Indapamide retard-ALSI, 1.5 mg 30 pcs

Hypotensive agent, thiazide-like diuretic with moderate potency and long duration of action, benzamide derivative. It has moderate saluretic and diuretic effects associated with blockade of reabsorption of sodium, chloride, hydrogen and, to a lesser extent, potassium ions in the proximal tubules and cortical segment of the distal tubule of the nephron.

Vasodilator effects and reduction of total peripheral vascular resistance are based on the following mechanisms: reduction of reactivity of the vascular wall to noradrenaline and angiotensin II, increased synthesis of prostaglandins, having vasodilator activity, inhibition of calcium ions flow in vascular smooth muscle walls. Reduces the tone of arterial smooth muscle, reduces total peripheral vascular resistance.

Contributes to the reduction of left ventricular hypertrophy. In therapeutic doses does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes).

Indications

Active ingredient

Composition

One sustained release coated tablet contains:

as the active ingredient:

indapamide – 1.5 mg;

excipients:

hypromellose – 77.36 mg,

lactose monohydrate (milk sugar) – 119.14 mg,

colloidal silicon dioxide (aerosil) – 1.0 mg,

magnesium stearate – 1.0 mg,

hypromellose – 2.24 mg,

lactose monohydrate – 2.88 mg,

polyethylene glycol – 0.80 mg,

titanium dioxide – 2.08 mg.

Interaction

Not recommended combinations Concomitant use with lithium preparations may increase the concentration of lithium ions in the blood plasma due to reduced renal excretion, accompanied by the appearance of signs of overdose (nephrotoxic effect), as well as when following a salt-free diet (reduced renal excretion of lithium ions).

Combinations requiring special attention.

1. Drugs that can cause pirouette-type heart rhythm disturbances: class IA antiarrhythmic agents (quinidine, hydroquinidine, disopyramide), class III antiarrhythmic agents (amiodarone, dofetilide, ibutilide, brettilia tozilate), sotalol, some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenones (droperidol, haloperidol) others (bepridil, cisapride, difemanil, erythromycin (intravenous (IV)), halofantrine, misolastin, pentamidine, sparfloxacin, moxifloxacin, vincamine (IV), astemisol. Concomitant use with any of these drugs, especially against the background of hypokalemia, increases the risk of ventricular arrhythmias of the type “pirouette”. Before starting combined therapy with Indapamide retard and the above drugs, plasma potassium content should be monitored and, if necessary, it should be corrected. It is recommended: control of clinical condition of the patient, as well as the content of plasma electrolytes and ECG. In patients with hypokalemia it is necessary to use drugs that do not provoke “pirouette” type arrhythmia.

2: concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) (when used systemically), including selective cyclooxygenase-2 (COX-2) inhibitors, high doses of salicylic acid (3 g/day or more) may: decrease antihypertensive effect of indapamide, development of acute renal failure in dehydrated patients (due to decrease of glomerular filtration rate). At the beginning of therapy with indapamide it is necessary to restore water-electrolyte balance and monitor renal function.

3. angiotensin-converting enzyme (ACE) inhibitors in patients with hyponatremia (especially in patients with renal artery stenosis) increase the risk of arterial hypotension and/or acute renal failure. Patients with arterial hypertension and possibly with hyponatremia due to diuretics should:

– discontinue the drug 3 days before starting therapy with ACE inhibitors and switch to therapy with potassium-saving diuretics;

– or start therapy with ACE inhibitors at low doses, with subsequent gradual increase of the dose if necessary. In the first week of therapy with ACE inhibitors, monitoring of plasma creatinine concentration is recommended.

4. other drugs that may cause hypokalemia:

– amphotericin B (IV), – gluco- and mineralocorticosteroids (if administered systemically) (see also information under “Combination therapy”). tetracosactide (see also information under “Drug combinations that require attention”), – intestinal motility-promoting laxatives (see also information under “Drug combinations that require attention”).

The simultaneous use of the above drugs with indapamide increases the risk of hypokalemia (additive effect). If necessary, the content of plasma potassium ions should be monitored and corrected.

5. concomitant therapy with baclofen enhances the antihypertensive effect of indapamide.

6. Cardiac glycosides: hypokalemia increases the toxic effects of cardiac glycosides (glycoside intoxication). When concomitant use of indapamide and cardiac glycosides the content of plasma potassium ions and ECG parameters should be monitored and, if necessary, the therapy should be adjusted.

Combinations of drugs requiring attention.

1. Simultaneous use with potassium-saving diuretics (amiloride, spironolactone, triamterene) is reasonable in some patients, but the possibility of hypokalemia is not excluded. Against the background of diabetes mellitus or renal insufficiency, hyperkalemia may develop. The content of potassium ions in plasma and ECG parameters should be monitored and, if necessary, the therapy should be adjusted.

2. Metformin increases the risk of lactic acidosis, as renal failure may develop with diuretics, especially loop diuretics. Metformin should not be taken when plasma creatinine concentration is more than 15 mg/l (135 µmol/L) in men and 12 mg/l (110 µmol/L) in women.

3. Simultaneous use of high doses of iodine-containing contrast agents against a background of hypovolemia and administration of diuretics increases the risk of acute renal failure. It is recommended to restore blood water-electrolyte balance before using the drugs.

4. tricyclic antidepressants (imipramine-like) and neuroleptics increase the hypotensive effect and the risk of orthostatic hypotension (additive effect).

5. calcium salt preparations increase the risk of hypercalcemia due to reduced renal excretion of calcium ions.

6. cyclosporine, tacrolimus – risk of increased plasma creatinine concentration without changes in circulating cyclosporine concentration.

7. Glucocorticosteroid drugs, tetracosactide (when used systemically) reduce the hypotensive effect (retention of sodium ions and fluid).

Directions for use

Orally, without chewing, with plenty of fluid, regardless of meals, preferably in the morning hours at a dose of 1.5 mg (1 tablet) per day.

If the desired therapeutic effect is not achieved after 4-8 weeks of therapy, it is not recommended to increase the dose of the drug (the risk of side effects increases without increasing of antihypertensive effect). Instead, it is recommended to include another antihypertensive drug, which is not a diuretic, into the scheme of medical treatment.

In cases where it is necessary to start treatment with two drugs, the dose of Indapamide retard remains 1.5 mg in the morning once daily.

In elderly patients the plasma creatinine concentration should be monitored taking into account age, body weight and sex, the drug can be used in elderly patients with normal or mildly impaired renal function (see also section on Contraindications).

Special Instructions

In patients with hepatic insufficiency when prescribing thiazide-like diuretics, hepatic encephalopathy may develop, especially if the water-electrolyte balance is impaired. If this occurs, diuretics should be discontinued.

Photosensitivity. There have been cases of photosensitivity reactions when using thiazide-like diuretics. If they develop, the drug should be discontinued. During the therapy with Indapamide retarde it is necessary to protect exposed parts of the body from sunlight and artificial ultraviolet radiation.

Water-electrolyte balance. Plasma sodium ion content: all diuretics may cause hyponatremia. The content of sodium ions in plasma should be measured before starting treatment with Indapamide retard, and then regularly during the treatment period. Determination of the content of sodium ions in blood plasma should be carried out before the beginning of therapy with Indapamide retarde, as well as during the therapy. It is important to monitor regularly the content of sodium ions in blood plasma, because initially hyponatremia may be asymptomatic. The most careful control of sodium ions content is recommended for elderly patients and patients with liver cirrhosis.

The content of plasma potassium ions: the greatest risk of treatment with thiazide-like diuretics is hypokalemia. Particular attention in prevention of hypokalemia (less than 3.4 mmol/l) is necessary in the following cases: weakened patients and/or receiving other therapy (antiarrhythmic drugs and agents that may prolong QT interval on ECG), elderly patients with cirrhosis of liver, peripheral edema and ascites; with ischemic heart disease and chronic heart failure. Hypokalemia in such patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia. Patients with prolonged QT interval on ECG are also at high risk. Hypokalemia is a predisposing factor for severe arrhythmias, especially pirouette arrhythmias, which may be fatal. In all the described cases, plasma potassium content should be regularly monitored. The first determination of plasma potassium should be made during the first week of therapy with Indapamide retard.

If hypokalemia is detected, appropriate therapy should be given.

Plasma calcium ion content: Thiazide and thiazide diuretics may decrease renal excretion of calcium ions, leading to mild and/or temporary hypercalcemia. Severe hypercalcemia on Indapamide Retard may be due to previously undiagnosed hyperparathyroidism.

Diuretics should be discontinued before parathyroid function tests.

Plasma glucose concentrations: In patients with diabetes mellitus, especially in the presence of hypokalemia, monitoring of plasma glucose concentrations is necessary.

Ureic acid: in patients with hyperuricemia may increase the frequency of attacks or exacerbations of gout.

Kidney function and diuretic drugs. Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly decreased renal function (creatinine of adult blood plasma less than 25 mg/l or 220 µmol/l). Severe hypovolemia may lead to development of acute renal failure (decrease of glomerular filtration rate), which may be accompanied with increase of concentration of urea and creatinine in blood plasma. With normal renal function, transient functional renal failure usually passes without consequences. With existing renal failure, the patient’s condition may worsen.

In elderly patients, regular monitoring of creatinine and plasma potassium concentrations is recommended, taking into account patient age, body weight and sex. Indapamide retard can be administered in elderly patients with preserved or slightly impaired renal function (CK over 30 ml/min).

Athletes. Indapamide retard may give a positive result in doping control.

The effect on the ability to drive motor vehicles and other complex mechanical devices. Use of indapamide retard does not lead to impairment of psychomotor reactions. However, various individual reactions may occur in some patients in response to BP decrease, especially at the beginning of therapy or when adding other hypotensive agents to the current therapy. Therefore, at the beginning of treatment with Indapamide retard is not recommended to drive motor transport or other complex mechanisms requiring increased attention.

Synopsis

Features

Contraindications

Hypersensitivity to indapamide, other sulfonamide derivatives or other components of the drug, acute impairment of cerebral circulation, severe renal (creatinine clearance less than 30 ml/min) and/or liver function disorders (including with hepatic encephalopathy), hypokalemia, pregnancy, lactation, age below 18 years (effectiveness and safety are not established).

The tablets contain lactose monohydrate (lactose sugar); therefore, the drug should not be taken by patients with rare hereditary diseases such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

With caution. Use the drug with caution in diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyponatremia and other disorders of the water-electrolyte balance, moderate hepatic and/or renal failure, chronic heart failure, hyperparathyroidism, In patients with prolonged QT interval on ECG or receiving concomitant therapy, which may result in QT interval prolongation (astemizole, erythromycin (IV), pentamidine, sultoprid, terfenadine, vincamine (IV), antiarrhythmic drugs of class IA (quinidine, disopramide) and class III (amiodarone, brettilia tozilate).

Side effects

The majority of adverse reactions (laboratory and clinical parameters) are dose-dependent.The frequency of adverse reactions that may be caused by thiazide-like diuretics, including indapamide, is given as the following gradations: Very common (>1/10); common (>1/100, <1/10); infrequent (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000); unspecified frequency (frequency cannot be calculated from available data).

Hematological and lymphatic system disorders. Very rare: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Central nervous system disorders. Rare: dizziness, fatigue, headache, paresthesias.

Cardiovascular system disorders. Very rare: arrhythmia, decreased blood pressure.

Digestive system disorders. Infrequent: vomiting. Rare: nausea, constipation, dry mouth. Very rare: pancreatitis.

With the urinary system. Very rare: renal failure.

Liver and biliary tract disorders. Very rare: liver dysfunction.

Unspecified frequency: possibility of hepatic encephalopathy in case of hepatic insufficiency.

Skin disorders. Hypersensitivity reactions, mainly dermatological, in patients with predisposition to allergic and asthmatic reactions:Frequent: maculopapular rash.Infrequent: hemorrhagic vasculitis. Very rare: angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome. Unspecified frequency: possible worsening in the presence of acute disseminated lupus erythematosus. Cases of photosensitivity have been described.

Laboratory indicators. In clinical trials hypokalemia (potassium content in 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, plasma potassium levels decreased, on average, by 0.23 mmol/l. Very rare hypercalcemia. Unspecified frequency: Hypokalemia; Hyponatremia accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous loss of chlorine ions may lead to compensatory metabolic alkalosis, but the incidence and severity of alkalosis is not significant; Increased plasma levels of uric acid and glucose.

Overdose

Symptoms: nausea, vomiting, weakness, gastrointestinal tract disorders (nausea, vomiting), water-electrolyte disorders, marked decrease of blood pressure, dizziness, somnolence, confusion, respiratory depression, polyuria, oliguria up to anuria, in patients with liver dysfunction there may be development of hepatic coma.

Treatment: gastric lavage and/or administration of activated charcoal, followed by restoration of normal water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Similarities