Arifon retard tablets, p / o 1,5 mg, no. 30

Arterial hypertension.

It is applied orally, 1 tablet per day, preferably in the morning; the tablet should be swallowed whole, without chewing, with water.
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 enhances the diuretic effect.
Elderly patients
In elderly patients, plasma creatinine levels should be monitored taking into account age, body weight and sex.
Arifon Ѓ 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').

Active ingredient: Indapamide 1.5 mg
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 - glycerol 0.219 mg, hypromellose 3.642 mg, macrogol 6000 0.219 mg, magnesium stearate 0.219 mg, titanium dioxide 0.701 mg.

• Hypersensitivity to indapamide, other sulfonamide derivatives or to any of the excipients.

• Severe renal failure (creatinine clearance less than 30 ml / min).

• Hepatic encephalopathy or severe liver dysfunction.

• Hypokalemia.

Due to the fact that the drug contains lactose, ArifonЃ retard is not recommended for patients with lactose intolerance, galactosemia, glucose-galactose malabsorption.

WITH CAUTION
(For details, see 'Special instructions')
Disorders of the liver and kidneys, disturbances in water and electrolyte balance, weakened patients or patients receiving combined therapy with other antiarrhythmic drugs (see 'Interaction with other drugs'), diabetes mellitus, elevated uric acid levels, patients with a 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.

Trade name of the drug : ArifonЃ retard
International non-proprietary name (INN) : Indapamide
Dosage form : controlled release film-coated tablets.

Composition
Active ingredient: Indapamide 1.5 mg
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 - glycerol 0.219 mg, hypromellose 3.642 mg, macrogol 6000 0.219 mg, magnesium stearate 0.219 mg, titanium dioxide 0.701 mg.

Description
White, round, biconvex film-coated tablets.

PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group:

diuretic.

ATX code: C03BA11

Pharmacodynamics
Indapamide belongs to sulfonamide derivatives 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 clinical studies of phases II and III, when using indapamide in monotherapy at doses that do 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 increase in the dose of the drug. Therefore, you should not increase the dose of the drug if the therapeutic effect is not achieved when taking the recommended dose.
In short, medium and long-term studies involving patients with arterial hypertension, it has been shown that indapamide:

• does not affect the indicators of lipid metabolism, including the level of triglycerides, cholesterol, low density lipoproteins and high density lipoproteins;

• does not affect the indicators of carbohydrate metabolism, including in patients with diabetes mellitus.

Pharmacokinetics
In ArifonЃ retard tablets, the active substance is contained in a special carrier matrix, which provides a gradual controlled release of indapamide in the gastrointestinal tract.

Absorption The
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 individual variability in the absorption of the drug.

Distribution
About 79% of the drug binds to blood plasma proteins. The half-life is 14-24 hours (average 18 hours).
Equilibrium concentration is achieved after 7 days of taking the drug.
With repeated administration of the drug, its cumulation is not observed.

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

High-risk
patients In patients with renal insufficiency, the pharmacokinetics of ArifonЃ retard does not change.

INDICATIONS FOR USE
Arterial hypertension.

CONTRAINDICATIONS

• Hypersensitivity to indapamide, other sulfonamide derivatives or to any of the excipients.

• Severe renal failure (creatinine clearance less than 30 ml / min).

• Hepatic encephalopathy or severe liver dysfunction.

• Hypokalemia.

Due to the fact that the drug contains lactose, ArifonЃ retard is not recommended for patients with lactose intolerance, galactosemia, glucose-galactose malabsorption.

WITH CAUTION
(For details, see 'Special instructions')
Disorders of the liver and kidneys, disturbances in water and electrolyte balance, weakened patients or patients receiving combined therapy with other antiarrhythmic drugs (see 'Interaction with other drugs'), diabetes mellitus, elevated uric acid levels, patients with a 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.

Pregnancy and lactation
Pregnancy
As a rule, diuretic drugs should not be prescribed during pregnancy. You cannot use these drugs to treat physiological edema during pregnancy. Diuretic drugs can cause placental ischemia and impair fetal development.
Breastfeeding period
It is not recommended to prescribe Arifon Ѓ retard to nursing mothers (indapamide is excreted in breast milk).

DOSAGE AND METHOD OF APPLICATION It
is administered orally, 1 tablet per day, preferably in the morning; the tablet should be swallowed whole without chewing with water.
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 enhances the diuretic effect.
Elderly patients
In elderly patients, plasma creatinine levels should be monitored taking into account age, body weight and gender.
Arifon Ѓ 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').

SIDE EFFECTS
Most of the adverse reactions (laboratory and clinical parameters) 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); ? common (1/100, the part of the circulatory and lymphatic system
Very rare: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
Central Nervous System From the
Rare: asthenia, headache, paresthesia, vertigo.
, unspecified frequency: syncope.
With side of the cardiovascular system
Very rare: arrhythmia, marked decrease in blood pressure.
Unspecified frequency:arrhythmia of the 'pirouette' type (possibly fatal) (see sections 'Interaction with other medicinal products' and 'Special instructions').
From the digestive system
Uncommon: vomiting.
Rarely: nausea, constipation, dryness of the oral mucosa.
Very rare: pancreatitis.
From the urinary system
Very rare: renal failure.
From the liver and biliary tract
Very rarely: liver dysfunction.
Unspecified frequency: the possibility of developing hepatic encephalopathy in case of liver failure (see sections 'Contraindications' and 'Special instructions'); hepatitis.
On the part of the skin and subcutaneous tissue
Hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions:

• Often: maculopapular rash;

• Uncommon: hemorrhagic vasculitis;

• Very rare: 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 sections 'Special instructions' and 'Interaction with other drugs').
Laboratory Indicators
Unspecified Frequency:

• Increase in the QT interval on the ECG (see the section 'Special instructions').

• Increasing the concentration 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' 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 content of potassium in the blood plasma decreased, on average, by 0.23 mmol / L.
Very rare: hypercalcemia.
Unspecified frequency:

• a decrease in potassium content and the development of hypokalemia, especially significant for patients at risk (see section 'Special instructions');

• hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous hypochloremia can lead to metabolic alkalosis of a compensatory nature (the likelihood and severity of this effect is low).

OVERDOSE
Indapamide, even in very high doses (up to 40 mg, i.e. 27 times more than the therapeutic dose), has no toxic effect.
Signs of acute drug poisoning are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). From the clinical symptoms of an overdose, nausea, vomiting, decreased blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria, leading to anuria (due to hypovolemia) may be noted.
Emergency measures are reduced to removing the drug from the body: gastric lavage and / or the appointment of activated charcoal, followed by restoration of the water-electrolyte balance.

INTERACTION WITH OTHER MEDICINAL PRODUCTS
UNWANTED COMBINATIONS OF MEDICINAL SUBSTANCES

- 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 an overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while the dose of drugs should be carefully selected, constantly monitoring the lithium content in the blood plasma.

COMBINATIONS OF DRUGS REQUIRING SPECIAL ATTENTION
Drugs that can cause pirouette-type arrhythmias:

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

• class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);

• some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluorperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

• others: bepridil, cisapride, diphemanil, erythromycin (i.v.), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (i.v.).

Increased risk of ventricular arrhythmias, especially pirouette 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, drugs that do not cause pirouette arrhythmias should be used.

- Non-steroidal anti-inflammatory drugs (for systemic administration), including selective inhibitors of 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 (due to a decrease in glomerular filtration) can develop. Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.

- Angiotensin-converting enzyme (ACE) inhibitors: The
administration of ACE inhibitors to patients with a reduced concentration of sodium ions in the blood (especially patients with renal artery stenosis) is accompanied by the 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 should:

• 3 days before starting treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, taking diuretics can be resumed;

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

In chronic heart failure, treatment with ACE inhibitors should be started at 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 renal function (plasma creatinine content).

- Other drugs that can cause hypokalemia: amphotericin B (i / v), gluco- and mineralocorticosteroids (for 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, correct it. Particular attention should be paid to patients who are simultaneously receiving cardiac glycosides. It is recommended to use laxatives that do not stimulate bowel movements

- 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 effects 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, the therapy should be adjusted.

COMBINATION OF PREPARATIONS REQUIRING ATTENTION

- Potassium-sparing diuretics (amiloride, spironolactone, triamterene):
Combination therapy with indapamide and potassium-sparing diuretics is advisable in some patients, but this does not exclude the possibility of 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.

- Metformin
Functional renal failure, which can occur on the background of diuretics, especially loop diuretics, with the simultaneous administration of metformin, increases the risk of lactic acidosis.
Do not use metformin if your creatinine level exceeds 15 mg / L (135 ?mol / L) in men and 12 mg / L (110 ?mol / L) in women.

- Iodine-containing contrast agents:
Dehydration of the body while taking diuretic drugs increases the risk of developing acute renal failure, especially when using high doses of iodine-containing contrast agents.
Before using iodine-containing contrast agents, patients need to compensate for the loss of fluid.

- “рициклические антидепрессанты, антипсихотические средства (нейролептики):
ѕрепараты этих классов усиливают антигипертензивное действие индапамида и увеличивают риск ортостатической гипотензии (аддитивный эффект).

- —оли кальци¤:
ѕри одновременном назначении возможно развитие гиперкальциемии вследствие снижени¤ выведени¤ ионов кальци¤ почками.

- ?иклоспорин, такролимус:
¬озможно увеличение содержани¤ креатинина в плазме крови без изменени¤ концентрации циркулирующего циклоспорина, даже при нормальном содержании жидкости и ионов натри¤.

-  ортикостероидные препараты, тетракозактид (при системном назначении):
—нижение гипотензивного действи¤ (задержка жидкости и ионов натри¤ в результате действи¤ кортикостероидов).

ќ—ќЅџ? ” ј«јЌ»я
Ќарушени¤ функции печени
ѕри назначении тиазидных и тиазидоподобных диуретиков у больных с нарушени¤ми функции печени возможно развитие печеночной энцефалопатии, особенно в случае нарушени¤ электролитного баланса. ¬ этом случае прием диуретиков следует немедленно прекратить.

‘оточувствительность
Ќа фоне приема тиазидных и тиазидоподобных диуретиков сообщалось о случа¤х развити¤ реакций фоточувствительности (см. Уѕобочное действиеФ). ¬ случае развити¤ реакций фоточувствительности на фоне приЄма препарата следует прекратить лечение. ѕри необходимости продолжени¤ терапии диуретиками, рекомендуетс¤ защищать кожные покровы от воздействи¤ солнечных лучей или искусственных ультрафиолетовых лучей.

¬одно-электролитный баланс:
- —одержание ионов натри¤ в плазме крови:
?о начала лечени¤ необходимо определить содержание ионов натри¤ в плазме крови. Ќа фоне приема препарата следует регул¤рно контролировать этот показатель. ¬се диуретические препараты могут вызывать гипонатриемию, привод¤щую иногда к крайне т¤желым последстви¤м. Ќеобходим посто¤нный контроль содержани¤ ионов натри¤, так как первоначально снижение концентрации натри¤ в плазме крови может и не сопровождатьс¤ по¤влением патологических симптомов. Ќаиболее тщательный контроль содержани¤ ионов натри¤ показан больным с циррозом печени и лицам пожилого возраста (см. разделы Ђѕобочное действиеї и Ђѕередозировкаї).

- —одержание ионов кали¤ в плазме крови:
ѕри терапии тиазидными и тиазидоподобными диуретиками основной риск заключаетс¤ в резком снижении уровн¤ кали¤ в плазме крови и развитии гипокалиемии. Ќеобходимо избегать риска развити¤ гипокалиемии (  роме того, к группе повышенного риска относ¤тс¤ больные с увеличенным интервалом QT, при этом не имеет значени¤, вызвано это увеличение врожденными причинами или действием лекарственных средств.
vипокалиеми¤, так же как и брадикарди¤, ¤вл¤етс¤ состо¤нием, способствующим развитию т¤желых аритмий и, особенно, аритмий типа УпируэтУ, которые могут приводить к летальному исходу. ¬о всех описанных выше случа¤х необходимо регул¤рно контролировать содержание кали¤ в плазме крови. ѕервое измерение концентрации ионов кали¤ в крови необходимо провести в течение первой недели от начала лечени¤.
ѕри по¤влении гипокалиемии должно быть назначено соответствующее лечение.

- —одержание кальци¤ в плазме крови:
—ледует иметь в виду, что тиазидные и тиазидоподобные диуретики могут уменьшать выведение ионов кальци¤ почками, привод¤ к незначительному и временному повышению концентрации кальци¤ в плазме крови. ¬ыраженна¤ гиперкальциеми¤ может быть следствием ранее не диагностированного гиперпаратиреоза.
—ледует отменить прием диуретических препаратов перед исследованием функции паращитовидных желез.

—одержание глюкозы в плазме крови:
Ќеобходимо контролировать уровень глюкозы в крови у пациентов с сахарным диабетом, особенно при наличии гипокалиемии.

ћочева¤ кислота:
” больных подагрой может увеличиватьс¤ частота возникновени¤ приступов или обостр¤тьс¤ течение подагры.

?иуретические препараты и функци¤ почек:
“иазидные и тиазидоподобные диуретики эффективны в полной мере только у больных с нормальной или незначительно нарушенной функцией почек (содержание креатинина в плазме крови у взрослых лиц ниже 25 мг/л или 220 мкмоль/л). ” пациентов пожилого возраста нормальный уровень креатинина в плазме крови рассчитывают с учетом возраста, массы тела и пола.
—ледует учитывать, что в начале лечени¤ у больных может наблюдатьс¤ снижение скорости клубочковой фильтрации, обусловленное гиповолемией, котора¤, в свою очередь, вызвана потерей жидкости и ионов натри¤ на фоне приема диуретических препаратов.  ак следствие, в плазме крови может увеличиватьс¤ концентраци¤ мочевины и креатинина. ?сли функци¤ почек не нарушена, така¤ временна¤ функциональна¤ почечна¤ недостаточность, как правило, проходит без последствий, однако при уже имеющейс¤ почечной недостаточности состо¤ние больного может ухудшитьс¤.

—портсмены
јктивное вещество, вход¤щее в состав препарата јрифон Ѓ ретард, может давать положительный результат при проведении допинг-контрол¤ у спортсменов.

¬ли¤ние на способность управл¤ть автомобилем и выполнение работ, требующих повышенной скорости физической и психической реакций
?ействие веществ, вход¤щих в состав препарата јрифон Ѓ ретард, не приводит к нарушению психомоторных реакций. ќднако у некоторых людей в ответ на снижение артериального давлени¤ могут развитьс¤ различные индивидуальные реакции, особенно в начале терапии или при добавлении к проводимой терапии других гипотензивных средств. ¬ этом случае способность управл¤ть автомобилем или другими механизмами может быть снижена.

‘ќ–ћј ¬џѕ”— ј
“аблетки с контролируемым высвобождением, покрытые пленочной оболочкой, 1,5 мг.
ѕо 15 таблеток в блистер (ѕ¬’/јл). ѕо 2 блистера вместе с инструкцией по применению в картонную пачку.
ѕо 30 таблеток в блистер (ѕ¬’/јл). ѕо 1 блистеру вместе с инструкцией по применению в картонную пачку.
ѕри расфасовке (упаковке)/ производстве на ќќќ Ђ—ердиксї:
“аблетки с контролируемым высвобождением, покрытые пленочной оболочкой, 1,5 мг.
ѕо 30 таблеток в блистер (ѕ¬’/јл). ѕо 1 блистеру вместе с инструкцией по применению в картонную пачку.
”паковка дл¤ стационаров:
ѕо 30 таблеток в блистер (ѕ¬’/јл). ѕо 3 блистера с инструкцией по медицинскому применению в пачку картонную.
30 tablets per blister (PVC / Al). 10 blisters in a cardboard box (the box is not marked). 3 packs of cardboard with instructions for medical use in a cardboard box.

STORAGE CONDITIONS
Store at a temperature not exceeding 30 ? —.
Keep out of the reach of children.

SHELF LIFE
2 years.
THE PREPARATION SHOULD NOT BE USED AFTER THE SHELF LIFE STATED ON THE PACKAGE.

TERMS OF RELEASE FROM PHARMACIES
By prescription.