Ravel SR - instructions for use, dose, side effects, contraindications

Excipients: hypromellose (hydroxypropylmethylcellulose), cellactose [lactose monohydrate 75%, cellulose 25%], povidone, silicon dioxide colloid, magnesium stearate.

SHELL:

Opadry Y-1-7000 (hypromellose, titanium dioxide and macrogol-400 (polyethylene glycol)).

Description:

Round, biconvex tablets, film-coated, white or almost white.

Pharmacotherapeutic group:diuretic

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

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 tubules 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 overall peripheral resistance of the vessels. 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; suppression of calcium current in smooth muscle cells of blood vessels.

Yingdapamid Helps reduce 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.

Pharmacokinetics:

The drug Ravel® SR is available in the form of tablets with prolonged release of the active substance. Indapamide quickly and almost completely absorbed in the gastrointestinal tract. Eating somewhat slows down absorption, but does not significantly affect the amount of absorbed drug. The maximum concentration in the blood plasma is achieved 12 hours after ingestion 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.

Communication with plasma proteins is 71-79%. The half-life (T_1/2) is from 14 to 24 hours (an average of 18 hours). The equilibrium concentration is established after 7 days of regular administration. Do not cumulate.

Has a high volume of distribution, penetrates through the histohematological barriers (including placental). Penetrates into breast milk.

Metabolized mainly in the liver. 70% of indapamide is excreted by the kidneys in the form of inactive metabolites (unchanged in about 5%) and 22% is excreted through the intestine.

In patients with renal insufficiency, the pharmacokinetic parameters of the preparation do not change significantly.

Indications:

Arterial hypertension.

Contraindications:

- Hypersensitivity to indapamide, other derivatives of sulfonamide or any component of the drug;

- severe renal failure (creatinine clearance (CK) less than 30 ml / min);

- severe hepatic insufficiency, incl. hepatic encephalopathy;

- hypokalemia;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome, because the drug Ravel® SR contains lactose;

- pregnancy and lactation;

- age to 18 years (efficacy and safety not established).

Carefully:

Impaired renal and / or liver function, diabetes mellitus in decompensation, water-electrolyte balance disorders, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyperparathyroidism; patients with an elongated interval QT on ECG or receiving therapy, as a result of which the lengthening of the interval is possible QT (astemizole, erythromycin (intravenously), pentamidine, sultopride, terfenadine, wincamine (IV), antiarrhythmic drugs IA class (quinidine, disopyramide) and III class (amiodarone, brethil tosylate).

Pregnancy and lactation:

Pregnant taking Ravel® SR is not recommended. 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 the period of breastfeeding, tk. indapamide penetrates into breast milk. If treatment with Ravel® SR is necessary during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

Inside, 1 tablet (1.5 mg) 1 time per day, preferably in the morning, regardless of food intake. Take, not liquid, squeezed with enough liquid. An increase in the dose of the drug does not lead to an increase in the hypotensive effect.

Side effects:

Classification of the incidence of adverse events (WHO): very often - 10% or more; often - 1% or more, less than 10%; infrequently, 0.1% or more, less than 1%; rarely - 0.01% or more, less than 0.1%; very rarely - 0,001% or more, less than 0,01%, including individual messages

From the cardiovascular system: very rarely - lowering blood pressure (BP), arrhythmia, orthostatic hypotension, palpitations, ECG changes typical of hypokalemia, hemorrhagic vasculitis.

From the hematopoiesis: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, bone marrow aplasia.

From the central and 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 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: separate messages - exacerbation of systemic lupus erythematosus (SLE), photosensitivity reactions.

Laboratory data: in clinical studies, hypokalemia (potassium in the blood plasma below 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 potassium content in the blood plasma decreased, on average, by 0.23 mmol / l. Very rarely - hypercalcemia; unspecified frequency: decreased potassium and hypokalemia, especially significant for patients at risk (see section "Special instructions"); 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.

Overdose:

Symptoms: marked reduction of blood pressure, aqueous electrolyte disturbances (hyponatremia, hypokalemia), nausea, vomiting, cramps, dizziness, drowsiness, lethargy, confusion, respiratory depression, polyuria, oliguria or anuria until (due to hypovolemia).Patients with cirrhosis may develop hepatic coma.

Treatment: symptomatic (gastric lavage and / or the appointment of activated charcoal, restoration of water-electrolyte balance). There is no specific antidote.

Interaction:

Unrecommended combinations

With simultaneous application from lithium preparations it is possible to increase the concentration of lithium ions in the blood plasma due to a decrease in excretion of it from the body by the kidneys, accompanied by the appearance of signs of an overdose (nephrotoxic action), as well as under observation salt-free diet ('decrease in the excretion of lithium ions by the kidneys).

Combinations that require special attention

1. Preparations that can cause a disturbance of the rhythm of the heart by the type of "pirouette": antiarrhythmic drugs of class (quinidine, hydroquinidine, disopyramide), antiarrhythmic drugs of III class (amiodarone, dofetilide, ibutilide, brethil tosylate), sotalol, some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other (bepridil, cisapride, difemanyl, erythromycin (intravenous (iv)), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, wincamine (w / w), astemizole. Simultaneous use with any of these drugs, especially against hypokalemia, increases the risk of ventricular arrhythmias as pirouettes. Before starting the combination therapy with Ravel® SR and the above preparations, you should monitor the potassium content in the blood plasma and, if necessary, adjust it. It is recommended: monitoring the clinical condition 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.

2. With simultaneous appointment non-steroidal anti-inflammatory drugs (NSAIDs) (for systemic use), including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of salicylic acid (3 g / day or more) possibly: a reduction in the antihypertensive effect of indapamide, the development of acute renal failure in dehydrated patients (due to a decrease in 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.

3. Angiotensin-converting enzyme (ACE inhibitors)) in patients with hyponatremia (especially in patients with renal artery stenosis) increase the risk of arterial hypotension and / or acute renal failure.

Patients with hypertension and possibly with hyponatraemia due to 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.

A. Other drugs that can cause hypokalemia:

- amphotericin In (in / in);

- gluco- and mineralocorticosteroids (for systemic administration) (see also the information in the "Combinations of drugs requiring attention" section);

- tetracosactide (see also the information in the "Combinations of drugs that require attention" section);

- laxatives, stimulating intestinal motility.

With the simultaneous administration of the above drugs with indapamide, the risk of developing hypokalemia (additive effect) increases.

If necessary, monitor and adjust the content of potassium ions in the blood plasma.

5. Simultaneous therapy from baclofen enhances the antihypertensive effect of indapamide.

6. Cardiac glycosides: hypokalemia increases the toxic effect of cardiac glycosides (glycoside intoxication). With the simultaneous use of indapamide and cardiac glycosides, the levels of potassium ions in the blood plasma should be monitored, the ECG parameters should be monitored and, if necessary, the therapy should be adjusted.

Combinations of drugs requiring attention

1. Simultaneous application from potassium-sparing diuretics (amiloride, spironolactone, triamterene) It is advisable in some patients, however, the possibility of hypokalemia development 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.

2. 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 of more than 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

3. Simultaneous application of large doses iodine-containing contrast agents against the background of hypovolemia and the use of diuretics increases the risk of acute renal failure. It is recommended to restore the electrolyte balance of blood before applying the drugs.

4. Tricyclic antidepressants (imipramine-like) and antipsychotics increase the hypotensive effect and the risk of developing orthostatic hypotension (additive effect).

5. Preparations containing calcium salts, increase the risk of hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

6. Cyclosporin, tacrolimus - The risk of increasing the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine.

7. Glucorticosteroid preparations, tetracosactide (with systemic application) reduce the hypotensive effect (retention of sodium and liquid ions).

Special instructions:

Dysfunction of the liver

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.

Photosensitivity

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® SR indapamide, it is necessary to protect the exposed areas of the body from exposure to sunlight and artificial ultraviolet radiation.

Water-electrolyte balance

- content of sodium ions in blood plasma: all diuretic drugs can cause hyponatraemia. The content of sodium ions in blood plasma should be measured before starting treatment with Ravel® SR, and then regularly during the treatment period. Determination of the content of sodium ions in the blood plasma should be performed before the beginning of therapy with the drug Ravel® SR, and also 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 thorough control of sodium ions is indicated in elderly patients and patients with cirrhosis of the liver;

- the content of potassium ions in the blood plasma: The greatest risk in the treatment of thiazide-like diuretics is hypokalemia.

Particular attention should be paid to prevent hypokalemia (less than 3.4 mmol / L) in the following cases: weakened patients and / or receiving other therapy (antiarrhythmic drugs and agents that can lengthen the interval QT on ECG), in old age, patients with cirrhosis of the liver, peripheral edema and 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.

The high-risk group also includes patients with an elongated interval QT on the ECG. Hypokalemia is a predisposing factor in the occurrence of severe arrhythmia, 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® SR.

If hypokalemia is detected, appropriate therapy should be performed;

- the content of calcium ions in the blood plasma: 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 the drug Ravel ® SR may be a consequence of previously undiagnosed hyperparathyroidism. It is necessary to abolish diuretics before examining the function of parathyroid glands;

- concentration of glucose in blood plasma: in patients with diabetes, especially in the presence of hypokalemia, it is necessary to monitor the concentration of glucose in the blood plasma.

- uric acid: in patients with hyperuricemia may increase the frequency of seizures or exacerbation of gout.

Kidney function and diuretic drugs

Taazidnye and thiazide-like diuretics are fully effective only in patients with normal or slightly decreased (creatinine plasma in adults less than 25 mg / L or 220 μmol / L) 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.

Elderly patients

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. Ravel® CP can be administered to elderly patients with preserved or slightly impaired renal function (QC above 30 ml / min).

Athletes

Indapamide can give a positive result in the conduct of doping control.

Effect on the ability to drive transp. cf. and fur:

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.In this context, at the beginning of treatment Ravel® SR is not recommended to drive vehicles or other complex mechanisms that require attention.

Form release / dosage:

Tablets of prolonged action, film-coated, 1.5 mg.

Packaging:

10 tablets per contour cell pack.

2, 3 or 6 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000406

Date of registration:21.04.2010

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp18.10.2015

Illustrated instructions

Instructions

Ravel® SR (Rawel® SR)