Vero-Indapamide (Tablets) Instructions for Use

Marketing Authorization Holder

Veropharm, JSC (Russia)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Dosage Form

Vero-Indapamide

Film-coated tablets, 2.5 mg: 20 or 30 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
20 pcs. – dark glass jars (1) – cardboard packs.
30 pcs. – dark glass jars (1) – cardboard packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Thiazide-like diuretic, antihypertensive agent. It causes a decrease in the tone of arterial smooth muscles, a reduction in total peripheral vascular resistance, and also has a moderate saluretic activity due to impaired reabsorption of sodium, chloride, and water ions in the cortical segment of the loop of Henle and the proximal convoluted tubule of the nephron. The reduction in total peripheral vascular resistance is due to several mechanisms: a decrease in the sensitivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandins with vasodilating activity; inhibition of calcium ion influx into the smooth muscle elements of the vascular wall. In therapeutic doses, it practically does not affect lipid and carbohydrate metabolism.

The hypotensive effect manifests only with initially elevated blood pressure, develops by the end of the first week, and reaches a maximum after 3 months of systematic administration.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract; C_max in plasma is reached in 1-2 hours. Plasma protein binding is 79%. It is widely distributed in the body. Does not accumulate.

T_1/2 is 18 hours. It is excreted by the kidneys mainly in the form of metabolites, 5% unchanged.

Indications

Arterial hypertension.

ICD codes

Dosage Regimen

Take orally, as a single daily dose, preferably in the morning to minimize nocturia.

The recommended initial dose is 2.5 mg (one tablet) once daily.

Do not exceed the maximum daily dose of 2.5 mg.

Higher doses do not enhance the antihypertensive effect but significantly increase the diuretic effect and the risk of adverse reactions.

Swallow the tablet whole with a sufficient amount of water; it can be taken with or without food.

The full therapeutic effect for arterial hypertension typically develops within one week and reaches its maximum after approximately three months of continuous therapy.

Regularly monitor blood pressure, plasma potassium, sodium, creatinine, and uric acid levels during treatment, especially at initiation and in high-risk patients.

If a dose is missed, take it as soon as remembered on the same day; do not double the dose the following day.

Adverse Reactions

From the hematopoietic system very rarely – thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the nervous system rarely – dizziness, fatigue, headache, paresthesia.

From the organ of vision frequency unknown – myopia, blurred vision, visual impairment.

From the cardiovascular system: very rarely – arrhythmia, arterial hypotension; frequency unknown – torsades de pointes type arrhythmia.

From the digestive system infrequently – vomiting; rarely – nausea, constipation, dry mouth mucosa; very rarely – pancreatitis.

From the liver and biliary tract very rarely – impaired liver function; frequency unknown – development of hepatic encephalopathy in case of liver failure.

From the skin and subcutaneous tissues: hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions. Often – maculopapular rash; infrequently – purpura; very rarely – angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; frequency unknown – in patients with acute systemic lupus erythematosus, a worsening of the disease course is possible, photosensitivity.

From the urinary system very rarely – renal failure.

From laboratory parameters very rarely – hypercalcemia; frequency unknown – increased QT interval on ECG, hyperuricemia, increased blood uric acid and glucose concentrations, increased activity of liver transaminases, decreased potassium content with the development of hypokalemia (especially important for patients in high-risk groups), hyponatremia with hypovolemia (leading to dehydration and orthostatic hypotension), hypochloremia (may cause secondary metabolic alkalosis).

Contraindications

Hypersensitivity to indapamide, other sulfonamide derivatives; severe renal failure; severe hepatic failure and hepatic encephalopathy; hypokalemia; pregnancy, breastfeeding period, age under 18 years (efficacy and safety not established).

With caution impaired liver and kidney function, water-electrolyte balance disorders, hyperparathyroidism, diabetes mellitus, hyperuricemia and gout; debilitated patients, ascites, coronary artery disease, chronic heart failure; in patients with an increased QT interval or in patients receiving concurrent therapy with drugs that can increase the QT interval.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic failure and hepatic encephalopathy. Should be used with caution in patients with impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal failure. Should be used with caution in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be prescribed with caution to elderly patients to avoid worsening of concomitant diseases.

Special Precautions

In case of impaired liver function, thiazide and thiazide-like diuretics may lead to the development of hepatic encephalopathy. In this case, the use of diuretics must be stopped immediately.

Cases of photosensitivity reactions have been reported with the use of thiazide and thiazide-like diuretics. If photosensitivity reactions develop during therapy, it is necessary to immediately discontinue indapamide. If continuation of diuretic therapy is necessary, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

The plasma sodium ion concentration must be determined before starting treatment and then this indicator should be regularly monitored. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chloride ion concentration can lead to secondary metabolic alkalosis. More frequent monitoring of plasma sodium ion concentration is indicated for patients with liver cirrhosis and elderly patients.

Long-term use of thiazide and thiazide-like diuretics poses a risk of decreased plasma potassium concentration and the development of hypokalemia. It is necessary to prevent the risk of developing hypokalemia (< 3.4 mmol/L), especially in elderly patients, debilitated patients, or those receiving combined drug therapy, in patients with liver cirrhosis accompanied by edema and ascites, in patients with coronary artery disease and heart failure, since hypokalemia entails the likelihood of arrhythmia (hypokalemia in these patient groups enhances the toxic effect of cardiac glycosides). The risk of hypokalemia is also possible in patients with a prolonged QT interval. Hypokalemia predisposes to the occurrence of severe arrhythmias, especially the deadly polymorphic ventricular tachycardia of the torsades de pointes type. It is necessary to regularly monitor the plasma potassium content in all the above cases.

Thiazide and thiazide-like diuretics can reduce the renal excretion of calcium ions, which can lead to a moderate and temporary increase in plasma calcium concentration.

It is necessary to regularly monitor plasma glucose concentration in patients with diabetes mellitus, especially in the presence of hypokalemia.

With increased uric acid concentration, gout attacks are possible; in such cases, the dose of indapamide should be adjusted accordingly.

Hypovolemia, caused by the loss of fluid and sodium ions during diuretic treatment, can cause a decrease in glomerular filtration, which may result in increased plasma urea and creatinine concentrations.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, patients who experience dizziness, fatigue, headache, or decreased blood pressure should refrain from driving vehicles and other activities requiring high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use of systemic corticosteroids, tetracosactide, the hypotensive effect is reduced due to water and sodium ion retention under the influence of corticosteroids.

With simultaneous use with ACE inhibitors, the risk of developing hyponatremia increases.

There is a risk of developing sudden arterial hypotension and/or acute renal failure in combination with ACE inhibitors against the background of an already existing reduced plasma sodium ion concentration (especially in patients with renal artery stenosis).

With simultaneous use with NSAIDs (for systemic use), a reduction in the hypotensive effect of indapamide is possible. With significant fluid loss, acute renal failure may develop (due to a sharp decrease in glomerular filtration).

With simultaneous use with calcium preparations, the development of hypercalcemia is possible due to reduced excretion of calcium ions in the urine.

With simultaneous use with cardiac glycosides, corticosteroids, the risk of developing hypokalemia increases.

With simultaneous use of agents that can cause hypokalemia (amphotericin B, gluco- and mineralocorticoids, tetracosactide, laxatives stimulating intestinal peristalsis), the risk of developing hypokalemia increases.

With simultaneous use with tricyclic antidepressants (including imipramine), the hypotensive effect is enhanced and the risk of developing orthostatic hypotension increases (additive effect).

With simultaneous use with astemizole, bepridil, erythromycin (IV), pentamidine, sultopride, terfenadine, vincamine, quinidine, disopyramide, amiodarone, bretylium tosilate, sotalol, there is a risk of developing torsades de pointes type arrhythmia.

With simultaneous use with baclofen, the hypotensive effect is enhanced.

With simultaneous use with halofantrine, the likelihood of cardiac rhythm disturbances (including ventricular arrhythmia of the torsades de pointes type) increases.

With simultaneous use with lithium carbonate, the risk of developing the toxic effect of lithium increases against the background of a decrease in its renal clearance.

With simultaneous use with metformin, lactic acidosis may occur, which is apparently associated with the development of functional renal failure caused by the action of diuretics (mainly “loop” diuretics).

With simultaneous use with cyclosporine, an increase in plasma creatinine content is possible, which is observed even with normal water and sodium ion content.

Dehydration of the body while taking diuretics increases the risk of developing acute renal failure, especially when using iodine-containing X-ray contrast agents in high doses. It is necessary to compensate for fluid loss before administering an iodine-containing X-ray contrast agent.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.