Active substanceTorasemideTorasemide
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  • Dosage form: & nbsppills
    Composition:

    For a dosage of 5 mg:

    Active substance: torasemide 5 mg.

    Excipients: cellulose microcrystalline - 44.0 mg, lactose monohydrate - 26.4 mg, povidone - 1.6 mg, sodium carboxymethyl starch (sodium starch glycol g) - 2.4 mg, magnesium stearate - 0.6 mg.

    For the dosage of 10 mg:

    Active substance: torasemide 10 mg.

    Excipients: cellulose microcrystalline - 88.0 mg, lactose monohydrate - 52.8 mg, povidone - 3.2 mg, sodium carboxymethyl starch (sodium starch glycolate) - 4.8 mg, magnesium stearate - 1.2 mg.

    Description:Tablets are round white or almost white in a flat-cylindrical shape with a facet and a risk.
    Pharmacotherapeutic group:Diuretics
    ATX: & nbsp

    C.03.C.A   Sulfonamide diuretics

    C.03.C.A.04   Torasemide

    Pharmacodynamics:

    Torasemide is a "loop" diuretic.The main mechanism of the drug is due to the reversible binding of torasemide to the cotransporter of nagrias / chlorine / potassium ions located in the apical membrane of the thick segment of the ascending section of the Henle loop. As a result, the reabsorption of sodium ions decreases or completely inhibits and the osmotic pressure decreases intracellular fluid and water reabsorption. It blocks aldosterone receptors in the myocardium, reduces fibrosis and improves diastolic function of the myocardium.

    Torasemide is less than furosemide, causes hypokalemia, while showing greater activity and its effect for a longer time.

    The maximum diuretic effect develops 2-3 hours after ingestion.

    Torasemide can be used for a long time.

    Pharmacokinetics:

    After oral administration torasemide quickly and almost completely absorbed from the gastrointestinal tract. The maximum concentration (CmAh) torasemide in plasma is achieved 1-2 hours after taking the drug inside after eating. Bioavailability is 80-90% with minor individual variations.

    Distribution

    Binding to plasma proteins is more than 99%. Volume of distribution (Vd) is 16 liters. In patients with cirrhosis of the liver Vd doubled.

    Metabolism

    Metabolized in the liver with the participation of cytochrome P450 isoenzymes. As a result of successive oxidation, hydroxylation or ring hydroxylation reactions, 3 metabolites are formed (Ml, M3 and M5), binding of which to plasma proteins is 86%, 95% and 97%, respectively.

    Excretion

    The half-life (T1 / 2) of torasemide and its metabolites is 3-4 hours and does not change with chronic renal failure.

    The total clearance is 40 ml / min, the renal clearance is 10 ml / min.

    On the average, about 83% of the accepted dose is excreted by the kidneys: in unchanged form (24%) and in the form of predominantly inactive metabolites (M1 - 12%, M3 - 3%, M5 - 41%).

    Pharmacokinetics in special clinical cases

    Features of the pharmacokinetics of torasemide in selected patient groups

    Application for violations of liver function

    The drug is contraindicated in hepatic coma and precomatosis. In 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 hepatic insufficiency, T1 / 2 torasemide and metabolite M5 is slightly increased, cumulation of the drug is unlikely.

    In patients with cirrhosis of the liver Vd, T1 / 2 and renal clearance are increased, but the overall clearance remains unchanged.

    Chronic heart failure

    In patients with chronic heart failure in the stage of decompensation, hepatic and renal clearance of the drug is decreased. In such patients, the total clearance of torasemide is 50% less than in healthy volunteers, while T1 / 2 and overall bioavailability are correspondingly higher.

    Application for violations of kidney function

    In patients with renal insufficiency, the renal clearance of torasemide is markedly reduced, but this does not affect the overall clearance. Diuretic effect in renal failure can be achieved by using in high doses. With renal insufficiency T1 / 2 torasemide does not change, T1 / 2 metabolites M3 and M5 increases. Torasemide and its metabolites are slightly excreted by hemodialysis and haemofiltration.

    The drug is contraindicated in renal failure with increasing azotemia.

    Use in children

    Contraindication: age under 18 years (efficacy and safety not established).

    Application in elderly patients

    Older patients are not required to select a specific dose. The pharmacokinetic profile of torasemide in elderly patients is similar to that in young patients, except that there is a decrease in renal clearance of the drug due to a characteristic age-related renal impairment in elderly patients. The total ground clearance and T1 / 2 do not change at the same time.

    Dependence on sex and race

    The influence of ethnic and racial affiliation on the pharmacokinetics of torasemide has not been studied.

    Indications:

    - Ocular syndrome of various genesis, incl. with chronic heart failure, liver, kidney and lung diseases;

    - arterial hypertension.

    Contraindications:

    - Hypersensitivity to torasemide or to any other component of the drug;

    - Renal failure with anuria;

    - hepatic coma and precoma;

    - refractory hypokalemia;

    - refractory hyponatremia;

    - hypovolemia (with or without arterial hypotension) or dehydration;

    - pronounced violations of the outflow of urine of any etiology (including unilateral urinary tract damage);

    - glycosidic intoxication;

    - acute glomerulonephritis;

    - sinoatrial and atrioventricular blockade of II - III degree;

    - Decompensated aortic and mitral stenosis;

    - hypertrophic obstructive cardiomyopathy;

    - Increase in central venous pressure (more than 10 mm Hg);

    - Hyperuricemia;

    - Children under 18 years of age (effectiveness and safety not established);

    - Pregnancy;

    - the period of breastfeeding;

    - allergy to sulfonamides (sulfanilamide antimicrobial agents or sulfonylureas);

    - simultaneous use of aminoglycosides and cephalosporins.

    Since the composition of the drug includes lactose, it is not recommended to use the drug in patients with rare hereditary intolerance to galactose, with a deficiency of lactase, glucose-galactose malabsorption.

    Carefully:

    FROM caution should be prescribed for arterial hypotension, stenosing cerebral artery atherosclerosis, hypoproteinemia, predisposition to hyperuricemia, violation of urine outflow (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis), ventricular arrhythmia in history,acute myocardial infarction (increased risk of developing cardiogenic shock), with diarrhea, pancreatitis, diabetes mellitus (decreased glucose tolerance), impaired liver and / or kidney function, hepatorenal syndrome, gout, anemia, hypokalemia, hyponatremia.

    Pregnancy and lactation:

    Pregnancy

    Controlled studies on the use of torasemide in pregnant women have not been conducted, the drug is not recommended for use during pregnancy.

    Torasemide does not have a teratogenic effect and fetotoxicity, it penetrates the placental barrier, causing disturbances in water-electrolyte metabolism and thrombocytopenia in the fetus.

    Lactation

    It is not known whether torasemide with breast milk. If it is necessary to use the drug torasemide During lactation, breastfeeding should be stopped.

    Dosing and Administration:

    The drug is taken orally once a day after meals, washed down with a small amount of water.

    Ocular syndrome of various genesis, incl. with chronic heart failure, liver, lung and kidney diseases.

    The therapeutic dose is 5 mg once a day.If necessary, the dose should be gradually increased to 20-40 mg once a day. The maximum single dose is 40 mg, it is not recommended to exceed it (there is no experience of application). The drug is prescribed for a long period or until the disappearance of edema.

    Arterial hypertension

    The initial dose is 2.5 mg (1/2 tablet with a dosage of 5 mg) once a day. If necessary, the dose can be increased to 5 - 10 mg once a day. If the dose of 10 mg does not give the desired effect, a hypotensive drug of another group should be added to the treatment regimen.

    Older patients do not need a dose adjustment.

    Side effects:

    The frequency of side effects listed below was determined according to the following (classification of the World Health Organization): very often (more than 10%); often (more than 1% and less than 10%); infrequently (more than 0.1% and less than 1%); rarely (more than 0.01% and less than 0.1%); very rarely (less than 0.01%), including individual reports; the frequency is not known (can not be estimated with the help of available data).

    On the part of the blood and lymphatic system

    Frequency not known - thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia.

    From the side of metabolism and nutrition

    Infrequently hypercholesterolemia, hypertriglyceridemia.

    Frequency not known - a decrease in glucose tolerance (possible manifestation of latent diabetes mellitus).

    From the nervous system

    Often - dizziness, headache, drowsiness; infrequently - cramps in the muscles of the lower limbs; frequency not known - confusion, fainting, paresthesia in the extremities (sensation of numbness, "crawling crawling" and tingling).

    From the side of the organ of vision

    Frequency not known - impaired vision.

    From the side of the hearing organ and labyrinthine disorders

    The frequency is not known? - hearing impairment, ringing in the ears and hearing loss (usually, reversible) usually in patients with renal insufficiency or hypoproteinemia (nephrotic syndrome).

    From the side of the cardiovascular system

    Infrequently - extrasystole, tachycardia, increased heart rate, redness of the face; frequency not known - excessive arterial hypotension, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism, hypovolemia.

    From the respiratory system

    Infrequently - nasal bleeding.

    From the digestive system

    Often - diarrhea; infrequently - pain in the abdomen, flatulence, polydipsia; frequency not known - dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspepsia, intrahepatic cholestasis.

    From the side of the kidneys and urinary tract

    Often - increased frequency of urination, polyuria, nocturia; infrequently - increased urge to urinate; frequency not known - oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria, increased urea and creatinine levels in the blood.

    From the genitals

    Frequency not known - a violation of potency.

    General disorders and disorders at the site of administration

    Infrequently - asthenia (exhaustion), thirst, weakness, increased fatigue, hyperactivity, nervousness.

    Laboratory indicators

    Infrequently - an increase in the number of platelets; frequency unknown - hyperglycemia, hyperuricemia, a decrease in the number of erythrocytes, leukocytes and platelets, a slight increase in the activity of alkaline phosphatase in the blood, an increase in the activity of certain hepatic enzymes (eg, gamma-glutamyltransferase).

    From the skin and subcutaneous tissues

    Frequency unknown - skin itching, rash, hives, polymorphic erythema, exfoliative dermatitis, purpura, vasculitis, photosensitivity.

    From the side of the musculoskeletal system

    Frequency not known - Muscular weakness.

    From the side of water-electrolyte and acid-base balance

    Frequency not known - hyponatremia, hypochloraemia, hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis. Symptoms that indicate the development of violations of the electrolyte and acid-base state can be headache, confusion, convulsions, tetany, muscle weakness, heart rhythm disorders and dyspeptic disorders; hypovolemia and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.

    If any of the side effects listed in the instruction are aggravated, or you notice any other side effects not listed in the instructions, inform the doctor about it.

    Overdose:

    Symptoms: excessively increased diuresis, accompanied by a decrease in the volume of circulating blood (BCC) and a violation of electrolyte blood balance, followed by a marked decrease in blood pressure, drowsiness, confusion, collapse; gastrointestinal disorders are possible. Treatment: there is no specific antidote.Vomiting, gastric lavage, prescribing Activated carbon. Treatment is symptomatic, dose reduction or drug withdrawal and at the same time replenishment of bcc and indicators of water electrolyte balance and acid-base balance under the control of serum concentrations of electrolytes, hematocrit. Hemodialysis is ineffective.

    Interaction:

    Torasemide increases the concentration and risk of developing nephro- and ototoxic effects of cephalosporins, aminoglycosides, chloramphenicol, ethacrynic acid, antibiotics, salicylates, platinum preparations (eg, cisplatin), amphotericin B (due to competitive kidney excretion).

    Torasemide increases the effectiveness of diazoxide and theophylline, reduces the effectiveness of hypoglycemic agents, allopurinol.

    Pressor amines and torasemide mutually reduce the effectiveness of each other. Bioavailability and, as a consequence, the effectiveness of torasemide can be reduced by joint therapy with colestyramine.

    Drugs that block tubular secretion, increase the concentration of torasemide in the blood serum.

    With the simultaneous use of mineral and glucocorticosteroids, amphotericin B increases the risk of developing hypokalemia, with cardiac glycosides - the risk of developing glycoside intoxication due to hypokalemia (for high and low-polar cardiac glycosides) and T1 / 2 prolongation (for low-polar cardiac glycosides) increases.

    Torasemide reduces the renal clearance of lithium preparations and increases the likelihood of intoxication.

    Non-steroidal anti-inflammatory drugs (NSAIDs), sucralfate reduce diuretic effect due to inhibition of prostaglandin synthesis, disturbance of renin activity in plasma and aldosterone removal.

    Torasemide enhances the effect of antihypertensive drugs, neuromuscular blockade of depolarizing muscle relaxants (suxamethonium) and weakens the action of nondepolarizing muscle relaxants (tubocurarine).

    With the simultaneous administration of salicylates in high doses against the background of torasemide therapy, the risk of their toxicity increases (due to competitive excretion by the kidneys).

    Sequential or simultaneous use of torasemide with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists can lead to a significant reduction in blood pressure.This can be avoided by lowering the dose of torasemide or temporarily abolishing it.

    When used simultaneously with probenecid or methotrexate, a decrease in the effectiveness of torasemide (the same pathway of secretion) is possible. On the other hand torasemide can lead to a decrease in renal elimination of these drugs.

    With the simultaneous use of cyclosporine and torasemide, the risk of gouty arthritis is increased due to the fact that ciclosporin may cause impairment of urate excretion by the kidneys, and torasemide hyperuricemia.

    It has been reported that in patients with a high risk of developing nephropathy receiving torasemide Inside, with the introduction of radiopaque agents, renal dysfunction was observed more often than in patients with a high risk of developing nephropathy, who received intravenous hydration prior to the administration of radiocontrast agents.
    Special instructions:

    Apply strictly according to the doctor's prescription.

    Diuretic effect persists up to 18 hours, this facilitates the tolerability of therapy because of the lack of very frequent urination in the first hours after taking the drug inside, limiting the activity of patients.

    Patients with hypersensitivity to sulfonamides and sulfonylureas may have cross-sensitivity to the drug torasemide. Patients receiving high doses of the drug torasemide for a long period, in order to avoid the development of hyponatremia, metabolic alkalosis and hypokalemia, a diet with a sufficient content of table salt and the use of potassium preparations is recommended.

    The risk of hypokalemia is greatest in patients with cirrhosis of the liver, expressed diuresis, with insufficient intake of electrolytes with food, as well as with simultaneous treatment with corticosteroids or ACTH (adrenocorticotropic hormone).

    Increased risk of development of violations of water-electrolyte balance is observed in patients with renal insufficiency. During the course of treatment, it is necessary to periodically monitor the concentration of electrolytes in the blood plasma (including sodium, calcium, potassium, magnesium), acid-base state, residual nitrogen, creatinine, uric acid, lipids and, if necessary, appropriate corrective therapy (with greater multiplicity in patients with frequent vomiting and against the background of parenterally injected fluids).

    When azotemia and oliguria occur in patients with severe progressive kidney disease, it is recommended to suspend treatment.

    Selection of the dosing regimen in patients with ascites against the background of liver cirrhosis should be carried out in a hospital (violations of water-electrolyte balance may lead to the development of hepatic coma). This category of patients shows regular monitoring of plasma electrolytes.

    Application of the drug torasemide can cause an exacerbation of gout.

    In patients with diabetes mellitus or with reduced glucose tolerance, periodic monitoring of glucose concentrations in the blood and urine is required.

    In patients with prostatic hyperplasia, narrowing of the ureters, diuretic control is necessary in connection with the possibility of acute urinary retention.

    In patients with diseases of the cardiovascular system, especially those taking cardiac glycosides, diuretic-induced hypokalemia can cause arrhythmias.

    In patients in the unconscious state, control of diuresis is necessary in connection with the possibility of acute urinary retention.

    Effect on the ability to drive transp. cf. and fur:During the treatment period, patients should refrain from driving vehicles and practicing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
    Form release / dosage:Tablets of 5 mg and 10 mg.
    Packaging:For 10 tablets in a contour mesh package, 30 or 100 tablets per can of polymer with a lid. Each jar or 2, or 3, or 6 contour mesh packages together with instructions for medical use in a pack of cardboard.
    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children!

    Shelf life:

    3 years. Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004320
    Date of registration:01.06.2017
    Expiration Date:01.06.2022
    The owner of the registration certificate:Berezovsky Pharmaceutical Plant, ZAO Berezovsky Pharmaceutical Plant, ZAO Russia
    Manufacturer: & nbsp
    Information update date: & nbsp24.06.2017
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