Indapamid ретард

General characteristics. Structure:

Active agent: индапамид 1,5 mg;
excipients: gipromelloz (gidroksipropilmetiltsellyuloz) of 17 mg; коллидон SR of 7,5 mg, including: [polyvinyl acetate of 6 mg, povidone of 1,425 mg, sodium lauryl sulfate of 0,06 mg, silicon dioxide of colloid anhydrous 0,015 mg]; коповидон 6,6 mg; silicon dioxide of colloid anhydrous 1,2 mg; lactoses monohydrate (sugar milk) 69,9 mg; magnesium stearate of 1,3 mg; cellulose of microcrystallic 25 mg.
excipients for receiving a film cover: Опадрай II white 4 mg, including: [polyvinyl alcohol of 1,6 mg; macrogoal (polyethyleneglycol 3350) of 0,808 mg; talc of 0,592 mg; titanium dioxide of 1 mg].

Description:
Tablets, film coated white or almost white color, round, biconvex. On cross section – almost white color.

Pharmacological properties:

Pharmacodynamics. Indapamid – derivative sulfonamide, on pharmacological properties is close to thiazide diuretics (disturbance of a reabsorption of ions of sodium in a cortical segment of a Henle's loop). Increases allocation by kidneys of ions of sodium, chlorine and to a lesser extent potassium ions and magnesium that is followed by increase in a diuresis and hypotensive effect. The hypotensive effect remains within 24 hours against the background of a single dose, at the same time moderate strengthening of a diuresis is observed.
Anti-hypertensive activity is connected with improvement of elastic properties of large arteries, reduction of arterial and general peripheric vascular resistance. Indapamid reduces a hypertrophy of a left ventricle. Thiazide and tiazidopodobny diuretics at a certain dose reach the plateau of therapeutic effect while the frequency of side effects continues to increase at further increase in a dose of drug. Therefore it is not necessary to increase a drug dose if at reception of the recommended dose do not reach therapeutic effect.
Indapamid does not influence the maintenance of lipids in a blood plasma (triglycerides, lipoproteins of low density, lipoproteins of high density); does not influence indicators of exchange of carbohydrates, including at patients with a diabetes mellitus.

Pharmacokinetics. Absorption
After intake it is quickly and completely soaked up from digestive tract; bioavailability high (93%). Meal slows down absorption speed a little, but does not influence amount of the soaked-up substance. The maximum concentration in a blood plasma is reached in 12 hours after intake of a single dose. At repeated methods of fluctuation of concentration of drug in a blood plasma in an interval between receptions of two doses decrease.
Distribution
Communication with blood proteins – 79%. The elimination half-life makes 14 - 24 hours (on average, 18 hours). Passes through gistogematichesky barriers (including placental), it is allocated in breast milk. Equilibrium concentration is reached in 7 days of administration of drug. At repeated reception of cumulation it is not observed.
Metabolism
Indapamid is brought in the form of inactive metabolites, generally by kidneys (70%), and through intestines (22%).
The patients belonging to group of high risk
At patients with a renal failure the pharmacokinetics of drug does not change.

Indications to use:

Arterial hypertension.

Route of administration and doses:

Inside, on 1 tablet a day, it is desirable in the morning. The tablet should be swallowed entirely, without chewing, washing down with water.
Increase in a dose does not lead to increase in anti-hypertensive action, but strengthens diuretic effect.
Elderly patients.
At elderly patients it is necessary to control plasma concentration of creatinine taking into account age, body weight and a floor.
Indapamid ретард elderly patients can apply from normal or insignificantly an impaired renal function.

Features of use:

Abnormal liver functions
At use of thiazide and tiazidopodobny diuretics for patients with abnormal liver functions development of hepatic encephalopathy, especially in case of disturbance of water and electrolytic balance is possible. In this case reception of diuretics should be stopped immediately.
Photosensitivity reaction
Against the background of reception of thiazide and tiazidopodobny diuretics it was reported about cases of development of reactions of photosensitivity (see. "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 patients of advanced age (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 patients of the following categories: 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 maintenance of potassium ions 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 mind that thiazide and tiazidopodobny diuretics can reduce removal of calcium ions kidneys, leading to slight and temporary increase of content of 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.
- Content 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 adults 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 that in an initiation of treatment at patients 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 can be observed. 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 failure, as a rule, passes without effects, however at already available renal failure the condition of the patient can worsen.
Athletes
The active agent which is a part of drug Indapamid ретард can yield a positive take when carrying out a drug test at athletes.

Influence on ability to manage vehicles and mechanisms:
Effect of the substances which are a part of drug Indapamid ретард does not lead to disturbance of psychomotor reactions. However at some patients in response to a lowering of arterial pressure various individual reactions, especially at the beginning of therapy can develop or at addition to the carried-out therapy of other antihypertensives. In this case ability to manage motor transport or other mechanisms can be reduced.

Side effects:

The majority of side reactions have dozozavisimy character.
From the alimentary system: nausea, anorexia, dryness of a mucous membrane of an oral cavity, gastralgia, vomiting, diarrhea, lock, abdominal pain, abnormal liver function, hepatic encephalopathy, hepatitis, increase in activity of "hepatic" transaminases, pancreatitis.
From system of a hemopoiesis: a hyperuricemia, a hyperglycemia, a hypopotassemia, a hypochloraemia, a hyponatremia, a hypomagnesiemia, a hypercalcemia, increase in an urea nitrogen blood plasma, a giperkreatininemiya, a glucosuria, thrombocytopenia, a leukopenia, an agranulocytosis, aplastic anemia, hemolitic anemia.
Allergic reactions: skin rash, Quincke's disease, small tortoiseshell, skin itch, toxic epidermal necrolysis, Stephens-Johnson's syndrome, hemorrhagic vasculitis.
From the central nervous system: adynamy, nervousness, headache, dizziness, drowsiness, вертиго, sleeplessness, depression, increased fatigue, general weakness, indisposition, spasm of muscles, paresthesias, tension, irritability, alarm.
From respiratory system: cough, pharyngitis, sinusitis, rhinitis.
From cardiovascular system: a syncope, the expressed decrease in the ABP, change on the electrocardiogram (ECG) (characteristic of a hypopotassemia), lengthening of an interval of QT on an ECG, arrhythmia, arrhythmia like "pirouette", a heart consciousness.
From an urinary system: frequent infections, nocturia, polyuria, renal failure.
Others: aggravation of a current of a system lupus erythematosus, reaction of a photosensitization.

Interaction with other medicines:

NOT RECOMMENDED COMBINATIONS
- 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 appointed in combination with lithium drugs, at the same time it is necessary to select carefully a dose of drugs, constantly controlling the content of lithium in a blood plasma.
THE COMBINATIONS DEMANDING EXTRA CARE
- The drugs capable to cause arrhythmia like "pirouette"
- antiarrhytmic drugs IA of a class (quinidine, hydroquinidine, 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 prior to the beginning of a combination therapy indapamidy and the drugs stated above. Control of a clinical condition of the patient, control of content of electrolytes of a blood plasma, ECG indicators is necessary.

Patients with a hypopotassemia need to appoint the drugs which are not causing arrhythmia like "pirouette".
- Non-steroidal anti-inflammatory drugs (at system use), including the selection inhibitors of cyclooxygenase-2 (TsOG-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 decrease in 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)
Use of APF inhibitors for patients with the reduced maintenance 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 use), 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, if necessary, correction is necessary. 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 hypotensive effect is noted. Patients need to offset liquid loss, 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 COMBINATIONS OF DRUGS REQUIRING ATTENTION
- Kaliysberegayushchy diuretics (amiloride, Spironolactonum, Triamterenum)
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 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 simultaneous use of Metforminum increases risk of development of lactic acidosis.
It is not necessary to appoint 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 simultaneous use 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 use)
Decrease in hypotensive action (a delay of liquid and ions of sodium as a result of action of corticosteroids).

Contraindications:

- Hypersensitivity to an indapamid, other derivatives of sulfonamide or to any of excipients;
- Severe form of a renal failure (clearance of creatinine less than 30 ml/min.);
- Hepatic encephalopathy or heavy abnormal liver functions;
- Hypopotassemia;
- Pregnancy, lactation period;
- Age up to 18 years (efficiency and safety are not established);
- A concomitant use of the drugs extending QT interval;
- Deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption.

With care:
To apply with care at abnormal liver functions and/or kidneys, disturbance of water and electrolytic balance, a hyperparathyreosis, to patients with the increased QT interval on an ECG or receiving the combined therapy, at a diabetes mellitus in a stage of a decompensation, a hyperuricemia (especially, the followed gout and an uratny nephrolithiasis).

Use during pregnancy and in the period of a lactation:
As a rule, during pregnancy diuretic drugs are not used.
It is impossible to use these drugs for treatment of physiological hypostases during pregnancy since they can cause fetoplacental ischemia and can lead to disturbance of fetation.
Indapamid is allocated with breast milk. If treatment by drug Indapamid ретард is necessary in the period of a lactation, then breastfeeding needs to be stopped.

Overdose:

Indapamid even in doses to 40 mg, i.e. in 27 times more of a therapeutic dose has no toxic effect.
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, a lowering of arterial pressure, spasms, dizziness, the drowsiness, confusion of consciousness, a polyuria or an oliguria leading to an anury can be noted (owing to a hypovolemia).
Treatment: a gastric lavage, and/or reception of absorbent carbon with the subsequent recovery of water and electrolytic balance. There is no specific antidote.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated, 1,5 mg.
On 10, 20, or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1, 2, 3, 6 blister strip packagings on 10 tablets or on 1, 2, 3, 4 blister strip packagings on 20 or 30 tablets together with the application instruction place in a pack from a cardboard.