Arifon retard pills 1,5mg №30

Mechanism of action

An antihypertensive (diuretic) drug, a sulfonamide derivative containing an indole ring. In terms of pharmacological properties, Indapamide is close to thiazide diuretics, whose action is associated with inhibition of the reverse absorption of sodium ions in the cortical segment of the nephron loop. Indapamide increases the excretion of sodium ions, chlorine and, to a lesser extent, potassium and Magnesium ions with urine, which is accompanied by increased diuresis. Indapamide has an antihypertensive effect in doses that do not have a pronounced diuretic effect. In addition, the hypotensive effect is associated with the ability of the drug to increase the elasticity of the walls of the arteries and reduce OPS.
The mechanism of action of indapamide is due to a change in the transmembrane current of ions (primarily calcium), which leads to relaxation of vascular smooth muscle cells, as well as increased synthesis of prostaglandins PGE₂ and prostacyclin PGI₂ (vasodilator and platelet aggregation inhibitor).
The drug helps reduce left ventricular hypertrophy.
Clinical trials of Arifon retard (phase II and III) showed that monotherapy develops a persistent hypotensive effect, which lasts for 24 hours; however, there was a moderate increase in diuresis.
Regardless of the duration of use, Arifon retard does not affect plasma lipids (triglycerides, cholesterol / LDL, cholesterol / HDL); does not change the parameters of carbohydrate metabolism (including in patients with hypertension and diabetes).
Indapamide is effective in patients with one kidney.
Indapamide has an antihypertensive effect in doses that do not have a pronounced diuretic effect.
When using indapamide in high doses, the hypotensive effect does not increase, but diuresis increases.

Suction
In Arifon retard tablets, the active substance is in a special carrier matrix, which ensures the gradual release of indapamide in the gastrointestinal tract, while C_max is achieved 12 hours after a single ingestion of 1 pill (1.5 mg).
With repeated doses of fluctuations in the concentration of indapamide in the blood plasma in the interval between doses of two doses are reduced.
Food intake somewhat slows down the rate of absorption of the drug, but it does not affect the amount of absorbed substance.
Distribution
Plasma protein binding is about 79%.
The equilibrium state is established after 7 days of regular intake.
When you take Arifon retard again, there is no accumulation of indapamide in the body.
Metabolism and excretion
Indapamide undergoes biotransformation and is excreted in the form of inactive metabolites, mainly with urine - 70% and feces - 22%.
T_1/2 is 14-24 hours (average 18 hours).
Pharmacokinetics in special clinical situations
In patients with renal insufficiency, the pharmacokinetic parameters of Arifon retard do not change.

Indications and usage

- Essential arterial hypertension.

Arifon retard is administered orally on 1 tab. / Day, preferably in the morning.

Adverse reactions

Fluid and electrolyte balance: possible reduction of potassium levels and the development of hypokalemia (especially pronounced in patients at risk). According to clinical studies of hypokalemia (the concentration of potassium ions in the blood plasma <3.4 mmol / l) was observed in 10% of patients who received Arifon retard. A decrease in the potassium content below 3.2 mmol / l after 4-6 weeks of taking indapamide was observed in 4% of patients. After 12 weeks of taking the drug, the average decrease in the concentration of potassium ions in the blood plasma was 0.23 mmol / l.
Possible hyponatremia, accompanied by hypovolemia, dehydration of the body and orthostatic hypotension. The simultaneous loss of chlorine ions can lead to a compensatory metabolic alkalosis, the frequency of development and the severity of which is small.
Extremely rare - increasing the level of Calcium in the body.
Metabolism: may increase the content of urea and glucose in the blood plasma.
Hemic and lymphatic: rarely - thrombocytopenia, leukopenia, aplastic anemia, hemolytic anemia, agranulocytosis.
Gastrointestinal: rarely - nausea, constipation, dry mouth; extremely rarely - pancreatitis.
Allergic reactions: in patients predisposed to allergic reactions and the development of attacks of bronchial asthma, skin manifestations of increased sensitivity to the drug are possible; rarely, hemorrhagic vasculitis, exacerbation of disseminated lupus erythematosus.
From the side of the central nervous system: rarely - dizziness, asthenia, paresthesia, headache (these effects usually disappear at lower doses of the drug). Patients with liver failure may develop hepatic encephalopathy.
Most side effects are dose-dependent.

Contraindications

- severe renal failure;
- hepatic encephalopathy;
- hypokalemia;
- hypersensitivity to indapamide and other sulfonamide derivatives.
The simultaneous use of Arifon retard and drugs that prolong the QT interval should be avoided.

Pregnancy and breastfeeding

As a rule, Arifon retard is not recommended for use in pregnancy, incl. to relieve physiological edema. It should be borne in mind that diuretics can cause placental ischemia and lead to impaired fetal development.
Due to the fact that indapamide is excreted in breast milk, the appointment of the drug in breastfeeding is also not recommended.

Special notes

When prescribing Arifon retard in patients with diabetes mellitus, it is extremely important to control glucose levels, especially in the presence of hypokalemia.
Patients with elevated uric acid have a tendency to increase the number of gout attacks.
In the appointment of thiazide diuretics in patients with hepatic impairment may develop hepatic encephalopathy. In such cases, the drug should be stopped immediately.
Thiazide diuretics show their effectiveness to the full only in the case of the absence of disturbances or with moderately expressed impaired renal function (creatinine content in the blood is less than 25 mg / l or 220 μmol / l).
In elderly patients, the normal level of creatinine in the blood plasma is calculated taking into account the age, body weight and sex of the patient according to Cockroft's formula:
Cl_CR= (140 - age / in years /) x body weight (kg) /0.814 x plasma creatinine (mcmol / l).
This formula is used in calculating the level of creatinine in men, for women, the final result should be multiplied by 0.85.
It should be borne in mind that at the beginning of treatment, patients may experience a decrease in glomerular filtration due to hypovolemia, which is caused by the loss of water and sodium ions while taking diuretics. As a result, urea and creatinine concentrations may increase in blood plasma. If the kidney function is not impaired, such temporary renal failure usually passes without consequences. However, with existing renal failure, the patient’s condition may worsen.
During therapy with Arifon retard, exacerbation of disseminated lupus erythematosus is possible.
Before treatment, determine the content of sodium ions in the blood plasma. In the course of treatment, regular monitoring of this indicator is necessary, since initially a decrease in sodium concentration in the blood plasma may not be accompanied by the appearance of pathological symptoms. Especially often such an analysis should be carried out in patients with cirrhosis of the liver and in the elderly.
During treatment with thiazide diuretics, the main risk is a sharp decrease in the content of potassium ions and the development of hypokalemia. In a certain category of patients, especially the elderly, weakened or receiving combined therapy, with cirrhosis of the liver with developed edema or ascites, ischemic heart disease, chronic heart failure , it is necessary to avoid the development of hypokalemia (<3.4 mmol / l). Hypokalemia in these patients leads to increased toxic effects of cardiac glycosides and increases the risk of arrhythmias. In addition, patients with bradycardia or with an increased QT interval on an ECG are in an increased risk group, and it does not matter if such an increase is caused by congenital causes or the presence of a pathological process.
Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe cardiac arrhythmias, especially of the "pirouette" type, often resulting in deaths. In all the cases described above, it is necessary to more frequently determine the content of potassium ions in the blood plasma.The first measurement of the concentration of potassium ions in the blood should be carried out during the first week from the start of treatment.
When hypokalemia occurs, appropriate treatment should be prescribed, while not allowing the use of drugs that cause arrhythmias such as "pirouette." In the event of such a disturbance of the rhythm, antiarrhythmic drugs should not be used, but an artificial pacemaker should be installed.
It should be borne in mind that thiazide diuretics can reduce the excretion of calcium ions in the urine, which leads to minor and temporary hypercalcemia. Severe hypercalcemia may result from previously undiagnosed hyperparathyroidism.
Diuretic administration should be discontinued before starting the study of the function of the parathyroid glands.
If necessary, the appointment on the background of therapy with Arifon retard laxatives, should be prescribed drugs that do not affect intestinal motility.
Against the background of taking indapamide, a positive result is possible during doping control in athletes.
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 thiazide diuretic therapy does not lead to the desired therapeutic effect, the dose of the drug should not be increased.
With simultaneous use with other antihypertensive drugs, the dose of Arifon retard should be reduced, at leastat the beginning of treatment.
Use in pediatrics
Due to the lack of sufficient clinical data, the drug is not recommended for use in children and teenagers under 18.
Influence on ability to drive motor transport and control mechanisms
The action of substances that are part of Arifon retard, does not lead to a violation of psychomotor reactions. However, it should be borne in mind that in some cases, with a decrease in blood pressure, individual reactions may occur (especially at the beginning of therapy or with a combination of several antihypertensive drugs). In this case, the ability to engage in activities that require increased attention and quickness of psychomotor reactions can be reduced.

Indapamide, even in very high concentrations (up to 40 mg, ie, 27 times the therapeutic dose), does not have a toxic effect.
Symptoms: water-electrolyte imbalance (hyponatremia, hypokalemia), nausea, vomiting, arterial hypotension, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria resulting in anuria (due to hypovolemia) are possible.
Treatment: urgent measures aimed at removing the drug from the body: washing the gastrointestinal tract and / or the appointment of Activated carbon , followed by the restoration of normal water-electrolyte balance.

With the simultaneous use of thiazide diuretics and lithium preparations, it is possible to increase the concentration of lithium in the blood plasma, accompanied by the appearance of signs of overdose (due to a decrease in the elimination of lithium in the urine).If necessary, the appointment of this combination should monitor the concentration of lithium in the blood plasma.
With the simultaneous use of diuretics with astemizole, bepridilom, Erythromycin (IV), halofantrin, pentamidine, sulphotom, terfenadine, vincamine increases the likelihood of arrhythmias of the type "pirouette". Hypokalemia, bradycardia, or prolonged QT interval may contribute to this condition.
With simultaneous use with NSAIDs (for systemic use), high doses of salicylates may reduce the hypotensive effect of indapamide. With a significant loss of fluid, acute renal failure may develop (due to a sharp decrease in glomerular filtration). If necessary, the appointment of NSAIDs during therapy with Arifon retard, should be compensated for the loss of water and carefully monitor kidney function.
With simultaneous use of indapamide with other drugs that can cause hypokalemia, including with amphotericin B (w / w), gluco-and mineralocorticoid (for systemic use), tetrakozaktidom, laxatives that stimulate intestinal motility, increases the risk of hypokalemia (requires constant monitoring of plasma potassium and, if necessary, appropriate treatment) .
With simultaneous use of thiazide diuretics with GCS, tetrakozaktid for systemic use, a decrease in the hypotensive effect due to the retention of water and sodium ions under the influence of GCS is observed.
With simultaneous use with cardiac glycosides, it is possible to enhance the toxic effect of the latter (it is necessary to monitor the level of potassium in the blood plasma and ECG values).
With simultaneous use of indapamide with Baclofen there is an increase in the hypotensive effect (it is necessary to compensate for the loss of water and at the beginning of treatment carefully monitor kidney function).
With simultaneous use of indapamide and potassium-sparing diuretics (including amiloride, spironolactone, triamterene), the possibility of the development of hypokalemia or hyperkalemia, especially in patients with diabetes mellitus and renal insufficiency, cannot be completely ruled out. In such cases, the level of potassium in the blood plasma, ECG parameters should be monitored and, if necessary, therapy should be adjusted.
With simultaneous use of indapamide with ACE inhibitors, hyponatremia in patients receiving ACE inhibitors, increases the risk of sudden arterial hypotension and / or acute renal failure (especially with renal artery stenosis). Patients with essential arterial hypertension and a reduced content of sodium ions in the blood plasma due to the intake of diuretics need 3 days before the start of treatment with ACE inhibitors to stop taking diuretics. In the future, if necessary, receive diuretics resume. In addition, prescribe low, gradually increasing doses of ACE inhibitors.In chronic heart failure, treatment should begin with low doses of ACE inhibitors, after reducing the dose of diuretics. In all cases, in the first week of taking ACE inhibitors, it is necessary to monitor kidney function (creatinine content in the blood plasma).
With the simultaneous appointment of indapamide and antiarrhythmic drugs that can cause arrhythmia of the "pirouette" type (including quinidine, hydroquinidine, disopyramide, Amiodarone , bretilium, sotalol), the risk of developing this condition increases (especially against the background of hypokalemia, bradycardia, initially extended QT). If necessary, the appointment of this combination should monitor the level of potassium in the blood plasma and the QT interval, adjusting the dosage regimen.
With the simultaneous use of diuretics and Metformin , the appearance of lactic acidosis is possible, which is associated, apparently, with the development of functional renal failure caused by the action of diuretics (to a greater extent "loop"). It is not recommended to use metformin in combination with Arifon retard with creatinine levels of more than 15 mg / l (135 μmol / l) in men and 12 mg / l (110 μmol / l) in women.
When using Iodine radiopaque drugs should be borne in mind that the diuretic effect of indapamide increases the risk of developing renal failure. This risk is especially high when using iodine-containing radiopaque substances in high doses.Before using iodine-containing radiopaque substances, patients need to restore fluid loss.
With simultaneous use of indapamide and tricyclic antidepressants such as imipramine, there is an increase in the hypotensive effect and an increased risk of developing orthostatic hypotension.
With the simultaneous use of thiazide diuretics and calcium salts, hypercalcemia may develop due to a decrease in the excretion of calcium ions in the urine.
With simultaneous use of indapamide and cyclosporine may increase the content of creatinine in the blood plasma, which is observed even with the normal content of water and sodium ions.

The drug should be stored in a dry place at room temperature (no higher than 30 ° C).