Indapamide - instructions for use, dose, side effects, contraindications

Excipients: silicon colloidal dioxide 1.8 mg, potato starch 50.0 mg, magnesium stearate 1.0 mg, microcrystalline cellulose 5.2 mg, lactose monohydrate 56.5 mg, povidone 3.0 mg;

excipients of the shell: hypromellose (hydroxypropylmethylcellulose) 2.4 mg, azorubin dye 0.006 mg, povidone low molecular weight 0.9 mg, polysorbate 80 mg 0.3 mg, titanium dioxide 0.894 mg, talc 0.5 mg.

Description:

Round, biconvex tablets, covered with a film shell of pink color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Hypotensive agent (diuretic, vasodilator). Indapamide reduces the tone of the smooth muscles of the arteries, has a vasodilating effect, reduces the overall peripheral resistance of blood vessels, helps to reduce left ventricular hypertrophy.

The mechanism of action of indapamide on vessels is apparently associated with several mechanisms:

- decreased sensitivity of the vascular wall to norepinephrine and angiotensin;

- increased synthesis of prostaglandins, in particular prostaglandin E2 and prostacyclin I2, having vasodilating activity;

- theoppression of the transmembrane current of calcium ions in smooth muscle cells vascular wall.

Indapamide has a moderate diuretic effect. Violates reabsorption ions of sodium and chlorine, to a lesser degree - potassium and magnesium in the cortical segment of the Henle loop and the proximal convoluted tubule of the nephron, thereby enhancing diuresis.

Indapamide has an antihypertensive effect in doses that do not have a pronounced diuretic effect.

An increase in the dose is not accompanied by an increase in the hypotensive effect, but may accompanied by an increased incidence of side effects.

Indapamide does not affects the lipid metabolism (triglycerides, cholesterol-LDL, cholesterol-HDL) and the metabolism of carbohydrates (including in patients with arterial hypertension suffering from diabetes mellitus).

Indapamide is effective in patients with one kidney. The hypotensive effect of indapamide persists in patients on hemodialysis.

With a regular intake, the hypotensive effect of indapamide develops in 1-2 weeks, reaches a maximum by 8-12 weeks and lasts up to 8 weeks. After single dose is given the maximum effect after 24 hours.

Pharmacokinetics:

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

The maximum concentration in the blood plasma - 1-2 hours after ingestion. At repeated receptions of fluctuation of concentration of a preparation in a blood plasma in an interval between receptions 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 gistogematicheskie barriers (including placental), absorbed 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, the pharmacokinetics do not change.

Do not cumulate.

Indications:

Arterial hypertension.

Contraindications:

Hypersensitivity to indapamide, other derivatives of sulfonamide or to any of the excipients; severe renal failure (creatinine clearance less than 30 ml / min); severe hepatic insufficiency incl. with hepatic encephalopathy; hypokalemia; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; pregnancy, lactation; will return to 18 years of age (effectiveness and safety not established).

Carefully:

Dysfunction of the liver and / or kidney, violations of water-electrolyte balance, patients with an elongated interval QT on the ECG or receiving therapy, as a result of which the lengthening of the interval is possible QT (see "Interaction with other drugs"), diabetes mellitus in the stage of decompensation, Hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyperparathyroidism.

Pregnancy and lactation:

Taking indapamide during pregnancy is not recommended. The use of the drug may cause fetoplacental ischemia with the risk of slowing the development of the fetus.

Reception of the drug during lactation is possible with the termination of breastfeeding.

Dosing and Administration:

Tablets are taken orally, without chewing.

The daily dose of the drug is 1 tablet (2.5 mg) per day (in the morning).

If after 4-8 weeks treatment did not achieve the desired therapeutic effect, increase the dose of the drug not recommended (increased risk of side effects without increasing the hypotensive effect). Instead, it is recommended that another antihypertensive drug that is not a diuretic be included in the drug regimen. In the case where treatment should begin with the admission of two the dose of Indapamide remains 2.5 mg in the morning once a day.

Side effects:

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 blood and lymphatic system:

Very rarely: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, bone marrow aplasia.

From the central and peripheral nervous system:

Rarely: dizziness, headache, paresthesia.

Frequency unknown: fainting.

From the side of the cardiovascular system:

Very rarely: arrhythmia, lowering blood pressure, orthostatic hypotension, a feeling of heartbeat, changes in the ECG, characteristic of hypokalemia.

Co hand digestive system:

Infrequently: vomiting.

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

Very rarely: pancreatitis, impaired liver function.

The frequency is unknown: in patients with hepatic insufficiency it is possible to develop hepatic encephalopathy; hepatitis.

From the urinary system:

Very rarely: renal failure.

Co skin:

Often: maculopapular rash.

Infrequent: hemorrhagic vasculitis.

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

The frequency is unknown: there may be a worsening of the course of the disease in patients with an acute form of systemic lupus erythematosus; cases of photosensitivity reactions are described.

Laboratory indicators:

Very rarely: hypercalcemia.

Frequency is unknown: decrease in potassium content and development of hypokalemia; 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 are negligible; an increase in the concentration of uric acid and glucose in the blood plasma; increased activity of "liver" transaminases: thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes.

Overdose:

Symptoms: nausea, vomiting, weakness, dysfunction of the gastrointestinal tract, water-electrolyte disorders, in some cases - a marked decrease in blood pressure,respiratory depression, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria. Patients with cirrhosis may develop hepatic coma.

Treatment: gastric lavage, correction of water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Interaction:

Unrecommended combinations

With the simultaneous use of indapamide and lithium preparations there may be an increase in the concentration of lithium ions in the blood plasma due to a decrease in its excretion from the body by the kidneys, 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.

Combinations that require special attention

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

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

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

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

- Others: beprideil, cisapride, difemanyl, erythromycin (intravenously), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (intravenously).

Simultaneous use with any of these drugs, especially against hypokalemia, increases the risk of ventricular arrhythmias, especially arrhythmias such as pirouettes.

Before starting the combination therapy with indapamide and the above drugs, you should monitor the potassium content in the blood plasma and, if necessary, adjust it. It is necessary to monitor the clinical state of the patient, control the level of electrolytes of blood plasma, ECG parameters.

Patients with hypokalemia should use drugs that do not cause piruet-type arrhythmia.

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

It is possible to reduce the hypotensive effect of indapamide.

With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration). 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 hyponatremia (especially to patients with renal artery stenosis) is accompanied by a risk of developing 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:

- Pto reduce the intake of diuretics 3 days before the start of treatment with an ACE inhibitor;

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

In the first week of taking ACE inhibitors in patients, it is necessary to monitor the kidney function (creatinine content in the blood plasma).

Other drugs that can cause hypokalemia: amphotericin in (intravenous), gluco- and mineralocorticosteroids (for systemic administration), tetracosactide, laxatives, stimulating bowel motility

With simultaneous admission with indapamide, the risk of hypokalemia (additive effect) increases.

It is necessary to constantly monitor the level of potassium in the blood plasma, if necessary - its correction.

Baclofen:

There is an increase in the hypotensive effect.

Cardiac glycosides:

Hypokalemia increases the toxic effect of cardiac glycosides.

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

Combinations of drugs requiring attention

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

The simultaneous use of indapamide and potassium-sparing diuretics is advisable 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:

Increases the risk of developing lactic acidosis, t. It is possible to develop renal failure with diuretics, especially "loop".

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

Iodine-containing contrast agents:

Simultaneous use with diuretics against hypovolemia increases the risk of acute renal failure.

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

Tricyclic antidepressants, antipsychotics (antipsychotics):

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

Preparations containing calcium salts:

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

Cyclosporin, tacrolimus:

The risk of increasing the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine.

Corticosteroids, tetracosactide (with system assignment):

Reduction of hypotensive effect (fluid retention and sodium ions).

Special instructions:

In patients taking cardiac glycosides, laxatives, against the background of hyperaldosteronism, as well as in the elderly, careful monitoring of the potassium and creatinine content is shown.

On the background of taking indapamide, the content of potassium, sodium, magnesium ions in the blood plasma should be systematically monitored (electrolyte disturbances may develop), pH, glucose, uric acid and residual nitrogen.

The most thorough control is indicated in patients with cirrhosis of the liver (especially with developed edema or ascites - the risk of developing metabolic alkalosis, increasing manifestations of hepatic encephalopathy), coronary heart disease, heart failure, and also in the elderly. The high-risk group also includes patients with an increased interval QT on an electrocardiogram (congenital or developed against a background of any pathological process), patients receiving antiarrhythmic drugs of I A class (quinidine, disopyramide) and grade III, or receiving therapy, as a result of which the lengthening of the interval S-T (astemizole, erythromycin (intravenously), pentamidine, sultopride, terfenadine, wincamine, (amiodarone, brethil tosylate).

The first measurement of the content of potassium ions in the blood should be carried out within the first week after the start of treatment.

Hypercalcemia with indapamide may be a consequence of previously unidentified hyperparathyroidism.

In patients with diabetes it is extremely important to monitor blood glucose levels, especially in the presence of hypokalemia.

Significant dehydration can lead to the development of acute renal failure (reduced glomerular filtration). Patients should complete the volume of circulating blood (BCC) and at the beginning of treatment carefully monitor the kidney function.

Indapamide can give a positive result in the conduct of doping control.

Patients with arterial hypertension and hyponatremia (due to taking diuretics) should stop taking diuretics 3 days before the initiation of angiotensin converting enzyme inhibitors (if necessary, diuretics can be taken a little later), or initially prescribe low doses of angiotensin converting enzyme inhibitors.

Derivatives of sulfonamide can aggravate the course of systemic lupus erythematosus (it should be borne in mind when administering indapamide).

Caution patient with increased uric acid content (a tendency to increase the number of gout attacks).

Before surgical treatment the patient should warn the anesthesiologist that he is taking indapamide.

The drug can cause hepatic encephalopathy with concomitant liver failure. If suspected of hepatic encephalopathy, the product should be discontinued immediately.

Elderly patients may have a high susceptibility to the product, even if they are given a regular dosage.

Efficiency and safety in children are not established.

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

During treatment with indapamide, one should refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, since vertigo is possible.

Form release / dosage:

Tablets, film-coated, 2.5 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30 tablets in cans of polymeric with screw caps or in bottles for medicines made of plastic with screw caps.

1 bottle or bottle, or 1, 2, 3, 4 or 5 contour packs together with instructions for use put in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003436 / 01

Date of registration:21.05.2009 / 14.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:AVVA RUS, OJSC AVVA RUS, OJSC Russia

Manufacturer: & nbsp

AVVA RUS, OJSC Russia

Representation: & nbspAVVA ENG JSC AVVA ENG JSC Russia

Information update date: & nbsp02.11.2017

Illustrated instructions

Instructions

Indapamide (Indapamide)