Indapamide CF Stada, 1.5 mg 30 pcs

Hypotensive agent (diuretic, vasodilator). Pharmacological properties are close to thiazide diuretics (disrupts sodium ions reabsorption in the cortical segment of the Genle loop).

It increases urinary excretion of sodium and chlorine ions and, to a lesser extent, potassium and magnesium ions accompanied with intensification of diuresis.

With its ability to selectively block “slow” calcium channels it increases arterial wall elasticity and decreases total peripheral vascular resistance.

It promotes reduction of left ventricular hypertrophy.

It does not affect the content of plasma lipids (triglycerides, low-density lipoproteins, high-density lipoproteins); it does not affect carbohydrate metabolism (including in patients with diabetes).

It decreases sensitivity of vascular wall to noradrenalin and angiotensin II, stimulates synthesis of prostaglandin E2 and prostacyclin PGI2, decreases production of free and stable oxygen radicals.

Indapamide produces hypotensive effect in doses without a marked diuretic effect. Hypotensive effect develops by the end of the first week and lasts for 24 hours after a single dose.

Pharmacokinetics

After oral administration it is quickly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%).

Food intake slightly slows down the absorption rate, but does not affect the amount absorbed.

Maximum concentration in plasma is reached 12 hours after oral administration. With repeated doses the fluctuations in plasma concentration of the drug in the interval between two doses are reduced.

The equilibrium concentration is established after 7 days of regular use. The half-life is 18 hours, the blood plasma protein binding is about 79%.

It also binds with elastin of smooth muscles of the vascular wall. It has a high volume of distribution, passes through the histohematic barriers (including the placental barrier), penetrates into breast milk.

Metabolized in the liver. The kidneys excrete 60-80% as metabolites (about 5% is excreted unchanged), through the intestines – 20%.

In patients with renal insufficiency pharmacokinetics is not changed. It does not cumulate.

Indications

Arterial hypertension.

Pharmacological effect

Antihypertensive agent (diuretic, vasodilator). Its pharmacological properties are similar to thiazide diuretics (impairs the reabsorption of sodium ions in the cortical segment of the loop of Henle).

Increases the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions in the urine, which is accompanied by increased diuresis.

Having the ability to selectively block “slow” calcium channels, it increases the elasticity of arterial walls and reduces overall peripheral vascular resistance.

Helps reduce hypertrophy of the left ventricle of the heart.

Does not affect the content of lipids in the blood plasma (triglycerides, low-density lipoproteins, high-density lipoproteins); does not affect carbohydrate metabolism (including in patients with diabetes).

Reduces the sensitivity of the vascular wall to norepinephrine and angiotensin II, stimulates the synthesis of prostaglandin E2 and prostacyclin PGI2, reduces the production of free and stable oxygen radicals.

Indapamide has a hypotensive effect in doses that do not have a pronounced diuretic effect. The hypotensive effect develops by the end of the first week and persists for 24 hours with a single dose.

Pharmacokinetics

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%).

Eating slightly slows down the rate of absorption, but does not affect the amount of substance absorbed.

The maximum concentration in blood plasma is achieved 12 hours after oral administration. With repeated doses, fluctuations in the concentration of the drug in the blood plasma in the interval between two doses decrease.

Equilibrium concentration is established after 7 days of regular use. The half-life is 18 hours, the binding to plasma proteins is about 79%.

It also binds to elastin of smooth muscles of the vascular wall. It has a high volume of distribution, passes through histohematic barriers (including placental), and penetrates into breast milk.

Metabolized in the liver. 60-80% is excreted by the kidneys in the form of metabolites (about 5% is excreted unchanged) and 20% is excreted through the intestines.

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

Special instructions

If there is insufficient effectiveness after 4-8 weeks, it is advisable to add an antihypertensive drug with a different mechanism of action to therapy.

It is not recommended to increase the dose of the drug (in the absence of a significant increase in the hypotensive effect, the risk of side effects increases).

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

While taking indapamide, you should systematically monitor the concentration of potassium, sodium, magnesium ions in the blood plasma (electrolyte disturbances may develop), pH, concentration of glucose, uric acid and residual nitrogen.

It is recommended to determine the content of sodium ions in blood plasma before starting treatment.

The first measurement of the concentration of potassium ions in the blood plasma should be carried out within the first week from the start of treatment.

The most careful monitoring is indicated in patients with coronary heart disease, heart failure, cirrhosis of the liver (especially with edema or ascites – the risk of developing metabolic alkalosis, which increases

manifestations of hepatic encephalopathy), weakened patients or those receiving combined drug therapy.

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) and patients taking, along with

with indapamide, drugs that prolong the QT interval (see “Interaction with other drugs”).

Thiazide diuretics may reduce the urinary excretion of calcium ions, resulting in mild and temporary hypercalcemia.

Severe hypercalcemia while taking indapamide may be a consequence of previously undiagnosed hyperparathyroidism.

Diuretics should be discontinued before testing parathyroid function.

When thiazide diuretics are prescribed to patients with liver failure, hepatic encephalopathy may develop. In such cases, the drug should be stopped immediately.

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 rate). Patients need to compensate for water loss and carefully monitor renal function at the beginning of treatment.

Indapamide may give a positive result during a doping test.

In patients with high levels of uric acid in the blood plasma, the frequency of gout attacks may increase during indapamide therapy.

Sulfonamide derivatives can aggravate the course of systemic lupus erythematosus (must be kept in mind when prescribing indapamide).

Impact on the ability to drive vehicles and operate machinery

Some patients, mainly at the beginning of treatment or when adding another antihypertensive agent, may experience drowsiness, dizziness and other side effects from the nervous system.

If they occur, the patient must take special precautions when driving a vehicle and working with complex mechanisms.

Active ingredient

Indapamide

Active components

Indapamide

Composition

1 tablet contains:

Active substance:

Indapamide – 1.5 mg;

Excipients:

Hypromellose (hypromellose 4000) – 42–78.4 mg;

Lactose monohydrate – 168.5–132.1 mg;

Colloidal silicon dioxide (Aerosil) – 1 mg;

Magnesium stearate – 2 mg;

Shell:

Hypromellose (hydroxypropyl methylcellulose) – 5.94 mg;

Macrogol (polyethylene glycol 4000) – 1.29 mg;

Talc – 0.462 mg;

Titanium dioxide – 1.29 mg;

Dye tropeolin O – 0.018 mg.

Pregnancy

Indapamide MB is not recommended during pregnancy and lactation.

Contraindications

Hypersensitivity to indapamide and other sulfonamide derivatives, severe renal failure (anuria stage), severe liver failure (including encephalopathy),

hypokalemia; pregnancy, lactation period; age under 18 years (efficacy and safety have not been established); lactose intolerance, galactosemia, glucose/galactose malabsorption syndrome (the drug contains lactose).

With caution

Impaired liver and/or kidney function, impaired water and electrolyte balance, hyperparathyroidism; prolongation of the QT interval or concomitant use of drugs that prolong the QT interval

(see “Interaction with other drugs”); diabetes mellitus in the stage of decompensation, hyperuricemia (especially accompanied by gout and urate nephrolithiasis).

If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

Side Effects

Determination of the frequency of adverse reactions: very often – 10% or more; often – 1% or more, less than 10%; infrequently – 0.1% or more, less than 1%; rarely – 0.01% or more, less than 0.1%; very rarely – less than 0.01%.

From the cardiovascular system: very rarely – arrhythmia, orthostatic hypotension, palpitations, changes in the electrocardiogram (ECG) characteristic of hypokalemia.

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

From the central and peripheral nervous system: rarely – dizziness, headache, paresthesia, increased excitability, asthenia, drowsiness, vertigo, insomnia, depression, increased fatigue, malaise, muscle spasms of the limbs, tension, irritability, anxiety.

Patients with liver failure may develop hepatic encephalopathy.

From the digestive system: infrequently – vomiting; rarely – nausea, constipation, dryness of the oral mucosa; very rarely – pancreatitis, anorexia, abdominal pain, diarrhea.

From the genitourinary system: very rarely – renal failure, nocturia, infections, polyuria.

From the respiratory system: cough, pharyngitis, sinusitis, rhinitis.

Allergic reactions: often – maculopapular rash; uncommon – purpura, very rare – angioedema and/or urticaria, hemorrhagic vasculitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus.

Other: isolated reports – exacerbation of systemic lupus erythematosus (SLE), photosensitivity reactions.

Laboratory data:

a decrease in potassium levels and the development of hypokalemia (especially pronounced in patients at risk).

In clinical studies, hypokalemia (plasma potassium less than 3.4 mmol/L) was observed in 10% of patients and 3.2 mmol/L in 4% of patients after 4–6 weeks of treatment.

After 12 weeks of therapy, the potassium content in the blood plasma decreased by an average of 0.23 mmol/l.

Very rarely – hypercalcemia; hyponatremia is possible, accompanied by hypovolemia and orthostatic hypotension.

The simultaneous loss of chlorine ions can lead to compensatory metabolic alkalosis, however, the incidence of metabolic alkalosis and its severity are insignificant; hyperuricemia and hyperglycemia (unspecified frequency), increased blood urea nitrogen concentration, hypercreatininemia, glycosuria.

If any of the above side effects get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

If you are taking any other medications, you should consult your doctor before starting treatment.

Not recommended combinations

When used simultaneously with lithium preparations, it is possible to increase the concentration of lithium ions in the blood plasma due to a decrease in its excretion from the body by the kidneys, accompanied by the appearance of signs of

overdose (nephrotoxic effect), as well as when following a salt-free diet (reduced excretion of lithium ions by the kidneys).

In case of simultaneous use with lithium preparations, careful monitoring of the concentration of lithium in the blood plasma and dosage adjustment are necessary.

Combinations requiring special attention

Drugs, when used simultaneously with which the likelihood of occurrence of arrhythmias of the “torsades de pointes” type increases: class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide),

class III antiarrhythmics (amiodarone, dofetilide, ibutilide, bretylium tosylate), sotalol, some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine),

benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), others (bepridil, cisapride, difemanil, erythromycin (intravenous (IV)), halofantrine, mizolastine,
pentamidine, sparfloxacin, moxifloxacin, vincamine (iv), astemizole.

Concomitant use with any of these drugs, especially against the background of hypokalemia, increases the risk of ventricular arrhythmias of the “pirouette” type.

Before starting combination therapy with indapamide and the above drugs, the potassium content in the blood plasma should be monitored and, if necessary, adjusted.

It is recommended to monitor the patient’s clinical condition, as well as the content of electrolytes in the blood plasma and ECG. In patients with hypokalemia, it is necessary to use drugs that do not provoke the development of pirouette-type arrhythmias.

With the simultaneous administration of nonsteroidal anti-inflammatory drugs (NSAIDs) (for systemic use), including selective cyclooxygenase-2 (COX-2) inhibitors, high doses of salicylic acid (3 g/day or more),

possible: decreased antihypertensive effect of indapamide, development of acute renal failure in dehydrated patients (due to decreased glomerular filtration rate).

At the beginning of indapamide therapy, it is necessary to restore water and electrolyte balance and monitor renal function.

Angiotensin-converting enzyme (ACE) inhibitors, when used concomitantly with indapamide in patients with hyponatremia (especially in patients with renal artery stenosis), increase the risk of sudden arterial hypotension and/or acute renal failure.

Patients with arterial hypertension and a reduced content of sodium ions in the blood plasma due to diuretics should stop taking diuretics 3 days before starting treatment with ACE inhibitors.

In the future, if necessary, resume taking diuretics. Therapy with ACE inhibitors should be started with low doses, followed by a gradual increase in dose if necessary.

In chronic heart failure, treatment should begin with low doses of ACE inhibitors, after first reducing the dose of diuretics.

In all cases, in the first week of taking ACE inhibitors, it is necessary to monitor kidney function (creatinine content in blood plasma).

Drugs that increase the risk of hypokalemia: amphotericin B (iv); gluco- and mineralocorticosteroids (if administered systemically), tetracosactide, laxatives that stimulate intestinal motility.

When taken simultaneously with indapamide, the above drugs increase the risk of developing hypokalemia (additive effect). If necessary, the content of potassium ions in the blood plasma should be monitored and adjusted.

Concomitant therapy with baclofen enhances the antihypertensive effect of indapamide.

Cardiac glycosides: hypokalemia increases the toxic effect of cardiac glycosides (glycoside intoxication).

With the simultaneous use of indapamide and cardiac glycosides, the content of potassium ions in the blood plasma, ECG parameters should be monitored, and, if necessary, therapy should be adjusted.

A combination with potassium-sparing diuretics (amiloride, spironolactone, triamterene) may be effective in some patients, however, the possibility of developing hypo- or hyperkalemia is not completely excluded, especially in patients with diabetes mellitus and renal failure.

In such cases, the level of potassium in the blood plasma, ECG parameters should be monitored and, if necessary, therapy should be adjusted.

With the simultaneous use of diuretics and metformin, the appearance of lactic acidosis is possible, which is apparently associated with the development of functional renal failure caused by the action of diuretics (mostly “loop”).

It is not recommended to use metformin in combination with indapamide if the creatinine level is more than 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.

When using iodine-containing radiocontrast agents, it should be borne in mind that the diuretic effect of indapamide increases the risk of developing renal failure.

This risk is especially high when using iodinated contrast agents in high doses. Before using iodinated contrast agents, patients need to restore fluid loss.

Tricyclic antidepressants and antipsychotics enhance the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).

Preparations containing calcium salts increase the risk of developing hypercalcemia due to decreased excretion of calcium ions by the kidneys.

With the simultaneous use of cyclosporine and tacrolimus, an increase in the content of creatinine in the blood plasma is possible (without changing the concentration of circulating cyclosporine), which is observed even with normal levels of water and sodium ions.

Glucocorticosteroid drugs, tetracosactide (when used systemically) reduce the hypotensive effect (sodium and fluid retention).

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

Strengthens the blockade of neuromuscular transmission that develops under the influence of non-depolarizing muscle relaxants.

Overdose

Symptoms:

Complete set of goods

Extended-release film-coated tablets, 1.5 mg.

10 tablets in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil.

3 blister packs along with instructions for use in a cardboard pack.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25ºС.

Keep out of the reach of children.

Shelf life

3 years. Do not use after the expiration date stated on the package.

Manufacturer

Hemofarm LLC, Russia