Indapamide Retard-Akrikhin (Tablets) Instructions for Use

Marketing Authorization Holder

M.J. Biopharm Pvt. Ltd. (India)

Manufactured By

M.J. Biopharm Pvt. Ltd. (India)

Packaging and Quality Control Release

M.J. BIOPHARM, Pvt. Ltd. (India)

Or

AKRIKHIN Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

M.J. Biopharm Pvt. Ltd. a division of M.J. Group Corporation (India)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN WHO registered)

Dosage Form

Indapamide Retard-Akrikhin

Modified-release tablets, coated, 1.5 mg: 10, 28, 30, or 50 pcs.

Dosage Form, Packaging, and Composition

Modified-release tablets, coated white, round, biconvex.

Excipients : guar gum (guar resin), lactose, sodium lauryl sulfate, purified talc, magnesium stearate, colloidal silicon dioxide, hypromellose, titanium dioxide, polyethylene glycol.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Diuretic. Antihypertensive drug. It belongs to sulfonamide derivatives and is close in pharmacological properties to thiazide diuretics. It inhibits sodium reabsorption in the cortical segment of the loop of Henle, which leads to an increased excretion of sodium and chloride ions in the urine and enhances diuresis. It increases the excretion of potassium and magnesium ions to a lesser extent.

In addition to the diuretic effect, Indapamide increases the elasticity of arterial walls and reduces total peripheral vascular resistance.

It exerts an antihypertensive effect at doses that do not cause a pronounced diuretic effect.

When prescribed in high doses, it does not affect the degree of blood pressure reduction, despite the increase in diuresis.

It reduces left ventricular hypertrophy.

It does not affect lipid and carbohydrate metabolism.

Pharmacokinetics

Absorption

Rapidly and almost completely absorbed from the gastrointestinal tract. Food intake somewhat slows down absorption but does not affect the amount of the absorbed drug. After oral administration, C_max is reached after 12 hours.

Distribution

With repeated administration, fluctuations in the plasma concentration of the drug between doses decrease. However, there are individual differences among patients.

Plasma protein binding is 79%. It does not accumulate in the body upon repeated administration.

Metabolism

Metabolized in the liver.

Excretion

T_1/2 is 14-26 hours (average 18 hours). 70% of indapamide is excreted by the kidneys as metabolites, about 5% is excreted unchanged. About 20% is excreted in the feces as inactive metabolites.

Pharmacokinetics in special clinical cases

In patients with renal failure, the pharmacokinetics of indapamide do not change significantly.

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

Take the drug orally, once daily.

Swallow one tablet whole with a sufficient amount of liquid.

Take the dose preferably in the morning to minimize nighttime urination.

Do not crush or chew the modified-release tablet.

Take the tablet with or without food; food intake may slow absorption but does not affect the overall amount of drug absorbed.

The standard therapeutic dose is 1.5 mg (one tablet) per day.

Higher doses do not provide an increased antihypertensive effect and may elevate the risk of adverse reactions.

In elderly patients, initiate therapy with the standard dose; no initial dosage adjustment is typically required.

For patients with renal impairment, use with caution; monitor renal function. The drug is not recommended in cases of severe renal failure (anuria).

For patients with hepatic impairment, use with caution; discontinue immediately if signs of hepatic encephalopathy appear.

Regularly monitor plasma potassium levels, especially during the first week of treatment and in patients at risk for hypokalemia.

Monitor blood pressure and electrolyte balance periodically during long-term therapy.

Adverse Reactions

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

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

From the respiratory system: cough, pharyngitis, sinusitis.

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

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

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

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

Laboratory parameters: hyperuricemia, hyperglycemia, hyponatremia, hypochloremia, hypercalcemia.

Other possible exacerbation of systemic lupus erythematosus.

Contraindications

• Hypokalemia;
• Severe renal failure (anuria stage);
• Severe hepatic failure (including with encephalopathy);
• Hepatic encephalopathy;
• Concomitant use of drugs that prolong the QT interval;
• Childhood and adolescence under 18 years (efficacy and safety not established);
• Hypersensitivity to the drug and other sulfonamide derivatives.

With caution the drug should be prescribed for impaired liver and/or kidney function, water-electrolyte imbalance, hyperparathyroidism, patients with an increased QT interval on ECG or receiving combination therapy, hyperuricemia (especially accompanied by gout and urate nephrolithiasis).

Use in Pregnancy and Lactation

Indapamide Retard-Akrikhin is not recommended for use during pregnancy, as the drug can cause fetoplacental ischemia and lead to fetal developmental delay.

Since Indapamide is excreted in breast milk, it is also not recommended to prescribe the drug during breastfeeding.

Use in Hepatic Impairment

With caution the drug should be prescribed for impaired liver function.

Use in Renal Impairment

With caution the drug should be prescribed for impaired kidney function.

Special Precautions

When prescribing thiazide diuretics to patients with impaired liver function, the development of hepatic encephalopathy is possible. In such cases, the drug should be discontinued immediately.

Before starting treatment, the plasma sodium ion level should be determined. During treatment, regular monitoring of this indicator is necessary, since the initial decrease in plasma sodium concentration may be asymptomatic. Such analysis should be performed especially often in patients with liver cirrhosis and in elderly individuals.

During therapy with thiazide diuretics, the main risk is the development of hypokalemia. In a certain category of patients (elderly patients, debilitated patients and/or those receiving combination therapy, with liver cirrhosis with developed edema or ascites, coronary artery disease, chronic heart failure), it is necessary to avoid the development of hypokalemia (<3.4 mmol/L). Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of arrhythmias. Furthermore, patients with bradycardia or with an increased QT interval on ECG are at increased risk, regardless of whether such an increase is caused by congenital reasons or a pathological process.

Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe cardiac arrhythmias, especially of the “torsades de pointes” type. In all the cases described above, it is necessary to determine plasma potassium ion levels more frequently. The first measurement of blood potassium ion concentration should be performed within the first week of starting treatment.

If hypokalemia develops, its correction is required.

When prescribing Indapamide Retard-Akrikhin to patients with diabetes mellitus, it is important to control glucose levels, especially in the presence of hypokalemia.

In patients with elevated uric acid levels, there is a tendency for an increased number of gout attacks.

Thiazide diuretics show their full effectiveness only in the absence of impairment or with moderately impaired renal function (blood creatinine level less than 2.5 mg/dL or 220 µmol/L).

In elderly patients, the normal plasma creatinine level is calculated taking into account age, body weight, and sex.

It should be considered that at the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which is caused by the loss of water and sodium ions while taking diuretics. As a result, the concentration of urea and creatinine in the plasma may increase. If renal function is not impaired, such temporary renal failure usually resolves without consequences. However, in the presence of pre-existing renal failure, the patient’s condition may worsen.

While taking indapamide, a positive result is possible during doping control in athletes.

Effect on the ability to drive vehicles and operate machinery

In some cases, when blood pressure decreases, individual reactions may occur (especially at the beginning of therapy or when combining several antihypertensive drugs). In this case, the ability to engage in activities requiring increased attention and speed of psychomotor reactions may be reduced.

Overdose

Symptoms possible disturbances of water-electrolyte balance (hyponatremia, hypokalemia), nausea, vomiting, decreased blood pressure, convulsions, dizziness, drowsiness, lethargy, polyuria or oliguria, ending in anuria (due to hypovolemia).

Treatment emergency measures aimed at removing the drug from the body: gastric lavage and/or administration of activated charcoal followed by restoration of normal water-electrolyte balance . Symptomatic therapy is indicated. There is no specific antidote.

Drug Interactions

With simultaneous use of indapamide and lithium preparations, an increase in the plasma concentration of lithium is possible, accompanied by signs of overdose (due to decreased urinary excretion of lithium). If it is necessary to prescribe this combination, the plasma concentration of lithium should be monitored and its dose adjusted if necessary.

With simultaneous use of indapamide with astemizole, bepridil, erythromycin (for intravenous administration), halofantrine, pentamidine, sultopride, terfenadine, vincamine, class IA antiarrhythmic drugs (including quinidine, hydroquinidine, disopyramide, amiodarone, bretylium, sotalol), the likelihood of “torsades de pointes” type arrhythmias increases. Hypokalemia, bradycardia, or QT interval prolongation may contribute to this condition.

With simultaneous use with NSAIDs (for systemic use), salicylates in high doses, the development of acute renal failure is possible in dehydrated patients (due to a sharp decrease in the glomerular filtration rate). If it is necessary to prescribe NSAIDs during therapy with Indapamide Retard-Akrikhin, fluid loss should be compensated and renal function carefully monitored.

With simultaneous use of indapamide with amphotericin B (for intravenous administration), glucocorticoids and mineralocorticoids (for systemic use), tetracosactide, laxatives that stimulate intestinal motility, cardiac glycosides, the risk of hypokalemia increases (additive effect). Plasma potassium levels and ECG parameters should be monitored; appropriate treatment is indicated if necessary.

With simultaneous use of indapamide with baclofen, an enhancement of the hypotensive effect is noted.

With simultaneous use of indapamide and cyclosporine, an increase in plasma creatinine content is possible with an unchanged concentration of cyclosporine.

With simultaneous use of indapamide and tricyclic antidepressants, antipsychotics, an enhancement of the hypotensive action and an increased risk of orthostatic hypotension (additive effect) are noted.

With simultaneous use of indapamide and calcium salts, the development of hypercalcemia is possible due to reduced excretion of calcium ions in the urine.

With simultaneous administration of indapamide with ACE inhibitors, the risk of arterial hypotension increases.

When combining indapamide with potassium-sparing diuretics (amiloride, spironolactone, triamterene), the risk of hypo- or hyperkalemia increases, especially in patients with diabetes mellitus and in patients with impaired renal function.

With simultaneous administration of indapamide with high doses of iodine-containing contrast agents, dehydration of the body and an increased risk of acute renal failure are possible. Before using iodine-containing contrast agents, patients must compensate for fluid loss.

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.