Instructions for Toraren tablets 10 mg blister No. 30
Composition
active ingredient: 1 tablet contains torasemide 10 mg;
Excipients: lactose monohydrate, corn starch, colloidal anhydrous silica, copovidone, croscarmellose sodium, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: flat-cylindrical tablets with a bevel and a score, white or almost white in color.
Pharmacotherapeutic group
Diuretics. Highly active diuretics.
ATX code C03C A04.
Pharmacological properties
Pharmacodynamics.
Torasemide acts as a saluretic, the action is associated with the inhibition of renal absorption of sodium and chlorine ions in the ascending part of the loop of Henle. In humans, the diuretic effect quickly reaches its maximum within the first 2-3 hours after intravenous and oral administration, respectively, and remains constant for almost 12 hours. There is information that in the dose range of 5-100 mg, a dose-proportional increase in diuresis (loop diuretic activity) was observed. An increase in diuresis was observed even in cases where other diuretics, for example, distally acting thiazide diuretics, no longer had the desired effect, for example, in renal failure. Due to this mechanism of action, torasemide leads to a decrease in edema. In heart failure, torasemide reduces the manifestations of the disease and improves myocardial function by reducing pre- and afterload. After oral administration, the antihypertensive effect of torasemide develops gradually, starting from the first week after the start of treatment. The maximum antihypertensive effect is achieved no later than 12 weeks. Torasemide reduces blood pressure by reducing total peripheral vascular resistance. This effect is explained by the normalization of disturbed electrolyte balance, mainly by reducing the increased activity of free calcium ions in the muscle cells of arterial vessels, which was found in patients suffering from arterial hypertension. This effect probably reduces the increased susceptibility of vessels to endogenous vasopressor substances, for example, catecholamines.
Pharmacokinetics.
After oral administration, torasemide is rapidly and completely absorbed. Peak serum concentrations are reached within 1-2 hours. Bioavailability is approximately 80-90%; with complete absorption, the maximum first-pass effect is 10-20%. Food reduces the rate (dynamic component) of torasemide absorption (Cmax decreases and tmax increases), but does not affect total absorption. Binding of torasemide to plasma proteins is more than 99%, and metabolites M1, M3, and M5 are 86%, 95%, and 97%, respectively. The apparent volume of distribution (Vz) is 16 l. In humans, torasemide is metabolized to form three metabolites: M1, M3, and M5. There is no evidence of the existence of other metabolites. Metabolites M1, M3 and M5 are formed as a result of oxidation of the methyl group located on the phenyl ring to carboxylic acid, metabolite M3 is formed as a result of hydroxylation of the ring. The pharmacokinetics of torasemide and its metabolites are characterized by a linear relationship. This means that its maximum concentration in the blood serum and the area under the serum concentration curve increase in proportion to the dosage. The terminal half-life (t1/2) of torasemide and its metabolites in healthy people is 3-4 hours. The total clearance of torasemide is 40 ml/min., renal clearance is approximately 10 ml/min. In healthy subjects, approximately 80% of the administered dose is excreted as torasemide and its metabolites in the urine in the following percentages: torasemide - approximately 24%, metabolite M1 - approximately 12%, metabolite M3 - approximately 3%, metabolite M5 - approximately 41%. The main metabolite M5 has no diuretic effect, and the active metabolites M1 and M3 together account for approximately 10% of the total pharmacodynamic effect. In renal failure, the total clearance and half-life of torasemide do not change, while the half-life of M3 and M5 is prolonged. However, the pharmacodynamic characteristics remain unchanged, and the severity of renal failure does not affect the duration of action. In patients with impaired liver function or heart failure, the half-life of torasemide and the metabolite M5 is slightly prolonged, and the amount of substance excreted in the urine is almost completely equal to the amount excreted in healthy people, so the accumulation of torasemide and its metabolites does not occur. Torasemide and its metabolites are practically not removed by hemodialysis and hemofiltration.
Indication
Treatment and prevention of recurrence of edema and/or effusions caused by heart failure.
Contraindication
Hypersensitivity to the active substance, sulfonylurea drugs and excipients of the drug. Renal failure with anuria. Hepatic coma or precoma. Arterial hypotension. Hypovolemia. Hyponatremia. Hypokalemia. Significant urinary disorders, for example, due to prostatic hypertrophy.
Torasemide enhances the effect of other antihypertensive agents, in particular angiotensin-converting enzyme inhibitors, which may cause excessive lowering of blood pressure during their simultaneous use. When torasemide is used simultaneously with digitalis drugs, potassium deficiency caused by the use of a diuretic may lead to an increase or intensification of the side effects of both drugs. Torasemide may reduce the effectiveness of antidiabetic agents. Probenecid and non-steroidal anti-inflammatory drugs (e.g. indomethacin, acetylsalicylic acid) may inhibit the diuretic and antihypertensive effects of torasemide. When treated with salicylates in high doses, torasemide may increase their toxic effect on the central nervous system. Torasemide, especially in high doses, may enhance the ototoxic and nephrotoxic effects of ethacrynic acid and aminoglycoside antibiotics, such as kanamycin, gentamicin, tobramycin and cytostatics - active platinum derivatives, and may also enhance the nephrotoxic effects of cephalosporins. Torasemide may enhance the effects of theophylline, as well as the effects of curare-like drugs. Laxatives, as well as mineralocorticoids and glucocorticoids may enhance the loss of potassium caused by torasemide. With the simultaneous use of torasemide and lithium preparations, an increase in the concentration of lithium in the blood plasma is possible, which may lead to increased exposure and increased side effects of lithium. Torasemide may reduce the vasoconstrictor effect of catecholamines, such as epinephrine and norepinephrine. When used simultaneously with cholestyramine, the absorption of torasemide and, accordingly, its expected effectiveness may be reduced.
Application features
Before starting the drug, it is necessary to eliminate existing hypokalemia, hyponatremia or hypovolemia. With prolonged use of torasemide, regular monitoring of electrolyte balance, in particular, serum potassium, is required, especially in patients who are simultaneously using digitalis glycosides, glucocorticosteroids, mineralocorticosteroids.
food or laxatives. In addition, it is necessary to regularly monitor the content of glucose, uric acid, creatinine and lipids in the blood. Torasemide should be used with special caution in patients suffering from liver diseases accompanied by cirrhosis of the liver and ascites, since 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 the use of torasemide, cases of ototoxicity (tinnitus and hearing loss) were 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, especially in elderly patients.
Patients with water and electrolyte imbalance should discontinue the drug and resume therapy, starting with lower doses, after the undesirable effects have resolved.
Due to the fact that during treatment with torasemide an increase in blood glucose levels may occur, careful monitoring of carbohydrate metabolism is necessary in patients with latent and overt diabetes. Blood counts (erythrocytes, leukocytes, platelets) should also be regularly monitored. Especially at the beginning of treatment in elderly patients, special attention should be paid to the appearance of symptoms of electrolyte loss and blood clotting.
In the absence of sufficient clinical experience, torasemide should not be prescribed for the following diseases and conditions: gout; arrhythmias, for example, sinoatrial block, atrioventricular block of the II and III degrees; pathological changes in acid-base metabolism; concomitant therapy with lithium, aminoglycosides or cephalosporins; pathological changes in the blood picture, for example, thrombocytopenia or anemia in patients without renal failure; impaired renal function caused by nephrotoxic substances.
The medicine contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The use of the drug Torasemide-Lugal may cause a positive result in a doping test. It is impossible to predict the impact on health if the drug Torasemide-Lugal is used incorrectly, i.e. for doping purposes, in which case possible harm to health cannot be excluded.
Use during pregnancy or breastfeeding
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 because they can reduce placental barrier perfusion and cause toxic effects on intrauterine fetal development. If torasemide is used to treat pregnant women with heart failure 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, torasemide is contraindicated during breastfeeding. 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.
Ability to influence reaction speed when driving vehicles or other mechanisms
Even when used properly, torasemide may affect the patient's reactions to such an extent that it will cause a significant negative impact on the ability to drive or operate machinery. This is particularly true when starting treatment, increasing the dose of the drug, changing the drug, or prescribing concomitant therapy. Therefore, extreme caution should be exercised when driving or operating machinery while using torasemide.
Method of administration and doses
Adults. Treatment should be started with a daily dose of 5 mg torasemide, which is ½ tablet of the drug Torasemid-Lugal. Usually this dose is considered a maintenance dose. To divide the tablet into two halves, perform the following actions: place the tablet on a hard surface and press with your thumbs to the right and left of the dividing line, which provides the opportunity to obtain the required dose. If the daily dose of 5 mg is insufficient, then a daily dose of 10 mg torasemide should be used, which is prescribed by the doctor daily. Depending on the severity of the patient's condition, the daily dose may be increased to 20 mg torasemide. Tablets should be taken on an empty stomach, not chewed and washed down with a small amount of liquid. The bioavailability of torasemide does not depend on food intake. Torasemid-Lugal can usually be used for a long time or until the severity of edema decreases.
Patients with hepatic insufficiency. Treatment of such patients should be carried out with caution, as an increase in plasma concentrations of torasemide is possible.
Elderly patients. No special dose adjustment is required. However, reliable studies comparing the effects of the drug in young and elderly patients have not been conducted.
Children and adolescents. The safety and efficacy of Torasemide-Lugal in children have not been established. Therefore, torasemide is contraindicated in children.
Children
Torasemide should not be used in children due to the lack of sufficient clinical experience.
Overdose
Typical symptoms are unknown. Overdose may cause excessive diuresis, including the risk of excessive loss of water and electrolytes, drowsiness, amentia (a form of impaired consciousness), symptomatic hypotension, cardiovascular failure and digestive disorders.
Treatment of overdose. Specific antidote is unknown. Symptoms of intoxication usually disappear when the dosage is reduced and the drug is discontinued and with appropriate fluid and electrolyte replacement (blood electrolyte levels should be monitored). Torasemide is not removed from the blood by hemodialysis.
Treatment in case of hypovolemia: fluid volume replacement.
Treatment for hypokalemia: prescribing potassium supplements.
Treatment of cardiovascular failure: place the patient in a supine position and, if necessary, prescribe symptomatic therapy.
Anaphylactic shock (immediate measures). At the first appearance of skin reactions (such as, for example, urticaria or redness of the skin), the patient's agitated state, headache, sweating, nausea, cyanosis, a vein catheterization should be performed; the patient should be placed in a horizontal position, ensure free air flow, and oxygen should be administered. If necessary, epinephrine, volume-replacing solutions, and glucocorticoid hormones should be administered.
Adverse reactions
Metabolism/electrolytes: increased metabolic alkalosis. Muscle spasms (especially at the beginning of treatment), indigestion, flatulence, urinary urgency, rash. Increased concentration of uric acid and glucose in the blood, as well as cholesterol and triglycerides. Hypokalemia with concomitant potassium-free diet, with vomiting, diarrhea, after excessive use of laxatives, as well as in patients with chronic liver dysfunction. Depending on the dosage and duration of treatment, disturbances of water and electrolyte balance are possible, e.g. hypovolemia, hypokalemia and/or hyponatremia. With significant fluid and electrolyte losses as a result of increased urination, arterial hypotension, headache, fatigue, drowsiness may occur, especially at the beginning of treatment and in elderly patients.
Cardiovascular system: due to possible blood thickening, thromboembolic complications, confusion, hypotension, as well as circulatory and cardiac disorders, including cardiac and cerebral ischemia, may occur, which can lead, for example, to arrhythmia, angina pectoris, acute myocardial infarction, syncope.
On the part of the digestive system: digestive system disorders (especially at the beginning of treatment), including lack of appetite, stomach pain, nausea, vomiting, diarrhea, constipation, pancreatitis.
Renal and urinary disorders: increased blood creatinine and urea concentrations. In patients with urinary disorders (e.g., prostatic hypertrophy), increased urine production may lead to urinary retention and overdistension of the bladder.
On the part of the liver: increased concentration of certain liver enzymes (gamma-glutamyl transpeptidase) in the blood.
Immune system disorders: allergic reactions, e.g. itching, exanthema, photosensitivity, severe skin reactions.
From the blood and hematopoietic system: decrease in the number of platelets, erythrocytes and/or leukocytes as a result of hemoconcentration.
General manifestations and reactions at the site of administration of the drug: headache, dizziness, increased fatigue, general weakness (especially at the beginning of treatment); dry mouth, unpleasant sensations in the extremities (paresthesia); visual disturbances, tinnitus, hearing loss.
Expiration date
3 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister; 1 or 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and address of its place of business
04073, Ukraine, Kyiv, Kopylivska St., 38.
