Torasemide, 20 pcs., 5 mg, tablets
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, paresthesia 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.
For the skin and subcutaneous tissues:
frequency unknown - skin itching, rash, urticaria, erythema multiforme, 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 side of metabolism:
frequency unknown - hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hypochloremia, metabolic alkalosis, hypovolemia, dehydration (more often in elderly patients).
From the laboratory parameters:
uncommon - 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-glutamyltransferase), thrombocytopenia, leukopenia, agranulocytosis, hyperglycemia, decrease glucose tolerance (possible manifestation of latent diabetes mellitus).
Other:
frequency unknown - aplastic or hemolytic anemia.
Torasemide
Adverse reactions are listed depending on the anatomical and physiological classification and occurrence. The frequency of occurrence is determined as follows:
very often ≥1/10, often ≥1/100 and <1/10, uncommon ≥1/1000 and <1/100, rarely ≥1/10000 and <1/1000 and very rarely <1/10000.
Metabolic and nutritional disorders: frequency unknown - hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia, 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.
Cardiac disorders: uncommon - extrasystole, tachycardia, arrhythmia.
Vascular disorders: frequency unknown - excessive decrease in blood pressure, orthostatic hypotension, collapse, decrease in circulating blood volume, deep vein thrombosis, thromboembolism.
Violations of laboratory and instrumental data: infrequently - hypercholesterolemia, hypertriglyceridemia; transient increase in the concentration of creatinine and urea in the blood; an increase in the concentration of uric acid in the blood, which can cause or worsen the manifestations of gout; decreased glucose tolerance (possible manifestation of latent diabetes mellitus), increased activity of liver enzymes.
Disorders of the kidneys and urinary tract: often - increased frequency of urination, polyuria, nocturia; infrequently - frequent urge to urinate; frequency unknown - oliguria, acute urinary retention (for example, with prostatic hyperplasia, narrowing of the urethra, hydronephrosis); interstitial nephritis, hematuria, decreased potency.
Gastrointestinal disorders, often - diarrhea, infrequently - abdominal pain, flatulence, polydipsia; frequency unknown - dry mouth, nausea, vomiting, loss of appetite, acute pancreatitis.
Disorders of the liver and biliary tract, intrahepatic cholestasis.
Hearing and labyrinthine disorders, infrequently - hearing loss, usually reversible, and/or tinnitus, especially in patients with renal failure or hypoproteinemia (nephrotic syndrome).
Nervous system disorders: often - headache, dizziness, drowsiness; infrequently - paresthesia.
Skin and subcutaneous tissue disorders, uncommon: pruritus, urticaria, other types of skin rash or bullous skin lesions, erythema multiforme, exfoliative dermatitis, purpura, fever, vasculitis, eosinophilia, photosensitivity.
Disturbances from general disorders and at the injection site, severe anaphylactic or anaphylactoid reactions up to shock, which until now have only been described after intravenous administration.
Blood and lymphatic system disorders: frequency unknown - thrombocytopenia; leukopenia; agranulocytosis, aplastic or hemolytic anemia.
Torasemide
Active ingredient: Torasemide Dosage form: tablets Composition:
For 1 tablet
Active substance:
Torsemide 5.0/10.0 mg
Excipients:
Lactose monohydrate 79.0 mg/158.0, microcrystalline cellulose 10.0 mg/20.0 mg, crospovidone 3.0 mg/6.0 mg, povidone K30 2.0 mg/4.0 mg, magnesium stearate 1.0 mg/2.0 mg.
Description:
Dosage 5 mg:
Oval biconvex tablets of white or almost white color with a score. On the side with the mark there is an engraving “56”, on the opposite side there is an engraving “H”.
Dosage 10 mg:
Oval biconvex tablets of white or almost white color with a score. On the side with the mark there is an engraving “57”, on the opposite side there is an engraving “H”.
Pharmacotherapeutic group: ATC diuretic: ,
C.03.CA, Sulfonamide diuretics
C.03.CA04 , ,Torasemide
Pharmacodynamics:
Torsemide is a loop diuretic. 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 limb of the 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 myocardial diastolic function.
Torasemide causes hypokalemia to a lesser extent than furosemide, but it is more active and its action is longer lasting.
Torsemide reduces systolic and diastolic blood pressure in the “lying” and “standing” positions.
The use of torasemide is the most reasonable choice for long-term therapy.
Pharmacokinetics:
Suction
After oral administration, torasemide is quickly and almost completely absorbed into the gastrointestinal tract. The maximum concentration of torasemide in the blood plasma is observed 1-2 hours after oral administration after a meal. 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.
Distribution
Communication with blood plasma proteins is more than 99%. The apparent volume of distribution is 16 l.
Metabolism
Metabolized in the liver using isoenzymes of the cytochrome P450 system. As a result of successive 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.
Removal
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%).
Pharmacokinetics in special groups of patients
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 the M5 metabolite is slightly increased, drug accumulation is unlikely.
Indications:
* Edema syndrome of various origins, incl. for chronic heart failure, liver, lung and kidney diseases,
* arterial hypertension.
Contraindications:
- Hypersensitivity to torasemide or any of the components of the drug, - allergy to sulfonamides (sulfonamide antimicrobial agents 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,
- sinoatrial and atrioventricular blockade of II-III degree,
- decompensated aortic and mitral stenosis,
- hypertrophic obstructive cardiomyopathy,
- increased central venous pressure (over 10 mm Hg),
- arrhythmia,
- chronic renal failure with increasing azotemia,
- hyperuricemia,
- age up to 18 years,
- pregnancy,
- breastfeeding period,
- simultaneous use of aminoglycosides and cephalosporins,
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Carefully:
- Arterial hypotension,
- stenosing atherosclerosis of the cerebral arteries,
- hypoproteinemia,
- predisposition to hyperuricemia, urinary outflow disorders (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis),
- history of ventricular arrhythmia,
— acute myocardial infarction (increased risk of developing cardiogenic shock),
- diarrhea,
- pancreatitis,
- hypokalemia,
- hyponatremia,
- diabetes mellitus (decreased glucose tolerance),
- liver dysfunction, liver cirrhosis, hepatorenal syndrome,
- kidney failure, gout,
- anemia,
- simultaneous use of cardiac glycosides, corticosteroids and adrenocorticosteroid hormone (ACTH).
Pregnancy and lactation:
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.
It is unknown whether torasemide passes into breast milk. If it is necessary to use the drug Torasemide during lactation, you must stop breastfeeding.
Directions for use and dosage:
Orally, once a day, after breakfast, without chewing, with a small amount of water.
Edema syndrome in chronic heart failure
The usual therapeutic dose is 10-20 mg orally once daily. If necessary, the dose should be gradually increased to 20-40 mg once a day until the desired effect is obtained.
Edema syndrome in kidney disease
The usual therapeutic dose is 20 mg orally once daily. If necessary, the dose should be gradually doubled until the desired effect is obtained.
Edema syndrome in liver disease
The usual therapeutic dose is 5-10 mg orally 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 time, or until the desired effect is obtained.
Arterial hypertension
The initial dose is 2.5 mg (1/2 tablet, 5 mg each) once a day. If necessary, the dose can be increased to 5 mg once daily.
If there is no adequate reduction in blood pressure when taking the drug at a dose of 5 mg once a day for 4-6 weeks, the dose is increased to 10 mg once a day. If a dose of 10 mg does not give the required result, an antihypertensive drug of another group must be added to the treatment regimen.
Elderly patients do not require dose adjustment.
Missing a dose: If you miss a regular dose, do not take a double dose of the drug. The forgotten dose should be taken immediately. The next dose is taken at the usual time the next day.
Side effects:
Adverse reactions are listed depending on the anatomical and physiological classification and occurrence. The frequency of occurrence is determined as follows:
very often ≥1/10, often ≥1/100 and <.1/10, infrequently ≥1/1000 and <.1/100, rarely 1/10000 and <.1/1000 and very rarely <.1/10000.
Metabolic and nutritional disorders: frequency unknown - hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis. Symptoms indicating the development of disorders of the water-electrolyte status and acid-base status may include: headache, confusion, convulsions, tetany, muscle weakness, cardiac arrhythmias and dyspepsia, hypovolemia and dehydration (more often in elderly patients), which may lead to hemoconcentration with a tendency to develop thrombosis.
Cardiac disorders: uncommon - extrasystole, tachycardia, arrhythmia.
Vascular disorders: frequency unknown - excessive decrease in blood pressure, orthostatic hypotension, collapse, decrease in circulating blood volume, deep vein thrombosis, thromboembolism.
Violations of laboratory and instrumental data: infrequently - hypercholesterolemia, hypertriglyceridemia, transient increase in the concentration of creatinine and urea in the blood, increase in the concentration of uric acid in the blood, which can cause or intensify the manifestations of gout, decreased glucose tolerance (possible manifestation of latent diabetes mellitus) , increased activity of liver enzymes.
Renal and urinary tract disorders: often - increased frequency of urination, polyuria, nocturia, infrequently frequent urge to urinate, frequency unknown - oliguria, acute urinary retention (for example, with prostatic hyperplasia, narrowing of the urethra, hydronephrosis), interstitial nephritis, hematuria, decreased potency.
Gastrointestinal disorders: often - diarrhea, infrequently - abdominal pain, flatulence, polydipsia, frequency unknown - dry mouth, nausea, vomiting, loss of appetite, acute pancreatitis.
Disorders of the liver and biliary tract: intrahepatic cholestasis.
Hearing and labyrinthine disorders: uncommon - hearing impairment, usually reversible, and/or tinnitus, especially in patients with renal failure or hypoproteinemia (nephrotic syndrome),
Nervous system disorders: often - headache, dizziness, drowsiness, infrequently - paresthesia.
Skin and subcutaneous tissue disorders: uncommon: pruritus, urticaria, other types of skin rash or bullous skin lesions, erythema multiforme, exfoliative dermatitis, purpura, fever, vasculitis, eosinophilia, photosensitivity.
Disorders from general disorders and at the injection site: severe anaphylactic or anaphylactoid reactions up to shock, which to date have only been described after intravenous administration.
Blood and lymphatic system disorders: frequency unknown - thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia.
Overdose:
Symptoms: excessively 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, 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 simultaneous replenishment of circulating blood volume and correction of water-electrolyte balance and acid-base status under the control of serum concentrations of electrolytes and hematocrit.
Hemodialysis is ineffective, since the elimination of torasemide and its metabolism are not accelerated.
Interaction:
With simultaneous use of torasemide with mineralo- and 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 cardiac glycosides) and prolongation of the half-life (for low-polarity cardiac glycosides).
Reduces the renal clearance of lithium drugs and increases the likelihood of intoxication.
Taking torasemide increases the concentration and risk of developing nephro- and ototoxic effects of cephalosporins, aminoglycosides, chloramphenicol, ethacrynic acid, antibiotics, salicylates, cisplatin, platinum drugs, amphotericin B (due to competitive renal excretion).
Sequential or simultaneous use of torasemide with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists can lead to a marked decrease in blood pressure. This can be avoided by reducing the dose of torasemide or temporarily stopping it.
Non-steroidal anti-inflammatory drugs, sucralfate, reduce the diuretic effect due to inhibition of prostaglandin synthesis, impaired renin activity in the blood plasma and the excretion of aldosterone.
Torsemide enhances 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).
Increases the effectiveness of diazoxide and theophylline, reduces the effectiveness of hypoglycemic agents, allopurinol.
Pressor amines and torasemide mutually reduce effectiveness.
Drugs that block tubular secretion increase the concentration of torasemide in the blood serum.
Concomitant use of probenecid or methotrexate may reduce the effectiveness of torsemide (same secretion route). On the other hand, torasemide may result in 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 was reported that in patients at high risk of developing nephropathy taking torasemide orally, renal dysfunction was observed more frequently when radiocontrast agents were administered than in patients at high risk of developing nephropathy who were given intravenous hydration before administration of radiocontrast agents. The bioavailability and, as a consequence, the effectiveness of torasemide may be reduced when combined with cholestyramine.
Special instructions:
Use the drug Torasemide strictly as prescribed by your doctor.
Patients with hypersensitivity to sulfonamides and sulfonylureas may have cross-sensitivity to torsemide. In patients receiving high doses of torasemide 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).
In patients who have developed fluid and electrolyte disturbances, hypovolemia, or prerenal azotemia, laboratory findings may include hyper- or hyponatremia, hyper- or hypochloremia, hyper- or hypokalemia, acid-base imbalance, and increased plasma urea concentrations. If these disorders occur, it is necessary to stop taking Torasemide until normal values are restored, and then resume treatment with Torasemide at a lower dose.
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 a hospital setting (disturbances in water and electrolyte balance can lead to the development of hepatic coma). This category of patients requires regular monitoring of blood plasma electrolytes.
The use of Torasemide may
Torasemid-SZ
WHO classification of the incidence of side effects:
very often - >1/10 prescriptions (>10%)
often - from >1/100 to 1% and
infrequently - from >1/1000 to 0.1% and
rarely - from >1/10000 to 0.01% and
very rarely -
frequency unknown—cannot be estimated from available data
Blood and lymphatic system disorders: frequency unknown: thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia.
Metabolic and nutritional disorders: uncommon: polydipsia, hypercholesterolemia, hypertriglyceridemia; frequency unknown: decreased glucose tolerance (possible manifestation of latent diabetes mellitus).
Nervous system disorders: often: dizziness, headache, drowsiness; uncommon: muscle cramps of the lower extremities; frequency unknown: confusion, fainting, paresthesia in the extremities (feeling of numbness, crawling and tingling).
Visual disorders: frequency unknown: visual impairment.
Hearing and labyrinthine disorders: frequency unknown: hearing impairment, tinnitus and hearing loss (usually reversible) usually in patients with renal failure or hypoproteinemia (nephrotic syndrome).
Cardiac disorders: uncommon: extrasystole, arrhythmia, tachycardia.
Vascular disorders: frequency unknown: excessive decrease in blood pressure, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism.
Respiratory, thoracic and mediastinal disorders: uncommon: nosebleeds.
Gastrointestinal disorders: often: diarrhea; uncommon: abdominal pain, flatulence; frequency unknown: dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspeptic disorders.
Liver and biliary tract disorders: frequency unknown: intrahepatic cholestasis.
Skin and subcutaneous tissue disorders: frequency unknown: pruritus, rash, urticaria, erythema multiforme, exfoliative dermatitis, purpura, vasculitis, photosensitivity.
Musculoskeletal and connective tissue disorders: frequency unknown: muscle weakness.
Renal and urinary tract disorders: often: increased frequency of urination, polyuria, nocturia; uncommon: increased urge to urinate; frequency unknown: oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria.
Disorders of the genital organs and breast: frequency unknown: decreased potency.
General disorders and administration site disorders: uncommon: fever, asthenia, weakness, fatigue, hyperactivity, nervousness. Severe anaphylactic reactions up to shock, which until now have only been described after intravenous administration.
Laboratory and instrumental data: frequency unknown: hypercholesterolemia, hypertriglyceridemia, hyperuricemia, 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-glutamyl transferase).
Disorders of water-electrolyte and acid-base balance: frequency unknown: hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hypochloremia, metabolic alkalosis, hypovolemia, dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop blood clots.
In case of an overdose of the drug, the following symptoms may develop: excessively increased diuresis, accompanied by a decrease in circulating blood volume (CBV) and an imbalance in the electrolyte balance of the blood, followed by a pronounced decrease in blood pressure, drowsiness and confusion, collapse. Gastrointestinal disturbances may occur.
A specific antidote is unknown. Vomiting is induced, gastric lavage is performed, and activated charcoal is prescribed. 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. Hemodialysis is not effective, since the elimination of torasemide and its metabolites is not accelerated.
