Ravel SR, tablets 1.5 mg 30 pcs

Ravel SR is a diuretic. An antihypertensive drug. Indapamide belongs to the sulfonamide derivatives and has pharmacological properties similar to thiazide diuretics.

Indapamide impairs reabsorption of sodium ions in the cortical segment of the renal tubules, which increases excretion of sodium and chlorine ions with urine and leads to increased diuresis. To a lesser extent, the drug increases excretion of potassium and magnesium ions.

In addition to the diuretic action, indapamide has an effect on vascular tone which is manifested by reduction of arteriolar and total peripheral resistance.

Indapamide has antihypertensive effect in doses that do not have a pronounced diuretic effect. At high doses it has no effect on the degree of BP reduction, despite the increase in diuresis. Indapamide, like other thiazide diuretics, reduces left ventricular hypertrophy. In therapeutic doses has almost no effect on lipid and carbohydrate metabolism.

Indications

Arterial hypertension.

Active ingredient

Composition

Prolong-acting, coated white or almost white, round, biconvex, containing

Indapamide 15 mg.

Auxiliary substances:

Hydroxypropyl methylcellulose (hypromellose),

Cellactose,

Povidone,

Colloidal anhydrous silicon oxide,

Magnesium stearate,

Opadry Y-1-7000 (mixture of hypromellose, Macrogol 400 and titanium oxide), Water.

How to take, the dosage

The drug is taken orally, 1.5 mg (1 tablet) 1 time per day, preferably in the morning, with plenty of fluid.

Interaction

In co-administration, indapamide increases the plasma concentration of lithium (due to reduced urinary excretion) and increases the likelihood of nephrotoxic reactions (close monitoring of plasma lithium concentration and dose adjustment is necessary).

Drugs co-administration with which may cause “pirouette” type arrhythmias. Co-administration of indapamide with astemizole, bepridine, erythromycin (for intravenous administration), halofantrine, pentamidine, sultopride, terfenadine, vincamine, Class IA antiarrhythmic drugs (quinidine, Class III (amiodarone, brettilia tosylate, sotalol) may lead to the development of pirouette-type arrhythmias (hypokalemia, bradycardia, and preceding prolongation of QT interval are predisposing factors).

In co-administration of indapamide with NSAIDs (when administered systemically) there is a risk of acute renal failure in patients with hypovolemia (due to decreased glomerular filtration rate). It is necessary to compensate for fluid loss and monitor renal function at the beginning of treatment.

Drugs coadministration with which may lead to hypokalemia. Co-administration of indapamide with amphotericin B (for intravenous administration); gluco- and mineralocorticoids (for systemic use), tetracosactide, intestinal motility stimulants, cardiac glycosides – the risk of hypokalemia increases (additive effect). Monitoring of plasma potassium levels, ECG is necessary, and if necessary, the prescription of appropriate therapy.

Baclofen Co-administration of indapamide with baclofen may increase the antihypertensive effect.

Tricyclic antidepressants and neuroleptics increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

When used together with indapamide, ACE inhibitors increase the risk of arterial hypotension.

The co-administration of indapamide with cyclosporine leads to increased plasma creatinine concentration with unchanged circulating cyclosporine concentration.

Indapamide increases the risk of renal dysfunction when using iodine containing X-ray contrast agents in high doses (dehydration of the body). Patients need to restore fluid loss before using iodine-containing contrasting medications.

The co-administration of indapamide with drugs containing calcium leads to increased concentrations of calcium ions in the blood plasma due to reduced excretion in the urine.

Combination of indapamide with potassium-saving diuretics (amiloride, spironolactone, triamterene) may lead to hypo- or hyperkalemia, especially in diabetic patients and patients with renal dysfunction.

Special Instructions

Indapamide administration may cause hepatic encephalopathy if liver function is impaired. If this occurs, the drug should be stopped immediately. Taking indapamide may cause hyponatremia, in some cases accompanied by serious consequences. Plasma sodium levels are measured before the start of treatment, and then during treatment at regular intervals.

The initial drop in plasma sodium concentration may be asymptomatic, so regular monitoring is important. In elderly patients and patients with liver cirrhosis monitoring should be even more frequent. Against the background of taking the drug, hypokalemia may develop. Careful and regular monitoring of potassium content in order to prevent hypokalemia (potassium content less than 3.4 mmol/l) should be performed in risk group patients, such as frail patients and/or patients taking several medicines simultaneously, elderly patients, patients with cirrhosis, peripheral edema and ascites, IBS and heart failure. In these patients hypokalemia increases toxic effects of cardiac glycosides and risk of arrhythmias.

The high-risk group also includes patients with prolonged QT interval on ECG, regardless of the cause, congenital or drug-induced. Hypokalemia (as well as bradycardia) is a predisposing factor for severe arrhythmias, especially potentially dangerous pirouettes. In all these patients, more frequent monitoring of plasma potassium concentration is required. The first measurement of plasma potassium concentration should be performed during the first week of treatment.

If low potassium levels are detected, their correction is required. Control of blood glucose levels is important in patients with diabetes, especially in the presence of hypokalemia. Patients with hyperuricemia may have an increased incidence of gout attacks. Thiazide and thiazide-like diuretics are fully effective only when renal function is normal or slightly decreased (serum creatinine below 25 mg/l or 220 µmol/l in adults). In elderly patients, serum creatinine content may vary depending on age, body weight and sex.

Secondary hypovolemia due to water and sodium loss induced by diuretics at the beginning of treatment causes decrease of glomerular filtration. This may lead to elevated plasma levels of urea and creatinine. If the patient’s renal function is not impaired, this transient functional renal failure usually passes without consequences, but may worsen pre-existing renal failure. Taking indapamide can cause a positive reaction in a doping control.

The efficacy and safety of the drug in children has not been established.

In some cases, individual reactions associated with BP changes are possible, especially at the beginning of treatment or when adding another antihypertensive agent. As a result, the ability to drive and operate machinery may be reduced.

Contraindications

– Severe renal failure (anuria stage).
– Severe hepatic failure (including encephalopathy).
– Hypokalemia.
– Concomitant use of drugs prolonging QT interval.
– Children and adolescents under 18 years old.
– Hypersensitivity to any component of the preparation and other sulphonamide derivatives.

The preparation is used with caution in diabetes mellitus, renal and/or hepatic function disorders, water-electrolyte balance disorders, hyperparathyroidism, prolongation of QT interval on ECG, hyperuricemia (especially manifested by gout or urate nephrolithiasis).

Side effects

Classification of the incidence of side effects (WHO): very common (≥10%), common (≥1% – < 10%), infrequent (≥0.1% – < 1%), rare (≥0.01% – < 0.1%), very rare (≥0.001% – < 0.01%, including individual reports).

Cardiovascular system disorders: very rare – decreased BP, arrhythmia, orthostatic hypotension, palpitations, ECG changes characteristic of hypokalemia, hemorrhagic vasculitis.

Hematopoietic organs: very rarely – thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, aplasia of bone marrow.

CNS and peripheral nervous system disorders: rarely – dizziness, headache, paresthesia, hyperexcitability, asthenia, somnolence, vertigo, insomnia, depression, increased fatigue, muscle spasms in extremities, tension, irritability, anxiety.

The digestive system: infrequent – vomiting; rare – nausea, constipation, dry mouth; very rare – pancreatitis, anorexia, abdominal pain, diarrhea. In patients with hepatic insufficiency, hepatic encephalopathy may develop.

Urogenital system disorders: very rarely – renal failure, nycturia, infections, polyuria.

Respiratory system disorders: cough, pharyngitis, sinusitis, rhinitis.

Allergic reactions: common – maculopapular rash; infrequent – purpura, very rare – angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, skin itching.

Others: individual reports – exacerbation of SLE, photosensitivity reactions.

Laboratory data: in clinical trials hypokalemia (potassium content in plasma 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 therapy. After 12 weeks of therapy, plasma potassium content decreased, on average, by 0.23 mmol/l.

Very rarely – hypercalcemia, unspecified frequency: decrease of potassium content and development of hypokalemia, especially significant for patients belonging to risk group; hyponatremia accompanied by hypovolemia and orthostatic hypotension. Simultaneous loss of chlorine ions may cause compensatory metabolic alkalosis, but the incidence and severity of metabolic alkalosis is insignificant; hyperuricemia and hyperglycemia (unspecified frequency), increased concentration of blood urea nitrogen, hypercreatininemia.

Overdose

Symptoms: water-electrolyte disorders (hyponatremia, hypokalemia) manifested as nausea, vomiting, decreased blood pressure, seizures, dizziness, drowsiness, lethargy, polyuria or oliguria, up to anuria (due to hypovolemia).

Treatment: gastric lavage, administration of activated charcoal, correction of water-electrolyte balance, symptomatic therapy; there is no specific antidote.

Pregnancy use

Prescription of indapamide during pregnancy is not recommended. Use of the drug may cause fetoplacental ischemia with the risk of fetal growth retardation.

The drug is not recommended during lactation (breast-feeding) because indapamide is excreted with breast milk.

Similarities