Pharmacological properties

Ravel sr — the antihypertensive medicament derivative of sulfonamide. pharmacodynamics. on pharmacological properties ravet sr it is similar to thiazide diuretics. indapamid works by slowing down of absorption of sodium in a cortical segment of nephron, increases renal excretion of ions of sodium and chlorides and increases a diuresis. has the significant antihypertensive action and insignificant diuretic effect. the hypotensive effect lasts 24 h indapamid also influences a tone of vessels, reducing resistance of arterioles and opss. indapamid reduces a hypertrophy of a left ventricle, hypotensive action of an indapamid remains at patients with ag and a renal failure.

Indapamid practically does not affect concentration of lipids in blood plasma (general XC, XC LDL, the XC LPVP, TG). Besides, it practically does not influence exchange of carbohydrates even at patients with diabetes and the accompanying hypertensia. The hypotensive effect of an indapamid amplifies at increase in a dose whereas side effects are in that case shown stronger and more often.

Pharmacokinetics. The fraction of an indapamid is released quickly and is almost completely soaked up in a GIT. Administration of medicament during consumption of food does not affect amount of the absorbed substance. The C _max an indapamid in blood serum is reached approximately in 9.8 h after administration of medicament at meal time and in 12.3 h — on an empty stomach. At constant administration of medicament of the C _max indapamida in blood serum is reached in 11 h after its oral introduction. Stable concentration in blood plasma is reached approximately in 7 days. Regular administration of medicament does not lead to cumulation.

Linking of an indapamid with proteins of blood plasma makes 79%. T _½ makes 14–24 h of blood plasma (on average — 18 h). At regular administration of medicament of T _½ 19.2 h

Metabolism of an indapamid happens generally in a liver. 70% of an indapamid are allocated with kidneys, generally in the form of metabolites (the fraction of not changed medicament makes about 5%). About 20% are removed with a stake in the form of inactive metabolites. At patients to a renal failure and the liver does not occur a significant change in pharmacokinetic parameters.

Indication

Ag.

Use

Is recommended to be accepted on 1 tablet of 1 times a day, it is desirable in the morning. the maximum daily dose — 1 tablet. duration of treatment depends on weight of a course of the disease and is defined individually.

Contraindication

Hypersensitivity to any of components of medicament or to other sulfonamides; profound renal failure, hepatic encephalopathy or profound abnormal liver function; hypopotassemia; period of pregnancy and feeding by a breast; children's age.

development of a hypopotassemia Is possible

. in clinical trials the hypopotassemia in 4–6 weeks of treatment indapamidy was noted at 10% of patients (potassium level in blood plasma of 3.4 mmol/l) and at 4% of patients (potassium level in blood plasma of 3.2 mmol/l). in 12 weeks the average decrease in potassium concentration in blood plasma was 0.23 mmol/l.

Are possible

a hyponatremia with a hypovolemia that can lead to dehydration and orthostatic hypotension; owing to the accompanying loss of chlorides the compensatory metabolic alkalosis can develop.

development of a hyperuricemia and hyperglycemia Is possible

therefore patients should appoint medicament with care with diabetes or gout.

Hypercalcemia, thrombocytopenia, a leukopenia, an agranulocytosis, an aplasia of marrow and hemolytic anemia are noted by

in isolated cases.

At patients with a liver failure the hepatic encephalopathy can develop.

Allergic reactions (makulopapulezny rash, a purpura) arise mainly at patients with tendency to hypersensitivity reactions.

aggravation of a system lupus erythematosus Is possible

.

Seldom note dizziness, a headache, paresthesias, increased fatigue, a constipation and dryness in a mouth, nausea.

pancreatitis In rare instances can develop.

Special instructions

with an abnormal liver function thiazide diuretics can cause development of encephalopathy In patients. in that case diuretic should be cancelled immediately.

Water and electrolytic balance

Concentration of sodium in blood plasma

Prolonged use of diuretic can cause development of a hyponatremia. Concentration of sodium in blood plasma needs to be defined prior to treatment and at regular intervals during treatment. At elderly people and patients with cirrhosis the definition of concentration of sodium in blood plasma needs to be carried out more often.

Potassium concentration in blood plasma

At patients at malnutrition, a concomitant use of several drugs, at elderly people, patients with cirrhosis and ascites, an ischemic heart disease and heart failure, patients with the increased Q–T interval on the ECG needs to prevent development of a hypopotassemia (3.4 mmol/l). At these patients the hypopotassemia increases cardiotoxicity of medicaments of a foxglove and risk of developing arrhythmia. The hypopotassemia contributes to the development of dangerous arrhythmias, in particular polymorphic ventricular tachycardia on the pirouette type. These patients should control more often potassium level in blood plasma.

Concentration of calcium in blood plasma

Thiazide and tiazidopodobny diuretics can reduce removal of calcium with urine and cause an insignificant tranzitorny hypercalcemia. The resistant hypercalcemia can be caused by presence of a hyperparathyreosis. Therefore treatment by diuretic needs to be stopped to assessment of function of an epithelial body.

glucose Level in blood

At patients with diabetes it is important to p to control glucose level in blood, especially at a hypopotassemia.

Uric acid

patients with a hyperuricemia can have gout attacks.

Thiazide and tiazidopodobny diuretics are most effective

at normal function of kidneys or at its insignificant disturbance (creatinine level in blood plasma at adult 25 mg/l or 220 µmol/l).

Hypovolemia arising at the beginning of use of diuretic owing to loss of water and sodium can cause decrease in glomerular filtration. It can lead to increase in level of urea and creatinine in blood plasma. At patients with normal function of kidneys such tranzitorny functional renal failure passes without any consequences, but at patients with the renal failure noted before treatment, the state can worsen.

Athletes

Ravel SR can cause positive reaction when conducting doping control in the athletes taking this drug.

Use during pregnancy and feeding by a breast. It is not necessary to appoint medicament during pregnancy as it can cause placentary ischemia and break fetation. During treatment it is recommended to stop feeding by a breast.

Influence on ability of control of vehicles and work with other mechanisms. Indapamid does not influence speed of response, but in certain cases, especially in an initiation of treatment or at the combined use with other antihypertensives, there can be phenomena connected with decrease in the ABP. Thereof the ability of control of vehicles or works with other mechanisms can be broken.

Interaction

does not recommend to use combined with ravely sr medicaments a lity (lithium discharge kidneys decreases), astemizol, bepridit, erythromycin for in/in introductions, galofantrin, pentamidine and Vincaminum (risk of developing arrhythmia increases, especially at a hypopotassemia, bradycardia and increase in an interval of q-t), npvp for system use, especially salicylates in high doses (risk of developing an acute heart failure at patients with significant shortage of liquid in an organism as a result of decrease in glomerular filtration). risk of development of a hypopotassemia (additive effect) at use of a ravel of sr with Amphotericinum increases in for in/in introductions, glyuko- and mineralokortikoidam for system use, tetrakozaktidy, the stimulating depletive. with care appoint to the patients taking the foxglove drugs.

Baclofenum strengthens hypotensive action of Ravel SR.

With care is applied Ravel SR with kaliysberegayushchy diuretics (amiloride, Spironolactonum, Triamterenum), especially at patients with a renal failure or diabetes in connection with danger of development of a hyperpotassemia. It is necessary to control potassium concentration in blood plasma and the ECG parameters.

At simultaneous use with APF inhibitors for patients with the reduced level of sodium (especially at patients with a renal artery stenosis) arterial hypotension and/or OPN can develop.

Antiarrhytmic means of Ia of a class (quinidine, methyl hydrocupreine, Disopyramidum), Amiodaronum, a bretylium, sotalol can cause development of polymorphic ventricular tachycardia in the pirouette type, especially at a hypopotassemia, bradycardia and the increased Q–T interval.

In the functional renal failure connected with use of diuretics, metformin can cause development of lactat acidosis. It is impossible to appoint metformin at creatinine level in blood plasma of 15 mg/l (135 µmol/l) at men and women have 12 mg/l (110 µmol/l).

At patients with dehydration owing to use of diuretics at use of iodinated contrast agents, especially in high doses, risk of development of OPN increases.

At simultaneous use of an indapamid with tricyclic antidepressants and neuroleptics the hypotensive effect amplifies and risk of developing orthostatic hypotension (additive action) increases; with calcium salts — risk of development of a hypercalcemia owing to calcium removal reduction by kidneys increases; with cyclosporine — concentration of creatinine in blood plasma increases; with GKS, estrogen, tetrakozaktidy (at system use) — the hypotensive effect can decrease (a delay of water and sodium in an organism).

Overdose

Indapamid in doses up to 40 mg, that is is about 27 times higher than a therapeutic dose, is non-toxic drug.

Symptoms of acute poisoning generally are disturbances of water and electrolytic balance (hyponatremia, hypopotassemias) which are shown nausea, vomiting, arterial hypotension, spasms, dizziness, drowsiness, confusion of consciousness, a polyuria, an oliguria and an anury (owing to a hypovolemia).

First aid — is fast removal of the taken medicament from an organism by gastric lavage, uses of activated carbon, recovery of water and electrolytic balance. Symptomatic therapy — according to indications.

Storage conditions

At a temperature not above 25 °C.