Indapamide-Astrapharm film-coated tablets 2.5 mg blister No. 30

Instructions Indapamide-Astrapharm film-coated tablets 2.5 mg blister No. 30

Composition

active ingredient: indapamide;

1 tablet contains indapamide 2.5 mg;

excipients: corn starch; lactose, monohydrate; povidone; magnesium stearate; sodium lauryl sulfate; coating: hypromellose 2910, 5 cPz; PEG 6000; titanium dioxide (E 171).

Dosage form

Film-coated tablets.

Main physicochemical properties: round tablets with a biconvex surface, coated with a white coating. Two layers are visible when broken.

Pharmacotherapeutic group

Non-thiazide diuretics with moderately pronounced activity. Sulfonamides, simple.

ATX code C03B A11.

Pharmacological properties

Pharmacodynamics

Indapamide is a sulfonamide diuretic that is pharmacologically related to thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment of the kidney.

This increases the excretion of sodium and chlorides in the urine and, to a lesser extent, the excretion of potassium and magnesium, thus increasing diuresis. The antihypertensive effect of indapamide is manifested at doses that produce a slight diuretic effect. Moreover, its antihypertensive effect is maintained even in hypertensive patients undergoing hemodialysis.

Indapamide acts at the vascular level by:

a decrease in the contractile ability of vascular smooth muscles, which is associated with changes in transmembrane ion exchange (mainly calcium);

stimulation of the synthesis of prostaglandin PGE2 and prostacyclin PGI2 (vasodilator and platelet aggregation inhibitor).

Indapamide reduces left ventricular hypertrophy.

Moreover, as studies of various durations (short, medium and long) involving patients with arterial hypertension have shown, indapamide:

does not affect the metabolism of lipids: triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol;

does not affect carbohydrate metabolism, even in patients with hypertension and diabetes.

When the recommended dose is exceeded, the therapeutic effect of thiazides and thiazide-like diuretics does not increase, while the number of undesirable effects increases. If the treatment is not effective enough, increasing the dose is not recommended.

Pharmacokinetics

Absorption. The bioavailability of indapamide is high – 93%. The maximum concentration in blood plasma is reached 1-2 hours after taking a dose of 2.5 mg.

Distribution. Plasma protein binding is above 75%. Half-life is 14-24 hours (average 18 hours). With regular administration, the steady-state plasma concentration of indapamide (plateau) increases compared to the plasma concentration of indapamide after a single dose. This plasma concentration remains stable for a long time without cumulation.

Excretion. Renal clearance accounts for 60-80% of total clearance. Indapamide is excreted mainly as metabolites, the proportion of the drug excreted by the kidneys unchanged is 5%. In patients with renal failure, pharmacokinetic parameters do not change.

Indication

Essential hypertension.

Contraindication

Hypersensitivity to indapamide, other sulfonamides or to any of the other ingredients of the drug. Severe renal failure, hepatic encephalopathy or severe liver dysfunction, hypokalemia.

Interaction with other medicinal products and other types of interactions

Not recommended combinations

Lithium: Increased plasma lithium levels and symptoms of overdose may occur, as with a salt-free diet (reduced urinary lithium excretion). If a diuretic is necessary, careful monitoring of plasma lithium levels and adjustment of the lithium dose are necessary.

Combinations requiring caution

Drugs that can cause paroxysmal torsades de pointes, such as, but not limited to:

Class Ia antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide);

Class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide, bretylium);

some antipsychotic drugs:

o phenothiazines (e.g. chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine);

o benzamides (e.g. amisulpride, sulpiride, sultopride, tiapride);

o butyrophenones (e.g. droperidol, haloperidol);

other antipsychotics (e.g. pimozide);

other medicines (e.g. bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, intravenous vincamine, methadone, astemizole, terfenadine).

When using indapamide with the above-mentioned drugs, the risk of ventricular arrhythmias increases, in particular torsades de pointes - paroxysmal ventricular tachycardia of the "pirouette" type (hypokalemia is a risk factor).

Nonsteroidal anti-inflammatory drugs (for systemic use), including selective COX-2 inhibitors, high doses of acetylsalicylic acid (more than 3 g/day):

may reduce the antihypertensive effect of indapamide;

Dehydrated patients are at increased risk of acute renal failure (due to decreased glomerular filtration). Before starting treatment, it is necessary to restore water balance and check kidney function.

ACE inhibitors: Sudden hypotension and/or acute renal failure may occur in patients with low sodium levels (especially in patients with renal artery stenosis).

Hypertension: In patients with hypertension in whom previous diuretic therapy has resulted in a decrease in sodium levels, the diuretic should be discontinued for 3 days before starting treatment with an ACE inhibitor and then, if necessary, the diuretic should be resumed; or the ACE inhibitor should be started at a low initial dose with subsequent gradual dose titration.

In congestive heart failure. Patients with congestive heart failure should be started on an ACE inhibitor at the lowest dose and, possibly, after reducing the dose of the previously prescribed potassium-sparing diuretic.

In any case, renal function (plasma creatinine) should be monitored during the first weeks of treatment with an ACE inhibitor.

Drugs that can cause hypokalemia: gluco- and mineralocorticoids (for systemic use), amphotericin B (intravenous), tetracosactide, laxatives that stimulate peristalsis increase the risk of hypokalemia (additive effect). It is necessary to monitor and, if necessary, correct the level of potassium in the blood plasma, especially with simultaneous therapy with cardiac glycosides. It is recommended to prescribe laxatives that do not stimulate peristalsis.

Digitalis preparations: Hypokalemia and/or hypomagnesemia contribute to digitalis toxicity. Monitoring of plasma potassium, magnesium and ECG is recommended and treatment should be adjusted if necessary.

Baclofen enhances the antihypertensive effect of the drug. At the beginning of therapy, it is necessary to restore the patient's water and electrolyte balance and monitor kidney function.

Combinations that require special attention

Allopurinol: Concomitant use with indapamide may lead to an increased incidence of hypersensitivity reactions to allopurinol.

Combinations that require attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene)

This combination does not exclude the possibility of hypokalemia (especially in patients with diabetes mellitus or renal insufficiency) or hyperkalemia. Monitoring of plasma potassium levels and ECG monitoring should be carried out and, if necessary, therapy should be adjusted.

Metformin: The risk of lactic acidosis is increased in the event of functional renal failure due to diuretics, especially loop diuretics. Metformin should not be prescribed if the plasma creatinine level exceeds 15 mg/l (135 μmol/l) in men and 12 mg/l (110 μmol/l) in women.

Iodine contrast media: In case of dehydration caused by diuretics, the risk of acute renal failure increases, especially when using large doses of iodinated contrast media. It is necessary to restore the water balance before administering iodinated contrast media.

Imipramine-like antidepressants, neuroleptics: increased risk of orthostatic hypotension due to antihypertensive effect (additive effect).

Calcium salts: hypercalcemia may occur due to decreased renal calcium elimination.

Cyclosporine, tacrolimus: plasma creatinine may increase without affecting circulating cyclosporine levels, even in the absence of water/sodium depletion.

Corticosteroids, tetracosactide (systemic): reduction of the antihypertensive effect of indapamide due to water and sodium retention under the influence of corticosteroids.

Application features

Special precautions

In patients with impaired liver function, the use of thiazide-like diuretics, especially in the presence of electrolyte imbalance, may cause hepatic encephalopathy, which may progress to hepatic coma. In such cases, the diuretic should be discontinued immediately.

Photosensitivity: Photosensitivity reactions have been reported in patients receiving thiazide and thiazide-like diuretics (see section 4.8). If such reactions occur, diuretic therapy should be discontinued. If diuretic therapy is re-introduced, it is recommended that exposed areas be protected from sunlight or artificial ultraviolet light.

Excipients

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

Precautions

Water and electrolyte balance

It is necessary to monitor the level of sodium in the blood plasma before starting treatment and then regularly during treatment. A decrease in the level of sodium in the blood plasma may be asymptomatic at first, therefore regular monitoring is necessary. Monitoring of sodium levels should be carried out more often in elderly patients and in patients with cirrhosis of the liver. Any diuretic can cause hyponatremia, which sometimes has serious consequences. Hyponatremia with hypovolemia can lead to dehydration and orthostatic hypotension; the concomitant loss of chloride ions can cause secondary compensatory metabolic alkalosis (the frequency and severity of this phenomenon are low).

Plasma potassium levels. A decrease in plasma potassium levels with hypokalaemia is the main risk with thiazide and thiazide-like diuretics. Hypokalaemia may cause muscle disorders. Cases of rhabdomyolysis have been reported, mostly in association with severe hypokalaemia. The risk of hypokalaemia (< 3.4 mmol/l) should be considered in certain high-risk patient groups, such as the elderly, malnourished and/or heavily medicated patients, patients with cirrhosis of the liver with oedema and ascites, patients with ischaemic heart disease and patients with heart failure. In this case, hypokalaemia increases the cardiotoxicity of cardiac glycosides and the risk of arrhythmias.

Patients with congenital or iatrogenic QT prolongation are also at risk. In such patients, hypokalemia, like bradycardia, can lead to the development of serious cardiac arrhythmias, including paroxysmal torsades de pointes, which can be fatal.

In all of the above cases, more frequent monitoring of blood potassium levels is required. The first analysis should be performed within the first week of treatment. If hypokalemia is detected, its correction is necessary.

Hypokalemia, identified in association with low serum magnesium concentrations, may be difficult to treat unless serum magnesium levels are corrected.

Magnesium in blood plasma

Thiazides and related diuretics, including indapamide, have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia (see sections 4.5 and 4.8).

Plasma calcium levels. Thiazide and thiazide-like diuretics may reduce urinary calcium excretion and lead to a slight and transient increase in plasma calcium levels. Marked hypercalcemia may be due to previously undiagnosed hyperparathyroidism. Treatment should be discontinued and parathyroid function should be monitored.

Blood glucose levels: In patients with diabetes, it is especially important to monitor blood glucose levels in the presence of hypokalemia.

Uric acid

Patients with elevated uric acid levels may have a tendency to have an increased number of gout attacks.

Renal function and diuretics. The use of the drug is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml/min). Thiazide and thiazide-like diuretics are most effective if renal function is not impaired or if the impairment is minor (plasma creatinine below 25 mg/l, i.e. 220 μmol/l in adults). In elderly patients, the plasma creatinine level should be appropriate for age, weight and sex. Hypovolemia caused by water and sodium loss due to diuretics causes a decrease in glomerular filtration rate at the beginning of treatment. This may lead to an increase in blood urea and plasma creatinine. This transient functional renal insufficiency has no consequences for individuals with normal renal function, but may worsen existing renal insufficiency.

In athletes, indapamide may cause a positive reaction during doping control.

Choroidal effusion, acute myopia (short-sightedness) and secondary angle-closure glaucoma. Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The mainstay of treatment is to discontinue the drug as soon as possible. If intraocular pressure remains uncontrolled, prompt medical or surgical treatment may be necessary. Risk factors for acute angle-closure glaucoma may include a history of allergy to sulfonamide or penicillin.

Use during pregnancy or breastfeeding

There are no or limited (less than 300) data from the use of indapamide in pregnant women. Prolonged use of a thiazide diuretic during the third trimester of pregnancy may result in a decrease in maternal blood volume and uteroplacental blood flow, which may lead to fetoplacental ischemia and fetal growth retardation. Animal studies do not indicate direct or indirect toxic effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of indapamide during pregnancy.

Breastfeeding period

There is insufficient data on the excretion of indapamide/metabolites in breast milk. Hypersensitivity to sulfonamide derivatives and hypokalemia may develop. A risk to the newborn/infants cannot be excluded. Indapamide belongs to the thiazide-like diuretics, the use of which during breastfeeding has been associated with a decrease or even suppression of lactation.

Indapamide is not recommended during breastfeeding.

Fertility

Reproductive toxicity studies showed no effect on fertility in male and female rats. No effect on human fertility is expected.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug does not impair attention, but in the event of symptoms associated with a decrease in blood pressure, especially at the beginning of treatment or in combination with another antihypertensive agent, it may affect the ability to drive a car or operate other mechanisms.

Method of administration and doses

For oral use: 1 tablet per day, preferably in the morning. The tablet should be swallowed whole, without chewing, with water. The tablet cannot be divided.

The maximum daily dose is 1 tablet.

The use of higher doses of the drug does not lead to an increase in the antihypertensive effect, but the diuretic effect increases.

Kidney failure

The drug is contraindicated in patients with severe renal insufficiency (creatinine clearance < 30 ml/min). Thiazide and thiazide-like diuretics are most effective if renal function is not impaired or if the impairment is minor.

Old age

In elderly patients, the level of creatinine in the blood plasma should correspond to age, body weight and gender. Indapamide-Astrapharm can be prescribed to elderly patients if renal function is not impaired or if the impairment is minor.

Patients with liver dysfunction

In case of severe liver dysfunction, treatment with the drug is contraindicated.

Children

The drug is not used in children due to insufficient data on safety and efficacy for this group of patients.

Overdose

First of all, manifestations of water and electrolyte disorders (hyponatremia, hypokalemia) are observed. Nausea, vomiting, arterial hypotension, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria up to anuria (caused by hypovolemia) may occur.

Treatment. First aid measures include rapid drug elimination by gastric lavage and/or administration of activated charcoal, followed by restoration of fluid and electrolyte balance in a hospital setting.

Side effects

The most commonly reported adverse reactions are hypokalemia, hypersensitivity reactions, mainly dermatological, in individuals with a predisposition to allergic and asthmatic reactions, and maculopapular rashes.

The following adverse reactions have been observed during treatment with indapamide with the following frequencies: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available information).

Description of selected adverse reactions.

In phase II and III studies comparing 1.5 and 2.5 mg indapamide, plasma potassium analysis showed a dose-dependent effect of indapamide:

Indapamide 1.5 mg: plasma potassium < 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 treatment, the mean fall in plasma potassium was 0.23 mmol/l.

Indapamide 2.5 mg: plasma potassium < 3.4 mmol/l was observed in 25% of patients and < 3.2 mmol/l in 10% of patients after 4-6 weeks of treatment. After 12 weeks of treatment, the mean fall in plasma potassium was 0.41 mmol/l.

Reporting of suspected adverse reactions. Reporting of suspected adverse reactions in the post-marketing period of a medicinal product is important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Expiration date

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

30 tablets in a blister, 1 blister in a box.

Vacation category

According to the recipe.

Producer

"ASTRAPHARM" LLC.

Address

Ukraine, 08132, Kyiv region, Kyiv-Svyatoshynskyi district, Vyshneve, Kyivska st., 6.