Composition, form of production and packaging
Tablets of prolonged action, covered with a film shell of white or almost white color, round, biconcave.
indapamide 1.5 mg
[PRING] hypromellose (hydroxypropylmethylcellulose) - 67 mg, cellactose (lactose monohydrate 75%, cellulose 25%) - 121.5 mg, povidone - 8.6 mg, silicon colloidal dioxide 0.4 mg, magnesium stearate 1 mg.
Composition of the shell: opadray Y-1-7000 - 5 mg (hypromellose, titanium dioxide, macrogol 400 (polyethylene glycol)).
10 pieces. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (6) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
Diuretic. Indapamide belongs to the sulfonamide derivatives and is pharmacologically similar to thiazide diuretics.
Has moderate saluretic and diuretic effects, which are due to inhibition of the reabsorption of sodium, chlorine and, to a lesser extent, potassium and magnesium ions in the proximal tubule of the kidneys and in the cortical segment of the distal tubule of the nephron.
Indapamide reduces the tone of the smooth muscles of the arteries and has a vasodilating effect, reduces the OPSS. These effects are mediated by a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II, an increase in the synthesis of prostaglandin E2, which has vasodilator activity, as well as suppression of calcium current in smooth muscle cells of blood vessels.
Indapamide reduces the hypertrophy of the left ventricle of the heart. Has antihypertensive effect in doses that do not have a pronounced diuretic effect. In therapeutic doses does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).
After taking a single dose, the maximum effect is observed after 24 hours.
After ingestion, indapamide is rapidly and almost completely absorbed from the digestive tract. Eating somewhat slows the rate of absorption, but does not significantly affect the amount of absorbed drug. C max is achieved 12 hours after the administration of a single dose. At repeated receptions fluctuations of concentration of a preparation in a blood plasma in an interval between receptions of a preparation are smoothed out. However, there is an individual variability in the absorption of the drug.
Binding to blood plasma proteins - 71-79%. C ss is established after 7 days of regular administration. Do not cumulate.
Has a large V d , penetrates through the histohematological barriers (including placental). Excreted in breast milk.
Metabolism and excretion
Metabolized mainly in the liver. T 1/2 - 14-24 hours (an average of 18 hours). 70% of indapamide is excreted in the urine in the form of inactive metabolites (in an unchanged form of about 5%) and 22% is excreted with feces.
Pharmacokinetics in special clinical cases
In patients with renal insufficiency, the pharmacokinetic parameters of the preparation do not change significantly.
- arterial hypertension.
The drug is taken orally, 1.5 mg (1 tab.) 1 time / day, preferably in the morning, regardless of food intake. Take without chewing, squeezed with enough liquid.
An increase in the dose does not lead to an increase in antihypertensive action.
Classification of the incidence of adverse events (WHO): very often (? 10%), often (? 1% - <10%), infrequently (? 0.1% - <1%), rarely (? 0.01% - <0.1%), very rarely (? 0.001% - <0.01%, including individual messages).
From the side of the cardiovascular system: very rarely - lowering blood pressure, arrhythmia, orthostatic hypotension, palpitations, ECG changes, characteristic of hypokalemia, hemorrhagic vasculitis.
On the part of the organs of hematopoiesis: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, bone marrow aplasia.
From the side of the central nervous system and the peripheral nervous system: rarely - dizziness, headache, paresthesia, increased excitability, asthenia, drowsiness, vertigo, insomnia, depression, fatigue, muscle spasms of the extremities, tension, irritability, anxiety.
From the side of the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the oral mucosa; very rarely - pancreatitis, anorexia, abdominal pain, diarrhea. Patients with hepatic insufficiency may develop hepatic encephalopathy.
From the genitourinary system: very rarely - renal failure, nocturia, infections, polyuria.
From the respiratory system: cough, pharyngitis, sinusitis, rhinitis.
Allergic reactions: often - maculopapular rash; infrequently - purpura, very rarely - angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, skin itching.
Other: individual reports - exacerbation of SLE, photosensitivity reactions.
Laboratory data: hypokalemia was observed in clinical studies (the content of potassium in the blood plasma was less than 3.4 mmol / l) was observed in 10% of patients and 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 rarely - hypercalcemia, unspecified frequency: decrease in potassium content and development of hypokalemia, especially significant for patients at risk; hyponatremia, accompanied by hypovolemia and orthostatic hypotension. Simultaneous loss of chloride ions can lead to compensatory metabolic alkalosis, however, the frequency of metabolic alkalosis and its severity is negligible; hyperuricemia and hyperglycemia (unspecified frequency), increased blood urea nitrogen concentration, hypercreatininaemia.
- renal failure of severe degree (CK <30 ml / min);
- severe hepatic insufficiency (including hepatic encephalopathy);
- Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (because the preparation Ravel В® SR contains lactose);
- lactation period;
- children and adolescents under 18 years of age (efficacy and safety not established);
- hypersensitivity to indapamide, other derivatives of sulfonamide or any component of the drug.
With caution appoint the drug for violations of kidney and / or liver function, diabetes mellitus in the stage of decompensation, violations of water-electrolyte balance, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyperparathyroidism, as well as patients with an extended QT interval on the ECG or receiving therapy, as a result of which the QT interval can be prolonged (astemizole, erythromycin (iv), pentamidine, sultopride, terfenadine, vincamine (IV), class IA antiarrhythmics (quinidine, disopyramide) and III class (amiodarone, brethilium tosylate).
PREGNANCY AND LACTATION
It is not recommended to administer the drug Ravel В® SR during pregnancy. The use of the drug may cause fetoplacental ischemia with the risk of slowing the development of the fetus.
It is not recommended to use the drug during lactation (breastfeeding), because indapamide is excreted in breast milk. If treatment with Ravel В® SR is necessary during lactation, then breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in patients with severe renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in severe hepatic insufficiency (including with encephalopathy).
APPLICATION FOR CHILDREN
Contraindication: children and adolescents under 18 years of age (efficacy and safety not established).
In patients with hepatic insufficiency in the appointment of thiazide-like diuretics, the development of hepatic encephalopathy is possible, especially if the water electrolyte balance is disturbed. With its development, diuretics should be discontinued.
With the use of thiazide-like diuretics, cases of the development of photosensitivity reactions were noted. If they develop, the drug should be discontinued. Against the background of therapy with the drug Ravel В® CP, it is necessary to protect the exposed areas of the body from exposure to sunlight and artificial ultraviolet radiation.
All diuretics can cause hyponatraemia. The content of sodium ions in the blood plasma should be measured before starting treatment with the drug Ravel В® CP, and then regularly during the treatment. Determination of the content of sodium ions in blood plasma should be performed before the beginning of therapy with the drug Ravel В® CP, as well as during the period of therapy. It is important to regularly monitor the content of sodium ions in blood plasma, tk. Initially, hyponatremia can be asymptomatic. The most careful control of the sodium ion content is indicated in elderly patients and patients with cirrhosis of the liver.
The greatest risk in the treatment of thiazide-like diuretics is hypokalemia. Particular attention should be given to weakened patients and / or receiving other therapy (antiarrhythmic drugs and drugs that can extend the QT interval on the ECG), elderly patients, patients with cirrhosis of the liver, peripheral edema, and / or hypothyroidism (less than 3.4 mmol / l). ascites, with ischemic heart disease and chronic heart failure. Hypokalemia in such patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.
Patients with an extended QT interval on the ECG also belong to the high-risk group. Hypokalemia is a predisposing factor in the occurrence of severe arrhythmias, and especially arrhythmias such as pirouettes, which can lead to death.
In all described cases, it is necessary to regularly monitor the potassium content in the blood plasma. The first determination of the potassium content in blood plasma should be performed during the first week of therapy with the drug Ravel В® CP. When detecting hypokalemia, appropriate therapy should be carried out.
Thiazide-like and thiazide diuretics can reduce the excretion of calcium ions by the kidneys, leading to minor and / or temporary hypercalcemia. Expressed hypercalcemia on the background of taking Ravel В® SR can be a consequence of previously undiagnosed hyperparathyroidism. It is necessary to cancel the use of diuretics before examining the function of parathyroid glands.
In patients with diabetes, especially in the presence of hypokalemia, it is necessary to monitor the concentration of glucose in the blood plasma.
In patients with hyperuricemia, taking Ravel В® CP may increase the incidence of attacks or exacerbation of gout.
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly reduced (serum creatinine in adults less than 25 mg / L or 220 Ојmol / L) of kidney function.
Expressed hypovolemia can lead to the development of acute renal failure (a decrease in the rate of glomerular filtration), which may be accompanied by an increase in the concentration of urea and creatinine in the blood plasma. With normal kidney function, transient functional renal failure, as a rule, passes without consequences.With existing renal failure, the patient's condition may worsen.
It is recommended to regularly monitor the concentration of creatinine and the content of potassium in the blood plasma, taking into account the patient's age, body weight and sex. Ravell В® CP can be administered to elderly patients with preserved or slightly impaired renal function (QC above 30 ml / min).
Indapamide can give a positive result in the conduct of doping control.
Use in Pediatrics
The effectiveness and safety of the drug in children are not established.
Impact on the ability to drive vehicles and manage mechanisms
The use of indapamide does not lead to a disturbance of psychomotor reactions. However, in some patients, in response to a decrease in blood pressure, various individual reactions may develop, especially at the onset of therapy or when other antihypertensive agents are added to the therapy. Therefore, at the beginning of treatment with Ravel В® SR, it is not recommended to drive vehicles or other complex mechanisms requiring increased attention.
Symptoms: marked decrease in blood pressure, water-electrolyte disorders (hyponatremia, hypokalemia), nausea, vomiting, convulsions, dizziness, drowsiness, confusion, confusion, respiratory depression, polyuria or oliguria up to anuria (due to hypovolemia). In patients with cirrhosis, the development of hepatic coma is possible.
Treatment: symptomatic (gastric lavage and / or the appointment of activated charcoal, restoration of water-electrolyte balance). There is no specific antidote.
With simultaneous use with lithium preparations, an increase in the concentration of lithium ions in the blood plasma is possible due to a decrease in its excretion from the body, accompanied by the appearance of signs of an overdose (nephrotoxic effect), as well as in the case of a salt-free diet (decrease in the excretion of lithium ions by the kidneys).
Combinations that require special attention
Simultaneous use with any of the drugs that can cause heart rhythm disturbance by the type of "pirouette", incl. antiarrhythmics of class IA (quinidine, hydroquinidine, disopyramide), antiarrhythmics of class III (amiodarone, dofetilide, ibutilide, brethilia tosilate), sotalol, some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride , sultopride, tiaprid), butyrophenones (droperidol, haloperidol), as well as bepridil, cisapride, difemanyl, erythromycin (iv), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine (iv), astemizole, especially in the background hypo aliemii, increases the risk of ventricular arrhythmias. Before the beginning of the combination therapy Ravel В® SR and the above drugs should monitor the potassium content in the blood plasma and, if necessary, adjust it. It is recommended to monitor the clinical state of the patient, as well as the content of plasma electrolytes and ECG. Patients with hypokalemia should use drugs that do not trigger the development of piruet-type arrhythmias.
When simultaneous administration of NSAIDs (with systemic administration), including selective COX-2 inhibitors, high doses of salicylic acid (3 g / day or more), possibly reducing the antihypertensive effect of indapamide, the development of acute renal failure in dehydrated patients (due to reduced glomerular filtration rate).At the beginning of therapy with indapamide, it is necessary to restore the water-electrolyte balance and control the function of the kidneys.
ACE Inhibitors in patients with hyponatraemia (especially in patients with renal artery stenosis) increase the risk of developing arterial hypotension and / or acute renal failure. Patients with hypertension and possibly with hyponatraemia, due to the intake of diuretics, should:
- stop taking the drug 3 days before the start of therapy with ACE inhibitors and switch to potassium-sparing diuretics;
- or initiate therapy with ACE inhibitors from low doses, followed by a gradual increase in dose if necessary. In the first week of therapy with ACE inhibitors, it is recommended to monitor the concentration of plasma creatinine.
With simultaneous admission with indapamide drugs that can cause hypokalemia, including. amphotericin B (IV), gluco- and mineralocorticoids (for systemic administration), tetracosactide, laxatives stimulating intestinal motility, the risk of hypokalemia (additive effect) increases. If necessary, monitor and adjust the content of potassium ions in the blood plasma.
Simultaneous therapy with baclofen enhances the antihypertensive effect of indapamide.
Hypokalemia caused by indapamide increases the toxic effect of cardiac glycosides (glycoside intoxication). With the simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium ions in the blood plasma, the ECG parameters, and, if necessary, adjust the therapy.
Combinations of drugs requiring attention
Simultaneous use with potassium-sparing diuretics (amiloride, spironolactone, triamterene) it is advisable in some patients, however, the possibility of developing hypokalemia is not ruled out. Against the background of diabetes or kidney failure may develop hyperkalemia. It is necessary to control the content of potassium ions in the blood plasma, the parameters of the ECG, and, if necessary, adjust the therapy.
Metformin increases the risk of developing lactic acidosis, t. It is possible to develop renal failure with diuretics, especially "loop". Metformin should not be taken at a plasma creatinine concentration greater than 15 mg / L (135 Ојmol / L) in men and 12 mg / L (110 Ојmol / L) in women.
Simultaneous use of large doses of iodine-containing contrast agents against hypovolemia and the use of diuretics increases the risk of acute renal failure. It is recommended to restore the water-electrolyte balance of blood before applying the drugs.
Tricyclic antidepressants (imipramine-like) and antipsychotics increase the hypotensive effect and the risk of developing orthostatic hypotension (additive effect).
Preparations containing calcium salts, increase the risk of hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.
Cyclosporin, tacrolimus increase the risk of increasing the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine.
GCS, tetrakozaktid (with systemic use) reduce the hypotensive effect of indapamide (delay of sodium and liquid ions).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 4 years.