Instructions Trifas 20 ampoules solution for injection 20 mg ampoule 4 ml No. 5
Composition
active substance: 1 ampoule (4 ml) of solution for injection contains 21.262 mg of torasemide sodium (equivalent to 20 mg of torasemide);
Excipients: sodium hydroxide, trometamol, polyethylene glycol 400, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent, colorless solution, practically free of mechanical inclusions. pH of Trifas®20 ampoules 8.5-9.5.
Pharmacotherapeutic group
Diuretics. Highly active diuretics.
ATX code C03C A04.
Pharmacological properties
Pharmacodynamics
Torasemide acts as a saluretic, its 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 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.
Pharmacokinetics
The binding of torasemide to plasma proteins is more than 99%, metabolites M1, M3, and M5 - 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 the stepwise oxidation of the methyl group attached to the phenyl ring to carboxylic acid, metabolite M3 is formed as a result of hydroxylation of the ring. Metabolites M2 and M4, which were found in animal experiments, could not be detected in humans.
The pharmacokinetics of torasemide and its metabolites are linear. This means that its maximum serum concentration and the area under the serum concentration curve increase in proportion to the dose. The terminal half-life (t1/2) of torasemide and its metabolites in healthy subjects 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 in the urine as torasemide and its metabolites with the following average percentage: 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 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 excreted during hemodialysis and hemofiltration.
Indication
Treatment of edema and/or effusions caused by heart failure, if intravenous administration of the drug is necessary, for example, in the case of pulmonary edema due to acute heart failure.
Contraindication
Hypersensitivity to the active substance, sulfonylurea drugs and to one of the excipients of the drug. Renal failure with anuria. Hepatic coma or precoma. Arterial hypotension. Hypovolemia. Hyponatremia. Hypokalemia. Acute urinary retention, for example, due to prostatic hypertrophy. Breastfeeding.
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 using torasemide simultaneously with digitalis drugs, potassium deficiency caused by the use of diuretics may lead to an increase and strengthening 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 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. 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. With simultaneous use with cholestyramine, the absorption of torasemide and, accordingly, its expected effectiveness may decrease.
Application features
Before starting the drug, it is necessary to eliminate existing hypokalemia, hyponatremia, or hypovolemia.
With prolonged use of torasemide, it is recommended to regularly monitor electrolyte balance, in particular serum potassium, 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 particular 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 together 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 other 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 or overt diabetes mellitus should be constantly carefully monitored for carbohydrate metabolism. Regular monitoring of the blood picture (erythrocytes, leukocytes, platelets) is also necessary. Especially at the beginning of treatment, elderly patients should pay special attention to the appearance of symptoms of electrolyte loss and blood clotting.
In the absence of sufficient clinical experience, torasemide should not be prescribed in the presence of 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 use of Trifas®20 ampoules may cause a positive result in a doping test. It is impossible to predict the impact on health if Trifas®20 ampoules 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. 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.
The effect of torasemide on fertility has not been studied in humans. In animal experiments, no such effect of torasemide was found.
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
Adults. Treatment should be started with a single dose of 2 ml of Trifas® 20 ampoules, equivalent to 10 mg of torasemide per day. If the effect is insufficient, the single dose can be increased to 4 ml of Trifas® 20 ampoules, equivalent to 20 mg of torasemide. If the effect is still insufficient, short-term (no more than 3 days) therapy with a daily dose of 8 ml of Trifas® 20 ampoules, equivalent to 40 mg of torasemide, can be used.
Acute pulmonary edema. Treatment should be initiated with a single intravenous dose of 4 ml of Trifas® 20 ampoules, equivalent to 20 mg of torasemide. Depending on the effect, this dose may be repeated at 30-minute intervals. The maximum daily dose of 20 ml of Trifas® 20 ampoules, equivalent to 100 mg of torasemide, must not be exceeded.
The solution for injection should be administered intravenously, slowly. It is forbidden to administer the solution intraarterially! Only administer a pure solution. In case of prolonged use, intravenous administration should be replaced by oral administration as soon as possible, since intravenous administration of torasemide is not recommended for more than 7 days.
Patients with hepatic insufficiency. Treatment of this category of patients should be carried out with caution, since an increase in the concentration of torasemide in the blood plasma is possible.
Elderly patients. Treatment of this category of patients does not require special dose selection. However, appropriate studies have not been conducted in elderly people compared with younger patients.
Note: Handling ampoules that open at one point.
There is no need to dust the ampoules.
| Turn the ampoule so that the dot is at the top. Tap the ampoule and shake it, allowing the solution contained in the neck of the ampoule to drain down. | Turn the ampoule so that the dot is at the top. Hold the ampoule at a slight angle. With a downward motion, break off the neck of the ampoule. |
Children
Torasemide should not be used in children and adolescents due to 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.
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 reactions: very common: ≥ 1/10, common: 1/100 - < 1/10, uncommon: ≥ 1/1000 - < 1/100, rare: ≥ 10,000 - < 1/1000, very rare: < 10,000, frequency unknown: cannot be estimated from the available data.
Metabolism/electrolytes. Common: increased metabolic alkalosis. Muscle spasms (especially at the beginning of treatment). Increased blood uric acid and glucose concentrations, 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, e.g. hypovolemia, hypokalemia and/or hyponatremia, are possible.
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 possible hemoconcentration.
From the digestive system. Often: multiple digestive system disorders (especially at the beginning of treatment), including lack of appetite, flatulence, stomach pain, nausea, vomiting, diarrhea, constipation. Very rare: pancreatitis.
From the kidneys and urinary tract. Sometimes: increased concentrations of creatinine and urea in the blood, urge to urinate. When there is a significant loss of water and electrolytes caused by excessive urine formation, especially at the beginning of treatment and in elderly patients, a decrease in blood pressure, headache, asthenia and drowsiness may occur.
In patients with urination disorders (e.g., prostatic hypertrophy), increased urine production may lead to urine retention and overdistension of the bladder.
Hepatic: Common: increased concentration of certain liver enzymes (gamma-glutamyl transpeptidase) in the blood.
Immune system disorders: Very rare: allergic reactions including pruritus, exanthema, photosensitivity, severe skin reactions. Acute, potentially life-threatening hypersensitivity reactions (anaphylactic shock) may occur after intravenous administration.
Blood and hematopoietic system disorders: Very rare: decrease in platelets, erythrocytes and/or leukocytes as a result of hemoconcentration.
General disorders and administration site conditions: Common: headache, dizziness, fatigue, general weakness (especially at the beginning of treatment). Uncommon: dry mouth, numbness in the extremities (paraesthesia). Very rare: visual disturbances, tinnitus, hearing loss. Frequency not known: local reactions after injections.
Expiration date
3 years. After first opening the ampoule, the solution should be used immediately.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Incompatibility
The drug Trifas® 20 ampoules cannot be mixed with other drugs for intravenous injections and/or infusions.
Packaging
4 ml in an ampoule, 5 ampoules in a cardboard box.
Vacation category
According to the recipe.
Producer
A. Menarini Manufacturing Logistics and Services S.r.L.
Location of the manufacturer and its business address
Via Sete Santi 3, 50131 Florence (FI), Italy.
Applicant
Menarini International Operations Luxembourg S.A.
Location of the applicant and its business address
1, Avenue de la Gare, L-1611, Luxembourg.
