Torasemide, tablets 10 mg 20 pcs

Pharmacotherapeutic group: Diuretic

ATC code: C03CA

Pharmacodynamics:

Torasemide is a “loop” diuretic.

The maximum diuretic effect develops 2-3 hours after oral administration.

The basic mechanism of action of the drug is due to the reversible binding of thorasemide to the sodium/chloride/potassium ion transporter situated in the apical membrane of the thick segment of the ascending loop of Genle. As a result, reabsorption of sodium ions is reduced or completely inhibited and osmotic pressure of intracellular fluid and reabsorption of water are decreased. It blocks myocardial aldosterone receptors; reduces fibrosis and improves diastolic function of the myocardium.

The diuretic effect is maintained for up to 18 hours which facilitates tolerance of therapy because there is no very frequent urination in the first hours after ingestion of the drug which limits patient activity.

Thorasemide causes hypokalemia to a lesser extent than furosemide but it is more active and its effect is longer lasting.

The use of thoracemide is the most reasonable choice for long-term therapy.

Pharmacokinetics:

Thorasemide is quickly and almost completely absorbed in the gastrointestinal tract after oral administration. Food intake has no significant effect on absorption of the drug.

The maximum concentration of torasemide in blood plasma is noted 1-2 hours after oral administration. Bioavailability is 80 – 90% with slight individual variations.

The binding to plasma proteins is more than 99%. Visible volume of distribution is 16 liters.

It is metabolized in the liver by cytochrome P450 system isoenzymes. As a result of sequential oxidation hydroxylation or ring hydroxylation reactions three metabolites (M1 M3 and M5) are formed, 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 thoracemide is 40 ml/min renal clearance is 10 ml/min. On average, about 83% of the taken dose is excreted by the kidneys: unchanged (24%) and as mostly inactive metabolites (M1 – 12% M3 – 3% M5 – 41%).

In renal insufficiency, the T1/2 is unchanged T1/2 of M3 and M5 metabolites is increased. Torasemide and its metabolites are slightly excreted by hemodialysis and hemofiltration.

In case of hepatic insufficiency, plasma concentrations of thoracemide are increased due to decreased metabolism of the drug in the liver. In patients with cardiac or hepatic insufficiency the T1/2 of thorasemide and M5 metabolite is slightly increased cumulation of the drug is unlikely.

Elderly patients

The pharmacokinetic profile of thorasemide in elderly patients is similar to that in younger patients with the exception that there is a decrease in renal clearance of thorasemide due to the characteristic age-related impairment of renal function in elderly patients. Total clearance and elimination half-life are unchanged.

Indications

– Edema syndrome of various origins, incl. for chronic heart failure, liver, lung and kidney diseases;

– arterial hypertension.

Pharmacological effect

Pharmacotherapeutic group: Diuretic

ATX code: C03CA

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.

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.

Torasemide causes hypokalemia to a lesser extent than furosemide, but it is more active and its effect is longer lasting.

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.

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 successive oxidation reactions of 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 hepatic insufficiency T1/2 of torasemide and the M5 metabolite, the accumulation of the drug is unlikely to be slightly increased.

Elderly patients

The pharmacokinetic profile of torasemide in elderly patients is similar to that in younger patients, with the exception that there is a decrease in the renal clearance of torasemide due to the characteristic age-related decline in renal function in elderly patients. The total clearance and half-life do not change.

Special instructions

Use strictly as prescribed by your doctor.

Patients with hypersensitivity to sulfonamides and sulfonylureas may have cross-sensitivity to Torasemide.

In patients, especially at the beginning of treatment with Torasemide and in the elderly, it is recommended to monitor the electrolyte balance of the volume and concentration of circulating blood.

During long-term treatment with Torasemide, it is recommended to regularly monitor the electrolyte balance (especially potassium levels), glucose, uric acid, creatinine, lipids and cellular components of the blood.

Patients receiving high doses of Torasemide for a long period to avoid the development of hyponatremia. metabolic alkalosis and hypokalemia, a diet with a sufficient content of table salt is recommended (it is not advisable to limit the consumption of table salt) and the use of potassium supplements.

The risk of hypokalemia is greatest in patients with liver cirrhosis, severe diuresis, insufficient dietary intake of electrolytes, and concomitant treatment with corticosteroids or ACTH.

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, and 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 or prerenal azotemia, laboratory findings may include hyper- or hyponatremia, hyper- or hypochloremia, hyper- or hypokalemia, acid-base imbalance, and increased blood urea levels. 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.

To prevent hypokalemia, it is recommended to use potassium supplements and potassium-sparing diuretics (primarily spironolactone), as well as following a diet rich in potassium.

The use of the drug Torasemide may 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 unconscious patients with prostatic hyperplasia and narrowing of the ureters, diuresis control is necessary due to the possibility of acute urinary retention.

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

Impact on the ability to drive vehicles. Wed and fur.:

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, as there is a risk of developing dizziness and drowsiness.

Active ingredient

Torasemide

Composition

For 1 tablet 10.0 mg:

Active ingredient:

torasemide – 10.0 mg.

Excipients:

lactose monohydrate (milk sugar) – 180.8 mg,

sodium carboxymethyl starch – 6.0 mg,

magnesium stearate – 1.6 mg,

colloidal silicon dioxide – 1.6 mg.

Pregnancy

Pregnancy

Torsemide does not have a teratogenic effect and fetotoxicity 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, and therefore the drug is not recommended for use during pregnancy.

Breastfeeding period

It is unknown whether torasemide passes into breast milk. If it is necessary to use the drug Torasemide during lactation, you must stop breastfeeding.

Contraindications

– Hypersensitivity to torasemide or to any of the components of the drug; Patients allergic to sulfonamides (sulfonamide antimicrobials or sulfonylureas) may experience cross-allergy to torsemide;

– 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;

– sinoatrial and atrioventricular blockade of II-III degree arrhythmia;

– increased central venous pressure (over 10 mm Hg);

– hyperuricemia;

– age up to 18 years;

– pregnancy, breastfeeding period;

– simultaneous use of aminoglycosides and cephalosporins;

– lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

With caution:

– Arterial hypotension;

– stenosing atherosclerosis of cerebral arteries;

– hypoproteinemia;

– disturbances in the outflow of urine (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis);

– history of ventricular arrhythmia;

– acute myocardial infarction (increased risk of developing cardiogenic shock);

– diarrhea;

– pancreatitis;

– diabetes mellitus (impaired glucose tolerance);

– hepatorenal syndrome;

– impaired liver function, cirrhosis of the liver;

– renal failure;

– gout;

– predisposition to hyperuricemia;

– anemia;

– simultaneous use of cardiac glycosides, glucocorticosteroids and adrenocorticotropic hormone (ACTH);

– hypokalemia;

– hyponatremia.

Side Effects

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% and < 10%)); uncommon: from ≥ 1/1000 to 01% and < 1%)); rare: from ≥ 1/10000 to 001% and < 01%)); very rare: <1/10000 (<001%); frequency unknown: frequency cannot be estimated from available data.

Nervous system disorders:

often – headache, dizziness, drowsiness;

infrequently – muscle cramps of the lower extremities, hyperactivity, nervousness;

frequency unknown – confusion, fainting, paresthesia in the extremities (feeling of numbness, “crawling” and tingling).

Visual disorders:

frequency unknown – visual impairment

Hearing and labyrinth disorders:

frequency unknown – hearing impairment, tinnitus and hearing loss (usually reversible), usually in patients with renal failure or hypoproteinemia (nephrotic syndrome).

Cardiovascular system disorders:

infrequently – extrasystole, arrhythmia, tachycardia;

frequency unknown – excessive decrease in blood pressure, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism, hypovolemia (decrease in circulating blood volume).

Respiratory system disorders:

infrequently – nosebleeds.

Digestive system disorders:

often – diarrhea;

infrequently – abdominal pain, flatulence, polydipsia;

frequency unknown – dry mouth nausea vomiting loss of appetite pancreatitis dyspeptic disorders intrahepatic cholestasis.

Disorders of the skin and subcutaneous tissues:

frequency unknown – skin itching, skin rash, urticaria, polymorphic erythema, exfoliative dermatitis, purpura, vasculitis, photosensitivity.

Musculoskeletal disorders:

frequency unknown – muscle weakness.

Urinary system disorders:

often – increased frequency of urination, polyuria nocturia;

infrequently – frequent urge to urinate;

frequency unknown – polyuria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria.

Reproductive system disorders:

frequency unknown – decreased potency.

Metabolic disorders:

uncommon – polydipsia

frequency unknown – hypokalemia hyponatremia hypomagnesemia hypocalcemia hypochloremia metabolic alkalosis hypovolemia dehydration (more often in elderly patients) impaired glucose tolerance (possible manifestation of latent diabetes mellitus)

Laboratory abnormalities:

uncommon – hypercholesterolemia, hypertriglyceridemia, thrombocytosis;

frequency unknown – hyperglycemia hyperuricemia slight increase in the activity of alkaline phosphatase in the blood plasma, increase in the concentration of creatinine and urea in the blood plasma, increase in the activity of some “liver” enzymes in the blood plasma (for example, gamma-glutamyl transferase) thrombocytopenia leukopenia agranulocytosis.

Blood and lymphatic system disorders:

frequency unknown – aplastic or hemolytic anemia.

General and administration site disorders

infrequently – asthenia thirst weakness increased fatigue

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).

Taking torasemide 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 and reduces the hypoglycemic agents allopurinol.

Sequential or simultaneous use of torasemide with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists can lead to a sharp 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 of torasemide due to inhibition of prostaglandin synthesis, impairment of 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).

Torsemide reduces the renal clearance of lithium drugs and increases the likelihood of intoxication.

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

Pressor amines and torasemide mutually reduce each other’s effectiveness.

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

Concomitant use of large doses of salicylates during torsemide therapy increases the risk of their toxicity (due to competitive renal excretion).

With the simultaneous use of cyclosporine and torasemide, the risk of developing gouty arthritis increases due to the fact that cyclosporine can cause a violation of urate excretion by the kidneys and torasemide can cause hyperuricemia.

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.

It was reported that in patients with a high risk of developing nephropathy taking torasemide orally with the introduction of radiocontrast agents, renal dysfunction was observed more often than in patients with a high risk of developing nephropathy who received intravenous hydration before the administration of radiocontrast agents.

Bioavailability and, as a consequence, the effectiveness of torasemide may be reduced when combined with cholestyramine.

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, collapse. Gastrointestinal disturbances may occur.

Treatment: there is no specific antidote. Provocation of vomiting, gastric lavage, activated charcoal. Treatment is a 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 hematocrit electrolytes; symptomatic treatment. Hemodialysis is ineffective.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life

3 years.

Do not use after expiration date.

Manufacturer

Ozon, Russia