Indapamide tablets 2.5 mg

INSTRUCTIONS

for medical use of the medicinal product

Indapamide

Registration number:

Brand name of the drug: Indapamide International nonproprietary name: indapamide Dosage form: film-coated tablets.

Composition

One tablet contains:

active substance: indapamide - 2.5 mg

excipients: colloidal silicon 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 (hydroxypropyl methylcellulose) - 2.4 mg, azorubine dye - 0.006 mg, low molecular weight povidone - 0.9 mg, polysorbate 80 - 0.3 mg, titanium dioxide - 0.894 mg, talc - 0.5 mg.

Description

Round, biconvex, pink, film-coated tablets. The core in cross-section is white or almost white.

Pharmacotherapeutic group: diuretic

ATC Code: C03BA11

Pharmacological properties

Pharmacodynamics. Antihypertensive agent (diuretic, vasodilator). Indapamide reduces the tone of arterial smooth muscles, has a vasodilating effect, reduces total peripheral vascular resistance, and helps reduce left ventricular hypertrophy.

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

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

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

- inhibition of transmembrane calcium ion flow into vascular wall smooth muscle cells.

Indapamide has a moderate diuretic effect. It impairs the reabsorption of sodium and chloride ions, and to a lesser extent potassium and magnesium, in the cortical segment of the loop of Henle and the proximal convoluted tubule of the nephron, thereby enhancing diuresis.

Indapamide exerts an antihypertensive effect at doses that do not have a pronounced diuretic effect.

Increasing the dose is not accompanied by an enhancement of the antihypertensive effect but may be accompanied by an increased frequency of side effects.

Indapamide does not affect lipid metabolism (triglycerides, LDL cholesterol, HDL cholesterol) or carbohydrate metabolism (including in patients with arterial hypertension suffering from diabetes mellitus).

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

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

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Food intake slightly slows the rate of absorption but does not affect the amount of substance absorbed. Maximum plasma concentration is 1-2 hours after oral administration. With repeated doses, fluctuations in plasma concentration of the drug between doses decrease. Steady-state concentration is reached after 7 days of regular use. Half-life is 18 hours, plasma protein binding is 79%. It also binds to elastin of vascular wall smooth muscles. It has a high volume of distribution, crosses histohematic barriers (including the placental barrier), and penetrates into breast milk. It is metabolized in the liver. 60-80% is excreted by the kidneys as metabolites (about 5% is excreted unchanged), and 20% through the intestines. In patients with renal failure, pharmacokinetics do not change. Does not accumulate.

Indications for use

Arterial hypertension.

Contraindications

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

With caution

Impaired liver and/or kidney function, water-electrolyte imbalance, patients with prolonged QT interval on ECG or receiving therapy that may prolong the QT interval (see "Interaction with other medicinal products"), decompensated diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyperparathyroidism.

Use during pregnancy and breastfeeding

Indapamide is not recommended during pregnancy. Use of the drug may cause fetoplacental ischemia with a risk of delayed fetal development. Use during lactation is possible only if breastfeeding is discontinued.

Dosage 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 the desired therapeutic effect is not achieved after 4-8 weeks of treatment, increasing the dose is not recommended (increased risk of side effects without enhancing the antihypertensive effect). Instead, it is recommended to include another antihypertensive drug that is not a diuretic in the medication regimen. When treatment needs to be started with two drugs, the dose of Indapamide remains 2.5 mg in the morning once daily.

Side effects

The frequency of adverse reactions that may be caused by thiazide-like diuretics, including indapamide, is presented using the following gradation: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000); frequency not known (frequency cannot be estimated from available data).

Blood and lymphatic system disorders: Very rare: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, bone marrow aplasia.

Nervous system disorders: Rare: dizziness, headache, paresthesia. Frequency not known: syncope.

Cardiac disorders: Very rare: arrhythmia, decreased blood pressure, orthostatic hypotension, palpitations, ECG changes characteristic of hypokalemia.

Gastrointestinal disorders: Uncommon: vomiting. Rare: nausea, constipation, dry oral mucosa. Very rare: pancreatitis, impaired liver function. Frequency not known: in patients with hepatic insufficiency, hepatic encephalopathy may develop; hepatitis.

Renal and urinary disorders: Very rare: renal failure.

Skin and subcutaneous tissue disorders: Common: maculopapular rash. Uncommon: hemorrhagic vasculitis. Very rare: angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome. Frequency not known: possible exacerbation of the disease in patients with acute systemic lupus erythematosus; cases of photosensitivity reactions have been described.

Laboratory parameters: Very rare: hypercalcemia. Frequency not known: decreased potassium levels and development of hypokalemia; hyponatremia accompanied by hypovolemia, dehydration and orthostatic hypotension; simultaneous loss of chloride ions can lead to compensatory metabolic alkalosis, but the frequency and severity of alkalosis are insignificant; increased plasma levels of uric acid and glucose; increased activity of "hepatic" transaminases: thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes mellitus.

Overdose

Symptoms: nausea, vomiting, weakness, gastrointestinal dysfunction, water-electrolyte imbalances, in some cases - pronounced decrease in blood pressure, respiratory depression, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria. In patients with liver cirrhosis, hepatic coma may develop.

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

Interaction with other medicinal products

Not recommended combinations:

Concomitant use of indapamide and lithium preparations may lead to increased plasma lithium ion concentrations due to reduced renal excretion, accompanied by signs of overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while the doses of the drugs should be carefully selected, constantly monitoring the lithium content in the blood plasma.

Combinations requiring special attention:

Drugs that can cause torsades de pointes type arrhythmia:

• Class IA antiarrhythmics (quinidine, hydroquinidine, disopyramide);

• Class III antiarrhythmics (amiodarone, dofetilide, ibutilide) and sotalol;

• Some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

• Others: bepridil, cisapride, difemanil, erythromycin (intravenous), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (intravenous).

Concomitant use with any of these drugs, especially against the background of hypokalemia, increases the risk of ventricular arrhythmias, especially torsades de pointes.

Before starting combination therapy with indapamide and the above drugs, plasma potassium levels should be monitored and, if necessary, corrected. Clinical monitoring of the patient, monitoring of plasma electrolyte levels, and ECG parameters are necessary. In patients with hypokalemia, drugs that do not cause torsades de pointes arrhythmia should be used.

Non-steroidal anti-inflammatory drugs (systemic use), including selective cyclooxygenase-2 (COX-2) inhibitors, high doses of salicylates (3 g/day): Possible reduction of the antihypertensive effect of indapamide. With significant fluid loss, acute renal failure may develop (due to decreased glomerular filtration). Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.

Angiotensin-converting enzyme (ACE) inhibitors: Prescribing ACE inhibitors to patients with hyponatremia (especially patients with renal artery stenosis) carries the risk of arterial hypotension and/or acute renal failure. For patients with arterial hypertension and possibly reduced plasma sodium ion levels due to diuretic use, it is necessary: - Stop taking diuretics 3 days before starting ACE inhibitor treatment. - Or start ACE inhibitor therapy with low doses, followed by a gradual increase in dose if necessary. During the first week of ACE inhibitor use, patients must have their kidney function monitored (plasma creatinine levels).

Other drugs that can cause hypokalemia: amphotericin B (intravenous), gluco- and mineralocorticosteroids (systemic use), tetracosactide, stimulant laxatives. Concomitant use with indapamide increases the risk of hypokalemia (additive effect). Constant monitoring of plasma potassium levels is necessary, and if necessary, its correction.

Baclofen: Enhanced hypotensive effect is noted.

Cardiac glycosides: Hypokalemia enhances the toxic effect of cardiac glycosides. When using indapamide and cardiac glycosides concomitantly, plasma potassium levels and ECG parameters should be monitored, and therapy should be adjusted if necessary.

Combinations requiring attention:

Potassium-sparing diuretics (amiloride, spironolactone, triamterene, eplerenone): Concomitant use of indapamide and potassium-sparing diuretics is appropriate in some patients, but the possibility of hypokalemia (especially in patients with diabetes and renal failure) or hyperkalemia is not excluded. It is necessary to monitor plasma potassium levels, ECG parameters, and, if necessary, adjust therapy.

Metformin: Increases the risk of lactic acidosis, as renal failure may develop while taking diuretics, especially "loop" diuretics. Metformin should not be used if creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.

Iodine-containing contrast agents: Concomitant use with diuretics against the background of hypovolemia increases the risk of acute renal failure. Before using iodine-containing contrast agents, patients must compensate for fluid loss.

Tricyclic antidepressants, antipsychotic agents (neuroleptics): Drugs of these classes enhance the hypotensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Calcium salt preparations: Concomitant use may lead to hypercalcemia due to reduced renal excretion of calcium ions.

Cyclosporine, tacrolimus: Risk of increased plasma creatinine concentration without changing the concentration of circulating cyclosporine.

Corticosteroid drugs, tetracosactide (systemic use): Reduction of the hypotensive effect (fluid and sodium ion retention).

Special instructions

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

While taking indapamide, plasma levels of potassium, sodium, and magnesium ions (electrolyte disturbances may develop), pH, glucose levels, uric acid, and residual nitrogen should be systematically monitored.

The most careful monitoring is indicated in patients with liver cirrhosis (especially with developed edema or ascites - risk of metabolic alkalosis, which enhances the manifestations of hepatic encephalopathy), coronary artery disease, heart failure, as well as in the elderly. The high-risk group also includes patients with an increased QT interval on the electrocardiogram (congenital or developed against the background of any pathological process), patients receiving class IA (quinidine, disopyramide) and class III antiarrhythmic drugs or receiving therapy that may prolong the S-T interval (astemizole, erythromycin (intravenous), pentamidine, sultopride, terfenadine, vincamine, (amiodarone, bretylium tosilate)).

The first measurement of blood potassium ions should be carried out within the first week of starting treatment. Hypercalcemia while taking indapamide may be a consequence of previously undiagnosed hyperparathyroidism.

In patients with diabetes mellitus, 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 (decreased glomerular filtration). Patients need to replenish circulating blood volume (CBV) and carefully monitor renal function at the beginning of treatment.

Indapamide may give a positive result in doping control. Patients with arterial hypertension and hyponatremia (due to diuretic use) must stop taking diuretics 3 days before starting angiotensin-converting enzyme inhibitors (if necessary, diuretics can be resumed later), or initially prescribe low doses of angiotensin-converting enzyme inhibitors.

Sulfonamide derivatives can exacerbate the course of systemic lupus erythematosus (must be kept in mind when prescribing indapamide).

Use with caution in patients with elevated uric acid levels (tendency to increase the number of gout attacks).

Before surgery, the patient must inform the anesthesiologist that he is taking indapamide. The drug can cause hepatic encephalopathy in cases of concomitant liver dysfunction. If hepatic encephalopathy is suspected, the product should be discontinued immediately. Elderly patients may exhibit high susceptibility to the product, even if prescribed the usual dosage. Efficacy and safety in children have not been established.

Effect on ability to drive vehicles and operate machinery

During treatment with indapamide, one should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as dizziness may develop.

Packaging

Film-coated tablets, 2.5 mg.

10 tablets in a blister strip made of polyvinyl chloride film and printed lacquered aluminum foil.