Pharmacological properties
Pharmacodynamics. Torsemide Sandoz is a loop diuretic; at low doses used for antihypertensive treatment, it has a weak diuretic and saluretic effect. at higher doses, torasemide enhances diuresis in a dose-dependent manner. Torsemide Sandoz exhibits maximum diuretic activity 2-3 hours after oral administration.
Pharmacokinetics. After oral administration, torasemide is rapidly and almost completely absorbed; C max in blood plasma is achieved 1-2 hours after administration. Systemic bioavailability is 80-90%. Binding of torasemide to blood plasma proteins is 99%, metabolites M 1, M 3 and M 5 - 86; 95 and 97%, respectively. The volume of distribution is 16 l. Torasemide is metabolized by oxidation and hydroxylation with the formation of three metabolites: M 1, M 3 and M 5. M 5 is pharmacologically inactive, and the active metabolites M 1 and M 3 account for about 10% of the pharmacological action of the drug. The final T ½ of torasemide and its metabolites is 3-4 hours in healthy volunteers. The total clearance of torasemide is 40 ml/min, renal clearance is about 10 ml/min. About 80% of the dose is excreted in the form of unchanged torasemide (24%) and its metabolites: M 1 (12%), M 3 (3%), M 5 (41%). In renal failure, T ½ of torasemide does not change, and T ½ of metabolites M 3 and M 5 is prolonged. Torasemide and its metabolites are practically not removed by hemodialysis or hemofiltration. In patients with impaired liver function or heart failure, T ½ of torasemide and metabolite M 5 are slightly prolonged, however, cumulation of torasemide and its metabolites is unlikely.
Indication
Tablets of 5 mg - ag.
Tablets of 5; 10 and 20 mg - edema caused by heart failure.
Tablets of 50; 100 and 200 mg - edema, increased blood pressure in severe renal failure (creatinine clearance 20 ml/min) in the presence of at least some final diuresis (200 ml in 24 hours), including during hemodialysis.
Application
The tablets should be taken in the morning, without chewing, with a small amount of liquid.
The duration of treatment depends on the course of the disease; in heart failure, treatment should continue until the edema disappears.
Hypertension. The recommended dose for adults is 2.5 mg/day (5 mg tablets have a risk and can be divided into 2.5 mg doses). If after 2 months of therapy with torasemide at a dose of 2.5 mg/day, normalization of blood pressure is not achieved, the dose can be increased to 5 mg (once a day). The maximum effect is usually observed 3 months after the start of treatment. The use of doses greater than 5 mg does not lead to an increase in the antihypertensive effect.
Edema. Therapy should be initiated at a dose of 5 mg/day. This dose is usually considered maintenance. If a daily dose of 5 mg is insufficient, a daily dose of 10 mg should be used, which should be administered daily. Depending on the severity of the patient's condition, the daily dose may be gradually increased to 20 mg of torasemide (once a day).
Cirrhosis of the liver. The total initial dose is 5-10 mg 1 time per day when used simultaneously with drugs - aldosterone antagonists or with diuretics that contribute to the retention of potassium in the body. In the absence of the necessary diuretic effect, the dose should be doubled (10-20 mg / day) until the desired effect is achieved.
In chronic renal failure, the dose is determined individually and depends on the degree of renal dysfunction. If the dose of 20 mg/day is insufficient, it can be increased to 50 mg of torasemide 1 time per day and, if necessary, gradually increased to the maximum - 200 mg 1 time per day. The maximum daily dose of 200 mg should be prescribed only to patients with severe renal dysfunction (creatinine clearance 20 ml/min) (including during hemodialysis) in the presence of diuresis of at least 200 ml/24 h.
Patients with hepatic insufficiency. Treatment of such patients should be carried out with caution, as an increase in the concentration of torasemide in the blood plasma is possible.
Elderly patients: No special dose adjustment is required.
Contraindication
Hypersensitivity to torasemide, to sulfonylurea derivatives or to any of the excipients. Renal failure with anuria, hepatic coma or precoma, arterial hypotension, arrhythmia. Hypovolemia, hyponatremia, hypokalemia. Significant urinary disorders, e.g. due to prostatic hypertrophy. Gout. Concomitant use with aminoglycosides or cephalosporins. Renal failure caused by nephrotoxic substances.
Side effects
Adverse reactions are classified according to frequency of occurrence: very common (≥1/10); common (≥1/100 and 1/10); uncommon (≥1/1000 and 1/100); rare (≥1/10,000 and 1/1000); very rare (1/10,000); unknown (frequency cannot be estimated due to lack of data).
From the cardiovascular system: very rarely - thrombosis, arterial hypotension, cardiac and cerebral ischemia with the possible development of cardiac arrhythmias, angina pectoris, acute myocardial infarction, syncope.
Gastrointestinal tract: often - loss of appetite, nausea, vomiting, stomach pain, indigestion and diarrhea, constipation, flatulence, mainly at the beginning of treatment; infrequently - dry mouth; very rarely - pancreatitis.
On the part of the urinary system: infrequently - in patients with urination disorders, for example, with prostatic hypertrophy, urinary retention and excessive distension of the bladder are possible; urge to urinate.
On the part of the liver: sometimes - an increase in the level of some liver enzymes (γ-glutamyl transpeptidase) in the blood plasma.
From the blood and lymphatic system: very rarely - a decrease in the number of platelets, erythrocytes and / or leukocytes.
Skin and subcutaneous tissue disorders: very rarely - allergic reactions (e.g. itching, rash, exanthema, photosensitivity), severe skin reactions have been reported.
On the part of the organ of vision: very rarely - visual impairment.
On the part of the organ of hearing: very rarely - tinnitus, hearing loss.
General disorders: often - confusion, increased fatigue, general weakness (especially at the beginning of treatment).
Laboratory tests: often - increased concentration of uric acid, glucose and lipids (cholesterol, triglycerides) in blood plasma; infrequently - possible increase in creatinine and urea levels in blood plasma.
Special instructions
Before starting the drug, it is necessary to eliminate existing hypokalemia, hyponatremia or hypovolemia and correct urinary disorders.
With prolonged treatment with a diuretic, it is recommended to regularly monitor electrolyte balance (especially in patients who are simultaneously using digitalis glycosides, corticosteroids, mineralocorticoids or laxatives), glucose, uric acid, creatinine and blood lipid levels.
Patients with a tendency to develop hyperuricemia and gout require special attention.
Patients with overt or latent diabetes mellitus need to monitor carbohydrate metabolism.
Due to the lack of sufficient clinical experience, it is not recommended to prescribe torasemide in pathological changes in acid-base balance; in pathological changes in the blood picture, such as thrombocytopenia or anemia in patients without renal failure; simultaneously with lithium, aminoglycosides, cephalosporins; in renal dysfunction caused by nephrotoxic substances; in children; in elderly patients (no dosage recommendations are available).
Torasemide should be used with extreme caution in patients with liver disease accompanied by cirrhosis and ascites, as sudden changes in water and electrolyte balance can lead to hepatic coma. Therapy with torasemide (as well as other diuretics) in patients of this group should be carried out in a hospital setting. To prevent hypokalemia and metabolic acidosis, the drug should be prescribed with aldosterone antagonists or drugs that promote potassium retention in the body.
After taking torasemide, ototoxicity (tinnitus and hearing loss) was observed, which were reversible, but a direct connection with the use of the drug has not been established.
When prescribing diuretics, it is necessary to carefully monitor clinical symptoms of electrolyte imbalance, hypovolemia, extrarenal azotemia and other disorders, which may manifest as dry mouth, thirst, weakness, lethargy, drowsiness, agitation, muscle pain or cramps, myasthenia gravis, hypotension, oliguria, tachycardia, nausea, vomiting. Excessive diuresis can cause dehydration, lead to a decrease in circulating blood volume, thrombosis and embolism of blood vessels, especially in elderly patients. Attention should be paid to signs of hemoconcentration and electrolyte loss at the beginning of treatment and in elderly patients.
Patients with water and electrolyte imbalance should discontinue use of the drug and resume therapy, starting with lower doses, after the undesirable effects have resolved.
When prescribing the drug, it is necessary to conduct regular laboratory monitoring of potassium and other electrolytes in the blood plasma. Blood cells (number of erythrocytes, leukocytes, platelets) should also be regularly monitored.
Information on dosage in patients with renal or hepatic impairment is limited. Patients with hepatic impairment should be treated with caution as increased plasma concentrations of torasemide may occur.
Torasemide Sandoz tablets 5 mg, 10 mg, 20 mg contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Torasemide SANDOZ tablets 50 mg, 100 mg, 200 mg contain hydrogenated castor oil, which may cause stomach upset and diarrhea.
Pregnancy. There are no reliable data on the effect of torasemide on the embryo and fetus in humans. There is information on the reproductive toxicity of torasemide. Torasemide penetrates the placental barrier. In connection with the above, torasemide can be used during pregnancy only for vital indications and in the minimum possible effective dose.
Diuretics are not suitable for standard treatment of hypertension or edema in pregnant women, as they can reduce placental barrier perfusion and affect intrauterine fetal development. If torasemide is used to treat pregnant women with heart or renal failure, careful monitoring of electrolytes and hematocrit, as well as fetal development, is necessary.
Breastfeeding. It is currently not known whether torasemide is excreted in animal or human breast milk. A risk to the newborn/infants cannot be excluded. Therefore, the use of the drug during breastfeeding is contraindicated. If it is necessary to use torasemide during this period, breastfeeding should be discontinued.
Fertility: Studies on the effect of torasemide on fertility in humans have not been conducted.
Children. The drug is not used in children due to lack of data.
Ability to influence the reaction rate when driving vehicles or working with mechanisms. Until the individual reaction to torasemide is determined during treatment, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. Pregnancy or breastfeeding.
Interactions
With simultaneous use of torasemide with cardiac glycosides, the sensitivity of the heart muscle to these drugs may increase due to potassium or magnesium deficiency. With simultaneous use with mineralo- and glucocorticoids, laxatives, the risk of potassium deficiency increases.
Torasemide enhances the effect of other antihypertensive drugs, in particular ACE inhibitors. Concomitant use with ACE inhibitors may lead to severe hypotension. This can be avoided by reducing the initial dose of the ACE inhibitor or the dose of torasemide 2-3 days before starting ACE inhibitors.
Torasemide may weaken the vasoconstrictor effect of adrenaline and noradrenaline.
Torasemide weakens the effect of antidiabetic drugs.
Torasemide, especially in high doses, may potentiate the nephrotoxic and ototoxic effects of aminoglycoside antibiotics (e.g. kanamycin, gentamicin, tobramycin), the toxic effects of platinum drugs and the nephrotoxic effects of cephalosporins.
Torasemide enhances the effect of theophylline and curare-like muscle relaxants.
Probenecid and non-steroidal anti-inflammatory drugs (e.g. indomethacin, propionic acid derivatives) weaken the diuretic and hypotensive effects of torasemide.
Concomitant use of torasemide and lithium preparations may increase the concentration of lithium in the blood and increase the cardio- and neurotoxicity of the latter.
When treated with salicylates in high doses, torasemide may enhance their toxic effect on the central nervous system.
When used simultaneously with cholestyramine, the absorption of torasemide may decrease, resulting in a decrease in the severity of its action.
Overdose
Symptoms. Typical symptoms are unknown. In case of overdose, forced diuresis may occur with the risk of excessive loss of fluid and electrolytes. Drowsiness, confusion, hypotension, cardiovascular failure and gastrointestinal disorders are possible.
Treatment. There is no specific antidote. Depending on the symptoms of overdose, a dose reduction or discontinuation of the drug is recommended. Measures are taken to restore water and electrolyte balance. Torasemide is not removed from the blood by hemodialysis. Treatment in case of hypovolemia: fluid volume replacement. Treatment in case of hypokalemia: administration of potassium preparations. Treatment of cardiovascular failure: sitting position of the patient and, if necessary, the appointment of symptomatic therapy.
Anaphylactic shock (emergency measures). At the first appearance of skin reactions (such as, for example, urticaria or redness of the skin), the patient's excited state, headache, increased sweating, nausea, cyanosis, perform catheterization of the vein; place the patient in a horizontal position, ensure free air flow, and administer oxygen. If necessary, administer adrenaline, solutions that replace fluid volume, and corticosteroids.
Storage conditions
At a temperature not exceeding 25 °C.
1-01-REC-CIS-0919
