Indapamide retard-OBL (Tablets) Instructions for Use

Marketing Authorization Holder

FP Obolenskoe, JSC (Russia)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Dosage Form

Indapamide retard-OBL

Extended-release tablets, film-coated, 1.5 mg: 10, 15, 20, 30, 40, 45, 50, 60, 75, 80, 90, 100, 120 or 150 pcs.

Dosage Form, Packaging, and Composition

Extended-release tablets, film-coated white or almost white, round, biconvex; the cross-section shows two layers, the inner layer is white or almost white.

Excipients: colloidal silicon dioxide (aerosil) – 0.9 mg, hypromellose (hydroxypropyl methylcellulose) – 55 mg, copovidone (copovidone) – 4.5 mg, magnesium stearate – 1.8 mg, lactose monohydrate – 58.2 mg, microcrystalline cellulose – 58.1 mg.

Film coating composition: hypromellose (hydroxypropyl methylcellulose) – 3.5 mg, macrogol 6000 (polyethylene glycol 6000) – 0.6 mg, talc – 0.2 mg, titanium dioxide – 0.7 mg.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Diuretic. Antihypertensive drug. It is a sulfonamide derivative and is pharmacologically similar to thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment of the renal tubules, which increases the urinary excretion of sodium and chloride ions and leads to increased diuresis. To a lesser extent, the drug increases the excretion of potassium and magnesium ions. In addition to its diuretic effect, Indapamide acts on blood vessels, reducing arteriolar and total peripheral vascular resistance. It exerts an antihypertensive effect at doses that do not cause a pronounced diuretic effect. Use in high doses does not lead to an increase in the degree of blood pressure reduction despite an increase in diuresis.

Indapamide reduces left ventricular hypertrophy. In therapeutic doses, it has practically no effect on lipid and carbohydrate metabolism.

Pharmacokinetics

Absorption

After oral administration, Indapamide is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake slightly slows absorption but does not significantly affect the amount of the drug absorbed. C_max in blood plasma is reached 12 hours after a single dose. With repeated doses, fluctuations in the drug concentration in the blood plasma between doses are smoothed out (individual variations are possible).

Distribution

Binding to plasma proteins is 79%. Regular use does not lead to accumulation.

Metabolism and excretion

It is metabolized in the liver. 70% of indapamide is excreted by the kidneys, mainly in the form of metabolites (unchanged – about 5%). About 20% is excreted in the feces as inactive metabolites. T_1/2 ranges from 14 to 24 hours (average 18 hours).

Pharmacokinetics in special clinical cases

In patients with impaired renal function, the pharmacokinetic parameters of the drug do not change significantly.

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

Take one 1.5 mg tablet once daily.

Administer the tablet in the morning with a sufficient amount of fluid.

Swallow the tablet whole; do not crush or chew it.

This regimen is for the treatment of arterial hypertension.

Regularly monitor plasma potassium levels, with the first measurement within the first week of therapy.

Monitor plasma sodium levels before treatment initiation and at regular intervals thereafter.

In patients with impaired renal function, exercise caution and monitor renal parameters.

In patients with impaired liver function, use with caution due to the risk of hepatic encephalopathy.

Discontinue use immediately if signs of hepatic encephalopathy occur.

For elderly patients, monitor electrolyte levels more frequently.

In patients with diabetes, monitor blood glucose levels, particularly in the presence of hypokalemia.

Do not exceed the prescribed dose.

Adverse Reactions

From the cardiovascular system: orthostatic hypotension, ECG changes (associated with hypokalemia), arrhythmia, palpitations.

From the central nervous system: headache, dizziness, nervousness, asthenia.

From the digestive system: constipation, diarrhea, dyspepsia, nausea, abdominal pain; possible development of hepatic encephalopathy; rarely – pancreatitis.

From the urinary system: frequent infections, nocturia, polyuria.

From the respiratory system: cough, pharyngitis, sinusitis.

From water-electrolyte balance: hypercalcemia, hyperuricemia, hypochloremia, hyponatremia, hypokalemia.

From the hematopoietic system: very rarely – thrombocytopenia, leukopenia, agranulocytosis, bone marrow aplasia and hemolytic anemia.

Allergic reactions: skin itching, maculopapular rash, urticaria, hemorrhagic vasculitis.

Other: possible exacerbation of systemic lupus erythematosus, hyperglycemia.

Contraindications

• Severe renal failure (anuria);
• Hepatic encephalopathy or severe hepatic failure;
• Hypokalemia;
• Concomitant use of drugs that prolong the QT interval;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to any component of the drug and other sulfonamide derivatives.

With caution the drug should be prescribed for diabetes mellitus, impaired renal and/or hepatic function, water-electrolyte imbalance, hyperparathyroidism, patients with a prolonged QT interval on ECG or receiving combination therapy, as well as for hyperuricemia (especially accompanied by gout or urate nephrolithiasis).

Use in Pregnancy and Lactation

The use of indapamide during pregnancy is not recommended. The use of the drug may cause fetoplacental ischemia with a risk of delayed fetal development.

It is not recommended to prescribe the drug during lactation (breastfeeding), as Indapamide is excreted in breast milk.

Use in Hepatic Impairment

The drug is contraindicated in hepatic encephalopathy or severe hepatic failure. With caution the drug should be prescribed for impaired liver function.

Use in Renal Impairment

The drug is contraindicated in severe renal failure (anuria). With caution the drug should be prescribed for impaired renal function.

Pediatric Use

The efficacy and safety of the drug in children under 18 years of age have not been established.

Special Precautions

In patients with impaired liver function, thiazide diuretics can cause hepatic encephalopathy; in this case, diuretic use should be discontinued immediately.

Any diuretic drug can cause hyponatremia, in some cases with serious consequences. Plasma sodium levels should be measured before starting and then during treatment at regular intervals. Initially, a drop in plasma sodium concentration may be asymptomatic, so regular monitoring is important. In elderly patients and patients with liver cirrhosis, monitoring should be even more frequent.

The most dangerous adverse effect of thiazide diuretic therapy is hypokalemia. The risk of hypokalemia (less than 3.4 mmol/L) must be prevented in certain high-risk patient groups (debilitated patients, patients taking multiple medications simultaneously, elderly individuals, patients with liver cirrhosis, peripheral edema and ascites, coronary artery disease and heart failure). In these patients, hypokalemia increases the toxic effect of cardiac glycosides and the risk of arrhythmias.

The high-risk group also includes patients with a prolonged QT interval on ECG (both congenital and drug-induced). Hypokalemia (as well as bradycardia) is a predisposing factor for the occurrence of severe arrhythmias, especially potentially dangerous ones of the “torsades de pointes” type. In all these patients, more frequent monitoring of plasma potassium levels is required. The first measurement of plasma potassium concentration should be performed within the first week of therapy. If potassium levels decrease, correction is required.

Monitoring blood glucose levels is important in patients with diabetes, especially in the presence of hypokalemia.

In patients with hyperuricemia, the frequency of gout attacks may increase.

Thiazide and thiazide-like diuretics are fully effective only when plasma creatinine levels are below 25 mg/L or 220 µmol/L. In elderly individuals, plasma creatinine levels may vary depending on age, body weight, and sex.

Secondary hypovolemia due to water and sodium loss induced by diuretics causes a decrease in glomerular filtration. This can lead to an increase in plasma urea and creatinine levels. If the patient’s renal function is not impaired, these transient functional disorders usually resolve without consequences, but pre-existing renal failure may worsen.

Athletes should be aware that Indapamide may cause a positive reaction in doping control.

Effect on the ability to drive vehicles and operate machinery

In some cases, individual reactions associated with changes in blood pressure are possible, especially at the beginning of treatment or when adding another antihypertensive agent, which may lead to a reduced ability to drive a car and engage in other activities requiring high concentration and speed of psychomotor reactions.

Overdose

Symptoms of acute overdose: mainly associated with water-electrolyte imbalances (hyponatremia, hypokalemia) and manifest as nausea, vomiting, decreased blood pressure, convulsions, dizziness, drowsiness, lethargy, polyuria, oliguria; in isolated cases – anuria (due to hypovolemia).

Treatment: gastric lavage and/or administration of activated charcoal. Subsequent measures carried out in a medical facility should be aimed at restoring water-electrolyte balance; if necessary, symptomatic therapy is performed. There is no specific antidote.

Drug Interactions

With simultaneous use of lithium preparations and indapamide, an increase in plasma lithium concentration with symptoms of overdose is possible (careful monitoring of plasma lithium concentration and dose adjustment is necessary), especially with simultaneous adherence to a salt-restricted diet (decreased urinary excretion of lithium).

With simultaneous use with astemizole, bepridil, erythromycin (with intravenous administration), halofantrine, pentamidine, sultopride, terfenadine and vincamine, class IA antiarrhythmic agents (quinidine, hydroquinidine, disopyramide), as well as with amiodarone, bretylium, sotalol), the likelihood of “torsades de pointes” type arrhythmias increases. Risk factors are hypokalemia, bradycardia, and pre-existing QT interval prolongation.

With simultaneous use with systemic NSAIDs, high-dose salicylates, there is a risk of acute renal failure in dehydrated patients (decreased glomerular filtration rate). It is necessary to compensate for fluid loss and monitor renal function at the beginning of therapy.

With simultaneous use with amphotericin B (for intravenous administration), glucocorticoids and mineralocorticoids (for systemic use), tetracosactide, laxatives stimulating intestinal motility, cardiac glycosides, the risk of hypokalemia increases (additive effect). Monitoring of plasma potassium levels and ECG is necessary, and if needed, appropriate therapy should be prescribed.

With simultaneous use with baclofen, an enhancement of the antihypertensive effect is possible.

With simultaneous use with cyclosporine – an increase in plasma creatinine concentration, with an unchanged concentration of circulating cyclosporine.

With simultaneous use, tricyclic antidepressants, neuroleptics enhance the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

With simultaneous use with ACE inhibitors, an increased risk of arterial hypotension is possible.

When administering iodine-containing contrast agents (in high doses), dehydration may develop and the risk of acute renal failure may increase. Before using iodine-containing contrast agents, patients must compensate for fluid loss.

With simultaneous use with calcium salts, an increase in plasma calcium ion concentration is possible due to reduced urinary excretion.

With simultaneous use with potassium-sparing diuretics (amiloride, spironolactone, triamterene), the risk of hypokalemia or hyperkalemia increases, especially in patients with diabetes and patients with impaired renal function.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

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.