Instructions for use Torasemide-Darnitsa tablets 10 mg No. 100
Composition
active ingredient: torasemide;
1 tablet contains torasemide 5 mg or 10 mg;
Excipients: lactose monohydrate, corn starch, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white or almost white tablets, oblong in shape, with a score and a bevel on both sides.
Pharmacotherapeutic group
Drugs affecting the cardiovascular system. Diuretics. Highly active diuretics. Sulfonamides. Torasemide. ATC code C03C A04.
Pharmacological properties
Pharmacodynamics.
Torsemide 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 parenteral 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. The increase in diuresis was observed even in cases where other diuretics, such as distally acting effective thiazide diuretics, no longer had the desired effect, for example in renal failure. Due to this mechanism of action, torasemide helps to reduce 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.
Absorption and distribution
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 overall absorption. The binding of torasemide to plasma proteins is more than 99%, and the metabolites M1, M3, and M5 are 86%, 95%, and 97%, respectively. The apparent volume of distribution (Vz) is 16 l.
Biotransformation
In humans, torasemide is metabolized to form three metabolites: M1, M3 and M5. There is no evidence for the existence of other metabolites. Metabolites M1, M3 and M5 are formed by oxidation of the methyl group on the phenyl ring to a carboxylic acid, metabolite M3 is formed by hydroxylation of the ring. Metabolites M2 and M4, identified in animal studies, have not been identified in humans.
Breeding
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, the 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 in the following percentages: torasemide - approximately 24%, metabolite M1 - approximately 12%, metabolite M3 - approximately 3%, metabolite M5 - approximately 41%. The main metabolite M5 does not have a 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, and 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 removed during hemodialysis and hemofiltration.
Linearity
Torasemide and its metabolites exhibit linear dose-dependent kinetics, meaning that their maximum plasma concentration and area under the pharmacokinetic curve increase proportionally with dose.
Indication
For 5 mg dosage: essential hypertension.
For 5 mg and 10 mg dosage: treatment and prevention of recurrence of edema and/or effusions caused by heart failure.
Contraindication
Renal failure with anuria.
Hepatic coma or precoma.
Arterial hypotension.
Hypovolemia.
Hyponatremia.
Hypokalemia.
Arrhythmia.
Significant urinary incontinence, for example due to prostatic hypertrophy.
Children's age (up to 18 years).
Breastfeeding period.
Interaction with other medicinal products and other types of interactions
Not recommended combinations
Torasemide, especially in high doses, may enhance the ototoxic and nephrotoxic side effects of aminoglycoside antibiotics (e.g. kanamycin, gentamicin, tobramycin), cytostatics - active platinum derivatives, as well as the nephrotoxic effects of cephalosporins.
Concomitant use of torasemide and lithium preparations may increase the concentration of lithium in the blood, which may lead to increased exposure and side effects of lithium.
Drug combinations that require caution
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 increased 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 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 increase potassium loss caused by torasemide.
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 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, careful monitoring of carbohydrate metabolism is necessary for patients with latent and overt diabetes. Blood counts (erythrocytes, leukocytes, platelets) should also be regularly monitored. 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; patient age under 18 years.
Torasemide-Darnitsa contains lactose, therefore patients with known intolerance to some sugars, as well as patients with rare hereditary diseases such as galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should consult their doctor before taking this medicine.
The use of torasemide may cause a positive doping test result and deterioration of health.
Use during pregnancy or breastfeeding
Pregnancy. There are no reliable data on the effects of torasemide on the embryo, fetus or pregnant woman in humans. In animal experiments, reproductive toxicity of torasemide was shown. Torasemide penetrates the placental barrier. Therefore, torasemide is not recommended for use during pregnancy, as well as for women of childbearing potential who are not using contraception. Use during pregnancy is possible only if absolutely necessary and in the minimum effective dose.
Diuretics are not suitable for the standard treatment of hypertension or edema in pregnant women, as they can reduce placental barrier perfusion and have a toxic effect 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 established whether torasemide is excreted in human or animal breast milk. The risk of exposure to the drug in newborns/infants cannot be excluded. Therefore, the use of torasemide during breastfeeding is contraindicated. If it is necessary to use torasemide during this period, breastfeeding should be discontinued. A decision to discontinue breastfeeding or to discontinue/abstain from Torasemide-Darnitsa should be made taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility: Studies on the effect of torasemide on fertility in humans have not been conducted. In animal experiments, no such effect of torasemide was detected.
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 have a significant negative impact on the ability to drive or use machines or perform dangerous work without insurance. This applies to a large extent to the beginning of treatment, increasing the dose of the drug, replacing the drug when prescribing concomitant therapy, as well as simultaneous use of alcohol. Therefore, during the use of torasemide, great care should be taken when driving or using other mechanisms.
Method of administration and doses
For a dosage of 5 mg.
Essential hypertension. Treatment should be started with ½ tablet of the drug Torasemid-Darnitsa 5 mg per day, which is equivalent to 2.5 mg of torasemide. The decrease in blood pressure occurs gradually, already during the first week of treatment, and reaches a maximum value no later than 12 weeks. If normalization of blood pressure with daily use of 2.5 mg of torasemide does not occur after 12 weeks of treatment, the daily dose may be increased to 5 mg of torasemide. With initially high blood pressure, as well as with limited kidney function, an additional decrease in blood pressure can be expected by increasing the dose. The indicated daily dose should not be exceeded, since no further decrease in blood pressure is expected.
For dosages of 5 mg and 10 mg.
Edema and/or effusions. Treatment begins with the use of 1 tablet per day of 5 mg or ½ tablet of the drug Torasemid-Darnitsa of 10 mg. Usually this dose is considered maintenance. If the daily dose of 5 mg is insufficient, then 2 tablets of 5 mg or 1 tablet of 10 mg per day should be used, which must be taken 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, without chewing and 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. The drug Torasemide-Darnitsa should usually be used for a long time or until the severity of edema decreases.
Recommendations for dividing the tablet. The tablet can be easily divided into two halves (the score line is on both sides), 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 score line. This ensures easy division of the tablet.
Special patient groups.
Patients with impaired liver function. Treatment of such patients should be carried out with caution, since an increase in the concentration of torasemide in the blood plasma is possible. Torasemide is contraindicated in patients in a state of hepatic coma or precoma.
Elderly patients: No special dose adjustment is required. However, there are no studies comparing the treatment of elderly patients with younger patients.
Children
The safety and efficacy of the drug Torasemid-Darnitsa in children and adolescents (under 18 years of age) have not been established. Therefore, torasemide should not be used in children and adolescents (under 18 years of age).
Overdose
Symptoms of intoxication.
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.
Overdose treatment.
There is no specific antidote. Symptoms of intoxication usually disappear when the dose is reduced, the drug is discontinued, and appropriate fluid and electrolyte replacement is carried out (monitoring is necessary!). 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 the 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, you should:
perform vein catheterization;
in addition to other emergency measures, place the patient in a horizontal position, ensure free air flow, and administer oxygen;
If necessary, administer epinephrine, volume replacement solutions, and glucocorticoid hormones.
Adverse reactions
The following classification was used to assess the frequency of adverse events: very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1000 to < 1/100; rare: ≥ 1/10,000 to < 1/1000; rare: < 1/10,000; unknown: frequency cannot be estimated due to lack of data.
On the part of the organs of vision: rare: visual disturbances.
From the side of the organs of hearing and vestibular apparatus: rare: tinnitus, hearing loss.
Gastrointestinal disorders: common: digestive system disorders (especially at the beginning of treatment), including lack of appetite, flatulence, stomach pain, nausea, vomiting, diarrhea, constipation; uncommon: xerostomia; rare: pancreatitis.
Hepatobiliary disorders: common: increased concentration of certain liver enzymes (gamma-glutamyl transpeptidase) in the blood.
Renal and urinary disorders: Uncommon: increased blood creatinine and urea concentration, urinary frequency. In patients with urinary disorders (e.g., prostatic hypertrophy), increased urine production may lead to urinary retention and overdistension of the bladder.
Metabolism and metabolism: often: intensification of metabolic alkalosis. Muscle spasms (especially at the beginning of treatment). Increased concentration of uric acid and glucose, as well as cholesterol and triglycerides in the blood. Hyperglycemia, 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, such as hypovolemia, hypokalemia and/or hyponatremia. With significant losses of fluid and electrolytes due to increased urination, arterial hypotension, headache, asthenia, drowsiness may occur, especially at the beginning of treatment and in elderly patients.
Nervous system disorders: common: headache, dizziness (especially at the beginning of treatment); uncommon: paresthesia; rare: syncope, cerebral ischemia, confusion.
Cardiovascular system: 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.
Blood and lymphatic system disorders: rare: blood thickening, decrease in platelets, red blood cells and/or white blood cells.
Immune system disorders: rare: hypersensitivity reactions, including pruritus, exanthema, photosensitivity, severe skin reactions (rash).
Skin and subcutaneous tissue disorders: rare: allergic skin reactions (e.g. pruritus, exanthema), photosensitivity reactions, severe skin reactions.
Musculoskeletal and connective tissue disorders: common: muscle spasms (especially at the beginning of treatment).
General disorders: common: headache, dizziness, fatigue, general weakness (especially at the beginning of treatment); uncommon: dry mouth, unpleasant sensations in the extremities (paresthesia).
Laboratory data: common: increased concentration of uric acid and lipids (triglycerides, cholesterol) in the blood; uncommon: increased concentration of urea and creatinine in the blood.
Reporting suspected adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
3 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
5 mg tablets: 10 tablets in a blister pack; 3 blister packs in a pack.
10 mg tablets: 10 tablets in a blister pack; 3 or 10 blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and address of its place of business.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
