administration of drug it is necessary to control this indicator regularly. All diuretic drugs can cause the hyponatremia leading sometimes to extremely serious consequences. Regular control of maintenance of ions of sodium as originally decrease in content of sodium in a blood plasma can not be followed by emergence of pathological symptoms is necessary. The most careful control of maintenance of ions of sodium is shown to patients with cirrhosis and to elderly people (see the sections "Side Effect" and "Overdose").

The maintenance of potassium ions in a blood plasma: at therapy by thiazide and tiazidopodobny diuretics the main risk consists in sharp decrease in content of potassium in a blood plasma and development of a hypopotassemia. It is necessary to avoid risk of development of a hypopotassemia (<3,4 mmol/l), at the patients of advanced age weakened or receiving the combined medicamentous therapy with other antiarrhytmic drugs and drugs which can increase QT interval, to patients with cirrhosis, peripheral hypostases or ascites, coronary heart disease, heart failure. The hypopotassemia at these patients strengthens toxic effect of cardiac glycosides and increases risk of development of arrhythmias.

Besides, patients with the increased QT interval treat group of the increased risk, at the same time does not matter, this increase is caused by the inborn reasons or effect of medicines.

Hypopotassemia as well as bradycardia, is the state promoting development of heavy arrhythmias and, especially, arrhythmias like "pirouette" which can lead to a lethal outcome. In all the cases described above it is regularly necessary to control the content of potassium in a blood plasma. The first measurement of content of potassium in blood needs to be taken within the first week from an initiation of treatment. At emergence of a hypopotassemia the corresponding treatment has to be appointed.

Content of calcium in a blood plasma: it must be kept in mindit must be kept in mind that thiazide and tiazidopodobny diuretics can reduce calcium removal by kidneys, leading to slight and temporary increase of contents, calcium in a blood plasma. The expressed hypercalcemia can be a consequence of earlier not diagnosed hyperparathyreosis.

It is necessary to cancel reception of diuretic drugs before a research of function of epithelial bodies.

Concentration of glucose in a blood plasma: it is necessary to control concentration of glucose in blood at patients with a diabetes mellitus, especially in the presence of a hypopotassemia.

Uric acid: at patients with gout the frequency of emergence of attacks can increase or become aggravated the course of gout.

Diuretic drugs and function of kidneys: thiazide and tiazidopodobny diuretics are effective fully only at patients from normal or insignificantly an impaired renal function (concentration of creatinine in a blood plasma at adult persons lower than 25 mg/l or 220 µmol/l). At patients of advanced age normal concentration of creatinine in a blood plasma is calculated taking into account age, body weight and a floor.

It is necessary to consider what in an initiation of treatment at patients can be observed, the reduction in the rate of glomerular filtering caused by a hypovolemia which, in turn, is caused by loss of liquid and ions of sodium against the background of reception of diuretic drugs. As a result, in a blood plasma concentration of urea and creatinine can increase. If function of kidneys is not broken, such temporary functional renal, insufficiency, as a rule, passes without effects, however at already available renal failure the condition of the patient can worsen.

Use for athletes. The active agent which is a part of drug INDAPAMID can yield a positive take when carrying out a drug test at athletes.

Influence on ability of control of motor transport and work with mechanisms. During treatment it is necessary to be careful at control of vehicles and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (risk of development of dizziness, drowsiness).

Side effects:

The majority of side reactions (laboratory and clinical indicators) have dozozavisimy character. Frequency of side reactions which can be caused by tiazidopodobny diuretics including индапамид, is specified in a type of the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000); not specified frequency (frequency cannot be counted according to available data). Frequency of development of side reactions is specified according to classification of World Health Organization.

From circulatory and lymphatic system: very seldom - thrombocytopenia, a leukopenia, an agranulocytosis, aplastic anemia, hemolitic anemia.

From the central nervous system: seldom - dizziness, increased fatigue, a headache, an adynamy, paresthesia; not specified frequency - a syncope.

From cardiovascular system: very seldom: arrhythmia, the expressed lowering of arterial pressure; not specified frequency – arrhythmia like "pirouette" (it is possible from the death), increase in an interval of QT at an ECG (see the section "Special Instructions").

From the alimentary system: infrequently – vomiting; seldom - nausea, a lock, dryness of a mucous membrane of an oral cavity; very seldom - pancreatitis.

From an urinary system: very seldom - a renal failure.

From a liver and biliary tract: very seldom - an abnormal liver function. Not specified frequency: a possibility of development - hepatic encephalopathy in case of a liver failure (see sections of "Contraindication", "Special Instructions"), hepatitis.

From integuments: hypersensitivity reactions, generally dermatological, at patients with predisposition to allergic and asthmatic reactions: often - makulopapulezny rash; infrequently - a hemorrhagic vasculitis; very seldom - a Quincke's disease and/or a small tortoiseshell, a toxic epidermal necrolysis, Stephens-Johnson's syndrome; not specified frequency - deterioration in a course of a disease in the presence at patients of an acute form of the disseminated lupus erythematosus is possible.

Cases of reactions of photosensitivity are described.

Laboratory indicators: very seldom: hypercalcemia. Not specified frequency:
- increase in activity of "hepatic" transaminases;
- decrease in content of potassium and development of a hypopotassemia, especially significant for the patients belonging to risk group (see the section "Special Instructions");
- the hyponatremia which is followed by a hypovolemia, dehydration and orthostatic hypotension.

Simultaneous loss of ions of chlorine can lead to a compensatory metabolic alkalosis, however the frequency of development of an alkalosis and its expressiveness is insignificant;
- increase in concentration of uric acid and glucose in a blood plasma.

Thiazide and tiazidopodobny diuretics should be applied with care at patients with gout and a diabetes mellitus.

Interaction with other medicines:

Undesirable combination of medicines.

Lithium drugs: at simultaneous use of an indapamid and drugs of lithium the increase in concentration of lithium in a blood plasma owing to decrease in its excretion which is followed by emergence of signs of overdose can be observed. If necessary diuretic drugs can be used in combination with lithium drugs, at the same time it is necessary to select carefully a dose of drugs, regularly controlling the content of lithium in a blood plasma.

The combination of drugs requiring special attention.

The drugs capable to cause arrhythmia like "pirouette":

- antiarrhytmic drugs IA of a class (hydroquinidine (quinidine), Disopyramidum), antiarrhytmic drugs III of a class (Amiodaronum, дофетилид, ибутилид), соталол;
- some neuroleptics: fenotiazina (Chlorpromazinum, циамемазин, levomepromazinum, thioridazine, трифторперазин), benzamides (амисульприд, Sulpiridum, сультоприд, тиаприд), phenyl propyl ketones (Droperidolum, haloperidol);
- others: bepridit, цизаприд, difemanit, erythromycin (in/in), галофантрин, мизоластин, pentamidine, спарфлоксацин, moxifloxacin, астемизол, Vincaminum (in/in).

Increase in risk of ventricular arrhythmias, especially arrhythmias like "pirouette" (risk factor - a hypopotassemia). It is necessary to determine the content of potassium in a blood plasma and if necessary to adjust it prior to the beginning of a combination therapy indapamidy and the drugs stated above. Control of a clinical condition of the patient, control of electrolytes of a blood plasma, indicators of the electrocardiogram (ECG) is necessary. At patients with a hypopotassemia it is necessary to use the drugs which are not causing arrhythmia like "pirouette".

Non-steroidal anti-inflammatory drugs (at system appointment), including the selection TsOG-2 inhibitors (cyclooxygenases-2), high doses of salicylates (≥ 3 g/days): decrease in anti-hypertensive effect of an indapamid is possible.

At considerable loss of liquid the acute renal failure can develop (owing to reduction in the rate of glomerular filtering). Patients need to offset loss of liquid and in an initiation of treatment carefully to control function of kidneys.

Inhibitors of an angiotensin-converting enzyme (APF): purpose of APF inhibitors to patients with reduced concentration of ions of sodium in blood (especially to patients with a renal artery stenosis) is followed by risk of sudden arterial hypotension and/or acute renal failure.

And perhaps reduced, owing to reception of diuretics, the maintenance of ions of sodium in a blood plasma it is necessary for patients with arterial hypertension: in 3 days prior to treatment by APF inhibitor to stop reception of diuretics. Further, if necessary, reception of diuretics can be resumed. Or to begin therapy with APF inhibitor with low doses, with the subsequent gradual increase in a dose in case of need.

At chronic heart failure treatment by APF inhibitors should be begun with low doses with possible preliminary decrease in doses of diuretics.

In all cases in the first week of reception of APF inhibitors at patients it is necessary to control function of kidneys (concentration of creatinine in a blood plasma).

Other drugs capable to cause a hypopotassemia: Amphotericinum In (in/in), glyuko-and mineralokortikosteroida (at system appointment), тетракозактид, the purgatives stimulating motility of intestines:

Increase in risk of development of a hypopotassemia (additive effect). Regular control of content of potassium in a blood plasma is necessary; if necessary - its correction. Special attention should be paid to the patients who are at the same time receiving cardiac glycosides. It is recommended to apply the purgatives which are not stimulating motility of intestines.

Baclofenum: strengthening of anti-hypertensive effect is noted. Patients need to offset loss of liquid and in an initiation of treatment carefully to control function of kidneys.

Cardiac glycosides: the hypopotassemia strengthens toxic effect of cardiac glycosides.

At simultaneous use of an indapamid, and cardiac glycosides it is necessary to control the content of potassium in a blood plasma, ECG indicators, and, if necessary, to adjust therapy.

The combination of drugs requiring attention. Kaliysberegayushchy diuretics (amiloride, Spironolactonum, Triamterenum, эплеренон (derivative Spironolactonum)): the combination therapy indapamidy and kaliysberegayushchy diuretics is reasonable at some patients, however at the same time the possibility of development of a hypopotassemia (especially at patients with a diabetes mellitus and patients with a renal failure) or hyperpotassemias is not excluded.

It is necessary to control the content of potassium in a blood plasma, indicators of an ECG and, if necessary, to adjust therapy.

Metforminum: the functional renal failure which can arise against the background of diuretics especially "loopback", at co-administration of Metforminum povndat risk developed lactic acidosis.

It is not necessary to apply Metforminum if concentration of creatinine exceeds 15 mg/l (135 µmol/l) at men and women have 12 mg/l (110 µmol/l).

Iodinated contrast agents: organism dehydration against the background of reception of diuretic drugs increases risk of development of an acute renal failure, especially at use of high doses of iodinated contrast agents.

Before use of iodinated contrast agents patients need to offset liquid loss.

Tricyclic antidepressants, antipsychotic means (neuroleptics): drugs of these classes strengthen anti-hypertensive action of an indapamid and increase risk of orthostatic hypotension (the additive effect).

Calcium salts: at co-administration development of a hypercalcemia owing to decrease in removal of calcium ions by kidneys is possible.

Cyclosporine, такролимус: increase in concentration of creatinine in a blood plasma without change of concentration of the circulating cyclosporine, even is possible at the normal content of liquid and ions of sodium.

Corticosteroid drugs, тетракозактид (at system appointment): decrease in anti-hypertensive action (a delay of liquid and ions of sodium as a result of action of corticosteroids).

Contraindications:

Hypersensitivity to an indapamid and other components of drug, and also to other derivatives of sulfonamide, a heavy renal failure (clearance of creatinine less than 30 ml/min.), a hypopotassemia, hepatic encephalopathy or heavy abnormal liver functions, an acute disorder of cerebral circulation, pregnancy, the lactation period, age up to 18 years (efficiency and safety are not established); a lactose intolerance, deficit of lactase, a syndrome of glyukozo-galaktozny malabsorption (drug contains lactose).

With care: at abnormal liver functions and/or kidneys, disturbances of water and electrolytic balance, a hyperparathyreosis, at the weakened patients or at the patients receiving the combined therapy with other antiarrhytmic means, at a concomitant use of the drugs extending QT interval (see the section "Interaction with Other Medicines"), a diabetes mellitus, a hyperuricemia (especially, the followed gout and an uratny nephrolithiasis).

Overdose:

Symptoms. Symptoms of acute poisoning with drug first of all are connected with disturbance of water and electrolytic balance (a hyponatremia, a hypopotassemia). From clinical symptoms of overdose nausea, vomiting, dysfunction of a GIT, a spasm, dizziness, the drowsiness, confusion of consciousness, a polyuria or an oliguria leading to an anury (owing to a hypovolemia), in certain cases – an excessive lowering of arterial pressure, depression of breath can be noted. At patients with cirrhosis development of a hepatic coma is possible.

Treatment. Measures of acute management come down to removal of drug from an organism: a gastric lavage and/or purpose of absorbent carbon with the subsequent recovery of water and electrolytic balance. There is no specific antidote.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the places unavailable to children. A period of validity - 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated, 2,5 mg. On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 1, 2, 3, 4, 5 blister strip packagings together with the application instruction place in a pack from a cardboard.