Indapamide Stada (Tablets) Instructions for Use

Marketing Authorization Holder

Nizhpharm JSC (Russia)

Manufactured By

Makiz-Pharma, LLC (Russia)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Dosage Form

Indapamide Stada

Film-coated tablets, 2.5 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; the cross-section shows two layers: an inner layer of white or white with a yellowish tint.

Excipients: ludipress, magnesium stearate, colloidal silicon dioxide (aerosil), hypromellose, titanium dioxide, polyethylene glycol, talc.

10 pcs. – blister packs (3) – cardboard packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Antihypertensive agent (diuretic, vasodilator). In its pharmacological properties, it is close to thiazide diuretics (impairs sodium reabsorption in the cortical segment of the loop of Henle). Increases the excretion of sodium and chloride ions in the urine, and to a lesser extent, potassium and magnesium ions. By selectively blocking “slow” calcium channels, it increases the elasticity of arterial walls and reduces total peripheral vascular resistance. Contributes to the reduction of left ventricular hypertrophy. Does not affect the lipid content in blood plasma (triglycerides, low-density lipoproteins, high-density lipoproteins); does not significantly affect carbohydrate metabolism, but in the presence of hypokalemia, blood glucose levels may increase. Reduces the sensitivity of the vascular wall to norepinephrine and angiotensin II, stimulates the synthesis of prostaglandin PgE2α and prostacyclin PgI2, reduces the production of free and stable oxygen radicals.

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

With systematic administration, the therapeutic effect is noted after 1-2 weeks, reaches a maximum by 8-12 weeks and persists for up to 8 weeks; after a single dose, the maximum effect is noted after 24 hours.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Food intake somewhat slows down the rate of absorption but does not affect the amount of the absorbed drug. C_max in blood plasma is reached 1-2 hours after oral administration. With repeated doses, fluctuations in the drug concentration in the blood plasma between two doses decrease. The equilibrium concentration is established after 7 days of regular intake.

T_1/2 averages 14-18 hours, plasma protein binding is 71-79%. It also binds to elastin of the vascular wall smooth muscles. Has a high volume of distribution, penetrates histohematic barriers (including the placental barrier), and passes into breast milk.

It is metabolized in the liver. 60-80% is excreted in the urine as metabolites (about 5% is excreted unchanged), and 20-23% is excreted through the intestines.

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

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

The tablets are taken orally, without chewing.

For arterial hypertension, 2.5 mg (1 tablet) is prescribed once a day in the morning. If the effect is insufficient after 4-8 weeks, it is advisable to add antihypertensive drugs with a different mechanism of action to the therapy (increasing the dose is not advisable – in the absence of a significant increase in effect, an increase in side effects is noted).

Adverse Reactions

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

From the nervous system asthenia, nervousness, headache, dizziness, drowsiness, vertigo, insomnia, depression; rarely – increased fatigue, malaise, muscle spasm, tension, irritability, anxiety.

From the digestive system nausea, vomiting, diarrhea or constipation, decreased appetite, dry mouth, abdominal pain, hepatic encephalopathy (against the background of hepatic insufficiency), pancreatitis may occur.

From the respiratory system cough, pharyngitis, sinusitis, rarely – rhinitis.

From the urinary system infections, nocturia, polyuria.

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

From the hematopoietic organs thrombocytopenia, leukopenia, agranulocytosis, bone marrow aplasia, hemolytic anemia.

Laboratory parameters: hyperuricemia, hyperglycemia, hypokalemia, hypochloremia, hyponatremia, hypercalcemia, increased blood urea nitrogen, hypercreatininemia, glucosuria.

Other exacerbation of systemic lupus erythematosus.

Contraindications

• Severe renal failure (anuria stage);
• Severe hepatic failure (including with encephalopathy);
• Hypokalemia;
• Lactase deficiency;
• Lactose intolerance;
• Glucose-galactose malabsorption (the drug contains lactose);
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety have not been established);
• Hypersensitivity to indapamide, other sulfonamide derivatives and drug components.

With caution in case of impaired liver and/or kidney function, water-electrolyte imbalance, hyperparathyroidism, patients with prolonged QT interval on ECG or simultaneous use of drugs that prolong the Q-T interval, decompensated diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis).

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure. Use with caution in case of impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal failure. Use with caution in case of impaired renal function.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

Use with caution in the elderly. In elderly individuals, regular monitoring of potassium ion and creatinine levels is indicated.

Special Precautions

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

During the administration of indapamide, the concentration of potassium, sodium, magnesium ions in the blood plasma (electrolyte disturbances may develop), pH, glucose concentration, uric acid and residual nitrogen should be systematically monitored.

The most thorough monitoring is indicated in patients with liver cirrhosis (especially with edema or ascites – risk of developing metabolic alkalosis, which enhances the manifestations of hepatic encephalopathy), coronary heart disease, chronic heart failure, as well as in elderly individuals. The high-risk group also includes patients with a prolonged 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 the first week of treatment.

Hypercalcemia during indapamide administration may be a consequence of previously undiagnosed hyperparathyroidism.

In patients with diabetes mellitus, 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 water loss and carefully monitor kidney function at the beginning of treatment. Indapamide may give a positive result during doping control. In patients with arterial hypertension and hyponatremia (due to diuretic intake), it is necessary to stop taking diuretics 3 days before starting ACE inhibitors (if necessary, diuretics can be resumed later), or they are prescribed initial low doses of ACE inhibitors.

Sulfonamide derivatives can exacerbate the course of systemic lupus erythematosus (must be taken into account when prescribing indapamide).

Effect on the ability to drive vehicles and mechanisms

During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms nausea, vomiting, weakness, gastrointestinal dysfunction, water-electrolyte disturbances, in some cases – excessive decrease in blood pressure, respiratory depression. In patients with liver cirrhosis, the development of hepatic coma is possible.

Treatment gastric lavage, correction of water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Drug Interactions

Saluretics (loop, thiazide), cardiac glycosides, gluco- and mineralocorticoids, tetracosactide, amphotericin B (intravenous), laxatives increase the risk of hypokalemia.

When taken simultaneously with cardiac glycosides, the likelihood of digitalis intoxication increases; with calcium preparations – hypercalcemia; with metformin – possible worsening of lactic acidosis.

Increases the concentration of lithium ions in the blood plasma (reduces urinary excretion), lithium has a nephrotoxic effect.

Astemizole, erythromycin (intravenous), pentamidine, sultopride, terfenadine, vincamine, class Ia antiarrhythmic drugs (quinidine, disopyramide) and class III (amiodarone, bretylium tosilate, sotalol) can lead to the development of torsades de pointes arrhythmia due to QT interval prolongation.

NSAIDs, corticosteroids, tetracosactide, sympathomimetics reduce the hypotensive effect, baclofen enhances it. The combination with potassium-sparing diuretics may be effective in some categories of patients, however, the possibility of developing hypo- or hyperkalemia is not completely excluded, especially in patients with diabetes mellitus and renal failure.

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

Increases the risk of renal function impairment when using high doses of iodine-containing contrast agents (dehydration of the body). Before using iodine-containing contrast agents, patients need to restore fluid loss.

Imipramine-type (tricyclic) antidepressants and antipsychotic drugs enhance the hypotensive effect and increase the risk of orthostatic hypotension.

Cyclosporine increases the risk of hypercreatininemia.

Reduces the effect of indirect anticoagulants (coumarin or indandione derivatives) due to an increase in the concentration of coagulation factors as a result of a decrease in the volume of circulating blood and an increase in their production by the liver (dose adjustment may be required).

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

Storage Conditions

List B. Store in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

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.