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 TABLE 1.5 MG No. 30
Compound
Active substance: indapamide 1.5 mg
Excipients:
- lactose monohydrate - 124.5 mg;
- hypromellose - 64 mg;
- magnesium stearate - 1 mg;
- povidone - 8.6 mg;
- colloidal silicon dioxide anhydrous - 0.4 mg.
film shell:
- glycerol - 0.219 mg;
- hypromellose - 3.642 mg;
- macrogol 6000 - 0.219 mg;
- magnesium stearate - 0.219 mg;
- titanium dioxide - 0.701 mg.
Nosological classification (ICD-10)
- I10 Essential (primary) hypertension
- I15 Secondary hypertension
Description of the dosage form
Round, biconvex, film-coated tablets, white.
pharmachologic effect
Pharmacological action - hypotensive, diuretic.
Pharmacodynamics
Indapamide is a sulfonamide derivative with an indole ring and is similar in pharmacological properties to thiazide diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. At the same time, the kidneys secrete sodium, chlorine ions and, to a lesser extent, potassium and magnesium ions, which is accompanied by an increase in diuresis and a hypotensive effect.
In clinical studies of phases II and III, using indapamide as monotherapy in doses that did not have a pronounced diuretic effect, a 24-hour hypotensive effect was demonstrated.
The antihypertensive activity of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in arteriolar and total peripheral vascular resistance.
Indapamide reduces 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-term, intermediate-term and long-term studies in patients with hypertension, indapamide has been shown to:
- does not affect lipid metabolism indicators, incl. on the level of triglycerides, cholesterol, LDL and HDL;
- does not affect carbohydrate metabolism, incl. in patients with diabetes mellitus.
Pharmacokinetics
In Arifon® retard tablets, the active substance is located in a special carrier matrix, which ensures gradual controlled release of indapamide in the gastrointestinal tract.
Suction
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
About 79% of the drug binds to blood plasma proteins. T1/2 - 14–24 hours (average 18 hours).
Css is achieved after 7 days of taking the drug.
When taking the drug repeatedly, no accumulation is observed.
Metabolism
Indapamide is excreted in the form of inactive metabolites, mainly by the kidneys (70% of the administered dose) and through the intestines (22%).
Patients at high risk
In patients with renal failure, the pharmacokinetics of Arifon® retard does not change.
Indications for the drug Arifon® retard
Arterial hypertension.
Contraindications
hypersensitivity to indapamide, other sulfonamide derivatives or any of the excipients;
severe form of renal failure (Cl creatinine <30 ml/min);
hepatic encephalopathy or severe liver dysfunction;
hypokalemia.
Due to the fact that the drug contains lactose, Arifon® retard is not recommended for patients with lactose intolerance, galactosemia, or glucose-galactose malabsorption.
With caution (for details, see “Special Instructions”): impaired liver and kidney function, water-electrolyte imbalance, debilitated patients or patients receiving combined therapy with other antiarrhythmic drugs (see “Interaction”), diabetes mellitus, increased urinary tract acids, patients with prolonged QT interval, hyperparathyroidism.
Due to the lack of sufficient clinical data, the drug is not recommended for use in children under 18 years of age.
Use during pregnancy and breastfeeding
Pregnancy
As a general rule, diuretics should not be prescribed during pregnancy. These drugs should not be used to treat physiological edema during pregnancy. Diuretics can cause fetoplacental ischemia and lead to impaired fetal development.
Breastfeeding period
It is not recommended to prescribe Arifon® retard to nursing mothers (indapamide is excreted in breast milk).
Side effects
Most adverse reactions (laboratory and clinical indicators) are dose-dependent.
The frequency of adverse reactions that can be caused by thiazide-like diuretics, including indapamide, is given in the following gradation: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); unspecified frequency (frequency cannot be calculated from available data).
From the circulatory and lymphatic system: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
From the side of the central nervous system: rarely - asthenia, headache, paresthesia, vertigo; unspecified frequency - fainting.
From the cardiovascular system: very rarely - arrhythmia, marked decrease in blood pressure; unspecified frequency - ari (possibly fatal) (see sections “Interaction” and “Special instructions”).
From the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the oral mucosa; very rarely - pancreatitis.
From the urinary system: very rarely - renal failure.
From the liver and biliary tract: very rarely - impaired liver function; unspecified frequency - the possibility of developing hepatic encephalopathy in case of liver failure (see “Contraindications”, “Special instructions”), hepatitis.
On the part of the skin and subcutaneous fat: hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions: often - maculopapular rash; uncommon - hemorrhagic vasculitis; very rarely - angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; unspecified frequency - in patients with an acute form of systemic lupus erythematosus, the course of the disease may worsen. Cases of photosensitivity reactions have been described (see sections “Special instructions” and “Interaction”).
Laboratory indicators: unspecified frequency - increase in QT interval on ECG (see “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 studies, hypokalemia (plasma potassium content less than 3.4 mmol/l) was observed in 10% of patients and less than 3.2 mmol/l in 4% of patients after 4–6 weeks of treatment. 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 - a decrease in potassium levels and the development of hypokalemia, especially significant for patients at risk (see “Special Instructions”); hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous hypochloremia can lead to compensatory metabolic alkalosis (the likelihood and severity of this effect is low).
Interaction
Undesirable combination of drugs
Lithium preparations. 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.
Combination of drugs requiring special attention
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).
Increased risk of ventricular arrhythmias, especially arrhythmias (risk factor - hypokalemia).
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.
NSAIDs (if administered systemically), including selective COX-2 inhibitors, high doses of salicylates (≥3 g/day). The antihypertensive effect of indapamide may be reduced. With significant fluid loss, acute renal failure may develop (due to decreased glomerular filtration). Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
ACE inhibitors. Prescribing ACE inhibitors to patients with a 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:
- 3 days before starting treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, diuretics can be resumed;
- or begin ACE inhibitor therapy with 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 a possible preliminary reduction in the doses of diuretics.
In all cases, in the first week of taking ACE inhibitors in patients, it is necessary to monitor renal function (plasma creatinine content).
Other drugs that can cause hypokalemia: amphotericin B (iv), corticosteroids and mineralocorticosteroids (when administered systemically), tetracosactide, laxatives that stimulate intestinal motility. Increased risk of hypokalemia (additive effect).
Constant monitoring of the level of potassium in the blood plasma is necessary, and, if necessary, its correction. Particular attention should be paid to patients simultaneously receiving cardiac glycosides. It is recommended to use laxatives that do not stimulate intestinal motility.
Baclofen. There is an increase in the hypotensive effect.
Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
Cardiac glycosides. Hypokalemia enhances the toxic effect of cardiac glycosides.
With the simultaneous use of indapamide and cardiac glycosides, the level of potassium in the blood plasma, ECG parameters should be monitored, and, if necessary, therapy should be adjusted.
Combination of drugs requiring 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 (especially in patients with diabetes mellitus and patients with renal failure) or hyperkalemia cannot be excluded.
It is necessary to monitor the level of potassium in the blood plasma, ECG parameters and, if necessary, adjust therapy.
Metformin. 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 if creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.
Iodinated contrast agents. 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.
Tricyclic antidepressants, antipsychotics (neuroleptics). Drugs in these classes enhance the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).
Calcium salts. With simultaneous administration, hypercalcemia may develop due to a decrease in the excretion of calcium ions by the kidneys.
Cyclosporine, 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.
Corticosteroid drugs, tetracosactide (if administered systemically). Reduced hypotensive effect (retention of fluid and sodium ions as a result of the action of corticosteroids).
Directions for use and doses
Inside, swallow whole, without chewing, with water, 1 tablet. per day, preferably in the morning.
When treating patients with arterial hypertension, increasing the dose of the drug does not lead to an increase in antihypertensive effect, but enhances the diuretic effect.
Elderly patients
In elderly patients, plasma creatinine levels 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 “Contraindications”).
Overdose
Indapamide, even in very high doses (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). Clinical symptoms of overdose may include nausea, vomiting, decreased blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia).
Emergency measures are limited to removing the drug from the body: gastric lavage and/or administration of activated charcoal, followed by restoration of water and electrolyte balance.
special instructions
Liver dysfunction
When prescribing thiazide and thiazide-like diuretics in patients with impaired liver function, hepatic encephalopathy may develop, especially in the case of electrolyte imbalance. In this case, diuretics should be stopped immediately.
Photosensitivity
Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics (see “Side effects”). 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 UV rays.
Water and electrolyte balance:
— Content of sodium ions in 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. All diuretic drugs can cause hyponatremia, sometimes leading to extremely serious consequences. Constant monitoring of the content of sodium ions is necessary, because Initially, a decrease in sodium concentration in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most careful monitoring of the content of sodium ions is indicated for patients with cirrhosis of the liver and the elderly (see “Side effects” and “Overdose”).
— Content of potassium ions in blood plasma. When treating with thiazide and thiazide-like diuretics, the main risk is a sharp decrease in the level of potassium in the blood plasma and the development of hypokalemia. It is necessary to avoid the risk of developing hypokalemia (<3.4 mmol/l) in patients of the following categories: elderly, debilitated or receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that can prolong the QT interval, patients with cirrhosis, peripheral edema or ascites ,IHD, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.
In addition, patients with an increased QT interval are at increased risk, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.
Hypokalemia, like bradycardia, is a condition that contributes to the development of severe arrhythmias and especially arrhythmias, which can be fatal. In all the cases described above, it is necessary to regularly monitor the potassium content in the blood plasma. The first measurement of the concentration of potassium ions in the blood must be carried out within the first week from the start of treatment.
If hypokalemia occurs, appropriate treatment should be prescribed.
— Calcium content in blood plasma. It should be borne in mind that thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism.
Diuretics should be discontinued before testing parathyroid function.
— Glucose content in blood plasma. It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.
- Uric acid. In patients with gout, the frequency of attacks may increase or the course of gout may worsen.
Diuretics and kidney function. Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg/l or 220 µmol/l). In elderly patients, normal plasma creatinine levels are calculated taking into account age, body weight and gender.
It should be taken into account that at the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which in turn is caused by the loss of fluid and sodium ions while taking diuretic drugs. As a result, the concentration of urea and creatinine in the blood plasma may increase. If renal function is not impaired, such temporary functional renal failure, as a rule, passes without consequences, however, with existing renal failure, the patient's condition may worsen.
Athletes
The active substance included in the drug Arifon® retard can give a positive result during doping control in athletes.
Impact on the ability to drive a car and perform work that requires increased speed of physical and mental reactions
The action of the substances included in the drug Arifon® retard does not lead to impairment of psychomotor reactions. However, some people may develop different individual reactions in response to lowering blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to therapy. In this case, the ability to drive a car or operate other machinery may be reduced.
Release form
Controlled-release film-coated tablets, 1.5 mg.
30 tablets each in a blister (PVC/Al). 1 blister is included in a cardboard box.
Packaging for hospitals:
30 tablets each in a blister (PVC/Al). 3 blisters are included in a cardboard pack.
30 tablets each in a blister (PVC/Al). 10 blisters in a cardboard pack (the pack is not marked). 3 cardboard packs are placed in a cardboard box.
Manufacturer
Registration certificate issued, France.
Manufactured by: Serdix LLC, Russia, 142150, Moscow, Sofiino village, building 1/1.
Tel.; Fax.
For any questions, please contact the Representative Office of Servier Laboratories JSC.
Representative office of Servier Laboratories JSC: 115054, Moscow, Paveletskaya sq., 2, building 3.
Tel.; Fax.
Conditions for dispensing from pharmacies
- On prescription.
Storage conditions for the drug Arifon® retard
- At a temperature not exceeding 30 °C.
- Keep out of the reach of children.
Shelf life of Arifon® retard
- 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®
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).
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® retard
UNDESIRABLE DRUG COMBINATION
— 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 lithium content in the blood plasma should be carefully monitored and the dose of the drug should be adjusted accordingly.
COMBINATION OF DRUGS REQUIRING SPECIAL ATTENTION
— Drugs that can cause pirouette-type arrhythmia:
- 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, diphemanil, erythromycin (iv), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (iv).
Increased risk of ventricular arrhythmias, especially pirouette-type arrhythmias (risk factor - hypokalemia).
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.
- Non-steroidal 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.
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.
— Angiotensin-converting enzyme (ACE) inhibitors:
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:
- 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 begin ACE inhibitor therapy with low doses, followed by a gradual increase in dose if necessary.
For chronic heart failure
Treatment with ACE inhibitors should be started with the lowest doses, with a possible preliminary reduction in diuretic doses.
In all cases
In the first weeks of taking ACE inhibitors in patients, it is necessary to monitor renal function (plasma creatinine content).
- Other drugs that can cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticosteroids (for systemic use), 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 hypotensive effect.
Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
— Cardiac glycosides:
Hypokalemia enhances the toxic effect 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.
COMBINATION OF DRUGS REQUIRING 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 concentration of potassium in the blood plasma, ECG indicators and, if necessary, adjust therapy.
— Metformin:
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 if creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.
— Iodine-containing 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 (neuroleptics):
Drugs in these classes enhance the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).
— Calcium salts:
With simultaneous administration, hypercalcemia may develop due to a decrease in the excretion of calcium ions by the kidneys.
- Cyclosporine, 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.
— Corticosteroid drugs, tetracosactide (if administered systemically):
Reduced hypotensive effect (retention of fluid 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.
