Indapen SR

General characteristics. Structure:

Active agent: индапамид 1,5 mg.

Pharmacological properties:

Pharmacodynamics. Indapamid is diuretic medicine. It concerns 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 gyrose tubules of nephron where causes the strengthened release of sodium and chlorides and to a lesser extent potassium and magnesium, thus increasing the volume of the emitted urine.
The hypotensive effect of an indapamid remains for 24 h. Such effect is characteristic of doses with moderate diuretic action.
Anti-hypertensive 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.
For tiazid and tiazidopodobny diuretics the dose above which the therapeutic effect amplifies is established, 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 drug dose.
Indapamid also does not influence concentration of lipids (the general XC, XC LPNP and TG), does not influence metabolism of glucose at patients with a diabetes mellitus 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 influence amount of the absorbed drug.
Concentration of medicine in a blood plasma reaches the maximum value in 12 h after introduction.
Multiple dose promotes decrease in a difference of concentration of medicine in a blood plasma in intervals between receptions, but there are individual distinctions.
Distribution. Indapamid for 79% contacts proteins of a blood plasma. T½ in a phase of elimination makes 14–24 h (on average 18 h). The condition of saturation is reached in 7 days. Multiple dose does not lead to drug cumulation.
Removal. Indapamid is brought from an organism preferential 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.
At patients with a renal failure pharmacokinetic parameters do not differ.

Indications to use:

Essential arterial hypertension.

Route of administration and doses:

Indapen SR apply on 1 tablet a day, it is desirable in the morning.
Tablets should be swallowed whole, washing down with water.
At use of an indapamid in high doses it has no more expressed anti-hypertensive effect, but the diuretic effect at the same time amplifies.
Patients with a liver failure
With an abnormal liver function 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.
At a liver failure of heavy degree use of medicine is contraindicated.
Patients with a renal failure
At a renal failure of heavy degree (clearance of creatinine <30 ml/min.) 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 patients of advanced age concentration of creatinine in a blood plasma should be korrigirovat 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.

Features of use:

At patients with a liver failure tiazidopodobny diuretic medicines can accelerate development of hepatic encephalopathy. In case of symptoms of hepatic encephalopathy reception of an indapamid should be stopped immediately.
Photosensitization. The allergic photoharmoses caused by use of thiazide diuretics and tiazidopodobny medicines are possible. If during treatment there is a reaction of a photosensitization, administration of drug should be stopped. In case of need repeated use of diuretic it is recommended to protect open sites of skin which sunshine or artificial ultraviolet radiation can influence.
Water and electrolytic balance. Concentration of sodium in a blood plasma. Before an initiation of treatment, and then periodically it is necessary to control concentration of sodium in a blood plasma. Any therapy by diuretics can lead to a hyponatremia, sometimes with serious effects. Decrease in concentration of sodium during an initial stage can take place asymptomatically 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 a blood plasma. Decrease in level of potassium in a blood plasma with emergence of a hypopotassemia is the main risk at use of thiazide and tiazidopodobny diuretics. The risk of development of a hypopotassemia (mmol/l <3,4) has to be prevented at certain categories of patients of high risk. Especially carefully elderly people should appoint such drugs the patient at whom the risk of development of a hypopotassemia is higher, for example; to the exhausted patients, and also patients accepting many other medicines; to patients with cirrhosis, hypostases and ascites, with an ischemic heart disease and heart failure. At a hypopotassemia cardiotoxicity of drugs of a foxglove increases and the risk of emergence of disturbances of a cordial rhythm increases. To risk group patients treat with increase in an interval of Q-T irrespective of, this disturbance inborn or iatrogenic is. The hypopotassemia, like bradycardia, promotes development of serious violations of a cordial rhythm, especially tremblings/ventricular fibrillations (torsades de pointes).
During treatment it is regularly necessary to control potassium concentration in a blood plasma. The first measurement should be taken in the 1st week of treatment. At development of a hypopotassemia it is necessary to compensate for the potassium deficiency.
Concentration of calcium in a 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 a latent hyperparathyreosis. In that case it is necessary to stop treatment and to inspect the patient concerning function of epithelial bodies.
Concentration of glucose in blood. At patients with a diabetes mellitus, especially with the accompanying hypopotassemia, it is necessary to control concentration of glucose in a blood plasma.
Patients with gout. Patients with a hyperuricemia can have a tendency to increase in frequency of attacks of gout.
Renal failure and diuretics. Tiazida and tiazidopodobny diuretic drugs are effective only on condition of normal function of kidneys or its insignificant disturbance (concentration of creatinine <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.
The hypovolemia caused by loss of liquid which can arise in an initiation of treatment diuretics leads to decrease in glomerular filtering that, in turn, causes increase in concentration of urea and creatinine in a blood plasma. Such temporary functional renal failure passes without effects at patients with normal function of kidneys, but 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 at patients with rare hereditary intolerance of a galactose, a lack of lactase of Lapp or a syndrome of disturbance of absorption of glucose galactose.
Use during pregnancy and feeding by a breast. At pregnant women it is not necessary to apply diuretics as they can cause fetoplacental ischemia with threat of disturbances of fetation.
Indapamid is allocated with breast milk therefore do not recommend to accept this drug during feeding by a breast.
Children. Considering lack of data on safety and efficiency, do not recommend to use drug in pediatric practice.
Ability to influence speed of response at control of vehicles or work with other mechanisms. At medicine use Indapen SR, especially in an initiation of treatment or at use in addition to other anti-hypertensive means, there can be symptoms connected with decrease in the ABP. In such situation recommend to refrain from control of vehicles and mechanisms.

Side effects:

During treatment the undesirable effects given below which were distributed on frequency as follows are noted:
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 diuretic medicines, including индапамид, can cause side reactions:
from system of blood and lymphatic system: very seldom — thrombocytopenia, a leukopenia, an agranulocytosis, aplastic anemia, hemolitic anemia.
From a nervous system: seldom — dizziness, feeling of fatigue, a headache, paresthesias, an adynamy.
From heart: very seldom — arrhythmia, decrease in the ABP.
From the alimentary system: seldom — nausea, a lock, dryness in a mouth; infrequently — vomiting; very seldom — pancreatitis.
From kidneys and urinary tract: very seldom — a renal failure.
From a liver and biliary tract: very seldom — an abnormal liver function; frequency is unknown — at patients with a liver failure possibly development of hepatic encephalopathy.
From skin and hypodermic fabric: hypersensitivity reactions, generally from skin, at the patients having tendency to allergic and asthmatic reactions; often — spotty and papular rashes; infrequently — a purpura; very seldom — vasculomotor hypostasis and/or a small tortoiseshell, a toxic epidermal necrolysis, Stephens's syndrome — Johnson; frequency is unknown — possibly an aggravation of symptoms of the accompanying system lupus erythematosus. It was reported about photosensitization cases.
Diagnostic testings. At some patients the hypopotassemia (potassium concentration of <3,4 of mmol/l) is noted. Potassium concentration of <3,2 of mmol/l is registered at some patients in 4–6 weeks of treatment. In 12 weeks of treatment indapamidy potassium concentration in a blood plasma decreased on average by 0,23 mmol/l. Very seldom — a hypercalcemia. Frequency is unknown — decrease in potassium concentration that is especially dangerous to patients with high risk of development of a hypopotassemia; a hyponatremia with a hypovolemia that causes dehydration (the risk of development 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 expressed secondary compensatory metabolic alkalosis; the increased concentration of uric acid and glucose in blood. At patients with a diabetes mellitus or gout it is necessary to consider expediency of use of diuretic medicines.

Interaction with other medicines:

Not recommended combinations
Lithium. Increase in level of lithium in a blood plasma and emergence of symptoms of overdose owing to lithium removal reduction (is possible as well as at an electrolyte-deficient diet). If purpose of diuretic is required, it is necessary to carry out careful monitoring of level of lithium in a blood plasma and to adapt its dose.
Medicines which should be applied with care along with indapamidy
The medicines influencing a cordial rhythm and defiant torsades de pointes:

• Ia group of antiarrhytmic medicines (quinidine, hydroquinidine, Disopyramidum);
• group III of antiarrhytmic medicines (Amiodaronum, соталол, дофетилид, ибутилид);
• some antipsychotic medicines: fenotiazina (Chlorpromazinum, циамемазин, levomepromazinum, thioridazine, трифлуорперазин), benzamides (амисульпирид, Sulpiridum, сультоприд, тиаприд), phenyl propyl ketones (Droperidolum, haloperidol) and others: bepridit, цизаприд, difemanit, erythromycin — at in introduction, галофантрин, pentamidine, мизоластин, спарфлоксацин, moxifloxacin, Vincaminum — at in introduction.
The 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 it is necessary to observe the patient regarding development of a hypopotassemia and if necessary to korrigirovat potassium concentration. It is also necessary to control concentration of electrolytes in a blood plasma and the ECG parameters.
At emergence of a hypopotassemia together with indapamidy it is necessary to use medicines which do not increase risk of emergence of torsades de pointes.
NPVP (for intake), including the selection TsOG-2 inhibitors and salicylates in high doses (> 3 g/days). Decrease in hypotensive action of an indapamid is possible. The risk of emergence of OPN at patients with dehydration increases (glomerular filtering is reduced). It is necessary to control a condition of hydration of the patient and to control function of kidneys.
APF inhibitors. If use of APF inhibitors is begun when the patient has a deficit of sodium (especially at patients with a renal artery stenosis), there is a risk of sharp decrease in the ABP and development of OPN.
Considering that the previous treatment by diuretics can cause shortage of sodium, at primary AG follows:

• to stop reception of diuretic in 3 days prior to reception of APF inhibitors, and then, if necessary, to return to reception of diuretic or
• to begin treatment with APF inhibitors in low doses, gradually raising them.
At congestive heart failure treatment should be begun with low doses of APF inhibitors, it is better after a diuretic dose decline (whenever possible).
Within 1 week of treatment by APF inhibitors it is necessary to control function of kidneys (concentration of creatinine).
Other medicines causing a hypopotassemia. Amphotericinum In at in introduction, GKS and mineralokortikosteroida (at intake), тетракозактид, the laxative medicines stimulating a peristaltics.
The risk of development of a hypopotassemia increases. It is necessary to control potassium concentration in a blood plasma, especially at simultaneous treatment by cardiac glycosides. It is not necessary to accept laxative medicines which stimulate an intestines peristaltics.
Baclofenum. Strengthens hypotensive action of an indapamid. It is necessary to provide the corresponding hydration of the patient and to control function of kidneys.
Cardiac glycosides. The hypopotassemia is the factor promoting 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.
The combined treatment which requires attention
Kaliysberegayushchy diuretics (amiloride, Spironolactonum, Triamterenum). Simultaneous use of these drugs is shown to some patients, but the risk of development of a hypopotassemia is not excluded, and at patients with a renal failure or a diabetes mellitus can lead to development of a hyperpotassemia. It is necessary to control potassium concentration in a blood plasma and the ECG parameters, and if necessary — to change treatment.
Metforminum can cause lactic acidosis. Acidosis can develop also at a functional renal failure owing to use of diuretics, especially loopback. It is not necessary to appoint Metforminum if concentration of creatinine in a blood plasma exceeds 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 high doses of yodosoderzhashchy X-ray contrast means increases. Before use of such means it is necessary to provide appropriate hydration of the patient.
Tricyclic antidepressants, neuroleptics. Strengthening of anti-hypertensive action and risk of development of orthostatic hypotension (additive action).
Calcium salts. Risk of development of a hypercalcemia owing to deterioration in release of calcium kidneys.
Cyclosporine, такролимус. Risk of increase in concentration of creatinine in a blood plasma without change of concentration of cyclosporine, even without deficit of water or sodium.
GKS, тетракозатид (at intake). Decrease in anti-hypertensive action (a delay of sodium and water as a result of action of GKS).

Contraindications:

Hypersensitivity to an indapamid and/or other components of drug or other sulfonamides. Heavy renal failure. Hepatic encephalopathy or other heavy abnormal liver functions. Hypopotassemia. Period of pregnancy and feeding by a breast. Children's age.

Overdose:

Owing to acute intoxication there can be disturbances of water and electrolytic balance (a hyponatremia, a hypopotassemia), nausea, vomiting, decrease in the ABP, a spasm, drowsiness, spasms of muscles, dizziness, fatigue, a disorientation, a polyuria or an oliguria to an anury (owing to a hypovolemia).
In case of overdose it is necessary to wash out a stomach (using absorbent carbon or without), and also to recover water and electrolytic balance in the conditions of a hospital, to carry out symptomatic therapy.

Storage conditions:

In the dry place protected from light at a temperature below 25 °C.

Issue conditions:

According to the recipe

Packaging:

The tab., п / oh, with модиф. высвоб. 1,5 mg blister, No. 28, No. 30, No. 56, No. 60.