Indapamide Retard-Teva, 1.5 mg 30 pcs

Pharmacotherapeutic group: diuretic

ATX code: C03BA11

Pharmacological properties

Pharmacodynamics

Indapamide is a sulfonamide derivative whose structure includes an indole ring.

It is characterized by pharmacological affinity with thiazide diuretics. Indapamide realizes its effects by inhibiting the reabsorption of sodium ions in the distal convoluted tubules. Under the action of indapamide the renal excretion of chlorine ions, sodium ions and, to a lesser extent, excretion of potassium and magnesium is increased, which is accompanied by increased diuresis and antihypertensive effect.

The results of clinical studies have shown that when using indapamide in monotherapy in doses not having significant diuretic effect, a 24-hour hypotensive effect was demonstrated.

The antihypertensive activity of indapamide is associated with improvement of elastic properties of large arteries, reduction of arteriolar and total peripheral vascular resistance.

Tiazide and thiazide-like diuretics at a certain dose are characterized by the formation of a plateau of therapeutic effect, while the severity of adverse effects continues to increase with further increase of the dose. If the desired therapeutic effect cannot be achieved, further dose escalation is not advisable.

In short-, medium-, and long-term studies in patients with arterial hypertension, it has been found that indapamide does not affect lipid metabolism (triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and carbohydrate metabolism (including in diabetic patients).

Pharmacokinetics

absorption.

Indapamide is rapidly and completely absorbed from the gastrointestinal (GI) tract. Food intake slightly increases the rate of absorption of indapamide, but has no effect on the completeness of absorption. Maximum plasma concentration of indapamide is reached 12 hours after a single oral dose. Fluctuations in plasma concentration of indapamide are smoothed with repeated doses.

Distribution and metabolism

The binding of indapamide to plasma proteins is 79 %. The equilibrium concentration is reached after 7 days of administration.

There is no cumulation with repeated administration of the drug.

Elimation

Indapamide is excreted primarily by the kidneys (70% of the dose) and through the intestine (22%) in the form of inactive metabolites.

The elimination half-life of indapamide from plasma varies from 14 to 24 hours (mean 18 hours).

In renal failure pharmacokinetic properties of indapamide do not change.

Indications

Active ingredient

Composition

How to take, the dosage

Overly, 1 tablet daily, preferably in the morning.

The tablet should be swallowed whole, without chewing, with plenty of water.

When treating patients with arterial hypertension, increasing the dose does not increase the antihypertensive effect, but it does increase the diuretic effect.

Use in patients with renal insufficiency (see Contraindications and Special Precautions).

In severe renal failure (CKI less than 30 ml/min), administration of Indapamide retard-Teva is contraindicated. Thiazide and thiazide-like diuretics are effective only in patients with normal or mild renal function impairment.

Application in patients with hepatic impairment (see sections “Contraindications to use in patients with hepatic impairment”). Sections “Contraindications” and “Special Precautions”

In severe hepatic impairment, administration of Indapamide Retard-Teva is contraindicated.

Elderly patients (see section “Special Indications”

In elderly patients, plasma creatinine concentration should be monitored with regard to age, body weight and sex. In elderly patients, Indapamide Retard-Teva may be prescribed only if renal function is normal or if there are minor renal impairments.

Children and adolescents under 18 years of age

Indapamide Retard-Teva is not recommended for use in children under 18 years of age due to insufficient data on the safety and effectiveness of this therapy.

Interaction

Unwanted combinations

Lithium preparations

Concomitant use of indapamide and lithium preparations, as well as adherence to a salt-free diet, may result in increased plasma lithium concentrations due to decreased excretion, accompanied by signs of overdose. Diuretics may be used with lithium preparations if necessary, but plasma lithium levels should be monitored carefully and the dose of the drug adjusted accordingly.

Combinations requiring special attention

Drugs that may cause pirouette tachycardia:

– Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);

– Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);

– some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenones (droperidol, haloperidol);

– others: Bepridil, cisapride, difemanil, IV erythromycin, halofantrine, misolastin, pentamidine, sparfloxacin, moxifloxacin, IV vincamine, astemizole.

In case of increased risk of ventricular arrhythmias, including pirouette type (hypokalemia is a risk factor), plasma potassium concentration should be determined and, if necessary, appropriate adjustments should be made before starting combined therapy with indapamide and the above drugs. In addition, in the course of combined therapy, monitoring of patient’s clinical condition, control of plasma electrolytes and ECG parameters is necessary.

In patients with hypokalemia, drugs that do not cause pirouette tachycardia should be used.

Non-steroidal anti-inflammatory drugs (intended for systemic use), including selective cyclooxygenase-2 (COX-2) inhibitors and high doses of acetylsalicylic acid (>3 g/day)

The antihypertensive effect of indapamide may decrease. There is a risk of acute renal failure due to decreased glomerular filtration rate. Patients should compensate fluid loss and monitor renal function regularly, both at the beginning of therapy and during treatment.

Angiotensin-converting enzyme (ACE) inhibitors

The administration of ACE inhibitors against a background of sodium deficiency (especially in patients with renal artery stenosis) is accompanied by the risk of sudden arterial hypotension and/or acute renal failure.

Patients with arterial hypertension and possibly decreased plasma sodium ion content due to diuretics should stop taking diuretics 3 days before starting ACE inhibitor treatment. Subsequently, if necessary, the non-caliber diuretic may be resumed. It is also possible to start ACE inhibitor therapy at a low dose, with subsequent gradual increase in dose if necessary.

In chronic heart failure, treatment with ACE inhibitors should be started at the lowest dose with possible prior reduction in doses of diuretics.

In all cases renal function (plasma creatinine) should be monitored in patients in the first weeks of taking ACE inhibitors.

Other drugs that may cause hypokalemia (intravenous amphotericin B, glucocorticosteroids, mineralocorticosteroids for systemic use, tetracosactide, intestinal motility stimulating laxatives)

The risk of hypokalemia increases (additive effect).

Potassium concentration in plasma must be constantly monitored, and corrected if necessary. Particular attention should be paid to patients concomitantly receiving cardiac glycosides. The use of laxatives that do not stimulate intestinal motility is recommended.

Baclofen

It is noted that the hypotensive effect of indapamide is increased. Patients should compensate for fluid loss and monitor renal function carefully at the beginning of treatment.

Cardiac glycosides

Hypokalemia increases toxic effects of cardiac glycosides. When concomitant use of indapamide and cardiac glycosides, plasma potassium concentration and ECG parameters should be monitored and therapy should be adjusted if necessary.

Combinations requiring attention

Potassium-saving diuretics (amiloride, spironolactone, triamterene)

Combined therapy with indapamide and potassium-saving diuretics is reasonable in some patients, but the possibility of hypokalemia or hyperkalemia cannot be excluded (especially in patients with renal insufficiency and/or diabetes mellitus). In this case the plasma potassium concentration and ECG parameters should be monitored and the therapy should be adjusted if necessary.

Metformin

Functional renal insufficiency, which may occur with diuretics, especially loop diuretics, when metformin is administered simultaneously, increases the risk of lactic acidosis.

Metformin should not be used if plasma creatinine concentrations exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.

Iodine-containing contrast agents

There is an increased risk of acute renal failure, especially with concomitant use of iodine-containing contrast agents in high doses, against a background of dehydration caused by diuretics.

Before iodine-containing contrast agents are administered, patients should compensate for fluid loss.

Tricyclic antidepressants, antipsychotics (neuroleptics)

The drugs in these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Calcium salts

Concomitant administration may result in hypercalcemia due to reduced renal excretion of calcium ions.

Cyclosporine, tacrolimus

Possible increase in plasma creatinine without change in circulating cyclosporine concentration, even with normal fluid and sodium ion levels.

Corticosteroid drugs, tetracosactide (when systemically administered)

Decrease the hypotensive effect of indapamide (corticosteroids cause fluid and sodium retention in the body).

Special Instructions

Hepatic dysfunction

Hepatic encephalopathy may develop in patients with hepatic dysfunction, especially in case of electrolyte imbalance. In this case the use of diuretics should be stopped immediately.

Photosensitivity

When using thiazide and thiazide-like diuretics, there have been reported cases of photosensitivity reactions (see section “Side effects”). In case of photosensitivity reactions during the drug administration, the treatment should be discontinued. If continuation of therapy with diuretics is necessary, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance

The plasma sodium ion content

The plasma sodium ion content should be determined before starting treatment. Against the background of the drug administration this indicator should be controlled regularly, because initially the decrease of sodium concentration in plasma may be asymptomatic. More frequent monitoring of sodium ions content is recommended for patients with liver cirrhosis and elderly people (see sections “Side effects” and “Overdosing”). All diuretic drugs can cause hyponatremia, which sometimes leads to extremely severe consequences. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. Concomitant decrease in the concentration of chlorine ions may lead to a secondary compensatory metabolic alkalosis: the frequency and severity of this effect is insignificant.

Potassium ion plasma concentrations

When therapy with thiazide and thiazide-like diuretics the main risk is plasma potassium concentration decrease and hypokalemia development. It is necessary to prevent the risk of hypokalemia (<3.4 mmol/l) in high-risk patients of the following categories: elderly, frail and/or receiving concomitant drug therapy, patients with cirrhosis, peripheral edema and ascites, patients with coronary heart disease, heart failure. Hypokalemia in these patients increases the toxic effects of cardiac glycosides and the risk of arrhythmias.

In addition, patients with an extended QT interval, both congenital and drug-induced, are at increased risk.

Hypokalemia, like bradycardia, is a contributing condition for severe arrhythmias, especially pirouette tachycardia, which can be fatal. The first measurement of blood potassium ion concentration should be done within the first week of initiating treatment.

If hypokalemia occurs, appropriate treatment must be given.

Plasma calcium

Please note that thiazide and thiazide-like diuretics may decrease renal excretion of calcium ions, resulting in a slight and temporary increase in plasma calcium concentration. Severe hypercalcemia may result from previously undiagnosed hyperparathyroidism.

Diuretics should be discontinued prior to parathyroid function testing.

Plasma glucose

Plasma glucose levels should be monitored in patients with diabetes mellitus, especially if hypokalemia is present.

Ureic acid

In patients with gout, the frequency of attacks may increase or the course of gout may worsen.

Diuretics and renal function

Tiazide and thiazide-like diuretics are only fully effective in patients with normal or mildly impaired renal function (plasma creatinine below 25 mg/L or 220 μmol/L in adults). In elderly patients the normal plasma creatinine level is calculated taking into account the age, body weight and sex.

It should be taken into account that at the beginning of treatment patients may have decrease of glomerular filtration rate caused by hypovolemia that in its turn is caused by loss of fluid and sodium ions due to diuretic drugs. As a consequence, plasma concentrations of urea and creatinine may increase. If renal function is not impaired, such temporary functional renal failure usually goes without consequences, but if renal failure is already present, the patient’s condition may worsen.

Athletes

Indapamide may test positive for doping controls in athletes.

Influence on ability to drive vehicles, mechanisms

The effect of the substances in the drug Indapamide retard-Teva does not lead to impairment of attention. However, some people may have various reactions in response to blood pressure decrease, especially at the beginning of therapy or when other hypotensive drugs are added to the current therapy. In this case, the ability to drive or operate other mechanisms may be impaired.

Synopsis

Contraindications

Cautious

Hepatic and renal dysfunction, electrolyte-water balance disorders; use in debilitated patients or in patients receiving concomitant therapy with antiarrhythmic drugs (see “Interaction with other drugs”). Interaction with other drugs”); diabetes mellitus, elevated uric acid levels, prolonged QT interval, hyperparathyroidism.

Side effects

The most common adverse reactions reported were hypersensitivity reactions, mainly dermatological, in patients with predisposition to allergic and asthmatic reactions, and maculopapular rash.

In clinical studies hypokalemia (potassium concentration less than 3.4 mmol/l) was observed in 10% of patients, and potassium concentration less than 3.2 mmol/l was observed in 4% of patients after 4-6 weeks of therapy.

After 12 weeks of therapy the average decrease in plasma potassium concentration was 0.23 mmol/l.

Most adverse reactions (laboratory and clinical parameters) are dose-dependent.

List of adverse reactions is given in the table

The frequency of adverse reactions that have been noted during therapy with indapamide is given as the following gradation:

Very common (≥1/10); common (≥1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); unspecified frequency (frequency cannot be calculated from available data).

MedDRA

Classes and organ systems

Unwanted reactions

Frequency

Blood and lymphatic system disorders

Agranulocytosis

Very rare

Aplastic anemia

Very rare

Hemolytic anemia

/p>

Very rare

Leukopenia

Very rare

Vertigo

Rarely

Extreme fatigue

Rarely

Headache

/p>

Rarely

Paresthesias

Rarely

Snap

Prevalence unknown

Visual disturbances

Myopia

Frequency unknown

Fuzzy vision

Frequency unknown

Visual impairment

/p>

Frequency unknown

Cardiac disorders

Arrhythmia

Very rare

Pirouette tachycardia (potentially fatal) (see “Special Considerations”).

Frequency unknown

Vascular disorders

Hypertension

Very rare

Gastrointestinal disorders

Vomiting

Infrequent

Nausea

Rarely

Shut up

Rarely

Mouth dryness

Rarely

Pancreatitis

Very rarely

Liver and biliary tract disorders

Liver function disorder

Very rare

Possible development of hepatic encephalopathy in cases of hepatic insufficiency (see Contraindications and Special Indications)

Frequency is unknown (see Sections “Contraindications” and “Special Indications. See “Contraindications” and “Special Directions”

Hepatitis

Frequency unknown

Skin and subcutaneous tissue disorders

Sensitivity reactions

/p>

Frequently

Maculopapular Rash

Frequently

Purpura

Infrequent

Angeoneurotic edema

/p>

Very rare

Crapsy

Very rare

Toxic epidermal necrolysis

/td>

Very rare

Stevens-Johnson syndrome

Very rare

Possible exacerbation of pre-existing acute systemic lupus erythematosus

Possible exacerbation of pre-existing systemic lupus erythematosus

Prevalence unknown

Photosensitivity (see “Special Indications. Special Indications)

Frequency unknown

Kidney and urinary tract disorders

Renal failure

/p>

Very rare

Deviations from normal laboratory values and examination results

Long QT interval on ECG (see Sections “Interaction between Interactions with ECG”). Interaction with other medicines and special notes)

Frequency unknown

Elevated blood glucose concentrations (see “Special Indications. Special Indications)

Frequency unknown

Elevated uric acid concentration (see “Special Indications. Special Indications)

Frequency unknown

Increased concentration of liver enzymes

Frequency unknown

Overdose

Symptoms

Indapamide even in very high doses (up to 40 mg, i.e. 27 times the therapeutic dose) has no toxic effect.

The signs of acute poisoning by the drug are primarily associated with disorders of water-electrolyte balance (hyponatremia, hypokalemia). Nausea, vomiting, decreased arterial pressure, convulsions, vertigo, drowsiness, confusion, polyuria or oliguria with possible transition to anuria (due to hypovolemia) may be noted as clinical symptoms of overdose.

Treatment

Emergency measures are limited to elimination of the drug from the body: gastric lavage and/or administration of activated charcoal followed by restoration of the water-electrolyte balance.

Pregnancy use

Pregnancy

There are currently insufficient data on the use of indapamide during pregnancy (fewer than 300 cases have been described).

Long-term use of thiazide diuretics in the third trimester of pregnancy may cause hypovolemia in the mother and reduced uterine-placental blood flow, resulting in fetal delay.

There have been no direct or indirect effects on pregnancy in animal studies.

The use of indapamide during pregnancy should be avoided.

Breastfeeding

It is not known whether indapamide or its metabolites are excreted with breast milk. The newborn may develop hypersensitivity to sulfonamide derivatives and hypokalemia. Therefore, the risk to the newborn/infant cannot be excluded. Indapamide is close to thiazide diuretics, administration of which causes reduction of breast milk or even suppression of lactation.

Do not use indapamide during breastfeeding.

Fertility

Preclinical studies have shown no effect on fertility in rats of either sex. There is presumably no effect on fertility in humans.

Similarities