INDAPAMID LONG RICHTER - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate - 118,50 mg, silicon dioxide colloid - 1,00 mg, cellulose microcrystalline - 12,00 mg, hypromellose - 66,00 mg, magnesium stearate - 1,00 mg.

Tablet casing: Opapray II white 85F18422 - 6.00 mg (polyvinyl alcohol - 2.40 mg, titanium dioxide (E171) - 1.50 mg, macrogol-3350 - 1.21 mg, talc - 0.89 mg).

Description:

Round, biconvex tablets, covered with a film shell of white or almost white color. The color of the tablet on the break is white or almost white.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide, an antihypertensive drug, refers to derivatives of a sulfonamide with an indole ring and is close to thiazide diuretics by pharmacological properties, which inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. This increases the release of kidney ions of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, which is accompanied by an increase in diuresis and antihypertensive effect. In the clinical studies of II and III phases with the use of 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 hypertrophy of the left ventricle.

Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the incidence of side effects continues to increase with a further increase in the dose of the drug.Therefore, do not increase the dose of the drug, if the recommended dose does not achieve a therapeutic effect.

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

- does not affect the lipid metabolism, including the concentration of triglycerides, cholesterol, low density lipoprotein (LDL), and high-density lipoprotein (HDL);

- does not affect the parameters of carbohydrate metabolism, including in patients with diabetes mellitus.

Pharmacokinetics:

The active substance of the drug INDAPAMID LONG RICHTER is located in a special carrier matrix that provides a gradual controlled release of indapamide in the gastrointestinal tract.

Suction

The released indapamide quickly and completely absorbed in the gastrointestinal tract. The intake of food slightly increases the time of absorption of indapamide, without affecting the completeness of absorption.

The maximum concentration of indapamide in blood plasma (C_mOh) is achieved 12 hours after ingestion of a single dose.With repeated administration of fluctuations in the concentration of indapamide in blood plasma in the interval between doses of the drug are smoothed. Individual variability of indapamide absorption indices is observed.

Distribution

About 79% of indapamide binds to plasma proteins. The half-life (T_1/2) of indapamide is 14-24 hours (on average, 18 hours).

The equilibrium concentration (C_ss) is achieved after 7 days of taking the drug. With repeated administration of the drug cumulation of indapamide is not observed.

Metabolism

Indapamide is excreted as inactive metabolites, mainly by the kidneys (70% of the dose taken) and through the intestine (22%).

Pharmacokinetics in selected patient groups

Patients with renal insufficiency

The pharmacokinetics of indapamide in patients with renal insufficiency does not change.

Indications:

Arterial hypertension.

Contraindications:

- Hypersensitivity to indapamide, other derivatives of sulfonamide or to any of the excipients;

- severe renal failure (creatinine clearance <30 mL / min);

- hepatic encephalopathy or severe liver dysfunction;

- hypokalemia;

- pregnancy and the period of breastfeeding;

- children under 18 years of age (data on effectiveness and safety is not enough);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:

Dysfunctions of the liver and kidneys, abnormal water-electrolyte balance, weakened patients or patients receiving combined therapy with antiarrhythmic drugs or drugs that can increase the interval QT on an electrocardiogram (ECG) (see "Interaction with other drugs"), diabetes mellitus, hyperuricemia (especially accompanied by gout and / or urate nephrolithiasis), patients with an elongated QT-interval on the ECG, hyperparathyroidism, ascites, ischemic heart disease, chronic heart failure.

Pregnancy and lactation:

Pregnancy

During pregnancy, do not prescribe diuretic drugs. Do not use these drugs to treat physiological swelling during pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development.The use of the drug INDAPAMID LONG RICHTER is contraindicated in pregnancy.

Breastfeeding period

The use of the drug INDAPAMID LONG RICHTER is contraindicated in the period of breastfeeding (indapamide penetrates into breast milk).

Dosing and Administration:

Inside 1 tablet per day, preferably in the morning; Tablets should be swallowed whole without chewing, drinking water.

In the treatment of patients with hypertension, increasing the dose of the drug does not increase the antihypertensive effect, but enhances the diuretic effect, so if after 4-8 weeks of treatment the desired therapeutic effect is not achieved, the dose of the drug should not be increased (the risk of side effects increases) add to the treatment of another antihypertensive drug that is not a diuretic.

Elderly patients

In elderly patients should monitor the concentration of creatinine in blood plasma, taking into account age, body weight and sex.

INDAPAMID LONG RICHTER at a dose of 1.5 mg / day (1 tablet) can be administered to elderly patients with normal or slightly impaired renal function (see section "Contraindications").

Side effects:

Most adverse reactions (laboratory and clinical indicators) are dose-dependent.

The incidence of adverse reactions that may be caused by thiazide-like diuretics, including indapamide, is given in the form of the following gradation: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1,000, <1/100); rarely (≥1 / 10,000, <1/1000); very rarely (<1/10 000); unspecified frequency (can not be estimated based on available data).

Violations of the blood and lymphatic system

Very rarely: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Disturbances from the nervous system

Rarely: asthenia, headache, paresthesia, vertigo;

Unspecified frequency: fainting.

Violations from the heart and blood vessels

Very rarely: arrhythmia, marked decrease in blood pressure;

Unspecified frequency: polymorphic ventricular tachycardia of the "pirouette" type (possibly fatal) (see "Interactions with other drugs" and "Special instructions").

Disorders from the gastrointestinal tract

Infrequent: vomiting;

Rarely: nausea, constipation, dryness of the oral mucosa;

Very rarely: pancreatitis.

Disturbances from the liver and bile ducts

Very rarely: a violation of the liver function;

Unspecified frequency: the possibility of developing hepatic encephalopathy in the case of liver failure (see the sections "Contraindications" and "Special instructions"), hepatitis.

Disorders from the kidneys and urinary tract

Very rarely: renal failure.

Disturbances from the skin and subcutaneous tissues

Hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions:

Often: maculopapular rash;

Infrequent: hemorrhagic vasculitis;

Very rarely: angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome;

Unspecified frequency: in patients with acute form of systemic lupus erythematosus, the course of the disease may worsen.

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

Impact on the results of laboratory and instrumental research

Unspecified frequency:

- enlargement QT interval on the ECG (see Fig.section "Special instructions"); increased concentrations 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."

In clinical trials, hypokalemia (potassium in the blood plasma <3.4 mmol / L) was observed in 10% of patients and <3.2 mmol / L in 4% of patients after 4-6 weeks of therapy. After 12 weeks of therapy, the potassium content in the blood plasma decreased by an average of 0.23 mmol / l.

Very rarely: hypercalcemia;

Unspecified frequency:

- decrease in potassium content and development of hypokalemia, especially significant for patients at risk (see section "Special instructions");

- hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous hypochloraemia can lead to compensatory metabolic alkalosis (the probability and severity of this effect is low).

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Indapamide does not have toxic effects even at very high doses (up to 40 mg, ie 27 times the therapeutic dose).

Symptoms:

Signs of acute poisoning with indapamide are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia).

Symptoms of an overdose: nausea, vomiting, lowering blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria, leading to anuria (due to hypovolemia).

Treatment:

Emergency measures are reduced to removing the drug from the body: gastric lavage and / or reception of activated charcoal, followed by restoration of the water electrolyte balance.

Interaction:

Undesirable combinations of drugs

Lithium preparations

With the simultaneous use of indapamide and lithium preparations, an increase in the lithium content in blood plasma can be observed due to a decrease in its excretion, accompanied by the appearance of signs of an overdose. If necessary, you can simultaneously use diuretic drugs and lithium preparations, while carefully selecting the dose of drugs, constantly monitoring the lithium content in blood plasma.

Combinations of drugs that require special attention

Medicinal products that can cause a polymorphic ventricular tachycardia such as "pirouette":

- antiarrhythmic drugs IA class (quinidine, hydroquinidine, disopyramide); - antiarrhythmic drugs of III class (amiodarone, sotalol, dofetilide, ibutilide);

- some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

- other: bepridil, cisapride, difemanyl, erythromycin (iv), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (w / w).

Increased risk of ventricular arrhythmias, especially polymorphic ventricular tachycardia such as pirouette (risk factor - hypokalemia).

It is necessary to determine the content of potassium in the blood plasma and, if necessary, adjust it before starting the combination therapy with indapamide and the above preparations.

The clinical condition of the patient, the electrolyte content in the blood plasma and the ECG parameters should be closely monitored.

Patients with hypokalemia should use drugs that do not cause polymorphic ventricular tachycardia such as pirouette.

Non-steroidal anti-inflammatory drugs (for systemic use), including selective inhibitors of COX-2, high doses of salicylates (≥ 3 g / day).

It is possible to reduce the antihypertensive effect of indapamide.

With a significant loss of fluid, acute renal failure may result (as a result of reduced glomerular filtration). In such cases, patients should compensate for fluid loss and closely monitor kidney function at the beginning of treatment.

Angiotensin converting enzyme (ACE) inhibitors

The use of ACE inhibitors in patients with a reduced content of sodium ions in blood plasma (especially in patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure. Patients with arterial hypertension and possibly reduced content of sodium ions in blood plasma, due to the intake of diuretics, should:

- stop diuretics 3 days before the start of treatment with an ACE inhibitor. In the future, if necessary, the reception of diuretics can be resumed;

- or initiate therapy with an ACE inhibitor from low doses, followed by a gradual increase in dose if necessary.

In chronic heart failure, treatment with ACE inhibitors should begin with low doses with the possible preliminary reduction of doses of diuretics. In all cases, the first week of taking ACE inhibitors in patients should monitor the kidney function (creatinine concentration in the blood plasma).

Other drugs that can cause hypokalemia: amphotericin B (IV), gluco- and mineralocorticosteroids (for systemic use), tetracosactide, laxatives, stimulating bowel motility

Increased risk of hypokalemia (additive effect).

A constant control of the potassium content in the blood plasma is necessary, if necessary, its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.

Baclofen

There is an increase in antihypertensive effect.

Patients should compensate for fluid loss and closely monitor kidney function at the beginning of treatment.

Cardiac glycosides

Hypokalemia increases the toxic effect of cardiac glycosides.

If both INDADAMPID LONG RICHTER and cardiac glycosides are used simultaneously, the potassium content in the blood plasma, the ECG parameters and, if necessary, adjust the therapy should be monitored.

Combinations of medicines requiring attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene)

Combination therapy with the use of potassium-sparing diuretics and the drug INDAPAMID LONG RICHTER is suitable in some patients, but the possibility of hypokalemia (especially in patients with diabetes mellitus and patients with renal insufficiency) or hyperkalemia is not ruled out.

It is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

Metformin

Functional renal failure, which can occur with the use of diuretic drugs, especially "loop" diuretics, with the simultaneous use of metformin increases the risk of lactic acidosis.

Do not use metformin, if the creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-containing contrast agents

Dehydration of the body, which develops against the background of diuretics, increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast agents, patients must compensate for fluid loss.

Tricyclic antidepressants, antipsychotics (antipsychotics) Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of development of orthostatic hypotension (additive effect).

Salts of calcium

With simultaneous application, it is possible to develop hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

Cyclosporin, tacrolimus

It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even with normal liquid and sodium ions.

Corticosteroids, tetracosactide (with systemic application)

Reduction of antihypertensive action of indapamide (fluid retention and sodium ions due to the action of corticosteroids).

Special instructions:

Impaired liver function

With the use of thiazide and thiazide-like diuretics in patients with impaired liver function, it is possible to develop hepatic encephalopathy, especially in the case of electrolyte imbalance. In this case, the taking of diuretics should be stopped immediately.

Photosensitivity

There have been reported cases of the development of photosensitivity reactions against thiazide and thiazide-like diuretics (see the "Side effect" section). In the case of developing photosensitivity reactions against the background of taking the drug INDAPAMID LONG RICHTER treatment should be discontinued. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance

Content of sodium ions in blood plasma

The content of sodium ions in the blood plasma must be determined before the start of treatment. This indicator should be monitored regularly against the background of taking the drug. All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. It is necessary to constantly monitor the content of sodium ions, since the initial decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms.Most carefully, the content of sodium ions should be monitored in patients with cirrhosis of the liver and in elderly patients (see the sections "Side effect" and "Overdose").

The content of potassium ions in the blood plasma

With thiazide and thiazide-like diuretics, the main risk is a sharp decrease in potassium in the blood plasma and development of hypokalemia. It is necessary to avoid the risk of developing hypokalemia (<3.4 mmol / L) in patients of the following categories: elderly patients, weakened patients or receiving concomitant drug therapy with antiarrhythmic drugs and drugs that may increase the interval QT, patients with cirrhosis of the liver, peripheral edema or ascites, ischemic heart disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias. In addition, the high-risk group includes patients with an increased interval QT, while it does not matter whether this increase is due to innate causes or effects of medications.

Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe arrhythmias and, especially, polymorphic ventricular tachycardia such as pirouettes, which can lead to death. In all cases described above, the level of potassium in the blood plasma should be monitored regularly. The first measurement of the content of potassium ions in the blood plasma should be carried out within the first week after the start of treatment.

With hypokalemia, appropriate treatment should be prescribed.

Calcium in the blood plasma

Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism.

It is necessary to cancel the use of diuretics before examining the function of parathyroid glands.

The content of glucose in the blood plasma

Thiazide and thiazide-like diuretics should be used with caution in patients with diabetes mellitus.

It is necessary to monitor the concentration of glucose in the blood in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

Thiazide and thiazide-like diuretics should be used with caution in patients with gout.

Patients with gout may note an increased incidence of attacks or exacerbations of gout.

Diuretic drugs and kidney function

The use of thiazide and thiazide-like diuretics is fully effective in patients with normal or slightly impaired renal function (plasma creatinine concentration in adults below 25 mg / L or 220 μmol / L).

In elderly patients, the concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.

It should be borne in mind that at the beginning of treatment in patients can decrease the glomerular filtration rate due to hypovolemia, which in turn is caused by the loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, plasma concentrations of urea and creatinine may increase. If the kidney function is not impaired, such temporary functional kidney failure usually passes without consequences, but the patient's condition may worsen with existing renal failure.

Athletes

The active ingredient, which is part of the drug INDAPAMID LONG RICHTER, can give a positive result in the conduct of doping control in athletes.

Lactose

The drug contains lactose, so it should not be taken to patients with such rare hereditary diseases as galactose intolerance, lactase Lappa deficiency or glucose-galactose malabsorption syndrome.

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

The action of substances included in the composition INDADAMPID LONG RICHTER does not lead to a disturbance of psychomotor reactions. However, in some patients, in response to a reduction in blood pressure, various individual reactions may develop, especially at the onset of therapy or when other antihypertensive drugs are added to the therapy. In this case, the ability to drive vehicles or other mechanisms can be reduced.

Form release / dosage:

Long-acting tablets, coated with a film sheath, 1.5 mg.

Packaging:

For 15 tablets in a blister of PVC / PVDC film and aluminum foil.

2 blisters per cardboard pack together with instructions for use.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003948

Date of registration:08.11.2016

Expiration Date:08.11.2021

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER ROMANIA, S.A. Romania

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp02.11.2017

Illustrated instructions

Instructions

INDAPAMID LONG RICHTER (INDAPAMIDE LONG RICHTER)