Arifon retard, 1.5 mg 30 pcs

Swelling, Blood Pressure, Hypertension (high blood pressure)Arterial hypertension.

Active ingredient

Composition

1 tablet contains:

Active ingredient:

Indapamide – 1.5 mg;

Associates:

Lactose monohydrate, 124.5 mg;

hypromellose, 64 mg;

Magnesium stearate, 1 mg;

povidone – 8.6 mg;

silicon dioxide colloid anhydrous – 0.4 mg;

Film film sheath:

Glycerol – 0.219 mg;

Hypromellose – 3.642 mg;

Macrogol 6000 – 0.219 mg;

Magnesium stearate – 0.219 mg;

Titanium dioxide – 0.701 mg.

How to take, the dosage

Overly, swallowed whole, without chewing, with water, 1 tablet daily, preferably in the morning.

When treating patients with arterial hypertension, increasing the dose of the drug does not increase the antihypertensive effect, but increases the diuretic effect.

Elderly patients

In elderly patients, plasma creatinine levels should be monitored with regard to age, body weight, and sex.

Arifone® retard at a dose of 1.5 mg/day (1 tablet) may be administered in elderly patients with normal or mildly impaired renal function.

Interaction

Cyclosporine, tacrolimus. Plasma creatinine may increase without changing circulating cyclosporine concentrations, even when fluid and sodium ions are normal.

Corticosteroid drugs, tetracosactide (when administered systemically). Reduced hypotensive effect (retention of fluid and sodium ions as a result of corticosteroids).

Indisposable combinations of drugs

Lithium preparations. Concomitant use of indapamide and lithium preparations may cause increase of lithium concentration in blood plasma due to decrease of its excretion, accompanied by signs of overdose. If necessary, diuretics may be used in combination with lithium preparations, and the dose of preparations should be carefully selected, constantly monitoring plasma lithium content.

Combinations of drugs requiring special attention

Drugs that may cause pirouette-type arrhythmias:

– Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);

– Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);

– some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluorperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenones (droperidol, haloperidol);

– others: Bepridil, cisapride, difemanil, erythromycin (w/v), halofantrine, misolastin, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (w/v).

An increased risk of ventricular arrhythmias, especially pirouette-type arrhythmias (hypokalemia is a risk factor).

Plasma potassium levels should be determined and, if necessary, corrected before starting combined therapy with indapamide and the above drugs. The patient’s clinical status, plasma electrolyte levels and ECG should be monitored.

In patients with hypokalemia, drugs that do not cause pirouette arrhythmias should be used.

NSAIDs (when administered systemically), including selective COX-2 inhibitors, high doses of salicylates (≥3 g/day). The antihypertensive effect of indapamide may be reduced. If significant fluid loss occurs, acute renal failure may develop (due to decreased glomerular filtration). Patients should compensate for fluid loss and carefully monitor renal function at the beginning of treatment.

ACE inhibitors. Administration of ACE inhibitors to patients with decreased concentration of sodium ions in 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 decreased plasma sodium ion content due to diuretics should:

– 3 days before starting treatment with an ACE inhibitor, discontinue diuretics. Subsequently, if necessary, the use of diuretics may be resumed;

– or begin therapy with an ACE inhibitor at low doses, with subsequent gradual increase of the dose if necessary.

In chronic heart failure, treatment with ACE inhibitors should be started at low doses with possible prior reduction in doses of diuretics.

In all cases in the first week of ACE inhibitor therapy, patients should have their renal function (plasma creatinine) monitored.

Other drugs that may cause hypokalemia: amphotericin B (IV), GCS and mineralocorticosteroids (when administered systemically), tetracosactide, laxatives that stimulate intestinal motility. Increased risk of hypokalemia (additive effect).

Potassium level in plasma should be constantly monitored, and if necessary – its correction. Particular attention should be paid to patients receiving cardiac glycosides concomitantly. The use of laxatives that do not stimulate intestinal motility is recommended.

Baclofen. Increased hypotensive effect has been noted.

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

Heart glycosides. Hypokalemia increases the toxic effects of cardiac glycosides.

In concomitant use of indapamide and cardiac glycosides, plasma potassium levels and ECG parameters should be monitored and, if necessary, therapy should be adjusted.

Combinations of drugs requiring attention

Kalium-saving diuretics (amiloride, spironolactone, triamterene). Combined therapy with indapamide and potassium-saving diuretics is reasonable in some patients; however, the possibility of hypokalemia (especially in diabetic patients and patients with renal insufficiency) or hyperkalemia cannot be excluded.

Phase plasma potassium levels and ECG parameters should be monitored and the therapy should be adjusted if necessary.

Metformin. Functional renal insufficiency, which may occur with diuretics, especially loop diuretics, when metformin is concomitantly administered increases the risk of lactic acidosis.

Do not use metformin 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. Dehydration from diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

Patients should compensate for fluid loss before using iodine-containing contrast agents.

Tricyclic antidepressants, antipsychotics (neuroleptics). Drugs of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Calcium salts. In concomitant administration, hypercalcemia may develop due to decreased renal excretion of calcium ions.

Special Instructions

Hepatic disorders

When prescribing thiazide and thiazide-like diuretics in patients with hepatic impairment, hepatic encephalopathy may develop, especially in case of electrolyte imbalance. In this case the use of diuretics should be immediately stopped.

Photosensitivity

During the use of thiazide and thiazide-like diuretics the cases of photosensitivity reactions have been reported. In case of photosensitivity reactions during the drug administration the treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect skin from sunlight or artificial ultraviolet rays.

Sodium ion content in plasma

Prior to the treatment it is necessary to determine sodium ion content in plasma. This index should be controlled regularly during the drug therapy. All diuretics may cause hyponatremia leading sometimes to extremely severe consequences. Continuous control of sodium ions content is necessary, because initially decrease of sodium concentration in blood plasma may not be accompanied by the appearance of pathological symptoms. The most careful control of sodium ions content is indicated for patients with liver cirrhosis and elderly patients.

Content of potassium ions in plasma

On therapy with thiazide and thiazide-like diuretics the main risk is sharp decrease of potassium level in plasma and development of hypokalemia. It is necessary to avoid the risk of hypokalemia (< 3.4 mmol/l) in patients of the following categories: elderly, weakened or receiving combined drug therapy with other antiarrhythmic drugs and drugs that may increase QT interval, patients with liver cirrhosis, peripheral edema or ascites, CHD, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias. In addition, the group of increased risk includes patients with prolonged QT interval, and it does not matter if the increase is caused by congenital causes or by the effect of drugs.

Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe arrhythmias and especially pirouette arrhythmias, which may be fatal. In all cases described above, plasma potassium content should be monitored regularly. The first measurement of blood potassium ion concentration should be made during the first week of treatment. In the case of hypokalemia appropriate treatment should be prescribed.

Plasma calcium content

It should be borne in mind that thiazide and thiazide-like diuretics may decrease renal excretion of calcium ions, leading to a slight and temporary increase in plasma calcium concentration. Severe hypercalcemia may result from previously undiagnosed hyperparathyroidism. Diuretic drugs should be cancelled before the study of parathyroid function.

Plasma glucose content

Blood glucose levels in patients with diabetes, especially in the presence of hypokalemia should be monitored.

Uric acid

Gout patients may increase the frequency of attacks or exacerbate the course of gout.

Diuretics and renal function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or mildly impaired renal function (creatinine plasma levels in adults below 25 mg/l or 220 μmol/L). In elderly patients the normal plasma creatinine level is calculated taking into account the age, body weight and sex.

It should be taken into account that at the beginning of treatment patients may have decreased glomerular filtration rate caused by hypovolemia that is in turn caused by loss of fluid and sodium ions due to diuretic drugs. As a consequence, plasma concentrations of urea and creatinine may increase. If renal function is not impaired, such temporary functional renal failure usually goes without consequences, but if renal failure is already present, the patient’s condition may worsen.

Athletes

Indapamide may give a positive result during doping control in athletes.

Effect on the ability to drive and operate machinery

The action of the substances in the drug Arifon® retard does not lead to impairment of psychomotor reactions. However, some people may have various individual reactions in response to blood pressure decrease, especially at the beginning of therapy or when other hypotensive drugs are added to the therapy. In this case, the ability to drive or operate other mechanisms may be reduced.

Contraindications

Ariphon® retard is not recommended for patients with lactose intolerance, galactosemia or glucose-galactose malabsorption because the drug contains lactose.

With caution: the drug should be administered in patients with liver and renal function disorders, disorders of water-electrolyte balance, weakened patients or patients receiving concomitant therapy with other antiarrhythmic drugs, in diabetes, elevated uric acid, hyperparathyroidism, patients with prolonged QT interval.

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

Side effects

Skin and subcutaneous fat: hypersensitivity reactions, mainly dermatological, in patients with predisposition to allergic and asthmatic reactions: frequent – maculopapular rash; infrequent – hemorrhagic vasculitis; very rare – angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; unspecified frequency – in patients with acute form of systemic lupus erythematosus may worsen the course of the disease. There have been described cases of photosensitivity reactions (see sections “Particular indications” and “Interaction”).

Hematological and lymphatic system disorders: very rarely – thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

CNS disorders: rarely – asthenia, headache, paresthesia, vertigo; unspecified frequency – syncope.

Particularly rare: very rare – arrhythmia, significant decrease in BP; of unspecified frequency – “pirouette”-type arrhythmia (possibly fatal) (see sections “Interaction” and “Cautions”).

The digestive system: infrequent – vomiting; rare – nausea, constipation, dry mouth; very rare – pancreatitis.

Any side effects of the urinary system: very rare – renal failure.

Hepatic and biliary tract disorders: very rare – hepatic impairment; unspecified frequency – possibility of hepatic encephalopathy in case of hepatic insufficiency (see “Contraindications”, “Special indications”), hepatitis.

Laboratory measures: unspecified frequency – increased QT interval on ECG increased uric acid and blood glucose concentrations: thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes; increased liver transaminase activity.

Overdose

Indapamide even in very high concentrations (up to 40 mg, i.e. 27 times the therapeutic dose) has no toxic effect.

Symptoms of acute poisoning by the drug are primarily associated with disruption of the water-electrolyte balance (hyponatremia, hypokalemia). Nausea, vomiting, decreased arterial blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia) may also be noted.

Treatment: emergency measures aimed at drug removal from the body: gastric lavage and/or administration of activated carbon followed by restoration of normal water-electrolyte balance.

Pregnancy use

As a rule, diuretics should not be prescribed in pregnancy. These drugs should not be used to treat physiological edema in pregnancy.

Diuretics may cause fetoplacental ischemia and lead to impaired fetal development.

Due to the fact that indapamide is excreted with breast milk, it is not recommended to prescribe the drug during breastfeeding.

Similarities