Composition:
Active ingredient: torasemide - 10 mg. Excipients: microcrystalline cellulose - 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.
Pharmacodynamics:
Torasemide is a “loop” diuretic. The main mechanism of action of the drug is due to the reversible binding of torasemide with the cotransporter of ions of potassium / chlorine / potassium 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 is reduced or completely inhibited, and the osmotic pressure of the intracellular fluid and the reabsorption of water are reduced. It blocks aldosterone receptors in the myocardium, reduces fibrosis and improves diastolic function of the myocardium. Torasemide to a lesser extent than furosemide causes hypokalemia, while it is more active and its effect is longer.
The maximum diuretic effect develops 2-3 hours after taking the drug inside. Torasemide can be used for a long time.
Pharmacokinetics:
After oral administration, torasemide is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration (Cmax) of 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 - more than 99%. The volume of distribution (Vd) is 16 liters. In patients with cirrhosis, Vd is doubled. Metabolism Metabolized in the liver with the participation of isoenzymes of the cytochrome P450 system. As a result of successive oxidation, hydroxylation, or ring hydroxylation reactions, 3 metabolites are formed (Ml, M3, and M5), the binding of which to plasma proteins is 86%, 95%, and 97%, respectively.
Withdrawal 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 is 40 ml / min, renal clearance - 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 clinical cases Features of the pharmacokinetics of torasemide in certain groups of patients Application for impaired liver function The drug is contraindicated in hepatic coma and precomatous state.
With 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 heart or liver failure T1 / 2 of torasemide and M5 metabolite 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 total 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 reduced.
In such patients, the total clearance of torasemide is 50% less than in healthy volunteers, and T1 / 2 and the overall bioavailability are correspondingly higher. Application for impaired renal function In patients with renal failure, the renal clearance of torasemide is markedly reduced, but this does not affect the overall clearance.
The diuretic effect in renal failure can be achieved by use in high doses. With renal failure, T1 / 2 of torasemide does not change, T1 / 2 of metabolites M3 and M5 increases. Torasemide and its metabolites are slightly excreted by hemodialysis and hemofiltration.
The drug is contraindicated in renal failure with increasing azotemia. Use in children Contraindication: age up to 18 years (effectiveness and safety have not been established). Application in elderly patients. Elderly patients do not need a special dose selection.
The pharmacokinetic profile of torasemide in elderly patients is similar to that in young patients, with the exception that there is a decrease in renal clearance of the drug due to a characteristic age-related renal impairment in elderly patients. The total clearance and T1 / 2 do not change. Dependence on gender and racial affiliation The influence of ethnic and racial affiliation on the pharmacokinetics of torasemide has not been studied.
Side effects:
The frequency of side effects 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 messages; the frequency is not known (cannot be estimated using the available data).
From the blood and lymphatic system Frequency is not known - thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia. From the side of metabolism and nutrition Infrequently - hypercholesterolemia, hypertriglyceridemia.
The frequency is 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 extremities; the frequency is not known - confusion, fainting, paresthesia in the limbs (numbness, "crawling" and tingling sensations). From the side of the organ of vision The frequency is not known - impaired vision.
On the part of the hearing organ and labyrinthine disorders The frequency is not known - hearing impairment, tinnitus and hearing loss (usually reversible) are usually found in patients with renal failure or hypoproteinemia (nephrotic syndrome).
From the cardiovascular system Infrequently - extrasystole, tachycardia, increased heartbeat, redness of the face; the frequency is not known - excessive arterial hypotension, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism, hypovolemia.
From the respiratory system Infrequently - nosebleeds. From the digestive system Often - diarrhea; infrequently - abdominal pain, flatulence, polydipsia; the frequency is not known - dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspepsia, intrahepatic cholestasis.
From the kidneys and urinary tract Often - an increase in the frequency of urination, polyuria, nocturia; infrequently - frequent urination; the frequency is not known - oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria, increased blood urea and creatinine.
On the part of the genitals, the frequency is not known - a violation of potency. General disorders and disorders at the injection site Infrequently - asthenia (exhaustion), thirst, weakness, increased fatigue, hyperactivity, nervousness.
Laboratory indicators Infrequently - an increase in the number of platelets; the frequency is unknown - hyperglycemia, hyperuricemia, a decrease in the number of red blood cells, white blood cells and platelets, a slight increase in the activity of alkaline phosphatase in the blood, an increase in the activity of some liver enzymes (for example, gamma-glutamyl transferase).
On the part of the skin and subcutaneous tissues Frequency unknown - itching, rash, urticaria, polymorphic erythema, exfoliative dermatitis, purpura, vasculitis, photosensitivity.
From the musculoskeletal system Frequency is not known - muscle weakness. On the part of the water-electrolyte and acid-base balance The frequency is not known
- hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis.
Symptoms indicating the development of electrolyte and acid-base conditions may include headache, confusion, cramps, tetany, muscle weakness, cardiac arrhythmias, and dyspeptic disorders; hypovolemia and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to thrombosis. If any of the side effects indicated in the instructions are exacerbated, or if you notice any other side effects not listed in the instructions, inform your doctor.
Special conditions:
Apply strictly as directed by your doctor. The diuretic effect lasts up to 18 hours, this facilitates the tolerability of therapy due to 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 sulfonylurea derivatives may have cross-sensitivity to tosemide. For patients receiving high doses of torasemide over a long period, in order to avoid the development of hyponatremia, metabolic alkalosis and hypokalemia, a diet with sufficient sodium chloride and the use of potassium preparations are recommended.
The risk of hypokalemia is greatest in patients with cirrhosis of the liver, expressed by diuresis, with insufficient consumption of electrolytes with food, as well as with simultaneous treatment with corticosteroids or ACTH (adrenocorticotropic hormone). An increased risk of water-electrolyte imbalance is observed in patients with renal failure. During the course of treatment, it is necessary to periodically monitor the concentration of electrolytes in blood plasma (including sodium, calcium, potassium, magnesium), the acid-base state, residual nitrogen, creatinine, uric acid, lipids and, if necessary, carry out appropriate corrective therapy (with more frequent in patients with frequent vomiting and against the background of parenteral fluids).
With the appearance or intensification of azotemia and oliguria in patients with severe progressive kidney disease, it is recommended to suspend treatment. The dosage regimen for patients with ascites against cirrhosis should be selected in a hospital setting (disturbances in the water-electrolyte balance can lead to the development of hepatic coma).
This category of patients shows regular monitoring of plasma electrolytes. The use of the drug torasemide can cause exacerbation of gout. In patients with diabetes mellitus or with reduced glucose tolerance, periodic monitoring of the concentration of glucose in the blood and urine is required.
In patients with prostatic hyperplasia, narrowing of the ureters, control of diuresis is necessary due to the possibility of acute urinary retention. In patients with diseases of the cardiovascular system, especially those taking cardiac glycosides, hypokalemia caused by diuretics can cause the development of arrhythmias.
In patients in an unconscious state, control of diuresis is necessary due to the possibility of acute urinary retention. The effect of the drug on the ability to drive vehicles and other mechanisms:
During the treatment period, patients should refrain from driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
Indications:
- Edematous syndrome of various origins, including in chronic heart failure, diseases of the liver, kidneys and lungs; - 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 damage to the urinary tract);
- glycosidic intoxication;
- acute glomerulonephritis; - sinoatrial and atrioventricular block 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 (efficacy and safety not established); - pregnancy; - period of breastfeeding; - Allergy to sulfonamides (sulfonamide antimicrobials or sulfonylurea preparations); - 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 galactose intolerance, with a deficiency of lactase, glucose-galactose malabsorption.
With caution: Caution should be given in case of arterial hypotension, stenosing atherosclerosis of cerebral arteries, hypoproteinemia, predisposition to hyperuricemia, impaired urine outflow (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis), a history of ventricular arrhythmia, an increase in myocardial infarction, cardiogenic shock), with diarrhea, pancreatitis, diabetes mellitus (decreased glucose tolerance), impaired liver and / or kidney function, atorenalnom syndrome, gout, anemia, hypokalaemia, hyponatraemia. Pregnancy and lactation:
Pregnancy There have been no controlled studies on the use of torasemide in pregnant women; the drug is not recommended for use during pregnancy. Torasemide does not have a teratogenic effect and fetotoxicity, penetrates the placental barrier, causing disturbances in water-electrolyte metabolism and thrombocytopenia in the fetus. Lactation It is not known whether torasemide is excreted in breast milk.
If you need to use the drug torasemide during lactation, you should stop breastfeeding
Drug Interactions:
Torasemide increases the concentration and risk of developing the nephro- and ototoxic effects of cephalosporins, aminoglycosides, chloramphenicol, ethacrine acid, antibiotics, salicylates, platinum preparations (e.g. cisplatin), amphotericin B (due to competitive excretion by the kidneys).
Torasemide increases the effectiveness of diazoxide and theophylline, reduces the effectiveness of hypoglycemic agents, allopurinol.
Pressor amines and torasemide mutually reduce each other's effectiveness. Bioavailability and, as a result, the effectiveness of torasemide can be reduced with co-therapy with colestyramine. Medicines that block tubular secretion increase the concentration of torasemide in the blood serum.
With the simultaneous use of mineral and glucocorticosteroids, amphotericin B, the risk of developing hypokalemia increases, with cardiac glycosides, the risk of developing glycoside intoxication due to hypokalemia (for high and low polar cardiac glycosides) and T1 / 2 lengthening (for low-polar cardiac glycosides) increases.
Torasemide reduces the renal clearance of lithium preparations and increases the likelihood of developing intoxication. Nonsteroidal anti-inflammatory drugs (NSAIDs), sucralfate reduce the diuretic effect due to inhibition of prostaglandin synthesis, impaired renin activity in blood plasma and excretion of aldosterone.
Torasemide enhances the action of antihypertensive drugs, neuromuscular blockade of depolarizing muscle relaxants (suxamethonium) and weakens the effect of non-depolarizing muscle relaxants (tubocurarine). With the simultaneous administration of salicylates in high doses during therapy with torasemide, the risk of their toxicity increases (due to competitive excretion by the kidneys).
The consecutive or simultaneous use of torasemide with angiotensin converting enzyme inhibitors (ACE) or angiotensin II receptor antagonists can lead to a significant decrease in blood pressure. This can be avoided by lowering the dose of torasemide or by temporarily canceling it. With simultaneous use with probenecid or methotrexate, a decrease in the effectiveness of torasemide is possible (the same secretion path). Torasemide, on the other hand, can lead to decreased renal elimination of these drugs.
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 the excretion of urate by the kidneys, and torasemide - hyperuricemia.
It was reported that in patients with a high risk of developing nephropathy receiving torasemide by mouth, when radiopaque agents were administered, renal dysfunction was observed more often than in patients with a high risk of nephropathy who had been given intravenous hydration before radiopaque was administered.
Dosage:
The drug is taken orally 1 time per day after meals, washed down with a small amount of water. Edematous syndrome of various origins, including with chronic heart failure, diseases of the liver, lungs and kidneys.
The therapeutic dose is 5 mg 1 time per 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 use).
The drug is prescribed for a long period or until the edema disappears. Arterial hypertension The initial dose is 2.5 mg (1/2 tablet with a dosage of 5 mg) 1 time per day.
If necessary, the dose can be increased to 5 to 10 mg once a day. If a dose of 10 mg does not give the desired effect, a hypotensive drug of another group must be added to the treatment regimen.
Elderly patients do not need dose adjustment.
Overdose:
Symptoms: excessively high diuresis, accompanied by a decrease in circulating blood volume (BCC) and a violation of the electrolyte balance of the blood, followed by a pronounced decrease in blood pressure, drowsiness, confusion, collapse; gastrointestinal upsets are possible. Treatment: there is no specific antidote.
It should cause vomiting, gastric lavage, prescribe activated charcoal. Symptomatic treatment, 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
