Arifon retard 1.5 mg 30 pcs. film-coated controlled-release tablets
pharmachologic effect
Diuretic, hypotensive.
Composition and release form Arifon retard 1.5 mg 30 pcs. film-coated controlled-release tablets
Controlled-release film-coated tablets - 1 tablet:
- 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.
Controlled-release film-coated tablets, 1.5 mg.
30 tablets each in a blister (PVC/Al). 1 blister along with instructions for use in a cardboard box.
During packaging (packing)/production at Serdix LLC:
Controlled-release film-coated tablets, 1.5 mg.
30 tablets in a blister (PVC/Al). 1 blister along with instructions for use in a cardboard box.
Packaging for hospitals
30 tablets each in a blister (PVC/Al). 3 blisters along with instructions for use in a cardboard pack.
30 tablets each in a blister (PVC/Al). 10 blisters per cardboard pack (the pack is not marked). 3 cardboard packs with instructions for medical use in a cardboard box.
Description of the dosage form
Round, biconvex, film-coated tablets, white.
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.
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 into 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 use Arifon retard 1.5 mg 30 pcs. film-coated controlled-release tablets
Arterial hypertension.
Contraindications
- hypersensitivity to indapamide, other sulfonamide derivatives or any of the excipients;
- severe form of renal failure (Cl creatinine
- 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: impaired liver and kidney function, water-electrolyte imbalance, debilitated patients or patients receiving combination therapy with other antiarrhythmic 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.
Application Arifon retard 1.5 mg 30 pcs. film-coated controlled-release tablets during pregnancy and lactation
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).
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. 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 sodium ion content is indicated for patients with liver cirrhosis and the elderly.
- 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. The risk of hypokalemia must be avoided (
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.
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.
Side effects Arifon retard 1.5 mg 30 pcs. film-coated controlled-release tablets
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,
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).
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, 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.
Laboratory indicators: unspecified frequency - increase in QT interval on the 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 level 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).
Drug interactions
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 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.
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).
