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

Excipients: hypromellose Methocel K 15 M Premium (hydroxypropylmethylcellulose) 77.36 mg, lactose monohydrate (tablets 80 mesh) 115.14 mg, povidone (polyvinylpyrrolidone low molecular weight) 4 mg, silicon dioxide colloid (aerosil) 1 mg, magnesium stearate 1 mg;

shell auxiliary substances: opedrai II (white) [polyvinyl alcohol 2,1 mg, macrogol-4000 (polyethylene glycol) 0,8 mg, titanium dioxide 1,2 mg, talc-0,9 mg] 5 mg.

Description:

The tablets covered with a film membrane, white or white with light brown or grayish shade of color, round, biconcave, slightly roughened.On the broken tablets are visible two layers: the core is white or almost white and the shell is white or white with a light brown or grayish hue of color.

Pharmacotherapeutic group:diuretic

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Hypotensive agent (diuretic, vasodilator).

According to its pharmacological properties, it is close to thiazide diuretics, whose action is related to the inhibition of the reabsorption of sodium ions in the cortical segment of the nephron loop. Increases the urinary excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions. Possessing the ability to selectively block "slow" calcium channels, increases the elasticity of the walls of the arteries and reduces the overall peripheral vascular resistance. Helps reduce hypertrophy of the left ventricle of the heart. Does not affect the concentration of lipids in the blood plasma (triglycerides, low density lipoproteins, high density lipoproteins), does not affect carbohydrate metabolism (including in patients with concomitant diabetes). Reduces the sensitivity of the vascular wall to noradrenaline and angiotensin II, stimulates the synthesis of prostaglandin (PgE2) and prostaglandin (PgI2), reduces the production of free and stable oxygen radicals.

The antihypertensive effect persists for 24 hours against a background of a single dose, with a moderate increase in diuresis.

Pharmacokinetics:

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

The maximum concentration in blood plasma is 12 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 of indapamide is an average of 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 the histohematological barriers (including placental), penetrates 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 ingredients and other sulfonamide derivatives, severe renal impairment (creatinine clearance less than 30 mL / min), anuria, hypokalemia, severe liver (including encephalopathy) deficiency, lactose intolerance, lactase deficiency, glucose -galactose mapping, age under 18 years (efficacy and safety not established).

Carefully:

Dysfunction of the liver and / or kidney, water-electrolyte balance disorders, hyperparathyroidism, diabetes mellitus in decompensation stage, hyperuricemia (especially accompanied by gout or urate nephrolithiasis).

Patients receiving concomitant drug therapy with lengthening intervals QT (see "Interaction with other medicinal products).

Pregnancy and lactation:

Pregnant reception of the drug Indapamide retard is not recommended. The use of the drug may cause fetoplacental ischemia with the risk of slowing the development of the fetus.

It is not recommended to use the drug during the period of breastfeeding, since indapamide penetrates into breast milk.

If treatment with Indapamide retard is necessary during lactation, then breast-feeding should be discontinued.

Dosing and Administration:

Tablets are taken orally, without chewing.

The daily dose of the drug - 1 tablet of the drug Indapamide retard 1 times a day (in the morning), with enough liquid.

Side effects:

From the digestive system: nausea, anorexia, dryness of the oral mucosa, gastralgia, vomiting, constipation, abdominal pain, possible development of hepatic encephalopathy, hepatitis, pancreatitis.

From the central nervous system: asthenia, nervousness, headache, dizziness, drowsiness, vertigo, insomnia, depression, fatigue, general weakness, malaise, muscle spasm, tension, irritability, anxiety, paresthesia.

From the respiratory system: cough, pharyngitis, sinusitis, rhinitis.

From the cardiovascular system: Orthostatic hypotension, changes in the electrocardiogram (hypokalemia), arrhythmia, palpitation, marked | lowering of blood pressure.

From the urinary system: kidney failure, infection, nocturia, polyuria.

Allergic reactions: skin rash, pruritus, urticaria, hemorrhagic vasculitis, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, purpura.

Laboratory indicators: hyperuricemia, hyperglycemia, hypokalemia, hyponatremia, hypochloremia, hypercalcemia, increase of urea nitrogen in the blood plasma hypercreatininemia, glycosuria.

From the hematopoiesis: thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia, aplastic anemia.

Other: exacerbation of the systemic lupus erythematosus.

Cases of photosensitivity reactions are described.

Overdose:

Symptoms: severe decrease in arterial pressure, water-electrolyte disorders (hyponatremia, hypokalemia), nausea, vomiting, convulsions, dizziness, drowsiness, confusion, confusion, respiratory depression, polyuria or oliguria up to anuria (due to hypovolemia). Patients with cirrhosis may develop hepatic coma.

Treatment: gastric lavage, administration of activated charcoal, correction fluid and electrolyte balance, symptomatic therapy. There is no specific antidote.

Interaction:

Unrecommended combinations:

When simultaneous application with lithium preparations, an increase in the concentration of lithium ions in blood plasma is possible due to a decrease in its excretion from the body by the kidneys, accompanied by evidence of overdose (neurotoxic effect), as well as when observing a salt-free diet (reduced excretion of lithium ions by the kidneys).

Combinations that require special attention:

1. Drugs that can cause heart rhythm disturbances as pirouettes: antiarrhythmics 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 administration), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, wincamine (intravenous administration), 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 electrocardiogram (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) (for systemic use), including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of salicylic acid (3 r/ day or more) is possible: reduction of antihypertensive effect of indapamide, 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 arterial hypertension and possibly with hyponatraemia, due to taking diuretics, need:

- 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 intravenously;

- gluco- and mineralocorticosteroids (for systemic administration) (see also the information in the section "Combinations of drugs requiring attention");

- tetrakozaktid (see also the information in the section "Combinations of drugs that require attention");

- laxatives, stimulating 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, it is necessary to monitor the potassium ions in the blood plasma, the parameters of the electrocardiogram (ECG), and, if necessary, adjust the therapy.

Combinations of drugs requiring 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 electrocardiogram (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 agents against hypovolemia and the use of diuretics increases the risk of acute renal failure. It is recommended to restore the 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. Cyclosporine, tacrolimus - The risk of increasing the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine.

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

Special instructions:

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

Against the background of taking indapamide should be systematically monitor the content of ions of potassium, sodium,magnesium in blood plasma (may cause electrolyte disorders), pH, glucose concentration, uric acid and residual nitrogen.

With the appointment of thiazide and thiazide-like diuretics in patients with impaired hepatic function, it is possible to develop hepatic encephalopathy, especially in the case of violations of the water-electrolyte balance. In this case, the taking of diuretics should be stopped immediately.

The most careful control is shown in patients with cirrhosis of the liver (especially with edema or ascites - the risk of metabolic alkalosis, which increases the manifestation 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 a pathological process).

The first measurement of the concentration in the blood of potassium ions 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 control the concentration of glucose in the blood, especially in the presence of hypokalemia.

Significant dehydration can lead to the development of acute renal failure (reduced glomerular filtration).

Patients need to replenish the volume of circulating blood (BCC) and at the beginning of treatment carefully monitor kidney function.

Patients with gout may increase the incidence of attacks or exacerbate the course of gout.

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).

Against the background of taking thiazide and thiazide-like diuretics, the development of photosensitivity reactions is possible. In this case, stop treatment with the drug.If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

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

Care must be taken when driving vehicles and working with machinery.

Form release / dosage:

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

Packaging:

For 10 or 15 tablets in a contour mesh package. 3 contour packs of 10 tablets or 2 contour packs of 15 tablets together with instructions for use are placed 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:LP-001322

Date of registration:02.12.2011

Date of cancellation:2016-12-02

The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia

Manufacturer: & nbsp

TATHIMFARMPREPARATY, JSC Russia

Representation: & nbspTATHIMFARM PREPARATIONS OJSC TATHIMFARM PREPARATIONS OJSC Russia

Information update date: & nbsp16.10.2015

Illustrated instructions

Instructions

Indapamide retard (Indapamide retard)