Indapamide retard - instructions for use, dose, side effects, contraindications

Composition of the tablet shell: Opapray II white (33G28435) 5.0 mg (hypromellose 40.0%, titanium dioxide 25.0%, lactose monohydrate 21.0%, macrogol 8.0%, triacetin - 6,0%).

Description:

The tablets are round, biconvex, covered with a film coat of white or almost white color.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide is an antihypertensive drug. It is a sulfonamide derivative whose structure includes an indole ring. By pharmacological properties indapamide is close to thiazide diuretics that 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, and, to a lesser extent, of potassium and magnesium ions, thereby strengthening diuresis and achieving an antihypertensive effect.

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

Antihypertensive activity of indapamide is associated with improving the elastic properties of large arteries, reducing arteriolar and general peripheral vascular resistance.

Indapamide reduces the hypertrophy of the left ventricle of the heart.

Thiazide and thiazide-like diuretics at a certain dose are characterized by the formation of a plateau of therapeutic effect, while the severity of unwanted effects continues to increase.

If the desired therapeutic effect is not achieved, a further increase in dose is not advisable.

Within the short, medium and long-term studies involving patients with hypertension, it was found that indapamid:

- does not affect the 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:

Suction

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

Distribution

About 79% of the drug binds to blood plasma proteins. The equilibrium concentration is achieved after 7 days of taking the drug. When you re-take the drug is not observed its cumulation.

Metabolism and excretion

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

When renal failure the pharmacokinetic properties of indapamide do not change.

Indications:

Arterial hypertension.

Contraindications:

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

Carefully:

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

Pregnancy and lactation:

The use of Indapamid Retard is contraindicated in pregnancy and during breastfeeding.

During pregnancy, do not prescribe diuretic drugs. Do not use these drugs to treat physiological swelling in pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development.

Dosing and Administration:

Inside, 1 tablet a day, in the morning.

The tablet should be swallowed with a sufficient amount of liquid. Tablets can not be broken or chewed.

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

When treating patients old age the threshold value of the concentration of creatinine in the blood plasma varies depending on age, body weight and gender.

Older patients with Indapamide Retard can be prescribed only with normal kidney function or with minimal disturbances.

Side effects:

Undesirable phenomena classified by organs and systems are listed below in order of decreasing detection frequency: very often (≥ 1/10), often (from ≥ 1/100 up to < 1/10), infrequently (from ≥ 1/1000 up to < 1/100), rarely (from ≥ 1/10 000 up to < 1/1 000), very rarely (< 1/10 000), the frequency is unknown (the frequency can not be calculated from the available data).

From the side of the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

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

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 section "Interaction with other drugs" 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 - kidney failure.

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

From the skin and subcutaneous fat: reactions of hypersensitivity, 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; frequency is unknown - in patients with acute form of systemic lupus erythematosus, the course of the disease may worsen.

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

Laboratory indicators: frequency unknown - increase QT interval for The ECG (see Fig. Special instructions "), increased 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 "liver" 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. To the initial measures of detoxification is the rapid removal of the drug by washing the stomach and the appointment of activated charcoal. Then, under the conditions of a specialized center, the water-electrolyte balance is restored. Indapamide even in very high doses (up to 40 mg, that is, 27 times more than the therapeutic dose) does not have a toxic effect.

Interaction:

Unrecommended combinations

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 an overdose.

If necessary, diuretic drugs can be used with lithium preparations, while monitoring the concentration of lithium in the blood plasma, and if necessary adjust the dose.

Combinations, requiring special attention, and other combinations of drugs

Indapamide should not be combined with diuretics that can cause hypokalemia (bumetanide, furosemide, piretanide, thiazide diuretics, xypamide).

Preparations can cause the development of polymorphic ventricular tachycardia such as "pirouette":

- antiarrhythmic drugs IA class (quinidine, hydroquinidine, disopyramide);

- antiarrhythmic drugs of III class (amiodarone, dofetilide, ibutilide) and sotalol;

- some neuroleptics: phenothiazines - chlorpromazine, cyamemazine, levomepromazine. thioridazine, trifluoperazine; benzamides - amisulpride, sulpiride, sultopride, tiaprid: butyrophenones - droperidol, haloperidol;

- other: bepridil, cisapride, difemanyl, erythromycin for intravenous use, halofantrine, misolastine, pentamidine. sparfloxacin, moxifloxacin. wincamine for intravenous use, astemizole.

An increased risk of polymorphic ventricular tachycardia such as "pirouette" (a risk factor is hypokalemia).

It is necessary to monitor the potassium content in the blood serum and, if necessary, appropriate correction before the beginning of the combination therapy.In addition, during the combined treatment should be carried out clinical monitoring, monitoring the content of electrolytes in the blood and ECG.

With simultaneous use of systemic action with non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase-2 (COX-2), with high doses of acetylsalicylic acid (more than 3 g / day), the antihypertensive effect of indapamide may decrease.

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.

When applied simultaneously with angiotensin-converting enzyme (ACE) inhibitors against a 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 are possible.

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

With simultaneous use with baclofen, an increase in the antihypertensive effect of indapamide is possible.

With simultaneous use with cardiac glycosides, hypokalemia can be developed, predisposing to the realization of toxic effects of cardiac glycosides.

When used simultaneously with potassium-sparing diuretics (amiloride, spironolactone, triamterene) the development of hypokalemia or hyperkalemia (especially in patients with renal insufficiency and (or) diabetes) is completely impossible to exclude.

With simultaneous use with metformin, the risk of developing lactic acidosis, induced by metformin, increases.

A predisposing factor may be functional renal failure associated with the use of diuretics (especially "loop" diuretics).

Against the background of dehydration caused by diuretics, there is an increased risk of acute renal failure, in particular, when using iodine-containing contrast agents in high doses.

Before the appointment of iodine-containing contrast agents, rehydration should be performed.

When used simultaneously 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 application with calcium salts, the risk of hypercalcemia increases in connection with a decrease in the excretion of calcium by the kidneys.

With simultaneous use with cyclosporine and tacrolimus, the risk 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.

When used simultaneously with corticosteroids (mineral and glucocorticosteroids) and tetracosactide (for systemic administration), the antihypertensive effect of indapamide may decrease (corticosteroids cause fluid and sodium retention in the body).

Special instructions:

In patients with impaired liver function, therapy with Indapamide Retard may lead to the development of hepatic encephalopathy,especially with accompanying violations of the water-electrolyte balance. In this case, the diuretic should be discontinued immediately.

In the treatment with the drug Indapamide Retard, individual cases of the development of photosensitivity reactions were recorded (see section "Side effect"). When signs of photosensitivity reaction appear, taking Indapamid Retard should be stopped. If it is necessary to resume therapy with the drug Indapamide Retard, it is recommended to protect the exposed areas of the body from direct sunlight and artificial ultraviolet radiation.

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

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

- stop diuretic therapy 3 days before the start of the ACE inhibitor and, if necessary, resume therapy with a diuretic or

- prescribe an ACE inhibitor at a low initial dose, and then gradually increase the dose of the drug.

With chronic heart failure it is necessary to start therapy with an ACE inhibitor with a very low initial dose. In addition, early treatment with an ACE inhibitor may require a reduction in the dose of a diuretic that can cause hypokalemia.

In all cases, during the first weeks after initiation of therapy with an ACE inhibitor, renal function (blood plasma creatinine) should be monitored.

Indapamide Retard therapy is characterized by a high risk of reducing the potassium content in the blood with the development of hypokalemia.

In the treatment of patients at risk (elderly patients, weakened patients, patients receiving multicomponent drug therapy, patients with cirrhosis with peripheral edema and ascites, patients with coronary heart disease, patients with heart failure) it is necessary to prevent hypokalemia.

In such patients, hypokalemia contributes to the cardiotoxicity of cardiac glycosides, and also increases the risk of heart rhythm disturbances.

Patients with an elongated interval QT (hereditary or iatrogenic pathology) also fall into the category of risk. Thus, hypokalemia, as well as bradycardia, acts as a factor predisposing to the development of serious cardiac rhythm disturbances, in particular polymorphic ventricular pirouette tachycardia.

In the treatment of 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 initiation of therapy with Indapamide Retard, detection of hypokalemia requires appropriate correction. Particular care should be taken with concomitant therapy with glycosides.

The drug Indapamide Retard reduces the excretion of calcium by the kidneys, which leads to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia can be observed in patients with previously unidentified hyperparathyroidism.Before starting the parathyroid gland function, therapy with Indapamid Retard should be stopped.

In the treatment of patients with diabetes, especially in the presence of hypokalemia, it is necessary to monitor the concentration of glucose in the blood.

In the treatment of patients with hyperuricemia, the likelihood of exacerbation of the gout current increases.

The drug Indapamid Retard is effective enough with normal kidney function or with its minimal disorders (creatinine concentration in the blood plasma is below 25 mg / l, that is, 220 μmol / l for an adult).

In the treatment of elderly patients, the threshold value of creatinine concentration in the blood plasma varies depending on age, body weight and gender. Hypovolemia secondary to such effects as a diuretic, such as loss of fluid and sodium, at the beginning of treatment leads to a decrease in the glomerular filtration rate. As a result, the concentration of urea and creatinine in the blood plasma increases. In patients with normal renal function, such transient functional renal failure passes without consequences.

For athletes,that the active substance of the drug Indapamide Retard can cause a positive test result for doping.

Effect on the ability to drive transp. cf. and fur:

The action of substances that make up the drug does not lead to a disturbance of psychomotor reactions.

Care must be taken when driving vehicles (especially at the beginning of therapy or when adding other antihypertensive drugs to the therapy).

Form release / dosage:

Controlled-release tablets coated with a film coat, 1.5 mg.

Packaging:

For 10 or 15 tablets in a contour mesh box made of PVC film and foil of aluminum printed lacquered.

By 2, 3, 4, 5, 6, 7, 8 or 9 outline cell packs of 10 tablets or 2, 4 or 6 contour cell packs of 15 tablets together with instructions for medical use are placed in a pack of cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003939

Date of registration:07.11.2016

Expiration Date:07.11.2021

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Representation: & nbspIZVARIN PHARMA LLC IZVARIN PHARMA LLC Russia

Information update date: & nbsp02.11.2017

Illustrated instructions

Instructions

Indapamide retard (Indapamide retard)