Arifon^® (Tablets) Instructions for Use

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretics; thiazide-like diuretics, sulfonamides

Pharmacological Action

A thiazide-like diuretic and antihypertensive agent. It causes a decrease in the tone of arterial smooth muscles and a reduction in total peripheral vascular resistance. It also has 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: decreased sensitivity of the vascular wall to norepinephrine and angiotensin II; increased synthesis of prostaglandins with vasodilating activity; inhibition of calcium ion influx into the smooth muscle elements of the vascular wall. In therapeutic doses, it has virtually no effect on lipid and carbohydrate metabolism.

The hypotensive effect manifests only with initially elevated blood pressure, develops by the end of the first week, and reaches its 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 after 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, once daily, preferably in the morning with a glass of water.

Initiate therapy at the recommended initial dose of 2.5 mg.

Do not exceed the maximum daily dose of 2.5 mg.

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

Administer the tablet whole; do not crush or chew.

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

Regularly monitor blood pressure to assess therapeutic response.

Prior to initiation and periodically during treatment, monitor serum electrolytes (potassium, sodium), uric acid, blood glucose, and renal function.

Monitor for clinical signs of fluid or electrolyte imbalance, such as hypokalemia, hyponatremia, or hypochloremic alkalosis.

Exercise increased caution in elderly patients and those with impaired renal or hepatic function.

Adjust dosage with caution in patients with a history of gout or diabetes mellitus.

Discontinue use if severe diuresis occurs.

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 oral mucosa; very rarely – pancreatitis.

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

From the skin and subcutaneous tissues: hypersensitivity reactions, mainly dermatological, in patients predisposed 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, 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 hepatic transaminases, decreased potassium content with the development of hypokalemia (especially important for high-risk patients), 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 prolonged QT interval or in patients receiving concurrent therapy with drugs that may prolong 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

Use in children and adolescents under 18 years of age is contraindicated.

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 can lead to the development of hepatic encephalopathy. In this case, the use of diuretics should 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 should be determined before starting treatment and then this indicator should be regularly monitored. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. 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, 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 potassium content in plasma 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 treatment with diuretics can cause a decrease in glomerular filtration, as a result of which the concentrations of urea and creatinine in plasma may increase.

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 systemic NSAIDs, 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, stimulant laxatives), 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, intravenous erythromycin, pentamidine, sultopride, terfenadine, vincamine, quinidine, disopyramide, amiodarone, bretylium tosilate, sotalol, there is a risk of developing torsades de pointes arrhythmia.

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

With simultaneous use with halofantrine, the likelihood of cardiac rhythm disturbances (including ventricular torsades de pointes arrhythmia) 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, the appearance of lactic acidosis is possible, 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 high doses of iodine-containing X-ray contrast agents. It is necessary to compensate for fluid loss before the administration of 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.