Ionik - instructions for use, doses, side effects, contraindications

Excipients: corn starch 52.5 mg, lactose monohydrate 80.7 mg, silicon dioxide colloid (aerosil) 1.5 mg, povidone 2.3 mg, carboxymethyl starch sodium (sodium starch glycolate) 9 mg, magnesium stearate 1.5 mg;

capsules, hard gelatinous:

capsule body - titanium dioxide 2%, gelatin up to 100%;

cap capsule - titanium dioxide 2%, dye blue patented 0.0176%, dye diamond black 0.0051%, gelatin to 100%.

Description:

Capsules №3 with the case of white color and a lid of blue color. The contents of capsules are white or almost white powder.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide belongs to the sulfonamide derivatives and is pharmacologically similar to thiazide diuretics. Indapamide increases the excretion of urine ions of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, which is accompanied by increased diuresis. Indapamide has an antihypertensive effect in doses that do not have a pronounced diuretic effect. Furthermore, indapamide is effective in patients with one kidney.

The mechanism of vasodilating action of indapamide on vessels, as well as other diuretic drugs, includes:

- change in the transmembrane current of ions (primarily calcium), which leads to relaxation of smooth muscle cells of the vessels;

- increased synthesis of prostaglandin PGE2 and prostacyclin PGI2 (vasodilator and platelet aggregation inhibitor).

Indapamide, like other thiazide diuretics, reduces hypertrophy of the left ventricle.

In addition, against the background of indapamide therapy:

- do not change the lipid metabolism, including the concentration of triglycerides, cholesterol, low-density lipoproteins and high-density lipoproteins;

- Do not change the metabolism of carbohydrates, including those with diabetes mellitus and hypertension.

An increase in the dose of indapamide above the optimal is not accompanied by an increase in the antihypertensive effect, but may be accompanied by the appearance of pronounced undesirable reactions. If therapy with indapamide does not lead to the desired therapeutic outcome, the dose should not be increased.

Pharmacokinetics:

Suction

Bioavailability of indapamide - 93%. The maximum concentration in blood plasma indapamide reaches 1-2 hours after ingestion of a single dose of 2.5 mg.

Distribution

About 75% of the drug binds to blood plasma proteins. The half-life of indapamide (T_1/2) is 14-24 hours (an average of 18 hours).

With regular administration of the drug, the equilibrium concentration of indapamide in the blood plasma increases (in comparison with a single dose). At the same time, the achieved equilibrium state persists for a long period of time, indicating that repeated use of the drug is not accompanied by the accumulation of indapamide in the body.

Metabolism and excretion

Indapamide is metabolized in the liver and is excreted as inactive metabolites mainly by the kidneys (60-80% of the administered dose). Not more than 5% of indapamide is excreted from the body by the kidneys in unchanged form.

In patients with renal insufficiency pharmacokinetic parameters of indapamide do not change.

Indications:

Arterial hypertension.

Contraindications:

Hypersensitivity to indapamide, other derivatives of sulfonamide or other components of the drug.

Severe renal insufficiency (creatinine clearance less than 30 ml / min).

Severe hepatic insufficiency or hepatic encephalopathy.

Refractory hypokalemia.

Age to 18 years (since efficiency and safety are not established).

Due to the fact that the preparation contains lactose monohydrate, its use is not recommended for patients with lactose intolerance, lactase deficiency, galactosemia, glucose-galactose malabsorption.

Carefully:

Dysfunction of the liver and kidneys (creatinine clearance more than 30 ml / min), disturbance of water-electrolyte balance, use in patients with an increased interval QT on an electrocardiogram (ECG), use in weakened patients or in patients receiving concomitant therapy with drugs that can increase the interval QT (see "Interaction with other drugs"), hyperparathyroidism, diabetes mellitus, hyperuricemia and gout.

Pregnancy and lactation:

Pregnancy

As a rule, during pregnancy, diuretic drugs should not be prescribed. Do not use these drugs to relieve the physiological edema during pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development.

Diuretics, however, are used in the treatment of cardiac, hepatic and renal genesis in pregnant women.

Breastfeeding period

It is not recommended to use the drug during lactation (indapamide excreted in breast milk). If you need to use the drug during breastfeeding, breast-feeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake, preferably in the morning, without chewing, washing with water. Assign 2.5 mg (1 capsule) 1 time per day.

The drug may be administered as a monotherapy or in combination with other antihypertensive agents.

If after 4-8 weeks of treatment the desired therapeutic effect is not achieved, the dose of the drug should not be exceeded (an increased risk of side effects without increasing the antihypertensive effect). Instead, another antihypertensive drug that is not a diuretic should be added to the treatment regimen. In cases where treatment should begin with the taking of two drugs, the dose of indapamide remains 2.5 mg in the morning once a day.

Side effects:

The incidence of unwanted reactions is presented according to the WHO classification: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (≥ 1/10000 and <1/1000 cases) and very rarely (<1/10000 cases). Undesirable reactions, the frequency of development of which can not be estimated from available data, have the designation "frequency is unknown".

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 cardiovascular system: very rarely - arrhythmia, marked decrease in blood pressure; frequency unknown - arrhythmia of the type "pirouette" (possibly fatal).

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

From the side of the kidneys and urinary tract: very rarely - kidney failure.

From the liver and bile ducts: very rarely - a violation of liver function; frequency unknown - the possibility of developing hepatic encephalopathy in the case of hepatic insufficiency, hepatitis.

From the skin and subcutaneous tissues: 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 deterioration of the course of the disease is possible, cases of photosensitivity reactions are described.

Laboratory indicators: very rarely - hypercalcemia; frequency unknown - interval increase QT on ECG, increased concentration of uric acid and blood glucose (thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes mellitus), increased activity of "liver" transaminases, decreased potassium content and development of hypokalemia (especially significant for patients belonging to risk group (see section "Special instructions")), hyponatremia, accompanied by hypovolemia leading to dehydration, and orthostatic hypotension. Simultaneous hypochloraemia can lead to metabolic alkalosis of compensatory nature (the probability and severity of this effect is low).

Overdose:

Symptoms

Indapamide even in very high doses (up to 40 mg, i.e. 16 times more than the therapeutic dose) does not have a toxic effect.

Signs of acute drug poisoning are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). Symptoms of overdose may include nausea, vomiting, severe lowering of blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria, resulting in anuria (due to hypovolemia).

Treatment

The first aid measures are reduced to removing the drug from the body: washing the stomach and / or the purpose of activated carbon, followed by the restoration of the water electrolyte balance.

Interaction:

Unwanted combination of drugs

Lithium preparations

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

Combination of drugs, requiring special attention

Medicines that can cause arrhythmia of the "pirouette" type:

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

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

- others: beprideil, cisapride, difemannil, erythromycin (intravenously (iv)), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (w / w).

Increased risk of ventricular arrhythmias, especially arrhythmias such as pirouettes (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 with the above drugs. It is necessary to monitor the clinical condition of the patient, control the content of plasma electrolytes, ECG parameters. Patients with hypokalemia should use drugs that do not cause arrhythmia such as "pirouette".

Nonsteroidal anti-inflammatory drugs (for systemic administration), including selective inhibitors of cyclooxygenase-2 (COX-2), high-dose salicylates (≥ 3 g / day)

It is possible to reduce the antihypertensive effect of indapamide. With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration). Patients need to compensate for fluid loss and regularly monitor kidney function, both at the beginning of treatment and during treatment.

Angiotensin converting enzyme (ACE) inhibitors

The use of ACE inhibitors in patients with hyponatremia (especially patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure.

Patients from arterial hypertension and possibly reduced, due to the intake of diuretics, the content of sodium ions in the blood plasma is necessary:

- Three days before the start of treatment with ACE inhibitors, stop taking diuretics; 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.

When chronic heart failure treatment with ACE inhibitors should be started with low doses with a possible preliminary reduction in the dose of diuretics.

In all cases In the first week of taking ACE inhibitors in patients, it is necessary to monitor renal function (creatinine concentration in the blood plasma).

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

Increased risk of hypokalemia (additive effect).

It is necessaryyangth control of the potassium content in the blood plasma, 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

Perhaps increased antihypertensive effect.

Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

Cardiac glycosides

Hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the potassium content in the blood plasma and the ECG parameters should be carefully monitored and, if necessary, the therapy should be reviewed.

A combination of drugs that requires attention

Potassium-sparing diuretics (amiloride, spironolactone and its derivative eplerenone, triamterene)

The simultaneous use of indapamide and potassium-sparing diuretics is advisable in some patients,However, the possibility of developing hypokalemia (especially in patients with diabetes mellitus and renal insufficiency) or hyperkalemia is not ruled out.

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

Metformin

Functional renal failure that can occur in patients receiving diuretics, particularly "loop", while 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 against the background of taking diuretics increases the risk of acute renal failure, especially when using high doses iodine containing contrasting substances.

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 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 a normal content of liquid and sodium ions.

Corticosteroids (mineral- and glucocorticosteroids), tetracosactide (with system assignment)

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

Special instructions:

Dysfunction of the liver

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

Photosensitivity

Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported. In the case of developing photosensitivity reactions against the background of taking the drug should stop treatment.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

Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug, these measurements should be carried out regularly. All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. It is necessary to constantly monitor the content of sodium ions, since initially a decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most careful control of the sodium ion content is necessary for patients with cirrhosis of the liver and elderly patients.

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 development of hypokalemia (potassium content less than 3.4 mmol / l), in patients of the following groups: the elderly,attenuated or receiving concomitant drug therapy with other 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 patients of these groups increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

In addition, the high-risk group includes patients with an increased interval QT, it does not matter whether this increase is due to innate causes or effects of drugs.

Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe cardiac arrhythmias and especially the "pirouette" type, which can lead to death. In all the cases described above, it is necessary to regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in blood plasma should be carried out within the first week from the start of treatment. When hypokalemia occurs, 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.

You should stop taking diuretic drugs before examining the function of parathyroid glands.

The concentration of glucose in the blood plasma

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

Uric acid

Patients with gout may increase the incidence of attacks or exacerbate the course of gout.

Diuretic drugs and kidney function

Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentration in adult patients is 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, patients may experience a decrease in glomerular filtration,caused by hypovolemia, which, in turn, is caused by the loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the kidney function is not impaired, such temporary renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen.

Athletes

Indapamide can give a positive result in the conduct of doping control in athletes.

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

Care must be taken when driving vehicles and when engaging in potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions (especially at the beginning of therapy or when adding other antihypertensive agents to therapy).

Form release / dosage:

Capsules, 2.5 mg.

Packaging:

For 10, 15 or 30 capsules in a contour cell box made of a polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2, 3 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° 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-002429

Date of registration:10.04.2014

Expiration Date:10.04.2019

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp27.11.2017

Illustrated instructions

Instructions

Ionik (Ionic)