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

Excipients: hypromellose 77.36 mg, lactose monohydrate (sugar milk) 119.14 mg, silicon dioxide colloid (aerosil) 1.00 mg, magnesium stearate 1.00 mg, opadrai II (hypromellose 2.24 mg, lactose monohydrate 2.88 mg , polyethylene glycol 0.80 mg, titanium dioxide 2.08 mg) 8 mg.

Description:

Round tablets of biconvex form, covered with a film coat of white color. On the cross-section - the inner layer of white or white with a creamy shade of color.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

A hypotensive agent, a thiazide-like diuretic with a moderate in strength and long duration of action, a benzamide derivative.

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 effects and the reduction of the overall peripheral vascular resistance are based on the following mechanisms: a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandins with vasodilating activity; inhibition of the current of calcium ions in the smooth-muscle walls of the vessels.

Reduces the tone of the smooth muscles of the arteries, reduces the overall peripheral resistance of the 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).

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 background of a single dose.

Pharmacokinetics:

After ingestion the drug is completely, but gradually 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 plasma is achieved 12 hours after ingestion of a single dose. 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 18-26 hours on average. It is excreted from the body by the kidneys (up to 80%) mainly in the form of metabolites, through the intestine - 20%. In patients with renal insufficiency, pharmacokinetics does not change. Do not cumulate.

Indications:

Arterial hypertension.

Contraindications:

Hypersensitivity to indapamide, other derivatives of sulfonamide or other components of the drug, acute impairment of cerebral circulation, severe renal dysfunction (creatinine clearance less than 30 ml / min) and / or liver (incl.with hepatic encephalopathy), hypokalemia, pregnancy, lactation, age under 18 (efficacy and safety not established).

These tablets contain lactose monohydrate (milk sugar); therefore, the drug should not be taken by patients with rare hereditary diseases, such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

In diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyponatremia and other disturbances of water-electrolyte balance, moderate hepatic and / or renal insufficiency, chronic heart failure, hyperparathyroidism, in patients with an increased interval QT on the ECG or receiving a combination therapy, as a result of which the lengthening of the interval is possible QT (astemizole, erythromycin (intravenously), pentamidine, sultopride, terfenadine, wincamine (IV), antiarrhythmic drugs IA class (quinidine, disopyramide) and III class (amiodarone, brethil tosylate).

Pregnancy and lactation:

The drug is not recommended for use during pregnancy, since diuretics can cause fetoplacental ischemia with a risk of fetal malnutrition. Indapamide It can not be used to treat physiological edema during pregnancy.

Indapamide is excreted in breast milk. Given the potential for adverse events in infants, breastfeeding during treatment is not recommended.

Dosing and Administration:

Inside, not liquid, squeezed enough liquid, regardless of food intake, mainly in the morning hours at a dose of 1.5 mg (1 tablet) per day.

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

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

In elderly patients, plasma concentration of creatinine should be monitored taking into account age, body weight and sex, the drug can be used in elderly patients with normal or slightly impaired renal function (see also "Contraindications").

Side effects:

Most adverse reactions (laboratory and clinical indicators) are dose-dependent.

The incidence of adverse reactions that may be caused by thiazide-like diuretics, including indapamide, is given in the form of the following gradations: 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 side of the blood and lymphatic system

Very rarely: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the central nervous system

Rarely: dizziness, fatigue, headache, paresthesia.

From the side of the cardiovascular system

Very rarely: arrhythmia, lowering blood pressure.

From the digestive system

Infrequently: vomiting.

Rarely: nausea, constipation, dry mouth.

Very rarely: pancreatitis.

From the urinary system

Very rarely: renal failure.

From the liver and biliary tract

Very rarely: a violation of the liver.

Unspecified frequency: the possibility of developing hepatic encephalopathy in the case of liver failure.

From the skin

Hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions:

Often: maculopapular rash.

Infrequent: hemorrhagic vasculitis.

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

Unspecified frequency: possibly worsening in the presence of an acute form of disseminated red lupus.

The cases of photosensitivity are described.

Laboratory indicators:

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

Very rarely: hypercalcemia.

Unspecified frequency:

· gand apokalemia;

· ghypnotriemia 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 is not significant;

· PAn increase in the level of uric acid and glucose in the blood plasma.

Overdose:

Symptoms: nausea, vomiting, weakness, dysfunction of the gastrointestinal tract (nausea, vomiting), water-electrolyte disorders, marked decrease in blood pressure, dizziness, drowsiness, confusion, respiratory depression, polyuria, oliguria up to anuria, in patients with impaired function liver development of the hepatic coma is possible.

Treatment: gastric lavage and / or the administration of activated charcoal, followed by restoration of 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 the 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 of an overdose (nephrotoxic effect) as well as in the case of a salt-free diet (decrease in the excretion of lithium ions by the kidneys).

Combinations requiring special attention

1. Drugs that can cause heart rhythm disturbances as pirouettes: antiarrhythmics IA class (quinidine, hydroquinidine, disopyramide), antiarrhythmics, III class agents (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 starting the combination therapy with the drug Indapamide retard 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 electrolytes of blood plasma and ECG. Patients with hypokalemia should use drugs that do not trigger the development of piruet-type arrhythmias.

2. With the simultaneous administration of non-steroidal anti-inflammatory drugs (NSAIDs) (for systemic use), including selective inhibitors of cyclooxygenase-2 (COX-2),high doses of salicylic acid (3 g / day or more) is possible: a reduction in the antihypertensive effect of indapamide, the development of acute renal failure in dehydrated patients (due to a decrease in 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 failure.

Patients with hypertension and possibly with hyponatraemia due to 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 (IV), gluco- and mineralocorticosteroids (for systemic administration) (see also the information in the "Combinations of drugs that require attention" section) 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 the toxic effect of cardiac glycosides (glycoside intoxication). With the simultaneous use of indapamide and cardiac glycosides, the levels of potassium ions in the blood plasma should be monitored, the ECG parameters should be monitored and, if necessary, the therapy should be adjusted.

Combinations of drugs requiring attention

1. Simultaneous use with potassium-sparing diuretics (amiloride, spironolactone, triamterene) is appropriate in some patients,however, the possibility of developing 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, because 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 agents against hypovolemia and the use of diuretics increases the risk of acute renal failure. It is recommended to restore the electrolyte blood balance before applying the drugs.

4. Tricyclic antidepressants (imipramine-like) and antipsychotics increase the hypotensive 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. Cyclosporine, 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 application) reduce the hypotensive effect (sodium and liquid ion retention).

Special instructions:

Dysfunction of the liver

In patients with hepatic insufficiency in the appointment of thiazide-like diuretics, the development of hepatic encephalopathy is possible, especially if the water electrolyte balance is disturbed. With its development, diuretics should be discontinued.

Photosensitivity

With the use of thiazide-like diuretics, cases of the development of photosensitivity reactions were noted. If they develop, the drug should be discontinued. On the background of therapy with the drug Indapamide retard, it is necessary to protect the exposed areas of the body from exposure to sunlight and artificial ultraviolet radiation.

Water-electrolyte balance

- content of sodium ions in blood plasma: all diuretics can cause hyponatraemia. The content of sodium ions in the blood plasma should be measured before starting treatment with the drug Indapamide retard, and then regularly during the treatment period.Determination of the content of sodium ions in the blood plasma should be done before the initiation of therapy with the drug Indapamide retard, as well as during therapy. It is important to regularly monitor the content of sodium ions in blood plasma, tk. Initially, hyponatremia can be asymptomatic. The most careful control of the sodium ion content is indicated in elderly patients and patients with cirrhosis of the liver.

- the content of potassium ions in the blood plasma: The greatest risk in the treatment of thiazide-like diuretics is hypokalemia. Particular attention should be paid to prevent hypokalemia (less than 3.4 mmol / L) in the following cases: weakened patients and / or receiving other therapy (antiarrhythmic drugs and agents that can lengthen the interval QT on ECG), in old age, patients with cirrhosis of the liver, peripheral edema and ascites, with ischemic heart disease and chronic heart failure.

Hypokalemia in such patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

The high-risk group also includes patients with an elongated interval QT on the ECG.

Hypokalemia is a predisposing factor in the occurrence of severe arrhythmia, and especially arrhythmias such as pirouettes, which can lead to death.

In all described cases, it is necessary to regularly monitor the potassium content in the blood plasma. The first determination of the potassium content in blood plasma should be performed during the first week of therapy with Indapamide Retard.

When detecting hypokalemia, appropriate therapy should be carried out.

- the content of calcium ions in the blood plasma: Thiazide-like and thiazide diuretics can reduce the excretion of calcium ions by the kidneys, leading to minor and / or temporary hypercalcemia. Expressed hypercalcemia on the background of taking the drug Indapamide retard may be a consequence of previously undiagnosed hyperparathyroidism.

It is necessary to cancel the use of diuretics before examining the function of parathyroid glands.

- concentration of glucose in blood plasma: in patients with diabetes, especially in the presence of hypokalemia, it is necessary to monitor the concentration of glucose in the blood plasma;

- uric acid: in patients with hyperuricemia may increase the incidence of attacks or exacerbation of the gout.

Kidney function and diuretic drugs

Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly reduced (creatinine plasma in adults less than 25 mg / L or 220 μmol / L) kidney function.

Expressed hypovolemia can lead to the development of acute renal failure (a decrease in the rate of glomerular filtration), which may be accompanied by an increase in the concentration of urea and creatinine in the blood plasma. With normal kidney function, transient functional renal failure, as a rule, passes without consequences. With existing renal failure, the patient's condition may worsen.

Elderly patients

It is recommended to regularly monitor the concentration of creatinine and the content of potassium in the blood plasma, taking into account the patient's age, body weight and sex. Indapamide retard can be prescribed to elderly patients with preserved or slightly impaired renal function (QC above 30 ml / min).

Athletes

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

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

The use of indapamide retard does not lead to a disturbance of psychomotor reactions. However, in some patients, in response to a decrease in blood pressure, various individual reactions may develop, especially at the onset of therapy or when other antihypertensive agents are added to the therapy. In this regard, at the beginning of treatment with the drug Indapamide retard, it is not recommended to drive vehicles or other complex mechanisms requiring increased attention.

Form release / dosage:

Tablets of prolonged action, film-coated, 1.5 mg.

Packaging:

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil.

1, 2, 3, 4 or 5 contour mesh packages with instructions for medical use 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:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-002460

Date of registration:29.08.2011

Expiration Date:Unlimited

The owner of the registration certificate:ALSI Pharma, ZAO ALSI Pharma, ZAO Russia

Manufacturer: & nbsp

ALSI Pharma, ZAO Russia

Representation: & nbspALSI Pharma CJSC ALSI Pharma CJSC Russia

Information update date: & nbsp02.11.2017

Illustrated instructions

Instructions

Indapamide retard (Indapamide retard)