Indiur (Tablets) Instructions for Use

Marketing Authorization Holder

Grodzisk Pharmaceutical Works Polfa, Co. Ltd. (Poland)

On Behalf Of

GEDEON RICHTER-RUS, AO (Russia)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Dosage Form

Indiur

Film-coated tablets, 2.5 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with a score on one side.

Excipients: corn starch, polyvinylpyrrolidone (Kollidon 25), magnesium stearate, talc, lactose.

Coating composition: hypromellose, macrogol 6000, titanium dioxide, talc.

15 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Antihypertensive agent, a thiazide-like diuretic with moderate potency and long duration of action, a derivative of benzamides. It reduces the tone of arterial smooth muscles and decreases total peripheral vascular resistance.

It has a moderate saluretic and diuretic effect, which are associated with the blockade of sodium, chloride, hydrogen ion reabsorption, and to a lesser extent potassium ions, in the proximal tubules and the cortical segment of the distal tubule of the nephron.

The vasodilatory effects and reduction of total peripheral vascular resistance are based on the following mechanisms: reducing vascular wall reactivity to norepinephrine and angiotensin II; increasing the synthesis of prostaglandins with vasodilatory activity; inhibiting calcium influx into vascular smooth muscle cells.

It contributes to the reduction of left ventricular hypertrophy. In therapeutic doses, it does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

The antihypertensive effect develops by the end of the first – beginning of the second week with continuous use of the drug and persists for 24 hours after a single dose.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is high (93%). Food intake slightly slows the rate but does not affect the completeness of absorption. C_max in blood is reached 1-2 hours after oral administration.

Steady-state concentration is achieved after 7 days of regular use. The drug is 70-80% bound to plasma proteins. It has a high V_d, passes through histohematic (including placental) barriers, and penetrates into breast milk.

It is metabolized in the liver. The T_1/2 of indapamide averages 14-18 hours. It is eliminated from the body by the kidneys (up to 80%), mainly in the form of metabolites, and through the intestines – 20%.

In patients with renal failure, the pharmacokinetics do not change. It does not accumulate.

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

Orally, regardless of meals, with a sufficient amount of liquid. It is preferable to take the drug in the morning. The dose is 2.5 mg (1 tab.)/day. If the desired therapeutic effect is not achieved after 4-8 weeks of treatment, it is not recommended to increase the dose of the drug (the risk of side effects increases without enhancing the antihypertensive effect).

Instead, it is recommended to include another antihypertensive drug that is not a diuretic in the medication regimen. In cases where treatment needs to be started with 2 drugs, the dose of Indiur remains 2.5 mg in the morning once a day.

Adverse Reactions

Metabolism: hypokalemia, hyponatremia, hypochloremic alkalosis, increased plasma urea nitrogen, hypercreatininemia, glucosuria, hypercalcemia.

Digestive system: constipation or diarrhea, abdominal discomfort, nausea, vomiting, anorexia, dry mouth.

CNS: asthenia, dizziness, nervousness, headache, drowsiness, increased fatigue, general weakness, insomnia, depression, malaise, muscle spasm, tension, irritability, anxiety.

Sensory organs: conjunctivitis, visual impairment.

Respiratory system: rhinitis, cough, pharyngitis, sinusitis.

Cardiovascular system: orthostatic hypotension, arrhythmia, palpitations, electrocardiogram changes characteristic of hypokalemia.

Urinary system: nocturia, polyuria, increased frequency of infections.

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

Other: flu-like syndrome, chest pain, back pain, decreased libido and potency, rhinorrhea, sweating, weight loss, paresthesia, pancreatitis, exacerbation of systemic lupus erythematosus.

Contraindications

• Decompensated renal (anuria) and/or hepatic function (including with encephalopathy);
• Hypokalemia;
• Concomitant use of drugs that prolong the QT interval;
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to indapamide, other sulfonamide derivatives, or other components of the drug.

With caution – decompensated diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis),

Use in Pregnancy and Lactation

Contraindicated.

Use in Hepatic Impairment

Contraindicated

• Decompensated liver function (including with encephalopathy).

Use in Renal Impairment

Contraindicated

• Decompensated renal function (anuria).

Pediatric Use

Contraindicated in children under 18 years.

Geriatric Use

In elderly patients, careful monitoring of potassium and creatinine levels is indicated.

Special Precautions

With long-term use or when taking Indiur in high doses, electrolyte disturbances such as hyponatremia, hypokalemia, and hypochloremic alkalosis may develop.

These disturbances are more often observed in patients with chronic heart failure (NYHA class II-III), liver diseases, with vomiting and diarrhea, as well as in individuals on a salt-free diet.

Concomitant administration of Indiur with cardiac glycosides and corticosteroids increases the risk of hypokalemia. Furthermore, urinary magnesium excretion may increase, which can lead to hypomagnesemia.

Orthostatic hypotension may occur, which can be provoked by alcohol intake, barbiturates, narcotic drugs, and simultaneous use of other antihypertensive agents.

In patients taking cardiac glycosides, laxatives, against the background of hyperaldosteronism, as well as in elderly individuals, careful monitoring of potassium and creatinine levels is indicated.

The most careful monitoring is indicated in patients with liver cirrhosis, coronary heart disease, and chronic heart failure.

The high-risk group also includes patients with an increased QT interval on the electrocardiogram (congenital or developed against the background of any pathological process).

The first measurement of blood potassium concentration should be performed within 1 week of treatment.

Hypercalcemia during Indiur use may be a consequence of previously undiagnosed hyperparathyroidism.

In diabetic patients, it is extremely important to control blood glucose levels, especially in the presence of hypokalemia.

Significant dehydration can lead to the development of acute renal failure (decreased glomerular filtration). Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.

Indapamide may give a positive result in doping control.

In patients with arterial hypertension and hyponatremia (due to diuretic use), it is necessary to stop diuretics 3 days before starting angiotensin-converting enzyme inhibitors (if necessary, diuretics can be resumed later), or they should be prescribed initial low doses of angiotensin-converting enzyme inhibitors.

Sulfonamide derivatives may exacerbate the course of systemic lupus erythematosus (this should be taken into account when prescribing Indiur).

Overdose

Symptoms: nausea, vomiting, weakness, gastrointestinal dysfunction, water-electrolyte imbalances, decreased blood pressure, dizziness, drowsiness, confusion, respiratory depression; in patients with impaired liver function, hepatic coma may develop.

Treatment: gastric lavage and/or administration of activated charcoal followed by restoration of normal water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Drug Interactions

With simultaneous use of indapamide with lithium preparations, an increase in plasma lithium concentration is possible.

Astemizole, erythromycin (with intravenous administration), pentamidine, sultopride, vincamine, class I A antiarrhythmics (quinidine, disopyramide) and class III antiarrhythmics (amiodarone, bretylium, sotalol) increase the likelihood of cardiac arrhythmias of the torsades de pointes type (polymorphic ventricular tachycardia).

NSAIDs, corticosteroids, tetracosactide, sympathomimetics reduce the antihypertensive effect, baclofen increases it.

Saluretics, cardiac glycosides, glucocorticoids and mineralocorticoids, tetracosactide, amphotericin B (with intravenous administration), laxatives increase the risk of hypokalemia.

With simultaneous use with cardiac glycosides, the likelihood of digitalis intoxication increases; with calcium preparations – hypercalcemia; with metformin – possible worsening of lactic acidosis.

The combination with potassium-sparing diuretics may be effective in some categories of patients, however, the possibility of developing hypo- and hyperkalemia is not completely excluded, especially in patients with diabetes and renal failure.

ACE inhibitors increase the risk of arterial hypotension and/or acute renal failure (especially with existing renal artery stenosis).

High-dose iodine-containing contrast agents increase the risk of renal function impairment (dehydration). Before using iodine-containing contrast agents, patients need to restore fluid loss.

Tricyclic antidepressants and antipsychotic drugs enhance the antihypertensive effect and increase the risk of orthostatic hypotension.

Cyclosporine increases the risk of hypercreatininemia.

It reduces the effect of indirect anticoagulants (coumarin or indandione derivatives) due to an increase in the concentration of clotting factors resulting from a decrease in circulating blood volume and increased production by the liver (dose adjustment may be required).

It enhances the neuromuscular blockade developing under the action of non-depolarizing muscle relaxants.

Storage Conditions

In a dry and light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 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.