Pharmacological properties

Pharmacodynamics. indapamid is diuretic medicine. it treats to group of not thiazide sulphonamide derivatives and contains Indo-fishing a ring. on pharmacological properties it is close to thiazide diuretics. like thiazide diuretics works in a proximal part of distal wavy tubules of nephron where causes the strengthened discharge of sodium and chlorides and, to a lesser extent, potassium and magnesium, thus increasing the volume of the emitted urine.

Hypotensive effect of an indapamid remains for 24 h. Such effect is characteristic of doses with moderate diuretic action.

Antihypertensive properties of an indapamid consist in improvement of elasticity of arteries and reduction of resistance of small arteries and OPSS.

Indapamid reduces a hypertrophy of a left ventricle.

to

For tiazid and tiazidopodobny diuretics established a dose above which the therapeutic effect amplifies, but the probability of emergence of side effects at the same time increases. So, if the carried-out treatment was inefficient, it is not necessary to raise a medicament dose.

Indapamid also does not affect concentration of lipids (general XC, XC LDL and TG) does not break metabolism of glucose at patients with diabetes and AG.

Pharmacokinetics.

Absorption. Indapamid is slowly released from a tablet and completely soaked up in a digestive tract. Food slightly accelerates absorption, but does not affect amount of the absorbed medicine.

indapamida in blood plasma is reached by

C _max in 1–2 h after oral administration. Multiple dose promotes reduction of a difference of concentration of medicine in blood plasma in intervals between receptions, but there are individual distinctions.

Distribution Indapamid for 79% contacts proteins of blood plasma. T _½ in a phase of elimination makes 14–24 h (on average 18 h). The condition of saturation is reached in 7 days. Reception of a repeated dose does not lead to medicament cumulation.

Removal Indapamid is brought by

from an organism mainly with urine (70%) and a stake (22%) in the form of inactive metabolites. Only 5–7% of a dose are removed with urine in not changed look.

pharmacokinetic parameters do not differ in

At patients with a renal failure.

Indication

Ag.

Use Indapen sr is intended to

by

for oral administration.

Indapen SR is applied on 1 tablet a day, it is desirable in the morning.

should swallow of

Tablet whole, washing down with water.

At use of an indapamid in high doses medicament has no bigger antihypertensive effect, but the diuretic effect at the same time amplifies.

Patients with a liver failure. With an abnormal liver function the use of tiazidopodobny diuretics can cause encephalopathy in patients, especially at disturbances of electrolytic balance. In that case use of diuretics should be stopped immediately.

use of medicine is contraindicated to

In a liver failure of heavy degree.

Patients with a renal failure. In a renal failure of heavy degree (clearance of creatinine of 30 ml/min.) the use of means is contraindicated. Thiazide diuretics and tiazidopodobny medicines are most effective at normal function of kidneys or easy degree of a renal failure.

Patients of advanced age. At elderly people the concentration of creatinine in blood plasma should be skorrigirovat taking into account age, body weight and a sex of the patient. Indapen SR it is possible to apply at patients of advanced age only at normal function of kidneys or easy degree of a renal failure.

Contraindication

Hypersensitivity to the indapamid and other sulfonamides and/or other substances which are a part of drug. heavy renal failure (anury). hepatic encephalopathy and heavy abnormal liver functions. hypopotassemia. period of pregnancy and feeding by a breast. children's age.

Side effects

during treatment revealed the side effects given below which were distributed on frequency as follows: very often (≥1/10); often (≥1/100, 1/10); infrequently (≥1/1000, 1/100); seldom (≥1/10,000, 1/1000); very seldom (1/10,000), frequency is unknown (frequency cannot be estimated on the basis of the existing data).

Tiazidopodobny diuretics, including indapamid, can cause the undesirable effects provided below.

from the system of blood and lymphatic system: very seldom — thrombocytopenia, a leukopenia, an agranulocytosis, aplastic anemia, hemolytic anemia.

from nervous system: seldom — dizziness, fatigue, a headache, paresthesias, an asthenia.

from a cardiovascular system: very seldom — arrhythmia, arterial hypotension.

from a GIT: seldom — nausea, vomiting, a constipation, dryness in a mouth, infrequently – vomiting, it is very rare — pancreatitis.

from kidneys and urinary tract: very seldom — a renal failure.

from a gepatobiliarny system: very seldom — an abnormal liver function, frequency it is unknown — in the presence of a liver failure possibly developing of hepatic encephalopathy.

from skin and hypodermic fabric: reactions of hypersensitivity, mainly from skin, at patients who have tendency to allergic and asthmatic reactions: often — macropapular rashes, infrequently — a purpura, it is very rare — a Quincke's disease and/or a small tortoiseshell, a toxic necrolysis of skin, Stephens's syndrome — Johnson; frequency is unknown — possibly aggravation of the existing system lupus erythematosus. It was reported about cases of reactions of photosensitivity.

Laboratory indicators. At a part of patients noted a hypopotassemia (potassium concentration of 3.4 mmol/l). Potassium concentration of 3.2 mmol/l is revealed at some patients in 4–6 weeks of treatment. In 12 weeks of treatment indapamidy potassium concentration in blood plasma decreased, on average by 0.23 mmol/l.

It is very rare — a hypercalcemia; frequency is unknown — decrease in potassium concentration is especially dangerous to patients with high risk of development of a hypopotassemia; the hyponatremia with a hypovolemia, causes dehydration (the risk of dehydration is increased at patients of advanced age and patients with heart failure) and decrease in the ABP in a standing position. Simultaneous loss of ions of chlorine can lead to slightly profound secondary compensatory metabolic alkalosis and the increased concentration of uric acid and glucose in blood. At patients with diabetes or gout it is necessary to consider expediency of use of diuretic medicines.

Special instructions

At patients with a liver failure tiazidopodobny diuretics can accelerate development of hepatic encephalopathy. in case of symptoms of hepatic encephalopathy the use of an indapamid should be stopped immediately.

Fotosensibilization's

. The manifestations of a photosensitization caused by use of thiazide diuretics and tiazidopodobny medicines are possible. If during treatment there is a reaction of a photosensitization, administration of medicament should be stopped. In need of repeated use of diuretic it is recommended to protect open sites of skin which sunshine or artificial ultra-violet radiation can affect.

Water and electrolytic balance

Concentration of sodium in blood plasma. Before an initiation of treatment, and then periodically it is necessary to control concentration of sodium in blood plasma. Any therapy by diuretics can lead to a hyponatremia, sometimes with serious consequences. Decrease in concentration of sodium during an initial stage is possible without symptoms therefore it is also necessary to control its concentration regularly. At elderly people or patients with cirrhosis such researches should be conducted more often.

Potassium concentration in blood plasma. Decrease in level of potassium in blood plasma with emergence of a hypopotassemia is the main risk at use of thiazide and tiazidopodobny diuretics. The risk of emergence of a hypopotassemia (3.4 mmol/l) has to be prevented at certain categories of patients of high risk.

Especially carefully should appoint such medicaments the patient at whom risk of development of a hypopotassemia is higher, for example to elderly people; the exhausted patient; it which accepted a large amount of other medicines; to patients with cirrhosis, hypostases and ascites; with an ischemic heart disease and heart failure. At a hypopotassemia the cardiotoxicity of medicaments of a foxglove and risk of emergence of disturbances of a warm rhythm increases. Patients with the increased Q–T interval treat risk group irrespective of whether this disturbance is inborn or iatrogenic. The hypopotassemia, like bradycardia, contributes to the development of serious violations of a warm rhythm, especially torsade de pointes of ventricles (torsades de pointes).

during treatment should control regularly potassium concentration in blood plasma. The first laboratory control should be carried out to the 1st week of treatment. At development of a hypopotassemia it is necessary to fill up a lack of potassium.

Concentration of calcium in blood plasma. Thiazide and tiazidopodobny diuretic medicines can reduce removal of calcium with urine, causing an easy temporary hypercalcemia. The expressed hypercalcemia can be a consequence of not diagnosed hyperparathyreosis. In that case it is necessary to stop treatment and to survey functions of epithelial bodies at the patient.

Concentration of glucose of blood. At patients with diabetes, especially with the accompanying hypopotassemia, it is necessary to watch concentration of glucose of blood.

Patients with gout. At patients with a hyperuricemia the tendency to growth of frequency of attacks of gout is possible.

Renal failure and diuretics. Tiazida and tiazidopodobny diuretic medicaments are effective only on condition of normal function of kidneys or its insignificant disturbance (concentration of creatinine of 25 mg/l, that is 220 µmol/l).

Estimating function of kidneys on the basis of concentration of creatinine, it is necessary to consider age, sex and body weight of the patient.

Hypovolemia caused by loss of liquid which can arise at the beginning of diuretic treatment leads

to reduction in the rate of glomerular filtration that, in turn, causes increase in concentration of urea and creatinine in blood serum. Such temporary functional renal failure passes without consequences at patients with normal function of kidneys, but at the same time can worsen the available renal failure.

Athletes. Medicine can become the reason of doubtful positive takes of anti-doping tests at athletes.

Excipients. Medicine contains lactose therefore it should not be applied the patient with rare hereditary intolerance of a galactose, a lack of lactase (Lappa type) or a syndrome of bad absorption of glucose — galactoses.

Period of pregnancy and feeding by a breast

Pregnancy. Usually pregnant it is necessary to avoid intake of diuretics. Diuretics cannot be applied in physiological hypostases of pregnant women as fetoplacental ischemia with risk of a growth disorder of a fruit can develop.

Feeding by a breast. Indapamid gets into breast milk therefore during administration of medicament the breastfeeding is not recommended.

Children. Taking into account lack of data on safety and efficiency it is not recommended to use medicament in pediatric practice.

Influence on ability to run vehicles and to work with mechanisms. At medicine use Indapen and Indapen SR, especially in an initiation of treatment or at use in addition to other antihypertensive drug, can appear the symptoms connected with decrease in the ABP. In such situation it is recommended to refrain from control of vehicles and work with mechanisms.

Interaction

not recommended combinations

Lities. Increase in level of lithium in blood plasma and emergence of symptoms of overdose owing to lithium removal reduction (is possible as well as at a saltless diet). If prescribing of diuretic is required, it is necessary to carry out careful monitoring of level of lithium in blood plasma and to adapt its dose.

Medicines which should be applied carefully along with indapamidy. The medicines influencing a warm rhythm and defiant torsades de pointes:

— the antiarrhytmic medicaments IIa of a class (quinidine, hydroquinidine, Disopyramidum);

— antiarrhytmic medicaments III of a class (Amiodaronum, sotalol, dofetilid, ibutilid);

— some antipsychotic medicines: fenotiazina (Chlorpromazinum, tsiamemazin, levomepromazinum, thioridazine, trifluorperazin), benzamides (amisulpirid, Sulpiridum, sultoprid, tiaprid), phenyl propyl ketones (Droperidolum, haloperidol) and others: bepridit, tsizaprid, difemanit, erythromycin — at in in introduction, galofantrin, pentamidine, mizolastin, sparfloksatsin, moxifloxacin, Vincaminum — at in in introduction.

Hypopotassemia, like bradycardia and continuous lengthening of an interval of Q-T, leads

to emergence of torsades de pointes.

In case of need uses of these medicines should observe the patient concerning development of a hypopotassemia and if necessary — to korrigirovat potassium concentration. It is also required to control concentration of electrolytes in blood plasma and the ECG parameters.

At emergence of a hypopotassemia together with indapamidy should use medicines which do not cause risk of torsades de pointes.

NPVP (for intake), including selection TsOG-2 inhibitors and salicylates in high doses (3 g/days). Decrease in hypotensive action of an indapamid is possible.

risk of emergence of OPN at patients with dehydration Increases (glomerular filtration is reduced).

Should control a condition of hydration of the patient and function of kidneys.

APF Inhibitors. If use of APF inhibitors is begun when at the patient the lack of sodium is observed (especially at persons with a renal artery stenosis), there is a risk of sharp decrease in the ABP and development of OPN.

Considering that preliminary treatment by diuretics can cause deficiency of sodium, at primary AG it is necessary:

-to stop intake of diuretic in 3 days prior to use of APF inhibitors, and then, if necessary, to return to intake of diuretic or;

-to begin treatment with APF inhibitors with low doses, gradually raising them.

should begin treatment with

In stagnant heart failure with low doses of APF inhibitors, it is better after a diuretic dose decline (whenever possible).

Within 1 week of treatment by APF inhibitors should control function of kidneys (concentration of creatinine).

Other medicines causing a hypopotassemia. Amphotericinum B at in in introduction, GKS and mineralokortikosteroida (at intake), tetrakozaktid, the laxative medicines stimulating a vermicular movement.

Increased risk of development of a hypopotassemia. It is necessary to control potassium concentration in blood plasma, especially at the combined treatment by cardiac glycosides. It is not necessary to take the laxative medicines stimulating an intestines vermicular movement.

Baclofenum. Strengthens antihypertensive action of an indapamid.

Should provide to

corresponding hydration of the patient and to control function of kidneys.

Cardiac glycosides. The hypopotassemia is a factor which contributes to the development of symptoms of toxicity after use of glycosides of a foxglove therefore it is necessary to control potassium concentration, the ECG parameters, and if necessary — to change treatment.

Combined treatment requiring attention

Kaliysberegayushchy diuretics (amiloride, Spironolactonum, Triamterenum). The simultaneous use of these medicaments shown to some patients does not exclude risk of emergence of a hypopotassemia, and at patients with a renal failure or patients with diabetes can lead to development of a hyperpotassemia. It is necessary to control potassium concentration in blood plasma and ECG indicators, and if necessary — to change treatment.

Metformin. Metformin can cause lactic acidosis. Acidosis can develop also in a functional renal failure owing to use of diuretics, especially loopback. It is not necessary to appoint metformin if concentration of creatinine in blood plasma of 15 mg/l (135 µmol/l) at men and 12 mg/l (110 µmol/l) — at women.

X-ray contrast yodosoderzhashchy means. In case of the dehydration caused by diuretics the risk of development of OPN, especially after use of yodosoderzhashchy X-ray contrast means in high doses increases. Before use of such means it is necessary to provide appropriate hydration of the patient.

Tricyclic antidepressants, neuroleptics. Strengthening of antihypertensive action and risk of developing orthostatic hypotension (additive action).

Salt of calcium. Risk of a hypercalcemia owing to deterioration in discharge of calcium kidneys.

Cyclosporine, takrolimus. Risk of increase in concentration of creatinine in blood plasma without change of concentration of cyclosporine, even without lack of water or sodium.

Corticosteroids, tetrakozatid (peroral). Decrease in antihypertensive action (a delay of sodium and water as a result of action of GKS).

Overdose

Symptoms of acute poisoning are water and electrolytic disturbances, such as hyponatremia and hypopotassemia. the overdose of an indapamid can be followed by nausea, vomiting, arterial hypotension, spasms, dizziness, drowsiness, confusion of consciousness, a polyuria or an oliguria which can pass into the anury caused by a hypovolemia.

Initial actions include fast removal of the accepted substances by gastric lavage and/or use of activated carbon with the subsequent recovery of water and electrolytic balance.

Storage conditions

B the dry and protected from light place at a temperature not above 25 °C. to store out of children's reach.