Indapamide retard tablets 1,5 mg, No. 30

Arterial hypertension.

Inside, 1 tablet per day, in the morning.

The tablet must be swallowed with a sufficient amount of liquid. Do not crush or chew tablets.

In case of insufficient effectiveness after 4-8 weeks, it is advisable to add a drug with a different mechanism of action that is not a diuretic to the therapy (increasing the dose is impractical, since the diuretic effect increases and the risk of side effects increases without increasing the antihypertensive effect).

When treating elderly patients, the threshold value of the concentration of creatinine in blood plasma varies depending on age, body weight and gender. Elderly patients can be prescribed Indapamide Retard only with normal renal function or with minimal impairment.

1 controlled release film-coated tablet contains:

The composition of the tablet core:
Active ingredient: indapamide - 1.5 mg.
Excipients: mannitol - 90.75 mg, hypromellose - 51.0 mg, povidone K-90 - 4.50 mg, magnesium stearate - 1.50 mg, colloidal silicon dioxide - 0.75 mg.

The composition of the tablet shell:
opadry II white (33G28435) - 5.0 mg (hypromellose - 40.0%, titanium dioxide - 25.0%, lactose monohydrate - 21.0%, macrogol - 8.0%, triacetin - 6.0% ).

Hypersensitivity to indapamide, other sulfonamide derivatives or any of the drug's components, severe renal failure (creatinine clearance (CC) less than 30 ml / min), severe liver dysfunction or hepatic encephalopathy, hypokalemia, pregnancy, breastfeeding, age up to 18 years (insufficient data on safety and effectiveness), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully

Dysfunction of the liver and kidneys, disturbances in water and electrolyte balance, use in patients with an increased QT interval on the ECG; use in debilitated patients or in patients receiving concomitant therapy with drugs that can increase the QT interval (see section 'Interaction with other drugs'); ascites, coronary heart disease, chronic heart failure, hyperparathyroidism, diabetes mellitus, hyperuricemia (especially accompanied by gout and / or urate nephrolithiasis).

Trade name of the drug:

Indapamide Retard

International non-proprietary name:

indapamide

Dosage form:

controlled release film-coated tablets

Composition

1 controlled release film-coated tablet contains:

The composition of the tablet core:
Active ingredient: indapamide - 1.5 mg.
Excipients: mannitol - 90.75 mg, hypromellose - 51.0 mg, povidone K-90 - 4.50 mg, magnesium stearate - 1.50 mg, colloidal silicon dioxide - 0.75 mg.

The composition of the tablet shell:
opadry II white (33G28435) - 5.0 mg (hypromellose - 40.0%, titanium dioxide - 25.0%, lactose monohydrate - 21.0%, macrogol - 8.0%, triacetin - 6.0% ).

Description

Tablets are round, biconvex, film-coated, white or almost white.

Pharmacotherapeutic group:

diuretic

Pharmacological properties

Pharmacodynamics
Indapamide is an antihypertensive drug. It is a sulfonamide derivative whose structure includes an indole ring. In terms of pharmacological properties, indapamide is close to thiazide diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. This increases the excretion of sodium and chlorine ions by the kidneys, as well as, to a lesser extent, potassium and magnesium ions, thereby increasing diuresis and achieving an antihypertensive effect.

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

The antihypertensive activity of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in arteriolar and total peripheral vascular resistance.

Indapamide helps to reduce left ventricular hypertrophy.

Thiazide and thiazide-like diuretics at a certain dose are characterized by the formation of a plateau of therapeutic effect, while the severity of undesirable effects continues to increase. If the desired therapeutic effect cannot be achieved, a further increase in the dose is impractical.

In the framework of short-term, medium-term and long-term studies involving patients with arterial hypertension, it was found that indapamide:

- does not affect the parameters of lipid metabolism (triglycerides, low density lipoprotein cholesterol and high density lipoprotein cholesterol);
- does not affect the metabolism of carbohydrates (even in patients with diabetes mellitus).

Pharmacokinetics
Absorption
Indapamide is rapidly and completely absorbed in the gastrointestinal tract (GIT). Food intake slightly increases the rate of absorption of indapamide, without affecting the completeness of absorption. The maximum concentration in blood plasma is reached 12 hours after ingestion of a single dose.

Distribution
About 79% of the drug binds to blood plasma proteins. Equilibrium concentration is achieved after 7 days of taking the drug. With repeated administration of the drug, its cumulation is not observed.

Metabolism and excretion
Indapamide is excreted in the form of inactive metabolites mainly by the kidneys (70% of the administered dose) and through the intestines (22%). The half-life is 14-24 hours (average 18 hours).

In renal failure, the pharmacokinetic properties of indapamide do not change.

Indications for use

Arterial hypertension.

Contraindications

Hypersensitivity to indapamide, other sulfonamide derivatives or any of the drug's components, severe renal failure (creatinine clearance (CC) less than 30 ml / min), severe liver dysfunction or hepatic encephalopathy, hypokalemia, pregnancy, breastfeeding, age up to 18 years (insufficient data on safety and effectiveness), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully

Dysfunction of the liver and kidneys, disturbances in water and electrolyte balance, use in patients with an increased QT interval on the ECG; use in debilitated patients or in patients receiving concomitant therapy with drugs that can increase the QT interval (see section 'Interaction with other drugs'); ascites, coronary heart disease, chronic heart failure, hyperparathyroidism, diabetes mellitus, hyperuricemia (especially accompanied by gout and / or urate nephrolithiasis).

Application during pregnancy and during breastfeeding

The use of the drug Indapamide Retard is contraindicated during pregnancy and during breastfeeding.
Diuretics should not be given during pregnancy. These drugs should not be used to treat physiological edema during pregnancy. Diuretic drugs can cause placental ischemia and impair fetal development.

Method of administration and dosage

Inside, 1 tablet per day, in the morning.

The tablet must be swallowed with a sufficient amount of liquid. Do not crush or chew tablets.

In case of insufficient effectiveness after 4-8 weeks, it is advisable to add a drug with a different mechanism of action that is not a diuretic to the therapy (increasing the dose is impractical, since the diuretic effect increases and the risk of side effects increases without increasing the antihypertensive effect).

When treating elderly patients, the threshold value of the concentration of creatinine in blood plasma varies depending on age, body weight and gender. Elderly patients can be prescribed Indapamide Retard only with normal renal function or with minimal impairment.

Side effect

Adverse events classified by organs and systems are listed below in order of decreasing frequency of detection: very often (> 1/10), often (from> 1/100 to <1/10), infrequently (from> 1/1000 to <1 / 100), rarely (from> 1/10 000 to <1/1 000). very rare (<1/10 000), the frequency is unknown (the frequency cannot be estimated from the available data).

On the part of the circulatory and lymphatic system: very rarely - thrombocytopenia. leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the side of the central nervous system: rarely - asthenia, headache, paresthesia, vertigo; frequency unknown - syncope.

From the side of the cardiovascular system: very rarely - arrhythmia, marked decrease in blood pressure; frequency unknown - polymorphic ventricular tachycardia of the 'pirouette' type (possibly fatal) (see the section 'Interaction with other medicinal products' and 'Special instructions').

From the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the oral mucosa; very rarely - pancreatitis.

From the urinary system: very rarely - renal failure.

From the liver and biliary tract: very rarely - liver dysfunction; the frequency is unknown - the possibility of developing hepatic encephalopathy in the case of liver failure (see sections 'Contraindications', 'Special instructions'), hepatitis.

On the part of the skin and subcutaneous fat: hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions: often - maculopapular rash; infrequently - hemorrhagic vasculitis; very rarely - angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; the frequency is unknown - in patients with an acute form of systemic lupus erythematosus, the course of the disease may worsen.

Cases of photosensitivity reactions are described (see the section 'Special instructions' and 'Interaction with other medicinal products').

Laboratory indicators: frequency is unknown - an increase in the QT interval on the ECG (see section 'Special instructions'), an increase in the concentration of uric acid and glucose in the blood: thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes mellitus; increased activity of 'hepatic' transaminases.

Overdose

Symptoms: nausea, vomiting, marked decrease in blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria. oliguria up to anuria (due to hypovolemia).
Treatment: there is no specific antidote for indapamide. Initial detoxification measures include prompt elimination of the drug by gastric lavage and administration of activated charcoal. Then, in a specialized center, the water-electrolyte balance is restored. Indapamide even in very high doses (up to 40 mg, i.e. 27 times more than the therapeutic dose) does not have a toxic effect.

Interaction with other medicinal products

Combinations not recommended
With the simultaneous use of indapamide with lithium preparations, the concentration of lithium in the blood plasma may increase due to a decrease in its excretion with signs of overdose. If necessary, diuretic drugs can be used with lithium preparations, while the concentration of lithium in the blood plasma should be monitored, and, if necessary, the dose should be adjusted.

Combinations requiring special attention and other combinations of drugs
Indapamide is not recommended to be combined with diuretics that can cause hypokalemia (bumetanide, furosemide, pyrethanide, thiazide diuretics, xypamide).

Drugs that can cause the development of polymorphic ventricular tachycardia of the 'pirouette' type:

- class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
- Class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide) and sotalol;
- some antipsychotics: phenothiazines - chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine; benzamides - amisulpride, sulpiride, sultoiride, tiapride; butyrophenones - droperidol, haloperidol;
- others: bepridil, cisapride, diphemanil, erythromycin for intravenous use, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine for intravenous use, astemizole.

Increased risk of pirouette-type polymorphic ventricular tachycardia (hypokalemia is a risk factor). It is necessary to control the content of potassium in the blood serum and, if necessary, appropriate correction before starting combination therapy. In addition, in the process of combined treatment, clinical monitoring, monitoring of the content of electrolytes in the blood and ECG should be carried out.

With simultaneous use with non-steroidal anti-inflammatory drugs of systemic action, including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of acetylsalicylic acid (more than 3 g / day), it is possible to reduce the antihypertensive effect of indapamide. There is a risk of developing acute renal failure in patients with dehydration (decreased glomerular filtration rate). Patients need to compensate for fluid loss and regularly monitor kidney function both at the beginning of therapy and during treatment.

With simultaneous use with angiotensin-converting enzyme (ACE) inhibitors against the background of sodium deficiency (especially in patients with renal artery stenosis), a sudden decrease in blood pressure and / or the development of acute renal failure is possible.

With simultaneous use with drugs that cause hypokalemia (amphotericin B for intravenous use, glucocorticosteroids, mineralocorticosteroids for systemic use, tetracosactide, laxatives that stimulate intestinal motility), the risk of hypokalemia (additive effect) increases.

With simultaneous use with baclofen, it is possible to enhance the antihypertensive effect of indapamide.

With simultaneous use with cardiac glycosides, hypokalemia may develop, predisposing to the toxic effects of cardiac glycosides.

With simultaneous use with potassium-sparing diuretics (amiloride, spironolactone, triamterene), the development of hypokalemia or hyperkalemia (especially in patients with renal failure and (or) diabetes mellitus) cannot be completely ruled out.

With simultaneous use with metformin, the risk of developing lactic acidosis induced by metformin increases. Functional renal failure associated with the use of diuretics (especially loop diuretics) may be a predisposing factor.

Against the background of diuretic-induced dehydration, there is an increased risk of acute renal failure, in particular, with the use of iodine-containing contrast agents in high doses.

Rehydration should be performed prior to administration of iodine-containing contrast media.

With simultaneous use with tricyclic antidepressants and neuroleptics, it is possible to increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

With simultaneous use with calcium salts, the risk of developing hypercalcemia increases due to a decrease in the excretion of calcium by the kidneys.

With simultaneous use with cyclosporine and tacrolimus, the risk of the formation of an increased concentration of creatinine in the blood plasma increases in the absence of any changes in the concentration of cyclosporine in the circulating blood, even without a deficiency of fluid or sodium in the body.

With simultaneous use with corticosteroids (mineral and glucocorticosteroids) and tetracosactide (for systemic administration), it is possible to reduce the antihypertensive effect of indapamide (corticosteroids cause fluid and sodium retention in the body).

special instructions

In patients with impaired liver function, therapy with Indapamide Retard can lead to the development of hepatic encephalopathy, especially with concomitant violations of water and electrolyte balance. In this case, the diuretic must be stopped immediately.

During therapy with Indapamide Retard, isolated cases of photosensitivity reactions have been reported (see the 'Side Effects' section). If signs of a photosensitivity reaction appear, the administration of Indapamide Retard should be discontinued. If it is necessary to resume therapy with Indapamide Retard, it is recommended to protect open areas of the body from exposure to direct sunlight and artificial ultraviolet radiation.

The sodium content in the blood plasma must be determined before starting therapy with Indapamide Retard, which may be accompanied by the development of hyponatremia, sometimes with very serious consequences. A decrease in plasma sodium may initially be asymptomatic, therefore regular monitoring is necessary. When treating elderly patients and patients with cirrhosis of the liver, the sodium content in the blood should be determined more often.

With arterial hypertension, when previous diuretic therapy could lead to sodium deficiency in the body, it is necessary:

- stop diuretic therapy 3 days before starting the use of an ACE inhibitor and, if necessary, resume diuretic therapy, or
- prescribe an ACE inhibitor at a low initial dose, and then gradually increase the dose of the drug.

In chronic heart failure, ACE inhibitor therapy should be started with a very low starting dose. In addition, at the beginning of therapy with an ACE inhibitor, it may be necessary to reduce the dose of a diuretic that can cause hypokalemia.

In all cases, during the first weeks after starting therapy with an ACE inhibitor, kidney function (plasma creatinine) should be monitored. Therapy with Indapamide Retard is characterized by a high risk of a decrease in the potassium content in the blood with the development of hypokalemia. When treating patients at risk (elderly patients, debilitated patients, patients receiving multicomponent drug therapy, patients with cirrhosis of the liver with peripheral edema and ascites, patients with ischemic heart disease, patients with heart failure), it is necessary to prevent hypokalemia. In such patients, hypokalemia increases the cardiotoxicity of cardiac glycosides, and also increases the risk of developing cardiac arrhythmias.

Patients with an extended QT interval (hereditary or iatrogenic pathology) are also at risk. Thus, hypokalemia, as well as bradycardia, acts as a factor predisposing to the development of serious cardiac arrhythmias, in particular, polymorphic ventricular tachycardia of the 'pirouette' type. When treating patients at risk, regular monitoring of the potassium content in the blood plasma is necessary. The initial measurement of the potassium content should be performed within the first week after the initiation of therapy with Indapamide Retard; detection of hypokalemia requires appropriate correction.

Particular care should be taken with concomitant therapy with cardiac glycosides.

ѕрепарат »ндапамид –етард уменьшает экскрецию кальци¤ почками, что приводит к незначительному и временному увеличению содержани¤ кальци¤ в плазме крови. ¬ыраженна¤ гиперкальциеми¤ может наблюдатьс¤ у пациентов с ранее не диагностированным гиперпаратиреозом. ѕеред началом исследовани¤ функции паращитовидных желез терапию препаратом »ндапамид –етард следует прекратить.

ѕри лечении пациентов с сахарным диабетом, особенно при наличии гипокалиемии, необходимо контролировать концентрацию глюкозы в крови.

ѕри лечении пациентов с гиперурикемией возрастает веро¤тность обострени¤ течени¤ подагры.

ѕрепарат »ндапамид –етард достаточно эффективен при нормальной функции почек или при ее минимальных нарушени¤х (концентраци¤ креатинина в плазме крови ниже 25 мг/л, то есть 220 мкмоль/л дл¤ взрослого человека). ѕри лечении пожилых пациентов пороговое значение концентрации креатинина в плазме крови варьирует в зависимости от возраста, массы тела и половой принадлежности. vиповолеми¤. вторична¤ по отношению к таким эффектам диуретика, как потер¤ жидкости и натри¤, в начале лечени¤ приводит к снижению скорости клубочковой фильтрации. ¬ результате возрастает концентраци¤ мочевины и креатинина в плазме крови. ” пациентов с нормальной функцией почек така¤ преход¤ща¤ функциональна¤ почечна¤ недостаточность проходит без последствий.

?л¤ спортсменов особое значение имеет тот факт, что действующее вещество препарата »ндапамид –етард может послужить причиной положительного результата теста на допинг.

¬ли¤ние на способность к управлению транспортными средствами и другими механизмами

?ействие веществ, вход¤щих в состав препарата, не приводит к нарушению психомоторных реакций.
Ќеобходимо соблюдать осторожность при управлении транспортными средствами (особенно в начале терапии или при добавлении к проводимой терапии других гипотензивных средств).

‘орма выпуска

Controlled-release film-coated tablets, 1.5 mg.
On 10 or 15 tablets in a blister strip packaging from PVC film and printed aluminum foil varnished.
2, 3, 4, 5, 6, 7, 8 or 9 blisters of 10 tablets or 2, 4 or 6 blisters of 15 tablets, together with instructions for medical use, are placed in a box made of cardboard.

Shelf life

3 years.
Do not use after the expiration date.

Storage conditions

In a dark place at a temperature not exceeding 25 ? C.
Keep out of the reach of children.

Vacation conditions

Dispensed by prescription.