Ionik^® (Capsules) Instructions for Use

Marketing Authorization Holder

FP Obolenskoe, JSC (Russia)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Dosage Form

Ionik®

Capsules 2.5 mg: 10, 15, 20, 30, 40, 45, 60 or 90 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 3 with a white body and a blue cap; capsule contents – a white or almost white powder.

Excipients: corn starch, lactose monohydrate, colloidal silicon dioxide (aerosil), povidone K30, sodium carboxymethyl starch (sodium starch glycolate), magnesium stearate.

Capsule body composition titanium dioxide, gelatin.
Capsule cap composition titanium dioxide, patent blue dye, brilliant black dye, gelatin.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
15 pcs. – blister packs (1) – cardboard packs.
15 pcs. – blister packs (2) – cardboard packs.
15 pcs. – blister packs (3) – cardboard packs.
30 pcs. – blister packs (1) – cardboard packs.
30 pcs. – blister packs (2) – cardboard packs.
30 pcs. – blister packs (3) – 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 decrease 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 decrease 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 the influx of calcium ions into the smooth muscle elements of the vascular wall. In therapeutic doses, it practically does not affect lipid and carbohydrate metabolism.

The hypotensive effect is manifested 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 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

Administer orally, as a single daily dose. Take preferably in the morning with a meal to minimize potential gastrointestinal discomfort.

The recommended initial and maximum daily dose is 2.5 mg (one capsule). Do not exceed this dose.

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

For most patients, the antihypertensive effect becomes apparent by the end of the first week of therapy and reaches its maximum after approximately three months of continuous treatment.

Regularly monitor blood pressure and serum potassium levels, especially during the initial phase of treatment and after dose adjustments of concomitant antihypertensive drugs.

In elderly patients or those with renal impairment, initiate therapy at the standard 2.5 mg dose while closely monitoring renal function and electrolyte balance.

For patients with impaired liver function, use with extreme caution and avoid in cases of severe hepatic insufficiency or hepatic encephalopathy.

If a dose is missed, take it as soon as remembered on the same day. Do not double the dose the following day to compensate for a missed dose.

Discontinuation of therapy should be gradual, under medical supervision, to avoid a rapid rebound increase in blood pressure.

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 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 concentration of uric acid and glucose in the blood, increased activity of hepatic 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 insufficiency 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 simultaneous therapy with drugs that can increase the QT interval.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency 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 can 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 stop taking indapamide. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

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

Long-term use of thiazide and thiazide-like diuretics poses a risk of decreasing the concentration of potassium in the blood plasma and developing 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 potassium content in the blood plasma in all the above cases.

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

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

With an increased concentration of uric acid, gout attacks are possible; in such cases, it is necessary to appropriately adjust the dose of indapamide.

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 the blood 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 that require high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use of systemic corticosteroids, tetracosactide, the antihypertensive effect is reduced due to the retention of water and sodium ions 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 concentration of sodium ions in the blood plasma (especially in patients with renal artery stenosis).

With simultaneous use with systemic NSAIDs, a decrease in the antihypertensive 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 a decrease in the 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 that stimulate 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 tosylate, 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, 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 the creatinine content in the blood plasma 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 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.