Arifon, retard pills 1.5mg, 30pcs

Composition

1 tablet contains:

Active ingredient:

indapamide – 1.5 mg;

Auxiliary substances:

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:

glycerol-0.219 mg;

hypromellose-3.642 mg;

macrogol 6000-0

.219 mg; magnesium stearate-0.219 mg;

titanium dioxide-0.701 mg

Pharmacological action

Pharmacotherapy group: diuretic. ATX code:  C03BA11

Pharmacodynamics

Indapamide belongs to the derivatives of sulfonamide 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 excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys increases, which is accompanied by an increase in diuresis and a hypotensive effect.

In phase II and III clinical trials, a 24-hour antihypertensive effect was demonstrated when indapamide was used as monotherapy in doses that did not have a pronounced diuretic effect.

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 increase in the dose of the drug. Therefore, do not increase the dose of the drug if the recommended dose does not achieve a therapeutic effect.

In short, medium-term and long-term studies involving patients with arterial hypertension, indapamide has been shown to:

• It does not affect the parameters of lipid metabolism, including the level of triglycerides, cholesterol, low-density lipoproteins and high-density lipoproteins;
• it does not affect the parameters of carbohydrate metabolism, including in patients with diabetes mellitus.

Pharmacokinetics

In Arifon ® retard tablets, the Active ingredient is contained in a special matrix carrier that provides a gradual controlled release of indapamide in the gastrointestinal tract.

Suction

Released indapamide is rapidly and completely absorbed in the gastrointestinal tract.

Food intake slightly increases the absorption time of the drug, without affecting the completeness of absorption.

The maximum concentration in blood plasma is reached 12 hours after ingestion 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 an individual variability in the absorption of the drug.

Distribution

About 79% of the drug binds to plasma proteins. The elimination half-life is 14-24 hours (on average,18 hours).

The equilibrium concentration is reached after 7 days of taking the drug.

With repeated use of the drug, its accumulation is not observed.

Metabolism

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

High-risk patients

In patients with renal insufficiency, the pharmacokinetics of Arifon ® retard do not change.

Indications

Arterial hypertension.

Use during pregnancy and lactation

As a rule, diuretics should not be prescribed during pregnancy. You can not use these drugs to treat physiological edema during pregnancy. Diuretics can cause fetoplacental ischemia and lead to impaired fetal development. Due to the fact that indapamide is excreted in breast milk, it is not recommended to prescribe the drug during breastfeeding.

Contraindications

• severe hepatic impairment;
• hypokalemia;
• severe renal failure (creatinine clearance less than 30 ml / min);
• hepatic encephalopathy;
• hypersensitivity to indapamide, other sulfonamide derivatives or any of the excipients.

Due to the fact that the drug contains lactose, Arifon® retard is not recommended for patients with lactose intolerance, galactosemia, glucose-galactose malabsorption. With caution: the drug should be prescribed for impaired liver and kidney function, impaired water and electrolyte balance, weakened patients or patients receiving concomitant therapy with other antiarrhythmic drugs, diabetes mellitus, elevated uric acid levels, hyperparathyroidism, patients with an extended QT interval. Due to the lack of sufficient clinical data, the drug is not recommended for use in children under 18 years of age.

Side effects

From the side of the skin and subcutaneous fat:  hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions: often-maculopapular rash; infrequently-hemorrhagic vasculitis; very rarely-angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; unspecified frequency — patients with acute systemic lupus erythematosus may worsen the course of the disease. Cases of photosensitivity reactions are described (see the sections “Special instructions” and “Interaction”).

From the circulatory and lymphatic system:  very rarely — thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the central nervous system:  rarely-asthenia, headache, paresthesia, vertigo; unspecified frequency-syncope.

From the CCC side:  very rarely — arrhythmia, marked decrease in blood pressure. Blood pressure; unspecified frequency-arrhythmia of the “pirouette” type (possibly fatal) (see the 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 — kidney failure.

Liver and biliary tract disorders:  very rarely-impaired liver function; unspecified frequency-the possibility of developing hepatic encephalopathy in case of liver failure (see “Contraindications”, “Special instructions”), hepatitis.

Laboratory parameters:  unspecified frequency-increased QT interval on the ECG increased uric acid and glucose concentrations in the blood: thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes mellitus; increased activity of hepatic transaminases.

Interaction of

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

Corticosteroid drugs, tetracosactide (with systemic use). Reduced hypotensive effect (fluid retention and sodium ions as a result of corticosteroids).

Undesirable combination of medicinal substances

Lithium preparations. When indapamide and lithium preparations are used simultaneously, an increase in the concentration of lithium in the blood plasma may occur 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 preparations, and the dose of drugs should be carefully selected, constantly monitoring the lithium content in the blood plasma.

A combination of drugs that requires special attention

Drugs that can cause pirouette-type arrhythmia:

– antiarrhythmic drugs of class IA (quinidine, gedragingen, disopyramide);

– anti-arrhythmic drugs class III (amiodarone, sotalol, dofetilide, ibutilide);

some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, triptorelin), benzamide (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

– others: bepridil, cisapride, was diphemanil, erythromycin (in/in), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine has (in/in).

Increased risk of ventricular arrhythmias, especially pirouette-type arrhythmias (risk factor — hypokalemia).

It is necessary to determine the level of potassium in the blood plasma and, if necessary, adjust it before starting combination therapy with indapamide and the above drugs. It is necessary to monitor the patient’s clinical condition, monitor the level of blood plasma electrolytes, and ECG indicators.

In patients with hypokalemia, it is necessary to use drugs that do not cause arrhythmia of the “pirouette”type.

NSAIDs (with systemic use), including selective COX-2 inhibitors, high doses of salicylates (≥3 g / day). It is possible to reduce the antihypertensive effect of indapamide. With significant fluid loss, acute renal failure may develop (due to a decrease in glomerular filtration). Patients need to compensate for fluid loss and carefully monitor kidney function at the beginning of treatment.

ACE inhibitors. The use of ACE inhibitors in patients with a reduced concentration of sodium ions in the blood (especially in patients with renal artery stenosis) is associated with the risk of sudden hypotension and/or acute renal failure.

Patients with arterial hypertension and possibly reduced due to the use of diuretics, the content of sodium ions in the blood plasma should:

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

– or start therapy with an ACE inhibitor at low doses, followed by a gradual increase in the dose if necessary.

In patients with chronic heart failure, treatment with ACE inhibitors should be initiated at low doses, with possible preliminary reductions in diuretic doses.

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

Other drugs that can cause hypokalemia: amphotericin B (IV), corticosteroids and mineralocorticosteroids (with systemic use), tetracosactide, laxatives that stimulate intestinal motility. Increased risk of hypokalemia (additive effect).

It is necessary to constantly monitor the level of potassium in the blood plasma, if necessary — its correction. Special attention should be paid to patients receiving concomitant 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 kidney function at the beginning of treatment.

Cardiac glycosides. Hypokalemia increases the toxic effect of cardiac glycosides.

When using indapamide and cardiac glycosides simultaneously, the level of potassium in the blood plasma, ECG indicators should be monitored, and, if necessary, therapy should be adjusted.

A combination of medications that requires attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene). Combination therapy with indapamide and potassium-sparing diuretics is appropriate in some patients, but the possibility of hypokalemia (especially in patients with diabetes mellitus and patients with renal insufficiency) or hyperkalemia is not excluded.

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 may occur with diuretics, especially loop diuretics, and concomitant use of metformin increases the risk of lactic acidosis.

Do not use metformin if the creatinine level exceeds 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

Iodine-containing contrast agents. Dehydration of the body while taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

Before using iodine-containing contrast agents, patients need to compensate for fluid loss.

Tricyclic antidepressants, antipsychotic drugs (neuroleptics). Drugs of these classes enhance the antihypertensive effect of indapamide and increase the risk of 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.

How to take, course of use and dosage

Inside, swallowing whole, without chewing, with water,1 tablet per day, preferably in the morning.

In the treatment of patients with arterial hypertension, an increase in the dose of the drug does not lead to an increase in the antihypertensive effect, but increases 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.

Overdose

Indapamide, even in very high concentrations (up to 40 mg, i. e. 27 times the therapeutic dose), does not have a toxic effect. Symptoms of acute poisoning with the drug are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). Nausea, vomiting, decreased blood pressure, seizures, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia) may also occur. Treatment: urgent measures aimed at removing the drug from the body: gastric lavage and / or use of activated charcoal, followed by restoration of normal water-electrolyte balance.

Special instructions

Impaired liver function When thiazide and thiazide-like diuretics are prescribed, patients with impaired liver function may develop hepatic encephalopathy, especially in the case of electrolyte imbalance. In this case, diuretics should be discontinued immediately. Photosensitivity Cases of photosensitivity reactions have been reported with thiazide and thiazide-like diuretics. 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. Sodium ion content in blood plasma Before starting treatment, it is necessary to determine the content of sodium ions in blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretic drugs can cause hyponatremia, sometimes leading to extremely severe consequences. It is necessary to constantly monitor the content of sodium ions, because initially a decrease in the concentration of sodium in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most careful monitoring of the sodium ion content is indicated for patients with cirrhosis of the liver and the elderly. Blood potassium ion content 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. The risk of hypokalemia should be avoided (/k) in patients of the following categories: elderly, weakened or receiving combined drug therapy with other antiarrhythmic drugs and drugs that may increase the QT interval, patients with cirrhosis of the liver, peripheral edema or ascites, coronary heart disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias. In addition, the increased risk group includes patients with an extended QT interval, and it does not matter whether this increase is caused by congenital causes or the action of medications. Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe arrhythmias and, especially, arrhythmias of the “pirouette” type, which can lead to death. In all the cases described above, it is necessary to regularly monitor the content of potassium in the blood plasma. The first measurement of the concentration of potassium ions in the blood should be carried out within the first week after the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. 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. You should stop taking diuretic medications before examining the function of the parathyroid glands. Blood glucose in blood plasma It is necessary to monitor the blood glucose level in patients with diabetes mellitus, especially in the presence of hypokalemia. Uric acid in patients with gout may increase the frequency of seizures or worsen the course of gout. Diuretics and function Renal thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (adult plasma creatinine levels below 25 mg / l or 220 mmol/L). In elderly patients, normal plasma creatinine levels are calculated based on age, body weight, and gender. It should be borne in mind that at the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which, in turn, is caused by loss of fluid and sodium ions against the background of taking diuretics. As a result, the concentration of urea and creatinine in the blood plasma may increase. If kidney function is not impaired, such temporary functional renal failure usually passes without consequences, but with existing renal failure, the patient’s condition may worsen. Athletes Indapamide can give a positive result during doping control in athletes. Influence on the ability to drive motor vehicles and manage mechanismthe action of substances included in the preparation Arifon ® retard does not lead to a violation of psychomotor reactions. However, some people may develop different individual reactions in response to a decrease in blood pressure, especially at the beginning of therapy or when other antihypertensive agents are added to the current therapy. In this case, the ability to drive a car or other mechanisms may be reduced.

Form of production

Tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

2 years

Active ingredient

Indapamide

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension