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

film sheath auxiliaries - 5 mg: methacrylic acid and methyl methacrylate copolymer [1: 1] 40.0%, talc 37.25%, titanium dioxide 15.0%, triethyl citrate 4.8%, colloidal anhydrous dioxide 1.25%, sodium bicarbonate 1.2%, sodium lauryl sulfate 0.5%.

Description:

Tablets are round, biconvex, covered with film shell white or almost white. Color of tablet core without shell white or almost white.

Pharmacotherapeutic group:diuretic

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide belongs to the sulfonamide derivatives and is pharmacologically similar to thiazide diuretics. Reduces the tone of the smooth muscles of the arteries, reduces the overall peripheral resistance of the vessels. Has moderate saluretic and diuretic effects, which are associated with the blockade of the reabsorption of sodium, chlorine, hydrogen ions and, to a lesser extent, potassium ions in the proximal tubules and the cortical segment of the distal tubule of the nephron. The vasodilator effect and the reduction of the total peripheral resistance of the vessels are mediated by a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandin E2, which has vasodilator activity; suppression of calcium current in smooth muscle cells of blood vessels. Helps reduce hypertrophy of the left ventricle of the heart. In therapeutic doses does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

The antihypertensive effect develops at the end of the first / beginning of the second week with a constant intake of the drug and persists for 24 hours against a backgroundsingle reception.

Pharmacokinetics:After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. Bioavailability is high (93%). Eating somewhat slows down the speed, but does not affect the completeness of absorption. The maximum concentration in the blood is reached 12 hours after ingestion. Equilibrium concentration is achieved after 7 days of regular intake. The preparation binds to blood plasma proteins by 70-80%. Has a high volume of distribution, passes through the histohematological (including placental) barriers, penetrates into breast milk. Metabolised in the liver. The half-life of indapamide is on average 14-18 hours. In patients with renal insufficiency, pharmacokinetics does not change. Do not cumulate.

Indications:

Arterial hypertension.

Contraindications:

Hypersensitivity to indapamide, other derivatives of the sulfonamide or other components of the preparation, severe renal impairment (creatinine clearance less than 30 mL / min), severe liver failure (including hepatic encephalopathy), hypokalemia, pregnancy, lactation, lactose intolerance, lactase deficiency, gluco-galactose malabsorption, age to 18 years (efficacy and safety not established).

Carefully:

With diabetes, violations kidney or liver function, water-electrolyte balance disorders, hyperparathyroidism, simultaneous use of drugs that extend the QT interval, hyperuricemia.

Pregnancy and lactation:

The use of indapamide in this category of patients is not recommended. Adequate and well-controlled studies of the safety of the use of indapamide during pregnancy and lactation were not conducted. Application of the drug indapamide can lead to placental insufficiency (fetoplacental ischemia) and impaired fetal development.

Indapamide is excreted in breast milk, so it should not be used during breastfeeding. If therapy is necessary, breastfeeding should be discontinued.

Dosing and Administration:

Inside, 1 tablet (1.5 mg) 1 time per day, preferably in the morning, regardless of food intake.

If after 4-8 weeks of treatment the desired therapeutic effect is not achieved, the dose of the drug should not be increased (the risk of side effects increases without increasing the antihypertensive effect).Instead, it is recommended to include another antihypertensive drug that is not a diuretic.

In cases where treatment should start with the taking of two drugs, the dose of indapamide remains 1.5 mg in the morning once a day.

Side effects:

Classification of the incidence of adverse events, adopted by the World the health organization (WHO): very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10000 and <1 / 1000), very rarely (<1/10000), the frequency is unknown.

From the cardiovascular system: very rarely - lowering blood pressure, (BP), arrhythmia, orthostatic hypotension, a feeling of heartbeat, changes in ECG, characteristic of hypokalemia.

From the hematopoiesis: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, bone marrow aplasia.

From the side, the central and peripheral nervous system: rarely - dizziness, headache, paresthesia, drowsiness, insomnia, fatigue, muscle spasms of the limbs; the frequency is unknown - syncope.

From the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the mucous membrane / oral cavity; very rarely - pancreatitis, diarrhea,abnormal liver function; the frequency is unknown - hepatic encephalopathy, hepatitis, increased activity of "hepatic transaminases."

From the genitourinary system: very rarely - kidney failure.

From the skin and subcutaneous tissue: often - maculopapular rash; infrequently - purpura, very rarely - angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, itching; frequency unknown - exacerbation of systemic lupus erythematosus (SLE), photosensitivity reactions.

Laboratory data: in clinical studies, hypokalemia (potassium in the blood plasma below 3.4 mmol / L) was observed in 10% of patients and 3.2 mmol / L in 4% of patients after 4-6 weeks of treatment. After 12 weeks of therapy, the potassium content in the blood plasma decreased, on average, by 0.23 mmol / l.

Very rarely - hypercalcemia; frequency is unknown - decrease in content potassium and the development of hypokalemia, especially significant for patients at risk; hyponatremia, accompanied by hypovolemia and orthostatic hypotension.

Simultaneous loss of chloride ions can lead to compensatory metabolic alkalosis, however, the frequency of development metabolic alkalosis and its severity is negligible; hyperuricemia and hyperglycemia (frequency unknown), increased blood urea nitrogen concentration; hypercreatininaemia.

Overdose:

Symptoms: nausea, vomiting, weakness, water-electrolyte disorders, marked decrease in blood pressure, dizziness, drowsiness, confusion, respiratory depression; in patients with impaired liver function, it is possible to develop hepatic coma, convulsions, polyuria, oliguria up to anuria.

Treatment: gastric lavage and / or the administration of activated charcoal, followed by restoration of the normal water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Interaction:

Unrecommended combinations:

With simultaneous use with lithium preparations, an increase in the concentration of lithium ions in blood plasma is possible due to a decrease in the excretion of it from the body by the kidneys; accompanied by the appearance of signs: overdose (nephrotoxic effect), as well as when observing a salt-free diet (reduced elimination of lithium ions by the kidneys).

Combinations that require special attention:

1) Drugs that can cause heart rhythm disturbances like "pirouette", antiarrhythmics of IA class (quinidine, hydroquinidine, disopyramide), antiarrhythmic drugs of III class (amiodarone, dofetilide, ibutilide, brethil tosylate), sotalol, some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other (bepridil, cisapride, difemanyl, erythromycin (intravenous (iv)), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, wincamine (w / w), astemizole. Simultaneous use with any of these drugs, especially against hypokalemia, increases the risk of ventricular arrhythmias as pirouettes. Before the beginning of combined therapy with the drug indapamide and the above drugs should monitor the potassium content in the blood plasma and, if necessary, adjust it.

Recommended: monitoring the clinical condition of the patient, as well as the content of plasma electrolytes and ECG.Patients with hypokalemia should use drugs that do not trigger the development of piruet-type arrhythmias.

2) With the simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) (including systemic use), including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of salicylic acid (3 g / day or more) are possible: reduction of the antihypertensive effect of indapamide, renal failure in dehydrated patients (due to reduced glomerular filtration rate). At the beginning of therapy with indapamide, it is necessary to restore the water-electrolyte balance and control the function of the kidneys.

3) Angiotensin converting enzyme (ACE) inhibitors in patients with hyponatremia (especially in patients with renal artery stenosis) increase the risk of developing arterial hypotension and / or acute renal disease insufficiency.

Patients with hypertension and possibly with hyponatremia, due to taking diuretics, should:

- stop taking the drug 3 days before the start of therapy with ACE inhibitors and switch to potassium-sparing diuretics;

- or initiate therapy with ACE inhibitors from low doses, followed by a gradual increase in dose if necessary. In the first week of therapy with ACE inhibitors, it is recommended to monitor the concentration of plasma creatinine.

4) Other drugs that can cause hypokalemia: amphotericin B; (in / in), gluco- and mineralocorticosteroids (for systemic administration) (see below). also the information in the section "Combinations of drugs requiring attention"), tetracosactide (see also the information in the section "Combinations of drugs that require attention"), laxatives that stimulate intestinal motility. With the simultaneous administration of the above drugs with indapamide, the risk of developing hypokalemia (additive effect) increases. If necessary, monitor and adjust the content of potassium ions in the blood plasma.

5) Simultaneous therapy with baclofen increases the antihypertensive effect of indapamide.

6) Cardiac glycosides hypokalemia increases toxic effects cardiac glycosides (glycoside intoxication). With simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the content of potassium ions in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

Combinations of drugs that require attention:

1) Simultaneous use with potassium-sparing diuretics (amiloride, spironolactone, triamterene) is useful in some patients, but the possibility of hypokalemia is not ruled out. Against the background of diabetes or kidney failure may develop hyperkalemia. It is necessary to control the content of potassium ions in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

2) Metformin increases the risk of developing lactic acidosis, since it is possible to develop renal failure with diuretics, especially "loop". Metformin should not be taken at a plasma creatinine concentration of more than 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

3) Simultaneous use of large doses of iodine-containing contrast media against hypovolemia and diuretic administration increases the risk of acute renal failure. It is recommended to restore the water-electrolyte balance of blood before applying the drugs.

4) Tricyclic antidepressants (imipramine-like) and antipsychotics increase the antihypertensive effect and the risk of developing orthostatic hypotension (additive effect).

5) Preparations containing calcium salts increase the risk of hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

6) Cyclosporin, tacrolimus - The risk of increasing the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine.

7) Glucorticosteroid preparations, tetracosactide (with systemic use) reduce the antihypertensive effect (sodium and liquid ion retention).

Special instructions:

With long-term use or when taking indapamide in large doses, electrolyte disorders such as hyponatremia, hypokalemia, hypochloraemic alkalosis can develop. These disorders are more often observed in patients with chronic heart failure (II-IV FK according to the NYHA classification), liver diseases, with vomiting and diarrhea, as well as in individuals on a salt-free diet.

The simultaneous use of indapamide with cardiac glycosides and corticosteroids increases the risk of hypokalemia.

In addition, the release of magnesium in the urine may increase, which can lead to hypomagnesemia.

Perhaps the appearance of orthostatic hypotension, which can be provoked by drinking alcohol, barbiturates, narcotic drugs and simultaneous reception of other antihypertensive drugs.

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

The most thorough control is indicated in patients with cirrhosis of the liver, ischemic heart disease, chronic heart failure.

Patients with an increased QT interval on an electrocardiogram (congenital or developing against a background of a pathological process) also belong to the high-risk group.

The first measurement of the potassium content in the blood plasma should be performed within 1 week of treatment.

Hypercalcemia on the background of taking indapamide may be a consequence of previously undiagnosed hyperparathyroidism.

In patients with diabetes, it is extremely important to control the concentration of glucose in the blood, especially when there is hypokalemia.

Significant dehydration can lead to the development of acute renal failure (reduced glomerular filtration). Patients must compensate for the loss of water 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 hyponatraemia (due to admission diuretics) it is necessary to stop taking diuretics 3 days before the start of angiotensin-converting enzyme inhibitors (if necessary, diuretics can be taken a little later) or they are given initial low doses of angiotensin-converting enzyme inhibitors.

Perhaps the development of hepatic encephalopathy due to a violation of liver function, the development of photosensitivity reactions, exacerbation of the gout.

It is necessary to systematically monitor the content of potassium, sodium, magnesium ions in the blood plasma (electrolyte disturbances may develop), pH, concentration of glucose, uric acid and residual nitrogen; determination of the content of sodium ions in the blood plasma is recommended to be performed before the beginning of treatment; The first measurement of the concentration of potassium ions in the blood plasma should be performed during the first week after the start of treatment.

Derivatives of sulfonamides can aggravate the course of systemic red lupus (should be borne in mind when administering indapamide).

Efficiency and safety in children are not established.

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

In some cases, individual reactions associated with changes in blood pressure are possible, especially at the beginning of treatment and with the addition of another antihypertensive drug. As a result, the ability to drive and work with mechanisms that require increased attention can be reduced.

Form release / dosage:Tablets of prolonged action, film-coated, 1.5 mg.

Packaging:

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

30 tablets in cans type BTS or in polymer cans with control covers of the first autopsy.

Each jar, 2, 3 or 6 contour squares with instruction on application is placed in a pack of cardboard.

Storage conditions:

In a dry place, protected from light and out of reach of children, at a temperature not exceeding 25 ° C.

Shelf life:

2 years.

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001235

Date of registration:17.11.2011

Date of cancellation:2016-11-17

The owner of the registration certificate:BIOCHEMIST, OJSC BIOCHEMIST, OJSC Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Representation: & nbspBIOCHEMICAL JSC BIOCHEMICAL JSC Russia

Information update date: & nbsp16.10.2015

Illustrated instructions

Instructions

Indapamide (Indapamide)