Instructions for Trifas Cor tablets 5 mg No. 30
Composition
active ingredient: 1 tablet contains torasemide 5 mg;
Excipients: lactose monohydrate, corn starch, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white, round, slightly biconvex tablets with a score line on one side.
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. In healthy probands, a dose-proportional increase in diuresis (loop diuretic activity) was observed in the dose range of 5-100 mg. An increase in diuresis was observed even in cases where other diuretics, for example, distally acting effective 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 (decreases Cmax and increases tmax), 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 a carboxylic acid, metabolite M3 is formed as a result of hydroxylation of the ring. Metabolites M2 and M4, identified in animal studies, have not been identified in humans. The pharmacokinetics of torasemide and its metabolites are characterized by a linear relationship. This means that its maximum concentration in 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 taken 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
Essential hypertension. Treatment and prevention of recurrence of edema and/or effusions caused by heart failure.
Contraindication
Hypersensitivity to the active substance, sulfonylurea drugs and to any of the excipients of Trifas® Cor. Renal failure with anuria. Hepatic coma or precoma. Arterial hypotension. Hypovolemia. Hyponatremia. Hypokalemia. Arrhythmia. Significant urinary disorders, e.g. due to prostatic hypertrophy.
Interaction with other medicinal products and other types of interactions
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 exacerbation 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 (CNS). Torasemide, especially in high doses, may enhance the ototoxic and nephrotoxic effects of aminoglycoside antibiotics, such as kanamycin, gentamicin, tobramycin and cytostatics - active platinum derivatives, as well as the nephrotoxic effects of cephalosporins. Torasemide may enhance the effects of theophylline, as well as the effects of curare-like drugs on muscle relaxation. 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, potassium in the blood serum, is required, especially in patients who are simultaneously using digitalis glycosides, glucocorticosteroids, mineralocorticosteroids 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 relationship 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 use of 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, patients with latent and overt diabetes mellitus should be carefully monitored for carbohydrate metabolism. 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, such as 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, such as thrombocytopenia or anemia in patients without renal failure; impaired renal function caused by nephrotoxic substances. The drug contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug.
The use of Trifas® Cor may cause a positive result in a doping test and deterioration of health.
Use during pregnancy or breastfeeding
Pregnancy. There are no reliable data on the effect of torasemide on the embryo and fetus in humans. Animal experiments have shown reproductive toxicity of torasemide. Torasemide penetrates the placental barrier. In connection with the above, torasemide is used during pregnancy only for vital indications and in the minimum possible effective dose. Diuretics are not suitable for the standard treatment regimen for arterial hypertension or edema in pregnant women, since they can reduce the perfusion of the placental barrier 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.
Lactation. It is currently not known whether torasemide is excreted in human or animal breast milk. A risk to the newborn/infants cannot be excluded. Therefore, torasemide is contraindicated during lactation. If it is necessary to use torasemide during this period, breastfeeding should be discontinued.
Fertility: No studies have been conducted on the effect of torasemide on fertility in humans. No such effect of torasemide was observed in animal experiments.
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 or perform work without safety precautions. This applies to a large extent to cases such as the start of treatment, an increase in the dose of the drug, a change in the drug or the appointment of concomitant therapy. Therefore, during the use of torasemide, great caution should be exercised when driving or operating machinery.
Method of administration and doses
Essential hypertension. Treatment should be started with ½ tablet of Trifas® Cor per day, equivalent to 2.5 mg of torasemide. The reduction in blood pressure occurs gradually, already during the first week of treatment, and reaches its maximum value no later than 12 weeks. If normalization of blood pressure with daily use of ½ tablet of the drug does not occur after 12 weeks of treatment, the daily dose can be increased to 1 tablet of Trifas® Cor, equivalent to 5 mg of torasemide. With initially high blood pressure, as well as with limited kidney function, an additional reduction in blood pressure can be expected by increasing the dose. The daily dose of Trifas® Cor, equal to 1 tablet, should not be exceeded, since no further reduction in blood pressure is expected.
Edema and effusions. Treatment begins with the use of 1 tablet of Trifas® Cor per day, which is equal to 5 mg of torasemide. Usually this dose is considered a maintenance dose. If the daily dose of 5 mg is insufficient, then 2 tablets of the drug per day, which is equal to 10 mg of torasemide, should be used, which is prescribed daily. Depending on the severity of the patient's condition, the daily dose may be increased to 20 mg of torasemide.
Tablets should be taken in the morning, not chewed and washed down with a small amount of liquid. The duration of treatment depends on the course of the disease. The bioavailability of torasemide does not depend on food intake.
Recommendations for dividing the tablet. The tablets can be easily divided into two halves (the dividing score is on one side), which ensures that the required dose can be obtained. Place the tablet on a hard surface. Then press with your thumbs to the right and left of the dividing score. This ensures easy division of the tablet.
Patients with impaired liver function. 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, adequate studies comparing the treatment of elderly patients with younger patients are lacking.
Children
Torasemide should not be used in children and adolescents in the absence 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.
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
The following frequency of occurrence was used to assess adverse events: very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1000 to < 1/100; rare: ≥ 1/10000 to < 1/1000; very rare: < 1/10000; unknown: cannot be determined due to lack of data.
Metabolism/electrolyte disorders: Common: increased metabolic alkalosis. Muscle spasms (especially at the beginning of treatment). Increased uric acid and glucose concentrations, as well as cholesterol and triglycerides in the blood. Hypokalemia (with concomitant low-potassium 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, for example, hypovolemia, hypokalemia and/or hyponatremia. With significant fluid and electrolyte losses due to increased urination, arterial hypotension, headache, asthenia, drowsiness may occur, especially at the beginning of treatment and in elderly patients.
Cardiovascular system: Very rare: thromboembolic complications, confusion, hypotension, as well as circulatory and cardiac disorders, including cardiac and cerebral ischemia, which may lead, for example, to arrhythmia, angina pectoris, acute myocardial infarction, syncope due to hemoconcentration.
From the digestive system. Often: various digestive disorders (especially at the beginning of treatment) including loss of appetite, flatulence, stomach pain, nausea, vomiting, diarrhea, constipation. Very rare: pancreatitis.
From the urinary system. Sometimes: increased concentration of creatinine and urea in the blood, urge to urinate. In patients with urination disorders (for example, with prostatic hypertrophy), increased urine production can lead to its retention and excessive stretching of the bladder.
Hepatobiliary system: Common: increased concentration of some liver enzymes (gamma-glutamyl transpeptidase) in the blood.
Immune system disorders: Very rare: allergic reactions, e.g. pruritus, exanthema, photosensitivity, severe skin reactions (rash).
From the blood and hematopoietic system: Very rare: decrease in the number of platelets, erythrocytes and/or leukocytes.
General manifestations. Often: headache, dizziness, increased fatigue, general weakness (especially at the beginning of treatment). Sometimes: dry mouth, unpleasant sensations in the extremities (paresthesia). Very rarely: visual disturbances, ringing in the ears, hearing loss.
Expiration date
5 years. Do not use the drug after the expiration date indicated on the package.
Storage conditions
No special storage conditions are required. Keep out of the reach of children.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
BERLIN-CHEMI AG.
Location of the manufacturer and its business address
Glienicker Weg 125, 12489, Berlin, Germany.
Applicant
Menarini International Operations Luxembourg S.A.
Location of the applicant and/or applicant's representative
1, Avenue de la Gare, L-1611 Luxembourg.
