Pharmacological properties of the drug Arifon retard
Indapamide ((RS)-4-chloro-3-(sulfamoyl)-N-(2,3-dihydro-1H-indol-1-yl)-benzamide) is a diuretic, antihypertensive agent. The chemical structure is a sulfonamide derivative with an indole ring. Its pharmacological properties are similar to thiazide diuretics. Due to the complex mechanism of action, Arifon has a pronounced hypotensive effect and does not cause a significant diuretic effect. The action is carried out at the level of the kidneys and blood vessels. At the kidney level, indapamide increases the excretion of sodium and chlorine ions in the urine, and to a lesser extent, the excretion of potassium and magnesium, contributing to a slight increase in diuresis. The effect of indapamide on the vascular wall is due to its high lipophilicity. Indapamide changes the transmembrane flow of ions (mainly calcium), reduces the sensitivity of the vascular wall to adrenaline and stimulates the synthesis of substances with vasodilatory activity - prostaglandin E2 and prostacyclin I2. This leads to dilation of arterioles, a decrease in peripheral vascular resistance and blood pressure. Arifon reduces left ventricular hypertrophy; does not affect lipid metabolism (TG, LDL cholesterol, HDL cholesterol) and carbohydrate metabolism, including in patients with hypertension (arterial hypertension) and diabetes mellitus, reduces the severity of microalbuminuria. The antihypertensive effect of the drug persists in patients on hemodialysis. The use of an innovative dosage form based on a hydrophilic matrix ensures uniform release of indapamide and effective blood pressure control for 24 hours, and also allows reducing the content of indapamide per tablet to 1.5 mg and thus reducing the risk of hypokalemia by 62%. When prescribed at a dose of more than 1.5 mg, the antihypertensive effect of the drug does not increase, while the likelihood of side effects increases. Indapamide is quickly and completely absorbed from the digestive tract. The maximum concentration in the blood serum after a single dose is reached after approximately 1–2 hours. The equilibrium state is achieved after 7 days from the start of treatment. 79% of indapamide binds to plasma proteins. The half-life averages 18 hours (14–24 hours). About 70% of indapamide is excreted in the urine, 22% in feces. The pharmacokinetics of the drug does not change in patients with renal failure. In patients with hepatic impairment, the use of thiazide or thiazide-like diuretics may cause the development of hepatic encephalopathy.
Arifon retard prolonged action tablets 1.5 mg No. 15x2
Name
Arifon retard tablet prolong.dey-ya with captivity. cover 1.5 mg per cont. cell pack No. 15x2
Description
Controlled-release, film-coated tablets, white, round, biconvex.
Main active ingredient
indapamide
Release form
Pills
Dosage
1.5 mg
special instructions
Liver dysfunction When thiazide and thiazide-like diuretics are prescribed in patients with liver dysfunction, hepatic encephalopathy may develop, especially in the case of electrolyte imbalance. In this case, diuretics should be stopped immediately. Photosensitivity While taking thiazide and thiazide-like diuretics, cases of photosensitivity reactions have been reported. If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays. Water-electrolyte balance, the content of sodium ions in the blood plasma: Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. Constant monitoring of the content of sodium ions is necessary, because Initially, a decrease in plasma sodium concentration may be asymptomatic. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly. All diuretic drugs can cause hyponatremia, sometimes leading to extremely serious consequences. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chloride ions can lead to secondary compensatory metabolic alkalosis: the frequency and severity of this effect are insignificant. content of potassium ions in the blood plasma: When treating with thiazide and thiazide-like diuretics, the main risk is a sharp decrease in the concentration of potassium in the blood plasma and the development of hypokalemia. It is necessary to prevent the risk of developing hypokalemia (
pharmachologic effect
Mechanism of action Indapamide is a sulfonamide derivative containing an indole ring. In terms of pharmacological properties, indapamide is close to thiazide diuretics, the action of which is associated with inhibition of the reverse absorption of sodium ions in the cortical segment of the nephron loop. At the same time, the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions in the urine increases, which is accompanied by increased diuresis and causes an antihypertensive effect.
Pharmacodynamics
In clinical studies of phases II and III, when indapamide was used as monotherapy in doses that did not have a pronounced diuretic effect, a hypotensive effect was demonstrated that persisted for 24 hours. The antihypertensive activity of indapamide is associated with improved elasticity of large arteries, a decrease in arterial vascular resistance and peripheral vascular resistance. Indapamide helps reduce left ventricular hypertrophy. Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the frequency of side effects continues to increase with further increases in the dose of the drug. Therefore, you should not increase the dose of the drug if a therapeutic effect is not achieved when taking the recommended dose. In short, medium-term and long-term studies involving patients with arterial hypertension, it was shown that indapamide does not affect lipid metabolism (including the level of triglycerides, cholesterol, LDL and HDL) and carbohydrate metabolism (including h. in patients with diabetes).
Pharmacokinetics
Absorption In Arifon retard tablets, the active substance is contained in a special carrier matrix, which ensures gradual controlled release of indapamide in the gastrointestinal tract. The released indapamide is quickly and completely absorbed from the gastrointestinal tract. Eating slightly increases the absorption time of the drug without affecting the completeness of absorption. Cmax in blood plasma is achieved 12 hours after oral administration of a single dose. With repeated doses, fluctuations in the concentration of the drug in the blood plasma in the interval between doses of the drug are smoothed out. There is individual variability in drug absorption rates. Distribution Plasma protein binding is about 79%. Css is achieved after 7 days of regular use. When taking the drug repeatedly, no accumulation is observed. Metabolism and excretion Indapamide undergoes biotransformation and is excreted in the form of inactive metabolites, mainly in urine - 70% and feces - 22%. T1/2 is 14-24 hours (average 18 hours). Pharmacokinetics in special clinical cases In patients with renal failure, the pharmacokinetic parameters of the drug Arifon retard do not change.
Indications for use
arterial hypertension in adults.
Directions for use and doses
Take 1 tablet/day orally, preferably in the morning. The tablet should be swallowed whole, without chewing, with water. When treating patients with arterial hypertension, increasing the dose of the drug does not lead to an increase in the antihypertensive effect, but enhances the diuretic effect. Indapamide is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). Thiazide and thiazide-like diuretics are effective only in patients with normal or mildly impaired renal function. The drug is contraindicated in patients with severe liver failure. In elderly patients, plasma creatinine concentrations should be monitored based on age, body weight and gender. Arifon retard at a dose of 1.5 mg/day (1 tablet) can be prescribed to elderly patients with normal or slightly impaired renal function (see section “Contraindications”). Currently, there is no data on the safety and effectiveness of Arifon retard in children and adolescents.
Use during pregnancy and lactation
Pregnancy There is currently insufficient data on the use of indapamide during pregnancy (less than 300 cases have been described). Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal growth retardation. Animal studies have shown no direct or indirect effects on pregnancy. The use of indapamide should be avoided during pregnancy. Breastfeeding It is not known whether indapamide or its metabolites are excreted in breast milk. The newborn may develop hypersensitivity to sulfonamide derivatives and hypokalemia. Therefore, a risk to the newborn/infant cannot be excluded. Indapamide is close to thiazide diuretics, the use of which causes a decrease in the amount of breast milk or even suppression of lactation. Indapamide should not be used during breastfeeding. Fertility Preclinical studies have shown no effects on reproductive function in rats of either sex. Presumably there is no effect on human fertility.
Interaction with other drugs
Not recommended combination of drugs With the simultaneous use of indapamide and lithium preparations, as well as when following a salt-free diet, an increase in the concentration of lithium in the blood plasma may be observed due to a decrease in its excretion, accompanied by the appearance of signs of overdose. If necessary, diuretic drugs can be used in combination with lithium drugs, and the dose of the drugs should be carefully selected, constantly monitoring the lithium content in the blood plasma. Combinations requiring special attention Drugs that can cause arrhythmias: class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide); some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol); others: bepridil, cisapride, difemanil, erythromycin (iv), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (iv). Hypokalemia increases the risk of developing ventricular arrhythmias, especially arrhythmias. The concentration of potassium in the blood plasma should be determined and, if necessary, adjusted before starting combination therapy with indapamide and the above drugs. It is necessary to monitor the patient’s clinical condition, monitor the level of electrolytes in the blood plasma, and ECG indicators. In patients with hypokalemia, drugs that do not cause ari should be used. When used simultaneously with NSAIDs (when administered systemically), including selective COX-2 inhibitors, high doses of acetylsalicylic acid (? 3 g/day), the antihypertensive effect of indapamide may be reduced. There is a risk of developing acute renal failure due to decreased glomerular filtration. Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment. Prescribing ACE inhibitors to patients with an initially reduced concentration of sodium ions in the blood (especially 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 levels of sodium ions in the blood plasma due to diuretics should: stop taking diuretics 3 days before starting treatment with ACE inhibitors. In the future, if necessary, resume taking diuretics; or start ACE inhibitor therapy with low doses, followed by a gradual increase in dose if necessary. In chronic heart failure, treatment should begin with low doses of ACE inhibitors, after first reducing the dose of diuretics. In all cases, in the first week of taking ACE inhibitors, it is necessary to monitor renal function (plasma creatinine content). When using indapamide simultaneously with other drugs that can cause hypokalemia, incl. with amphotericin B (iv), gluco- and mineralocorticoids (when administered systemically), tetracosactide, laxatives that stimulate intestinal motility, the risk of hypokalemia increases due to an additive effect. Constant monitoring of potassium concentration in the blood plasma and, if necessary, its correction is necessary. Particular attention should be paid to patients simultaneously receiving cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility. With simultaneous use of indapamide with baclofen, an increase in the hypotensive effect is observed. It is necessary to compensate for fluid loss and carefully monitor renal function at the beginning of treatment. When used simultaneously with cardiac glycosides, the toxic effect of the latter may be enhanced due to hypokalemia. It is necessary to monitor the concentration of potassium in the blood plasma and ECG parameters and, if necessary, adjust therapy. Combinations requiring attention: Concomitant therapy with indapamide and potassium-sparing diuretics (amiloride, spironolactone, triamterene) is advisable in some patients, but the possibility of developing hypokalemia or hyperkalemia cannot be excluded (especially in patients with renal failure or patients with diabetes mellitus). It is necessary to monitor the concentration of potassium in the blood plasma, ECG indicators and, if necessary, adjust therapy. Functional renal failure, which can occur against the background of diuretics, especially loop diuretics, with simultaneous administration of metformin increases the risk of developing lactic acidosis. Metformin should not be used in combination with Arifon retard if the creatinine level is more than 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women. In case of dehydration while taking diuretics, the risk of developing acute renal failure increases, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast agents, patients must compensate for fluid loss. With the simultaneous use of indapamide and tricyclic antidepressants, antipsychotics (neuroleptics), there is an increase in the hypotensive effect of indapamide and an increased risk of developing orthostatic hypotension (additive effect). With the simultaneous use of thiazide diuretics and calcium salts, hypercalcemia may develop due to a decrease in the excretion of calcium ions in the urine. With the simultaneous use of thiazide diuretics with cyclosporine and tacrolimus, it is possible to increase the creatinine content in the blood plasma without changing the concentration of circulating cyclosporine, even with normal fluid and sodium ion levels. With the simultaneous use of thiazide diuretics with corticosteroids, tetracosactide (when administered systemically), a decrease in the hypotensive effect is observed due to the retention of water and sodium ions under the influence of corticosteroids.
Contraindications
severe renal failure (creatinine clearance less than 30 ml/min); severe liver failure or hepatic encephalopathy; hypokalemia; hypersensitivity to the active substance, other sulfonamide derivatives or to any of the excipients (see section “Composition and release form”). Due to the fact that the drug contains lactose, Arifon retard is not recommended for patients with lactose intolerance, galactosemia, and glucose-galactose malabsorption. With caution: impaired liver and kidney function; water-electrolyte imbalance; weakened patients or patients receiving combination therapy with other antiarrhythmic drugs; diabetes; increased uric acid levels; hyperparathyroidism; patients with a prolonged QT interval. Due to the lack of sufficient clinical data, the drug is not recommended for use in children and adolescents under 18 years of age.
Compound
Excipients: lactose monohydrate - 124.5 mg, hypromellose - 64 mg, magnesium stearate - 1 mg, povidone - 8.6 mg, colloidal anhydrous silicon dioxide - 0.4 mg. Film shell composition: glycerol - 0.219 mg, hypromellose - 3.642 mg, macrogol 6000 - 0.219 mg, magnesium stearate - 0.219 mg, titanium dioxide - 0.701 mg. 15 pcs. - blisters (2) - cardboard packs, with first opening control (if necessary). 30 pcs. - blisters (1) - cardboard packs, with first opening control (if necessary).
Overdose
Symptoms Indapamide, even in very high concentrations (up to 40 mg, i.e. 27 times the therapeutic dose), does not have a toxic effect. Signs of acute drug poisoning are primarily associated with water and electrolyte imbalance (hyponatremia, hypokalemia). Nausea, vomiting, decreased blood pressure, convulsions, vertigo, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia) may also occur. Treatment Emergency measures aimed at removing the drug from the body: gastric lavage and/or administration of activated charcoal followed by restoration of water and electrolyte balance.
Side effect
The most common adverse reactions reported were hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions, and maculopapular rash. In clinical studies, hypokalemia (potassium concentration less than 3.4 mmol/L) was observed in 10% of patients, and potassium concentration less than 3.2 mmol/L was observed in 4% of patients 4-6 weeks after the start of therapy. After 12 weeks of therapy, the average decrease in plasma potassium concentration was 0.23 mmol/L. Most adverse reactions (laboratory and clinical indicators) are dose-dependent. The frequency of adverse reactions that were noted during therapy with indapamide is given in the following gradation: very often (? 1/10); often (?1/100,
Storage conditions
The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life: 2 years. Do not use after the expiration date stated on the package.
Side effects of the drug Arifon retard
Considering the fact that most of the side effects of indapamide are dose-dependent, reducing the content of the active substance in the Arifona retard tablet to 1.5 mg made it possible to significantly reduce the likelihood of developing side effects. Hypokalemia may develop (especially in patients at risk); hyponatremia, accompanied by hypovolemia and dehydration with the possible development of orthostatic hypotension. Concomitant loss of chloride ions may secondary cause compensatory metabolic alkalosis. Hyperuricemia and hyperglycemia are possible; hypercalcemia is very rare. Hematological disorders develop extremely rarely: leukopenia, thrombocytopenia, agranulocytosis, hemolytic or aplastic anemia. From the digestive tract, nausea, constipation, dry mouth are observed, in isolated cases - pancreatitis, in patients with liver failure - hepatic encephalopathy. From the central nervous system - dizziness, asthenia, paresthesia, headache. Hypersensitivity reactions are possible in patients prone to them (maculopapular rash, purpura, exacerbation of systemic lupus erythematosus).
Special instructions for the use of the drug Arifon retard
Before starting treatment and during the period of use of the drug, the level of potassium, sodium, calcium and glucose in the blood plasma should be monitored, kidney function should be monitored (creatinine and urea levels in the blood plasma) and ECG monitoring, especially in cases of water-electrolyte balance disorders and gout , diabetes mellitus, liver or kidney failure, in elderly patients. Hypokalemia (less than 3.4 mmol/l) is a predisposing factor in the development of dangerous arrhythmias and increases the toxicity of cardiac glycosides. Such patients should more often monitor the level of potassium in the blood serum and correct it, especially in patients at risk (elderly people, with an unbalanced diet, in patients with liver cirrhosis, coronary artery diseases, heart failure, with a prolongation of the QT by ECG). The possible development of hyperuricemia contributes to the occurrence of gout attacks. The use of the drug in athletes may cause a positive reaction during doping control. The drug is not recommended for use in children. Arifon retard does not interfere with psychomotor reactions and can affect the ability to drive vehicles and operate dangerous machinery only in the event of a sharp decrease in blood pressure. It is not recommended to prescribe the drug during pregnancy and breastfeeding.
Arifon® retard
Not recommended combination of drugs
With the simultaneous use of indapamide and lithium preparations, an increase in the concentration of lithium in the blood plasma may be observed due to a decrease in its excretion, accompanied by the appearance of signs of overdose. If necessary, diuretic drugs can be used in combination with lithium drugs, and the dose of the drugs should be carefully selected, constantly monitoring the lithium content in the blood plasma.
Combinations requiring special control
Drugs that can cause aritis:
- class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
- class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);
- some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);
- others: bepridil, cisapride, difemanil, erythromycin (iv), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (iv).
Hypokalemia increases the risk of developing ventricular arrhythmias, especially arrhythmias. The level of potassium in the blood plasma should be determined and, if necessary, adjusted before starting combination therapy with indapamide and the above drugs. It is necessary to monitor the patient’s clinical condition, monitor the level of electrolytes in the blood plasma, and ECG indicators.
In patients with hypokalemia, drugs that do not cause ari should be used.
When used simultaneously with NSAIDs (for systemic use), including selective COX-2 inhibitors, high doses of salicylates (more than 3 g/day), the hypotensive effect of indapamide may be reduced. With significant fluid loss, acute renal failure may develop (due to decreased glomerular filtration). If it is necessary to prescribe NSAIDs during therapy with Arifon retard, the loss of water should be compensated and renal function should be carefully monitored.
When indapamide is used concomitantly with ACE inhibitors, hyponatremia in patients receiving ACE inhibitors increases the risk of sudden arterial hypotension and/or acute renal failure (especially with renal artery stenosis). Patients with arterial hypertension and a reduced content of sodium ions in the blood plasma due to diuretics should:
- 3 days before starting treatment with ACE inhibitors, stop taking diuretics. In the future, if necessary, resume taking diuretics;
- or begin therapy with ACE inhibitors with low, gradually increasing doses of ACE inhibitors.
In chronic heart failure, treatment should begin with low doses of ACE inhibitors, after first reducing the dose of diuretics. In all cases, in the first week of taking ACE inhibitors, it is necessary to monitor renal function (plasma creatinine content).
When using indapamide simultaneously with other drugs that can cause hypokalemia, incl. with amphotericin B (iv), gluco- and mineralocorticoids (with systemic use), tetracosactide, laxatives that stimulate intestinal motility, the risk of hypokalemia increases due to an additive effect (constant monitoring of the level of potassium in the blood plasma is required and, if necessary, appropriate treatment). Particular attention should be paid to patients simultaneously receiving cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.
With simultaneous use of indapamide with baclofen, an increase in the hypotensive effect is observed (it is necessary to compensate for the loss of water and carefully monitor renal function at the beginning of treatment).
When used simultaneously with cardiac glycosides, the toxic effect of the latter may be enhanced due to hypokalemia (it is necessary to monitor the level of potassium in the blood plasma and ECG readings and, if necessary, adjust therapy).
Combinations requiring special attention
Concomitant therapy with indapamide and potassium-sparing diuretics is advisable in some patients, but this does not exclude the possibility of developing hypokalemia (especially in patients with diabetes mellitus and patients with renal failure) or hyperkalemia. It is necessary to monitor the level of potassium in the blood plasma, ECG indicators and, if necessary, adjust therapy.
Functional renal failure, which can occur against the background of diuretics, especially loop diuretics, with simultaneous administration of metformin increases the risk of developing lactic acidosis. It is not recommended to use metformin in combination with Arifon retard if the creatinine level is more than 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.
Dehydration while taking diuretics increases the risk of developing acute renal failure, especially when using high doses of iodinated contrast agents. Before using iodine-containing contrast agents, patients must compensate for fluid loss.
With the simultaneous use of indapamide and tricyclic antidepressants, antipsychotics, there is an increase in the hypotensive effect of indapamide and an increased risk of developing orthostatic hypotension (additive effect).
With the simultaneous use of thiazide diuretics and calcium salts, hypercalcemia may develop due to a decrease in the excretion of calcium ions in the urine.
With the simultaneous use of thiazide diuretics with cyclosporine and tacrolimus, it is possible to increase the creatinine content in the blood plasma without changing the concentration of circulating cyclosporine, even with normal fluid and sodium ion levels.
With the simultaneous use of thiazide diuretics with GCS, tetracosactide for systemic use, a decrease in the hypotensive effect is observed due to the retention of water and sodium ions under the influence of GCS.
Interactions of the drug Arifon retard
The simultaneous administration of the following drugs with Arifon retard is not recommended: lithium salts (an increase in the concentration of lithium in the blood serum with the development of toxic manifestations; if it is necessary to prescribe such a combination, the level of lithium in the blood serum should be monitored), astemizole, bepridil, erythromycin, halofantrine, pentamidine, sultopride , terfenadine, vincamine (increased risk of developing ventricular flutter-fibrillation, especially in the presence of hypokalemia, bradycardia or prolongation of the QT ). The following drugs should be prescribed with caution along with Arifon retard: NSAIDs for systemic use, including salicylates in high doses (possible development of acute renal failure in patients with dehydration; it is necessary to monitor kidney function and rehydrate), drugs that reduce the level of potassium in the blood - amphotericin B with intravenous administration, gluco- and mineralocorticoids for oral administration, tetracosactide, laxatives that stimulate peristalsis (increase the risk of hypokalemia), corticosteroids, tetracosactide (reduced antihypertensive effect as a result of water and sodium retention in the body), cardiac glycosides ( hypokalemia increases the risk of developing toxic effects of digitalis), potassium-sparing diuretics - amiloride, triamterene, spironolactone (possible development of hyperkalemia in patients with renal failure), ACE inhibitors (possible development of sudden arterial hypotension or renal failure due to hyponatremia in patients with dehydration; it is recommended to stop using the diuretic 3 days before prescribing ACE inhibitors, then, if necessary, the diuretic is resumed), antiarrhythmic drugs - quinidine, hydroquinidine, disopyramide, bretylium tosylate, sotalol and amiodarone (the risk of developing paroxysms of flutter-ventricular fibrillation increases, especially in the presence of hypokalemia or prolongation of the QT interval), metformin (risk of developing lactic acidosis due to the development of renal failure), iodine-containing contrast agents (with dehydration caused by the use of diuretics, the risk of developing acute renal failure increases; fluid and electrolyte balance should be restored before contrast administration), tricyclic antidepressants ( potentiate the hypotensive effect and increase the risk of developing orthostatic hypotension), calcium salts (risk of developing hypercalcemia), cyclosporine (increased serum creatinine levels), estrogens (due to fluid retention in the body, the hypotensive effect of the drug may be reduced).
Arifon®
Combinations not recommended for use
Lithium preparations:
With the simultaneous use of indapamide and lithium preparations, as well as when following a salt-free diet, an increase in the concentration of lithium in the blood plasma may be observed due to a decrease in its excretion, accompanied by the appearance of signs of overdose. If necessary, diuretics can be used in combination with lithium preparations, and the concentration of lithium in the blood plasma should be carefully monitored and the dose of the drug should be adjusted accordingly.
Combinations requiring precautions
— Drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type:
- antiarrhythmic drugs class IA (quinidine, hydroquinidine, disopyramide, procainamide) and class IC (flecainide);
- class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide, bretylium tosylate, dronedarone);
- neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol); pimozide, sertindole;
- antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (citalopram, escitalopram);
- antibacterial agents: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin); macrolides (erythromycin for intravenous administration, azithromycin, clarithromycin, roxithromycin, spiramycin), co-trimoxazole;
- antifungal agents of a number of azoles (voriconazole, itraconazole, ketoconazole, fluconazole);
- antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);
- antianginal drugs (ranolazine, bepridil);
- antitumor drugs and immunomodulators (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus, anagrelide);
- antiemetics (ondansetron);
- drugs that affect gastrointestinal motility (cisapride, domperidone);
- antihistamines (astemizole, terfenadine, mizolastine);
- others: pentamidine, difemanil, vincamine for intravenous administration, vasopressin, terlipressin, ketanserin. probucol, propofol, sevoflurane, terodiline, cilostazol.
Increased risk of developing ventricular arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type (risk factor - hypokalemia).
Before prescribing combination therapy with indapamide and the above drugs, a study should be conducted to identify hypokalemia and, if necessary, correction should be made. It is necessary to monitor the patient’s clinical condition, monitor the level of electrolytes in the blood plasma, and ECG indicators.
In patients with hypokalemia, it is necessary to use drugs that do not cause polymorphic ventricular tachycardia of the “pirouette” type.
Nonsteroidal anti-inflammatory drugs (when administered systemically), including selective COX-2 inhibitors, high doses of acetylsalicylic acid (≥ 3 g/day):
The antihypertensive effect of indapamide may be reduced.
Dehydrated patients are at risk of developing acute renal failure due to decreased glomerular filtration. Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
Angiotensin-converting enzyme (ACE) inhibitors:
Prescribing ACE inhibitors to patients with an initially reduced concentration of sodium ions in the blood is accompanied by a risk of sudden arterial hypotension and/or acute renal failure (in particular, patients with renal artery stenosis).
For patients with arterial hypertension
and possibly reduced, due to previous use of diuretics, the concentration of sodium ions in the blood plasma, it is necessary:
-3 days before starting treatment with an ACE inhibitor, stop taking the diuretic. In the future, if necessary, the use of a non-potassium-sparing diuretic can be resumed;
-or start ACE inhibitor therapy with low doses, followed by a gradual increase in dose if necessary.
For chronic heart failure
Treatment with ACE inhibitors should begin with the lowest doses, with a possible preliminary reduction in the dose of a non-potassium-sparing diuretic.
In all cases
In the first weeks of taking ACE inhibitors in patients, it is necessary to monitor renal function (plasma creatinine concentration).
Other drugs that can cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticoids (when used systemically), tetracosactide, laxatives that stimulate intestinal motility:
Increased risk of hypokalemia (additive effect).
Constant monitoring of the concentration of potassium in the blood plasma is necessary, and, if necessary, its correction. Particular attention should be paid to patients concomitantly receiving cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.
Baclofen:
There is an increase in the antihypertensive effect.
Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
Cardiac glycosides:
Hypokalemia enhances the toxic effects of cardiac glycosides.
With the simultaneous use of indapamide and cardiac glycosides, the concentration of potassium in the blood plasma, ECG readings should be monitored, and, if necessary, therapy should be adjusted.
Combinations requiring special attention
— Allopurinol:
Concomitant use with indapamide may increase the risk of hypersensitivity reactions during treatment with allopurinol.
Combinations that require attention
— Potassium-sparing diuretics (amiloride, spironolactone, triamterene):
Combination therapy with indapamide and potassium-sparing diuretics is advisable in some patients, but the possibility of developing hypokalemia or hyperkalemia cannot be excluded (especially in patients with renal failure or in patients with diabetes mellitus).
It is necessary to monitor the level of potassium in the blood plasma, ECG indicators and, if necessary, adjust therapy.
— Metformin:
Functional renal failure, which can occur while taking diuretics, especially loop diuretics, increases the risk of developing metformin-induced lactic acidosis.
Metformin should not be used if creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.
— Iodinated contrast agents:
In case of dehydration while taking diuretics, the risk of developing acute renal failure increases, especially when using high doses of iodine-containing contrast agents.
Before using iodinated contrast agents, patients need to compensate for fluid loss.
— Tricyclic antidepressants, antipsychotics:
Drugs of these classes enhance the antihypertensive effect of indapamide and increase the risk of developing orthostatic hypotension (additive effect).
— Calcium (salts):
With simultaneous use, hypercalcemia may develop due to a decrease in the excretion of calcium ions by the kidneys.
— Cyclosporine, tacrolimus:
It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even in the absence of loss of water and sodium ions.
— Corticosteroid drugs, tetracosactide (for systemic use):
Reduced antihypertensive effect (retention of water and sodium ions as a result of the action of corticosteroids).
Overdose of the drug Arifon retard, symptoms and treatment
Symptoms of overdose (taking very large doses) are primarily manifestations of water and electrolyte disturbances (hyponatremia, hypokalemia). Clinically, nausea, vomiting, hypotension, convulsions, drowsiness, dizziness, polyuria or oliguria up to anuria (which is a consequence of hypovolemia) may occur. First aid measures include rapid elimination of the drug by gastric lavage and/or administration of activated carbon, followed by restoration of water and electrolyte balance in a hospital setting.
