Arifon - instructions for use, dose, side effects, contraindications

film sheath: glycerol 0.087 mg, macrogol-6000 0.035 mg, magnesium stearate 0.087 mg, hypromellose 1.449 mg, sodium lauryl sulfate 0.017 mg, titanium dioxide 0.278 mg, white beeswax 0.047 mg.

Description:

Round, biconvex tablets, covered with a film coat, white.

Pharmacotherapeutic group:diuretic

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

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

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

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

- Increased prostaglandin synthesis PGE2 and prostacyclin PGI2 (a vasodilator and an inhibitor of platelet aggregation).

Indapamide, like other thiazide diuretics, reduces hypertrophy of the left ventricle. Moreover, against the background of short-term, medium-term and long-term courses of therapy with indapamide:

- lipid metabolism parameters are not changed, including the level of triglycerides, cholesterol, low density lipoproteins and high-density lipoproteins;

- the indices of carbohydrate metabolism do not change, including in patients with diabetes mellitus and arterial hypertension.

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

Pharmacokinetics:

Suction

Bioavailability of indapamide - 93%.

The maximum concentration in the blood plasma (T_mOh) the drug reaches 1-2 hours after oral administration of a single dose of 2.5 mg.

Distribution

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

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

Allocation

Indapamide is excreted as inactive; metabolites mainly with urine (60-80% of the administered dose).

Not more than 5% of indapamide is excreted from the body with urine in unchanged form.

In patients with renal insufficiency, the pharmacokinetic properties of indapamide do not change.

Indications:

Arterial hypertension.

Contraindications:

- Hypersensitivity to indapamide, other derivatives of sulfonamide or any of the excipients of the drug;

- severe renal insufficiency;

- severe hepatic insufficiency or hepatic encephalopathy;

hypokalemia.

Due to the fact that lactose is included in the formulation, Arifone® is not recommended for patients with intolerance to lactose, lactase deficiency, galactosemia, glucose-galactose malabsorption.

Due to the lack of clinical data, the drug is not recommended for use in children under 18 years of age.

Carefully:

Dysfunction of the liver and kidneys, violations of water-electrolyte balance, use in patients with an increased interval QT on ECG, use in weakened patients or in patients receiving concomitant therapy with drugs that can increase the interval QT (see the section "Interaction with other medicinal products"), hyperparathyroidism, diabetes mellitus, hyperuricemia and gout.

Pregnancy and lactation:

Pregnancy

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

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

Lactation

It is not recommended to administer Arifon® to nursing mothers (indapamide is excreted with milk).

Dosing and Administration:

Is administered orally 1 tablet / day, preferably in the morning.

When treating patients with arterial hypertension, the dose of the drug should not exceed 2.5 mg / day (increased risk of side effects without increasing antihypertensive effect).

Side effects:

Most adverse reactions (laboratory and clinical indicators) are dose-dependent.

The incidence of adverse reactions that may be caused by thiazide-like diuretics, including indapamide,

is given in the form of the following gradation: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000); frequency (frequency can not be calculated from available data).

From the side of the blood and lymphatic system

Highly rarely: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the central nervous system

Rarely: asthenia, headache, paresthesia, vertigo;

Unspecified frequency: fainting.

From the side of the cardiovascular system

Rarely: arrhythmia, marked decrease in blood pressure;

Unspecified frequency: an arrhythmia of the "pirouette" type (possibly fatal) (see the sections "Interaction with other medicinal products" and "Special instructions").

From the digestive system

Infrequently: vomiting;

Rarely: nausea, constipation, dryness of the oral mucosa;

Rarely: pancreatitis.

From the urinary system

Rarely: renal insufficiency.

From the liver and biliary tract

Rarely: abnormal liver function;

Unspecified frequency: the possibility of the development of hepatic encephalopathy in case of liver failure (see the sections "Contraindications" and "Special instructions"), hepatitis.

From 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;

Rarely: angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome;

Unspecified frequency: y patients with acute form of systemic lupus erythematosus may worsen the course of the disease. Cases of photosensitivity reactions are described (see sections "Special instructions" and "Interaction with other medicinal products ").

Laboratory indicators

Unspecified frequency:

- enlargement QT interval on ECG (compare section "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 "hepatic" transaminase.

In clinical studies, hypokalemia (a potassium level in the blood plasma of less than 3.4 mmol / L) was observed in 25% of patients and less than 3.2 mmol / L in 10% of patients after 4-6 weeks of treatment. After 12 weeks of therapy, the potassium content in the blood plasma decreased, on average, by 0.41 mmol / l.

Rarely: hypercalcemia.

Unspecified frequency:decrease in potassium content and development of hypokalemia, especially significant for patients at risk (see section "Special instructions"); hyponatremia, accompanied by hypovolemia leading to dehydration, and orthostatic hypotension.

Simultaneous hypochloraemia can lead to metabolic alkalosis of compensatory nature (the probability and severity of this effect is low).

Overdose:

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

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

Emergency measures are reduced to removing the drug from the body: washing the stomach and / or the appointment of activated carbon, followed by the restoration of the water-electrolyte balance.

Interaction:

UNDESIRABLE CONVERSIONS OF MEDICINAL DRUGS

Lithium preparations:

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

COMBINATIONS OF MEDICINAL DRUGS, REQUIRING SPECIAL ATTENTION

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

- antiarrhythmic drugs IA class (quinidine, hydroquinidine, disopyramide);

- antiarrhythmic drugs of III class (amiodarone, dofetilide, ibutilide) and sotalol;

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

- other: bepridil, cisapride, difemanyl, erythromycin (iv), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (w / w).

Increased risk of ventricular arrhythmias, especially arrhythmias such as pirouettes (risk factor - hypokalemia).

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

Patients with hypokalemia should use drugs that do not cause arrhythmia such as "pirouette".

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

It is possible to reduce the antihypertensive effect of indapamide.

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

- Angiotensin-converting enzyme (ACE) inhibitors:

The appointment of ACE inhibitors to patients with hyponatremia (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, due to the intake of diuretics, the content of sodium ions in the blood plasma is necessary:

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

- or initiate therapy with an ACE inhibitor from low doses, followed by a posterior increase in dose if necessary.

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

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

- Other drugs that can cause hypokalemia: amphotericin B (IV), glucose- and mineralocorticosteroids (for systemic administration), tetrakozaktid, laxatives, stimulating intestinal motility:

Increased risk of hypokalemia (additive effect).

It is necessary to regularly monitor the potassium content in the blood plasma, if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides.It is recommended to use laxatives that do not stimulate intestinal motility.

- Baclofen:

Perhaps increased antihypertensive effect.

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

- Cardiac glycosides:

Hypokalemia increases the toxic effect of cardiac glycosides.

With the simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG, and, if necessary, adjust the therapy.

COMPOSITION OF THE PREPARATIONS REQUIRING ATTENTION

- Potassium-sparing diuretics (amiloride, spironolactone, triamterene):

Simultaneous administration of indapamide with potassium-sparing diuretics is advisable in some patients, but the possibility of hypokalemia (especially in patients with diabetes mellitus and renal insufficiency) or hyperkalemia is not ruled out.

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

- Metformin:

Functional renal failure, which can occur against the background of taking diuretics, especially "loop"while concomitant administration of metformin increases the risk of developing lactic acidosis.

Do not use metformin, if the creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

- Iodine-containing contrast agents:

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

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

- Tricyclic antidepressants, antipsychotics (antipsychotics):

Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

- Salts of calcium:

With simultaneous administration, it is possible to develop hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

- Cyclosporin, tacrolimus:

It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even with a normal content of liquid and sodium ions.

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

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

Special instructions:

Dysfunction of the liver

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

Photosensitivity

Against the background of administration of thiazide and thiazide-like diuretics, cases of development of reactions photosensitivity (see section "Side effect"). In the case of the development of reactions photosensitivity against the background of taking the drug should stop treatment. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance:

- Content of sodium ions in blood plasma:

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

- The content of potassium ions in blood plasma:

With thiazide and thiazide-like diuretics, the main risk is a sharp decrease in potassium in the blood plasma and development of hypokalemia. It is necessary to avoid the risk of developing hypokalemia (potassium content less than 3.4 mmol / l), in patients of the following groups: elderly, weakened or receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the interval QT, patients with cirrhosis of the liver, peripheral edema or ascites, ischemic heart disease, heart failure.Hypokalemia in patients of these groups increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

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

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

When hypokalemia occurs, appropriate treatment should be prescribed.

- Calcium in the blood plasma:

Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism.

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

Concentration of glucose in blood plasma:

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

Uric acid:

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

Diuretic drugs and kidney function

Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentration in adult patients is below 25 mg / L or 220 μmol / L). In elderly patients, the concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.

It should be borne in mind that at the beginning of treatment, patients may experience a decrease in the glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine.If the function of the kidneys is not impaired, such temporary functional renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen.

Athletes

The active substance, which is a part of the preparation Arifon®, can give a positive result in the conduct of doping control in athletes.

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

The action of the substances that make up Arifone® does not lead to a disturbance of psychomotor reactions. Care must be taken when driving vehicles (especially at the beginning of therapy or when adding other antihypertensive agents to the therapy).

Form release / dosage:

Tablets, film-coated, 2.5 mg.

Packaging:

30 tablets per blister (PVC / Al).

One blister along with the instructions for use are placed in a cardboard box.

Storage conditions:

Special storage conditions are not required.

Keep out of the reach of children.

Shelf life:

5 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014098 / 01

Date of registration:31.05.2007

The owner of the registration certificate:Servier LaboratoriesServier Laboratories France

Manufacturer: & nbsp

Les Laboratoires Servier Industrie France

Representation: & nbspServier Laboratories Servier Laboratories France

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Arifon® (Arifon®)