Instructions Indopres film-coated tablets 2.5 mg blister No. 30
Composition
active ingredient: indapamide;
1 tablet contains 2.5 mg of indapamide, calculated as 100% anhydrous substance;
excipients: lactose monohydrate, sodium lauryl sulfate, calcium stearate; film-forming coating: hydroxypropyl cellulose, lactose monohydrate, titanium dioxide (E 171), polyethylene glycol 3000, triacetin.
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white in color, with a biconvex surface. Two layers of different structure are visible on the cross section.
Pharmacotherapeutic group
Drugs affecting the cardiovascular system. Non-thiazide diuretics with moderately pronounced activity. Sulfonamides, simple. Indapamide. ATC code S0ZV 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 urinary excretion of sodium and chloride and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing diuresis.
The antihypertensive effect of indapamide is manifested at doses at which the diuretic effect is insignificant. Moreover, its antihypertensive effect is maintained even in patients with arterial hypertension who are on hemodialysis.
Indapamide acts at the vascular level by:
decreased contractility 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.
As shown in studies of various durations (short, medium and long) in patients with arterial hypertension, indapamide does not affect:
on lipid metabolism (triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol);
on carbohydrate metabolism, even in patients with diabetes and hypertension.
When the recommended dose is exceeded, the therapeutic effect of thiazides and thiazide-like diuretics is not increased, while the risk 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 plasma concentration (Tmax) after taking a dose of 2.5 mg is reached after approximately 1-2 hours.
Distribution
Plasma protein binding is above 75%.
The half-life is 14 to 24 hours (average 18 hours).
With regular administration of indapamide, the steady-state plasma concentration (plateau) increases compared to the plasma concentration of indapamide after a single dose. This plasma concentration level remains stable for a long time without cumulation.
Breeding
Renal clearance accounts for 60-80% of total clearance.
Indapamide is excreted mainly in the form of metabolites, the proportion of the drug excreted by the kidneys in unchanged form is 5%.
Patients with renal insufficiency: pharmacokinetic parameters are not changed.
Indication
Essential hypertension.
Contraindication
Hypersensitivity to indapamide, to any component of the drug, other sulfonamides or their derivatives;
hepatic encephalopathy, severe liver dysfunction;
severe renal failure;
hypokalemia.
Interaction with other medicinal products and other types of interactions
The drug can be used both as monotherapy and in combination with other antihypertensive drugs.
Not recommended combinations.
Lithium: Increased plasma lithium levels (due to decreased excretion) and symptoms of overdose. If such a combination is necessary, lithium plasma levels should be monitored and the dose adjusted.
Combinations that require caution.
Drugs that can cause torsade de pointes:
Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
Class III antiarrhythmic drugs (amiodarone, bretylium, sotalol, dofetilide, ibutilide);
some antipsychotic drugs:
phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine);
benzamides (amisulpride, sulpiride, sultopride, tiapride);
butyrophenones (droperidol, haloperidol);
pimozide, sertindole, zotepine;
drugs of other groups: astemizole, mizolastine, terfenadine, bepridil, cisapride, diphemanil, atomoxetine, arsenic compounds, erythromycin for intravenous administration, clarithromycin, halofantrine, pentamidine, sparfloxacin, moxifloxacin, vincamine for intravenous administration.
Drugs that do not cause torsade de pointes-type arrhythmias should be used in hypokalemia.
Systemic nonsteroidal anti-inflammatory drugs, including COX-2 selective inhibitors, high doses of salicylates (≥ 3 g/day): possible reduction of the hypotensive effect of indapamide. In dehydrated patients, acute renal failure may occur (glomerular filtration is reduced). Renal function should be monitored before/during treatment and water imbalance should be compensated.
ACE inhibitors, angiotensin-II receptor antagonists: risk of sudden arterial hypotension and/or acute renal failure at the beginning of treatment with ACE inhibitors or angiotensin-II receptor antagonists with pre-existing hyponatremia (especially in patients with renal artery stenosis).
In arterial hypertension, when previous diuretic treatment has caused the development of hyponatremia, it is recommended:
3 days before starting treatment with ACE inhibitors/angiotensin-II receptor antagonists, discontinue the use of diuretics (later, if necessary, resume their use);
or start treatment with low doses of ACE inhibitors/angiotensin-II receptor antagonists with gradual dose increases.
In congestive heart failure, treatment should be initiated with very low doses of ACE inhibitors/angiotensin-II receptor antagonists while reducing the dose of the concomitant potassium-sparing diuretic.
In all cases, monitoring of renal function (plasma creatinine level) is mandatory during the first weeks of treatment with ACE inhibitors/angiotensin-II receptor antagonists.
Alpha-blockers: increased hypotensive effect; increased risk of first-dose hypotension with postsynaptic alpha-blockers such as prazosin.
Diuretics that can cause hypokalemia (e.g. bumetanide, furosemide, piretanide, thiazides, xipamide, acetazolamide): increased risk of hypokalemia. Plasma potassium levels should be carefully monitored and corrected if necessary.
Other drugs that can cause hypokalemia (amphotericin B (intravenously), high doses of beta2-sympathomimetics, systemic gluco- and mineralocorticoids, tetracosactide, theophylline, laxatives that stimulate peristalsis, reboxetine): the risk of hypokalemia increases (additive effect). The level of potassium in the blood plasma should be monitored, which is especially important during concomitant therapy with cardiac glycosides, and adjusted if necessary. Use laxatives that do not stimulate intestinal peristalsis.
Baclofen: increased antihypertensive effect. It is necessary to rehydrate the patient and monitor renal function at the beginning of treatment.
Cardiac glycosides (digitalis preparations): there is a risk of increased toxicity of cardiac glycosides (digitalis) (due to possible diuretic-induced hypokalemia and/or hypomagnesemia). Monitoring of plasma potassium and magnesium levels and ECG monitoring should be performed, and treatment should be reviewed if necessary.
Flecainide: Diuretic-induced hypokalemia enhances the cardiotoxicity of flecainide.
Lidocaine, mexiletine: Diuretic-induced hypokalemia counteracts the effects of lidocaine and mexiletine.
Combinations that require attention.
Potassium-sparing diuretics (amiloride, spironolactone, triamterene): although this combination may be beneficial in some patients, there is a risk of hypokalemia (especially in patients with diabetes mellitus, renal failure) or hyperkalemia. Plasma potassium levels, ECG should be monitored and treatment should be reviewed if necessary.
Metformin: Increased risk of metformin-induced lactic acidosis due to functional renal failure associated with diuretics, especially loop diuretics. Do not use metformin if plasma creatinine levels exceed 15 mg/L (135 mmol/L) in men and 12 mg/L (110 mmol/L) in women.
Iodinated contrast media: In case of dehydration caused by diuretic administration, the risk of acute renal failure increases, especially when high doses of iodinated contrast media are used. Rehydration should be performed before their administration.
Calcium salts, vitamin D, toremifene: increased risk of hypercalcemia as a result of reduced urinary calcium elimination.
Oxcarbazepine, carbamazepine: increased risk of hyponatremia when used with indapamide.
Imipramine-like antidepressants, neuroleptics, anxiolytics and hypnotics, MAO inhibitors, alprostadil, aldesleukin, levodopa, general anesthetics: increased hypotensive effect of indapamide, increased risk of orthostatic hypotension.
Other antihypertensive drugs (including beta-blockers, calcium channel blockers, nitrates, vasodilators, methyldopa, moxonidine, clonidine): increased hypotensive effect and increased risk of orthostatic hypotension (additive effect).
Cyclosporines, tacrolimus: risk of increased plasma creatinine levels without any changes in circulating cyclosporine levels, even in the absence of water and sodium depletion.
Corticosteroids, tetracosactide (systemic): reduction of the hypotensive effect of indapamide due to water and sodium retention under the influence of glucocorticosteroids.
Estrogens: possible reduction in the antihypertensive effect of the drug due to fluid retention in the body.
Indirect anticoagulants (coumarin or indandione derivatives): decreased effect due to increased concentration of blood clotting factors due to decreased circulating blood volume and increased production of them by the liver (dose adjustment is possible).
Non-depolarizing muscle relaxants: increased blockade of neuromuscular transmission.
Allopurinol: Concomitant treatment with indapamide may increase the frequency of hypersensitivity reactions to allopurinol.
Gives a positive reaction during doping control.
Application features
Patients with impaired liver function.
In cases of impaired liver function, thiazide-like diuretics may cause hepatic encephalopathy, especially in the presence of electrolyte imbalance. In this case, or if symptoms of worsening renal failure occur, the drug should be discontinued immediately.
Photosensitization.
Photosensitivity reactions have been reported with thiazide and thiazide-like diuretics. If photosensitivity reactions occur during treatment, it is recommended to immediately discontinue the drug. If the need for the drug persists, it is recommended to protect exposed areas of the body from direct sunlight and artificial ultraviolet radiation.
Choroidal effusion, acute myopia, and secondary angle-closure glaucoma.
Sulfonamide- or sulfonamide-derived drugs, including indapamide, may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, acute 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 irreversible vision loss. The first line of treatment is to discontinue indapamide as soon as possible. If intraocular pressure remains uncontrolled, urgent medical or surgical treatment should be considered. Risk factors for the development of acute angle-closure glaucoma may include a history of allergy to sulfonamides or penicillins.
Excipients.
The drug contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.
The drug contains sodium lauryl sulfate, which should be taken into account by patients on a controlled sodium diet.
Water and electrolyte balance.
Blood sodium. Before starting treatment with Indopress, it is necessary to determine the level of sodium in the blood plasma, and then check it at regular intervals. Treatment with any diuretic can lead to hyponatremia, sometimes with very serious consequences. A decrease in the level of sodium in the blood plasma may initially be asymptomatic, so regular monitoring in this context is extremely important and should be carried out more often in elderly patients and in patients with cirrhosis of the liver.
Hyponatremia with hypovolemia can cause dehydration and orthostatic hypotension. The concomitant loss of chloride ions can lead to secondary compensatory metabolic alkalosis: the frequency and extent of this effect are low.
Cases of serious hyponatremia in combination with hypokalemia have been reported with treatment at recommended doses, more often in elderly women.
Blood potassium. A decrease in plasma potassium with the development of hypokalemia is the main risk in the treatment of thiazide and thiazide-like diuretics. Hypokalemia (< 3.4 mmol/l) should be prevented, especially in patients from high-risk groups (elderly patients, patients taking many medications, patients with unbalanced/insufficient nutrition, patients with hyperaldosteronism, patients with cirrhosis of the liver with edema and ascites, patients with ischemic heart disease, with heart failure). In such cases, hypokalemia increases the cardiotoxicity of cardiac glycosides and the risk of arrhythmias. Individuals with a prolonged QT interval (congenital or iatrogenic) are also at risk.
Hypokalemia, like bradycardia, can contribute to the development of severe arrhythmias, in particular paroxysmal ventricular tachycardia of the torsade de pointes type, sometimes with fatal outcome.
In all of the above cases, it is necessary to monitor the blood potassium level more frequently. The first measurements should be made during the first week of treatment. If hypokalemia is detected, it should be corrected. Hypokalemia detected in connection with low serum magnesium concentration may be refractory to treatment if serum magnesium level is not corrected.
Blood calcium. Thiazide and thiazide-like diuretics may reduce urinary calcium excretion and, as a result, cause a slight transient increase in its level in the blood plasma. Marked hypercalcemia is possible in the presence of previously undiagnosed hyperparathyroidism. Indapamide may reduce the plasma level of parathyroid hormone. Treatment with indapamide should be discontinued before testing the function of the parathyroid glands.
Since blood glucose levels may increase during treatment with indapamide, monitoring of this indicator is important for patients with diabetes, especially in the presence of hypokalemia.
Due to a possible increase in the level of uric acid in the blood during treatment, patients with hyperuricemia may experience an increase in the number of gout attacks.
Renal function and diuretics. Thiazide and thiazide-like diuretics are fully effective only in normal or minimally impaired renal function (plasma creatinine level below 25 mg/L (220 mmol/L) in adults). It should be noted that in elderly patients this indicator depends on age, body weight, and sex.
Hypovolemia due to water and sodium loss caused by diuretics leads to a decrease in glomerular filtration rate, which may cause an increase in blood urea and creatinine levels. This transient functional renal failure is of no consequence in patients with normal renal function, but may worsen pre-existing renal failure. It should be used with caution in patients with nephrotic syndrome.
When using indapamide, a positive result is possible during doping control in athletes.
Use during pregnancy or breastfeeding
Pregnancy.
There are no or limited data from the use of indapamide in pregnant women (less than 300 cases). Prolonged use of diuretics during the third trimester of pregnancy may reduce maternal plasma volume and uteroplacental blood flow, which may cause fetoplacental ischemia with a risk of 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.
Breast-feeding.
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 contraindicated 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 psychomotor functions, but in the event of adverse reactions (see section "Adverse reactions"), including symptoms associated with a sudden decrease in blood pressure, especially at the beginning of treatment or in combination with other antihypertensive agents, it may affect the reaction rate when driving vehicles or other mechanisms.
Method of administration and doses
For oral use. Indopres is prescribed at a dose of 2.5 mg (1 tablet) once a day (in the morning), before meals.
The effect of the drug is manifested gradually. Increasing the dose of the drug is inappropriate, since at higher doses the antihypertensive effect does not increase significantly, but the diuretic effect increases. In case of insufficient effect, combination therapy with other antihypertensive agents is recommended. Combination therapy with diuretics, which can cause hypokalemia, is not recommended.
The duration of treatment is determined by the course of the disease and the effectiveness of therapy.
There is no evidence of rebound hypertension after discontinuation of indapamide treatment.
Renal impairment. The use of the drug is contraindicated in patients with severe renal impairment (creatinine clearance < 30 ml/min). Thiazide and thiazide-like diuretics are most effective in normal or minimally impaired renal function (see sections "Special warnings and precautions for use" and "Contraindications").
Elderly patients. In elderly patients, plasma creatinine levels should be determined taking into account age, body weight and gender. Indopres should be prescribed to patients in this age group with normal or minimally impaired renal function (see section "Special instructions").
Hepatic impairment. In case of severe hepatic impairment, treatment with the drug is contraindicated (see sections "Special instructions for use" and "Contraindications").
Children
The drug is not recommended for use in children due to insufficient data on the safety and efficacy of indapamide in this group of patients.
Overdose
Indopress may cause a slight toxic effect when used in doses exceeding 40 mg. First of all, signs of overdose are in the form of water and electrolyte disorders (hyponatremia, hypokalemia). Clinical manifestations: nausea, vomiting, dyspepsia, arterial hypotension, muscle weakness, convulsions, respiratory depression, dizziness, drowsiness, confusion, polyuria or oliguria (anuria due to hypovolemia is possible).
Treatment. It is necessary to wash the stomach, use activated charcoal and restore water and electrolyte balance in a hospital setting. Symptomatic therapy.
Side effects
Treatment with Indopres is usually well tolerated. Most clinical and laboratory adverse events are dose-dependent. The risk of their development can be significantly reduced by using the minimum effective dose.
The most frequently reported adverse reactions were hypokalemia, hypersensitivity reactions, mainly dermatological, in individuals with a predisposition to allergic and asthmatic reactions, and maculopapular rashes.
Metabolic disorders:
decrease in potassium levels and the occurrence of hypokalemia, which may be particularly serious in patients from high-risk groups (see section "Special instructions for use");
hypercalcemia;
hyponatremia, which can lead to hypovolemia and dehydration of the body with possible development of orthostatic hypotension. The concomitant loss of chloride ions can cause compensatory metabolic alkalosis: the scale and degree of this effect are insignificant. Warning signs of electrolyte disorders may be a feeling of increased thirst, confusion, muscle cramps, muscle weakness and heart rhythm disturbances;
hypochloremia;
hypomagnesemia;
Hyperuricemia and hyperglycemia during treatment; a slight decrease in glucose tolerance is possible in patients with diabetes mellitus. The appropriateness of using this drug in patients with gout and diabetes mellitus should be carefully considered.
Hematological disorders: thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia, aplastic anemia.
Neurological disorders: dizziness (vertigo), feeling of fatigue, paresthesia, headache, fainting (syncope).
Cardiovascular disorders: prolongation of the QT interval on the ECG, arrhythmias, including potentially fatal ones of the torsade de pointes type, arterial hypotension.
Gastrointestinal disorders: vomiting, nausea, constipation, dry mouth, pancreatitis.
Hepatobiliary disorders: liver function abnormalities, including increased hepatic transaminase activity, hepatitis. In patients with pre-existing liver failure, hepatic encephalopathy may develop.
Urinary system disorders: renal failure. Abnormal renal function tests (increased blood urea, plasma creatinine) associated with hypovolemia have been reported.
Immune system, skin and subcutaneous tissue disorders: hypersensitivity reactions (mostly in the form of dermatological reactions, especially in patients prone to allergic and asthmatic reactions) - maculopapular rashes, purpura, angioedema and/or urticaria, pruritus, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Photosensitivity reactions and exacerbation of existing systemic lupus erythematosus are possible.
Organs of vision: choroidal effusion, reversible acute myopia, secondary acute angle-closure glaucoma, blurred vision, visual impairment.
Reproductive system and breast: erectile dysfunction.
Description of selected adverse reactions
In phase II and III studies comparing 1.5 mg and 2.5 mg indapamide, analysis of plasma potassium levels showed a dose-dependent effect of indapamide:
Indapamide 1.5 mg: plasma potassium levels < 3.4 mmol/l were 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 decrease in plasma potassium levels was 0.23 mmol/l.
Indapamide 2.5 mg: plasma potassium levels < 3.4 mmol/l were 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.
Expiration date
4 years.
Do not use the drug after the expiration date indicated on the package!
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
Public Joint Stock Company "Research and Production Center "Borshchagov Chemical and Pharmaceutical Plant".
Address
Ukraine, 03134, Kyiv, Myru St., 17.
