Torasemid-SZ
Registration number
LP-003307
Dosage form
pills
Compound
1 tablet contains:
dosage 5 mg:
active substance: torasemide - 5 mg excipients: lactose monohydrate (lacto press) (milk sugar) - 89.3 mg; pregelatinized starch (starch 1500) - 24.5 mg; colloidal silicon dioxide (aerosil) - 0.6 mg; magnesium stearate - 0.6 mg.
dosage 10 mg:
active substance: torasemide - 10 mg excipients: lactose monohydrate (lacto press) (milk sugar) - 178.6 mg; pregelatinized starch (starch 1500) - 49.0 mg; colloidal silicon dioxide (aerosil) -1.2 mg; magnesium stearate - 1.2 mg.
Description
Tablets are white or almost white, round, flat cylindrical with a chamfer and a score on one side.
ATX code
C03CA04
Pharmacological properties
Pharmacodynamics
Torsemide is a loop diuretic. The maximum diuretic effect develops 2-3 hours after taking the drug orally. The main mechanism of action of the drug is due to the reversible binding of torasemide to the sodium/chlorine/potassium ion contransporter located in the apical membrane of the thick segment of the ascending loop of Henle, as a result of which the reabsorption of sodium ions is reduced or completely inhibited and the osmotic pressure of intracellular fluid and water reabsorption are reduced. . Blocks myocardial aldosterone receptors; reduces fibrosis and improves diastolic myocardial function.
Torasemide causes hypokalemia to a lesser extent than furosemide, but it is more active and its action lasts longer. The use of torasemide is the most reasonable choice for long-term therapy.
Pharmacokinetics
After oral administration, torasemide is quickly and almost completely absorbed from the gastrointestinal tract. Food intake does not have a significant effect on the absorption of the drug. The maximum concentration of torasemide in the blood plasma is observed 1-2 hours after oral administration. Bioavailability is 80 - 90% with minor individual variations.
The diuretic effect lasts up to 18 hours, which facilitates the tolerability of therapy due to the absence of very frequent urination in the first hours after taking the drug orally, which limits the activity of patients.
Communication with blood plasma proteins is more than 99%. The apparent volume of distribution is 16 l. Metabolized in the liver using isoenzymes of the cytochrome P450 system. As a result of sequential reactions of oxidation, hydroxylation or ring hydroxylation, three metabolites are formed (M1, M3 and M5), which bind to plasma proteins by 86%, 95% and 97%, respectively.
The half-life (T1/2) of torasemide and its metabolites is 3-4 hours and does not change in chronic renal failure. The total clearance of torasemide is 40 ml/min, renal clearance is 10 ml/min. On average, about 83% of the dose taken is excreted by the kidneys: unchanged (24%) and in the form of predominantly inactive metabolites (M1 - 12%, M3 - 3%, M5 -41%). In renal failure, T1/2 does not change, T1/2 of metabolites M3 and M5 increases. Torsemide and its metabolites are slightly eliminated by hemodialysis and hemofiltration.
In case of liver failure, the concentration of torasemide in the blood plasma increases due to a decrease in the metabolism of the drug in the liver. In patients with cardiac or liver failure, T1/2 of torasemide and metabolite M5 is slightly increased, drug accumulation is unlikely.
Indications for use
• edema syndrome of various origins, including in chronic heart failure, diseases of the liver, lungs and kidneys;
• arterial hypertension.
Contraindications
Hypersensitivity to torsemide or to any of the components of the drug; in patients with an allergy to sulfonamides (sulfonamide antimicrobials or sulfonylureas); renal failure with anuria; hepatic coma and precoma; refractory hypokalemia/refractory hyponatremia; hypovolemia (with or without arterial hypotension) or dehydration; pronounced disturbances in the outflow of urine of any etiology (including unilateral damage to the urinary tract); glycoside intoxication; acute glomerulonephritis; decompensated aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy; increased central venous pressure (over 10 mm Hg); hyperuricemia; simultaneous use of aminoglycosides and cephalosporins; age under 18 years; pregnancy, breastfeeding period; lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
CAREFULLY
Arterial hypotension, stenosing cerebral artery atherosclerosis, hypoproteinemia, predisposition to hyperuricemia, urinary flow disorders (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis), history of ventricular arrhythmia, acute myocardial infarction (increased risk of cardiogenic shock), diarrhea , pancreatitis, diabetes mellitus (decreased glucose tolerance), hepatorenal syndrome, gout, anemia; simultaneous use of cardiac glycosides, corticosteroids and adrenocorticotropic hormone (ACTH).
USE IN PREGNANCY AND DURING THE PERIOD
Torsemide does not have a teratogenic effect or fetotoxicity; it penetrates the placental barrier, causing disturbances in water-electrolyte metabolism and thrombocytopenia in the fetus.
There have been no controlled studies on the use of torasemide in pregnant women; the drug is not recommended for use during pregnancy. It is not known whether torasemide passes into breast milk. If it is necessary to use the drug Torasemide-SZ during lactation, you must stop breastfeeding.
Directions for use and doses
Orally, once a day, without chewing, with a sufficient amount of water. The tablets can be taken at any convenient time, regardless of meals. Edema syndrome in chronic heart failure
The usual starting dose is 10-20 mg once daily. If necessary, the dose can be doubled until the desired effect is obtained. Edema syndrome in kidney disease
The usual starting dose is 20 mg once daily. If necessary, the dose can be doubled until the desired effect is obtained. Edema syndrome in liver disease
The usual starting dose is 5-10 mg once daily. If necessary, the dose can be doubled until the desired effect is obtained. The maximum single dose is 40 mg; it is not recommended to exceed it (there is no experience with use). The drug is used for a long period or until swelling disappears.
Arterial hypertension
The starting dose is 2.5 mg (1/2 5 mg tablet) once daily. If there is no therapeutic effect within 4 weeks, the dose is increased to 5 mg once a day. If there is no adequate reduction in blood pressure when taken at a dose of 5 mg once a day for 4-6 weeks, the dose is increased to 10 mg once a day. If the use of the drug at a dose of 10 mg per day does not give the required effect, an antihypertensive drug of another group is added to the treatment regimen.
Elderly patients do not require dose adjustment.
Side effect
The incidence of side effects is classified according to the recommendations of the World Health Organization: very common: > 1/10 (> 10%); often: from>1/100 to <1/10 (>1% and <10%);
uncommon: > 1/1000 to < 1/100 (> 0.1% and < 1%); rare: from > 1/10000 to < 1/1000 (> 0.01% and < 0.1%); very rare: <1/10000 (<0.01%); frequency unknown: frequency cannot be estimated from available data. From the nervous system: often - headache, dizziness, drowsiness; infrequently - muscle cramps of the lower extremities; frequency unknown - confusion, fainting, parasthesia in the extremities (feeling of numbness, “crawling” and tingling). From the senses: frequency unknown - visual impairment, hearing impairment, tinnitus and hearing loss (usually reversible), usually in patients with renal failure or hypoproteinemia (nephrotic syndrome). From the cardiovascular system: infrequently - extrasystole, arrhythmia, tachycardia; frequency unknown - excessive decrease in blood pressure, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism, decrease in circulating blood volume. From the respiratory system: infrequently - nosebleeds.
From the digestive system.
often - diarrhea; uncommon - abdominal pain, flatulence, polydipsia; frequency unknown - dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspeptic disorders, intrahepatic cholestasis. From the skin and subcutaneous tissues: frequency unknown - skin itching, rash, urticaria, erythema polymorphosus, exfoliative dermatitis, purpura, vasculitis, photosensitivity. From the musculoskeletal system: frequency unknown - muscle weakness. From the urinary system: often - increased frequency of urination, polyuria, nocturia; infrequently - frequent urge to urinate; frequency unknown - oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria. From the reproductive system: frequency unknown - decreased potency. From the metabolic side: frequency unknown - hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hypochloremia, metabolic alkalosis, hypovolemia, dehydration (more often in elderly patients). From laboratory parameters: infrequently - hypercholesterolemia, hypertriglyceridemia; frequency unknown - hyperuricemia, a slight increase in the activity of alkaline phosphatase in the blood plasma, an increase in the concentration of creatinine and urea in the blood plasma, an increase in the activity of some “liver” enzymes in the blood plasma (for example, gamma-glutamyl transferase), thrombocytopenia, leukopenia, agranulocysis toz, hyperglycemia, decreased glucose tolerance (possible manifestation of latent diabetes mellitus).
Other:
frequency unknown - aplastic or hemolytic anemia.
Overdose
Symptoms: increased diuresis, accompanied by a decrease in circulating blood volume and disturbances in the water-electrolyte balance of the blood, followed by a pronounced decrease in blood pressure, drowsiness and confusion, and collapse. Gastrointestinal disturbances may occur.
Treatment: there is no specific antidote. Provocation of vomiting, gastric lavage, activated charcoal. Treatment is symptomatic, dose reduction or discontinuation of the drug and at the same time replenishment of blood volume and indicators of water-electrolyte balance and acid-base status under the control of serum concentrations of electrolytes, hematocrit, symptomatic treatment.
Hemodialysis is ineffective.
Interaction with other drugs
Increases the concentration and risk of developing nephro- and ototoxic effects of cephalosporins, aminoglycosides, chloramphenicol, ethacrynic acid, cisplatin, amphotericin B (due to competitive renal excretion). Increases the effectiveness of diazoxide and theophylline, reduces the effectiveness of hypoglycemic agents, allopurinol. Pressor amines and torasemide mutually reduce the effectiveness. Drugs that block tubular secretion increase the concentration of torasemide in the blood serum. With the simultaneous use of glucocorticosteroids, amphotericin B, the risk of developing hypokalemia increases, with cardiac glycosides - the risk of developing glycoside intoxication increases due to hypokalemia (for high- and low-polarity) and prolongation of the half-life (for low-polarity). Reduces the renal clearance of lithium drugs and increases the likelihood of intoxication. Nonsteroidal anti-inflammatory drugs, sucralfate, reduce the diuretic effect due to inhibition of prostaglandin synthesis, disruption of renin activity in the blood plasma and excretion of aldosterone. Strengthens the antihypertensive effect of antihypertensive drugs, neuromuscular blockade of depolarizing muscle relaxants (suxamethonium) and weakens the effect of non-depolarizing muscle relaxants (tubocurarine). Concomitant use of large doses of salicylates during torsemide therapy increases the risk of their toxicity (due to competitive renal excretion). Sequential or simultaneous use of Torsemide with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists can lead to a significant decrease in blood pressure. This can be avoided by reducing the dose of torasemide or temporarily stopping it.
Concomitant use of probenecid or methotrexate may reduce the effectiveness of torsemide (same secretion route). On the other hand, torasemide may lead to decreased renal elimination of these drugs.
With simultaneous use of cyclosporine and torasemide, the risk of developing gouty arthritis increases due to the fact that cyclosporine can cause impaired renal urate excretion, and torasemide can cause hyperuricemia.
It has been reported that in patients at high risk of developing nephropathy taking torasemide orally, renal dysfunction was observed more often during the administration of radiocontrast agents than in patients at high risk of developing nephropathy who received intravenous hydration before the administration of radiocontrast agents. The bioavailability and, as a consequence, the effectiveness of torasemi may be reduced when combined with cholestyramine.
special instructions
Use strictly as prescribed by your doctor. Patients with hypersensitivity to sulfanilamides and sulfonylurea derivatives may have cross-sensitivity to Torasemide-SZ. For patients receiving high doses of Torasemide-SZ for a long period, in order to avoid the development of hyponatremia, metabolic alkalosis and hypokalemia, a diet with sufficient salt content and the use of potassium supplements are recommended.
An increased risk of developing fluid and electrolyte imbalances is observed in patients with renal failure. During the course of treatment, it is necessary to periodically monitor the concentration of blood plasma electrolytes (including sodium, calcium, potassium, magnesium), acid-base status, residual nitrogen, creatinine, uric acid and, if necessary, carry out appropriate corrective therapy (with a higher frequency in patients with frequent vomiting and against the background of parenterally administered fluids).
If azotemia and oliguria appear or worsen in patients with severe progressive kidney disease, it is recommended to suspend treatment.
The selection of a dosage regimen for patients with ascites against the background of liver cirrhosis should be carried out in hospital conditions (violations of water and electrolyte balance can lead to the development of hepatic coma). Regular monitoring of blood plasma electrolytes is indicated for this category of patients.
In patients with diabetes mellitus or with reduced glucose tolerance, periodic monitoring of glucose concentrations in the blood and urine is required. In unconscious patients with prostatic hyperplasia and narrowing of the ureters, diuresis control is necessary due to the possibility of acute urinary retention.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, patients should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (risk of dizziness and drowsiness).
Release form
Tablets 5 mg and 10 mg. 10 tablets per blister pack. 30 tablets in a polymer jar made of low-density polyethylene with a lid made of high-density polyethylene or in a polymer bottle made of low-density polyethylene with a lid made of high-density polyethylene. Each jar, bottle, 2, 3, 6, 10 blister packs along with instructions for use are placed in a cardboard box.
Best before date
3 years. Do not use after the expiration date stated on the packaging.
Storage conditions
In a dry place, protected from light, at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Vacation conditions
Dispensed by prescription.
Prescription drug
Prescription drug
Torasemide Medisorb, 10 mg, tablets, 20 pcs.
Adverse reactions are listed depending on the anatomical and physiological classification and frequency of occurrence. The frequency of adverse reactions listed below was determined according to the following (World Health Organization classification): very often ≥1/10, often ≥1/100 and
Blood and lymphatic system disorders: frequency unknown - thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia.
Immune system disorders: frequency unknown - severe anaphylactic reactions up to shock, which have so far been described only after intravenous administration.
Metabolic and nutritional disorders: frequency unknown - hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia, decreased glucose tolerance (possible manifestation of latent diabetes mellitus), metabolic alkalosis.
Symptoms indicating the development of fluid-electrolyte and acid-base imbalances may include headache, confusion, convulsions, tetany, muscle weakness, cardiac arrhythmias and dyspepsia; hypovolemia and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.
Nervous system disorders: often - dizziness, headache, drowsiness; infrequently - muscle cramps of the lower extremities; frequency unknown - confusion, fainting, paresthesia (feeling of numbness, “crawling” and tingling in the limbs).
Visual disturbances: frequency unknown - visual disturbances.
Hearing and labyrinthine disorders: frequency unknown - hearing impairment, tinnitus and/or hearing loss (usually reversible), usually in patients with renal failure or hypoproteinemia (nephrotic syndrome).
Cardiac disorders: uncommon - extrasystole, tachycardia, arrhythmia, palpitations.
Vascular disorders: frequency unknown - excessive decrease in blood pressure, orthostatic hypotension, collapse, decrease in circulating blood volume, deep vein thrombosis, thromboembolism.
Disorders of the respiratory system, chest and mediastinal organs: infrequently - nosebleeds.
Gastrointestinal disorders: often - diarrhea; uncommon - abdominal pain, flatulence, polydipsia; frequency unknown - dry mouth, nausea, vomiting, loss of appetite, dyspeptic disorders, acute pancreatitis.
Disorders of the liver and biliary tract: frequency unknown - intrahepatic cholestasis.
Disorders of the skin and subcutaneous tissues: infrequently - redness of the face; frequency unknown - skin itching, skin rash, urticaria, erythema multiforme, exfoliative dermatitis, purpura, vasculitis, photosensitivity.
Muscle, skeletal and connective tissue disorders: frequency unknown - muscle weakness.
Renal and urinary tract disorders: often - increased frequency of urination, polyuria, nocturia; infrequently - frequent urge to urinate; frequency unknown - oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria.
Disorders of the reproductive system and mammary glands: frequency unknown - impaired potency.
General disorders and reactions at the injection site: uncommon - fever, asthenia, weakness, fatigue, hyperactivity, nervousness.
Laboratory and instrumental data: frequency unknown - hyperglycemia, hypercholesterolemia, hypertriglyceridemia, hyperuricemia (an increase in the concentration of uric acid in the blood can cause or intensify the manifestation of gout), a slight increase in the concentration of alkaline phosphatase in the blood, a transient increase in the concentration of creatinine and urea in the blood, an increase in the activity of some "liver" enzymes (for example, gamma-glutamyltransferase).
Description of the drug AUDITOR
After oral administration, torasemide is absorbed from the gastrointestinal tract with a limited first-pass effect through the liver. Cmax in blood plasma is achieved within 1.5 hours after oral administration. Food intake does not have a significant effect on absorption. Impaired renal and/or liver function do not affect absorption.
More than 99% of torasemide is bound to plasma proteins.
Vd in healthy volunteers and in patients with mild to moderate renal failure or chronic heart failure - from 12 to 15 l. In patients with liver cirrhosis, Vd doubles.
Metabolized in the liver with the participation of the CYP2C9 isoenzyme with the formation of three metabolites.
The main metabolite is a carboxylic acid derivative and is pharmacologically inactive. Two other metabolites, which are formed in small quantities in the body, have some diuretic activity, but their concentration is too low to have any significant clinical effect.
T1/2 of torasemide in healthy volunteers is 4 hours. About 80% of the dose taken orally is excreted by the kidneys in the form of metabolites and about 20% unchanged (in patients with normal renal function). The total clearance of torasemide is 41 ml/min and the renal clearance is about 10 ml/min, which corresponds to approximately 25% of the total.
In patients with chronic heart failure in the stage of decompensation, hepatic and renal clearance of the drug is reduced. In such patients, the total clearance of torasemide is 50% less than in healthy volunteers, and T1/2 and total bioavailability are correspondingly higher.
In patients with renal insufficiency, the renal clearance of torasemide is markedly reduced, but this does not affect the total clearance. The diuretic effect in renal failure can be achieved by use in high doses. The total clearance of torasemide and T1/2 remain at the same level in the case of reduced renal function, due to metabolism in the liver.
In patients with liver cirrhosis, Vd, T1/2 and renal clearance are increased, but the overall clearance remains unchanged.
The pharmacokinetic profile of torasemide in elderly patients is similar to that in younger patients, with the exception that there is a decrease in renal clearance of the drug due to the characteristic age-related decline in renal function in elderly patients. The overall clearance and T1/2 do not change.
