Torsemide, 5 mg, tablets, 60 pcs.

Torasemide

The frequency of the side effects listed below was determined according to the following (World Health Organization classification): very common (more than 10%); often (more than 1% and less than 10%); uncommon (more than 0.1% and less than 1%); rare (more than 0.01% and less than 0.1%); very rarely (less than 0.01%), including isolated reports; frequency unknown (cannot be estimated from available data).

From the blood and lymphatic system

Frequency unknown

- thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia.

Metabolism and nutrition

Infrequently

- hypercholesterolemia, hypertriglyceridemia.

Frequency unknown

- decreased glucose tolerance (possible manifestation of latent diabetes mellitus).

From the nervous system

Often -

dizziness, headache, drowsiness;
infrequently -
muscle cramps of the lower extremities;
frequency is unknown
- confusion, fainting, paresthesia in the extremities (feeling of numbness, “crawling” and tingling).

From the side of the organ of vision

Frequency unknown -

visual impairment.

Hearing and labyrinth disorders

Frequency not known? 1a —

Hearing impairment, tinnitus and hearing loss (usually reversible) usually occur in patients with renal failure or hypoproteinemia (nephrotic syndrome).

From the cardiovascular system

Infrequently -

extrasystole, tachycardia, increased heartbeat, facial flushing;
frequency not known -
excessive arterial hypotension, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism, hypovolemia.

From the respiratory system

Infrequently -

nosebleeds.

From the digestive system

Often

- diarrhea;
uncommon
- abdominal pain, flatulence, polydipsia;
frequency is unknown -
dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspeptic symptoms, intrahepatic cholestasis.

From the kidneys and urinary tract

Often -

increased frequency of urination, polyuria, nocturia;
infrequently -
frequent urge to urinate;
frequency unknown
- oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria, increased concentrations of urea and creatinine in the blood.

From the genital organs

Frequency unknown

- violation of potency.

General and administration site disorders

Infrequently

- asthenia (exhaustion), thirst, weakness, increased fatigue, hyperactivity, nervousness.

Laboratory indicators

Infrequently -

increase in platelet count;
frequency unknown -
hyperglycemia, hyperuricemia, decrease in the number of red blood cells, leukocytes and platelets, a slight increase in the activity of alkaline phosphatase in the blood, increased activity of some liver enzymes (for example, gamma-glutamyl transferase).

From the skin and subcutaneous tissues

Frequency unknown

- skin itching, rash, urticaria, erythema multiforme, exfoliative dermatitis, purpura, vasculitis, photosensitivity.

From the musculoskeletal system

Frequency unknown

- muscle weakness.

From the side of water-electrolyte and acid-base balance

Frequency unknown

- hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis. Symptoms indicating the development of electrolyte and acid-base disorders may include headache, confusion, convulsions, tetany, muscle weakness, cardiac arrhythmias and dyspeptic disorders; hypovolemia and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.

If any of the side effects indicated in the instructions get worse ,
or you notice any other side effects not listed in the instructions, tell your doctor.

TORESEMIDE (tablets)

ie.
Doctors shrug their shoulders - many years of serious illness and age. On her last visit, the doctor prescribed my mother a new drug, Torasemide-3C, which, according to her, is very effective and has a number of advantages over Furosemide. Compared to Furosemide, the diuretic drug Torasemide is less active in reducing the level of potassium in the blood, has a longer and more powerful effect, and its duration of action is up to 18 hours. And yet, unlike Furosemide, the drug Torasemide can be taken for a long time without a threat to health. The doctor prescribed taking the drug Torasemide at a dose of 5 mg tablet once a day, regardless of meals, with a sufficient amount of water, but at the same time. And she also warned that due to the diuretic effect of the drug, blood pressure decreases, so it needs to be constantly monitored. According to the doctor, with constant use of Torasemide, the dose will gradually decrease over time and in order to adjust the blood pressure, you need to correctly correlate the antihypertensive drug you are taking with Torasemide. It’s too early to talk about this now, it takes time, but we are constantly monitoring the pressure. The diuretic drug “Torasemide-C3”, which I bought in a dose of 10 mg (again, I only took one plate so far) costs 240 rubles - 60 tablets, “Leningrad region . The pharmacist gave me a plate of the drug (10 tablets) with packaging and instructions (there was one blister left in the package). The box is informative, the necessary information is given on all sides. By the way, on one of the sides it is indicated that the drug is dispensed by prescription - nothing like that! I decided to look through the entire instructions, but there is so much information there that my head is spinning. This is correct, but the doctor must delve into all this and be interested in it so as not to harm the patient. It is indicated that it should be taken only as prescribed by a doctor.

Here are the indications for the use of “Torasemide”, contraindications and who to take with caution: “Torasemide” tablets are white, the score is divided in half, so it is convenient to take a larger dosage - it turns out cheaper. We noticed that after just 4-5 days of taking Torasemide, the swelling in the legs decreased and breathing became easier, and this is already an achievement. And yet, after taking Torasemide, you don’t have to run to the toilet every minute, like with Furosemide. All this happens less frequently, smoothly over 15-18 hours. This is convenient, especially for bed patients. I hope that in the future the situation will become even better. The record is running out, we'll take the next one. I am very glad that the drug improved my mother’s general condition, and most importantly, shortness of breath decreased and breathing became easier.

I recommend the drug “Torasemide”, the drug is good and the price is affordable. The only thing is that self-medication is unacceptable, especially in severe cases, so take the drug only as directed and under the supervision of a doctor. Do not be ill!

Edema-ascitic syndrome is the most common complication of liver cirrhosis. Its appearance indicates progression of the disease and is associated with a 50% mortality rate over the next 5 years [1–3]. The key drugs for the treatment of edematous-ascitic syndrome include loop diuretics, which improve the quality of life of patients and prevent the development of spontaneous bacterial peritonitis and hepatorenal syndrome. Conservative treatment includes an aldosterone antagonist, spironolactone, and loop diuretics—furosemide and torsemide [4–6]. This combination makes it possible to achieve regression of edematous-ascitic syndrome in approximately 60–75% of patients, especially in the early stages of treatment. For some patients, diuretic therapy may be ineffective due to loss of sensitivity to diuretic therapy with the formation of refractory ascites, in the presence of which the one-year survival rate is only 25% [7]. The use of diuretics in recommended doses limits such adverse events as hypotension, electrolyte disturbances, deterioration of renal function and azotemia, and an increase in hepatic encephalopathy [1, 4]. Resistance to diuretics and side effects of the traditional regimen provided the impetus for the search for new treatment algorithms for patients with edematous-ascitic syndrome. As an alternative, torasemide SR has proven itself, the clinical advantages of which include a greater diuretic effect and a lower risk of developing electrolyte disturbances [1, 8–10]. Important features of the drug (unlike furosemide) are its blocking effect on aldosterone receptors and the absence of the rebound phenomenon, which is associated with sodium and water retention. This makes the use of torasemide SR justified in liver cirrhosis. Torsemide has proven its effectiveness in both patients with chronic heart failure [11–13] and patients with liver cirrhosis. Compared with furosemide, therapy with torasemide SR was accompanied by a decrease in the number of hospitalizations and a decrease in mortality in patients with edematous-ascitic syndrome in cirrhosis of the liver [14]. In recent years, sustained-release torsemide (SR) has become available. Possessing all the properties of torasemide, the prolonged form (Britomar) provides a gradual release of the drug, which allows reducing fluctuations in the concentration of torasemide in the blood plasma [15, 16]. High and predictable bioavailability and a long half-life determine the stability of natriuresis and diuretic effect of torasemide 3V, minimize electrolyte disturbances, and improve the quality of life of patients [17–19]. The use of torasemide ZV in patients with edematous-ascitic syndrome against the background of liver cirrhosis has not been sufficiently studied.

The purpose of the study was to evaluate the effectiveness and safety of the use of torasemide ZV (Britomar) in patients with edematous-ascitic syndrome against the background of decompensated liver cirrhosis.

Material and methods

The study included 42 patients (including 20 women) with liver cirrhosis and edematous-ascitic syndrome. The average age was 57.4±11.5 years. Exclusion criteria were age <18 years, hepatorenal syndrome, hyponatremia <125 mmol/L, hypokalemia <3.5 mmol/L, hyperkalemia >5.5 mmol/L, worsening hepatic encephalopathy or hepatic coma, hypersensitivity to extended-release torsemide , anuria, sinoatrial and atrioventricular blockade of II–III degrees, arterial hypotension (BP <90/60 mm Hg). The study did not include patients with severe acute alcoholic hepatitis.

All patients followed a diet limiting table salt to 3 g/day, abstained from drinking alcohol and received standard therapy for liver cirrhosis: transfusion of albumin, fresh frozen plasma, lactulose, ciprofloxacin, propranolol.

During randomization, patients were divided into 2 groups. The main group received torasemide ZV (n=20), the control group received furosemide (n=22). All patients received spironolactone. The drugs were taken orally in tablet form for an average of 3 weeks. The initial doses of diuretics (torasemide ZV 10 mg, furosemide 40 mg, spironolactone 100 mg/day) were increased by 2 times every 3 days in case of body weight loss of less than 300 g/day. The limitation was a decrease in body weight of more than 500 g/day in patients without peripheral edema [1, 5, 6].

All patients underwent a clinical assessment, laboratory examination, which included a complete blood count, biochemical parameters of blood serum (total protein, albumin, creatinine, electrolytes, alkaline phosphatase, bilirubin, alanine aminotransferase - ALT, aspartate aminotransferase - AST, γ-glutamyl transpeptidase, coagulation system parameters, general urine analysis, daily urinary sodium excretion. In addition, instrumental studies were carried out, including electrocardiography, chest radiography, ultrasound examination of the liver, esophagogastroduodenoscopy. Ultrasound elastometry of the liver using the Fibroscan 502 Touch device (Echosens, France) was performed in all patients after reduction of ascites. The alcoholic genesis of liver cirrhosis was confirmed by the presence of signs of chronic alcohol intoxication. All patients underwent a serological study of markers of viral hepatitis. In patients under 35 years of age, ceruloplasmin was studied. To exclude hemochromatosis, serum iron and ferritin were studied.

The effectiveness and safety of therapy was assessed daily using the following indicators: daily diuresis, body weight, abdominal circumference, edema, blood pressure (BP), heart rate. The level of electrolytes and creatinine in the blood was determined every 3 days, and daily natriuresis was determined before and after diuretic therapy.

Statistical processing of the obtained data was carried out using the Statistica 7.0 program. To assess the statistical significance of differences between groups, nonparametric Mann–Whitney and Wilcoxon tests were used. Correlation analysis was carried out using Spearman statistics. All data are presented as means ± SD. Differences were considered statistically significant at p<0.05.

results

According to the main clinical and demographic indicators, the study groups were comparable (Table 1). In all patients, liver cirrhosis was of alcoholic origin; in 31%, markers of viral hepatitis were detected; in 71%, liver cirrhosis corresponded to Child–Pugh class C. In 14.2% of them, the diagnosis of liver cirrhosis was established for the first time. In all patients, the course of liver cirrhosis was complicated by the development of ascites; in 86%, ascites had grade III severity; 43% had previously taken diuretic therapy. No patient required laparocentesis either earlier or during the study. All of them had swelling of the lower extremities, jaundice, signs of hepatic encephalopathy, and a decrease in the synthetic function of the liver.

The liver density in the torasemide SV group averaged 56±8 kPa, in the furosemide group – 60±10 kPa. By the end of the study, the average dose of torasemide pollutants was 8±2 mg/day, furosemide 60.0±35 mg/day. At the same time, in the furosemide group, the dose of furosemide was increased in 11 (50%) patients, and 2 times in 7. In the torasemide 3 group, no dose increase was required. The groups were comparable in terms of concomitant therapy. Against the background of diuretic therapy, a decrease in edema syndrome was noted in both groups: in the torasemide ZV group, 2 (10%) people remained pasty in the legs and feet; in the furosemide group – in 6 (27%).

All patients experienced regression of ascites to grade I. A more pronounced diuretic effect was observed in the torasemide ZV group.

In the torasemide group, diuresis increased on average by 865±660 ml, and in the furosemide group – by 400±300 ml (p=0.018). At the same time, no statistically significant differences in the dynamics of body weight were detected between the groups: in the torasemide ZV group, body weight decreased by 8±4 kg, in the furosemide group - by 5.8±3.8 kg (p=0.06).

In the long-acting torsemide group, there was a statistically significant increase in daily urinary sodium excretion (93±63.0 mmol/day compared to the furosemide group 51±20 mmol/day; p=0.012). There were no statistically significant differences in the levels of potassium and sodium in the blood plasma in the two groups.

During treatment, renal function was stable, creatinine levels did not increase.

The effect of diuretic therapy on blood pressure, electrolytes and creatinine levels is presented in Table. 2. By the end of the study, all patients showed a statistically significant decrease in the average Child–Pugh score (p = 0.003) and a decrease in the severity of liver cirrhosis (p = 0.003). However, no statistically significant differences were found between the groups (Figure).

Thus, when comparing torasemide ZV with furosemide in the study group, a significantly greater diuretic and saluretic effect was obtained. At the same time, no statistically significant differences in body weight loss and regression of edema syndrome were identified.

Discussion

For the treatment of edematous-ascitic syndrome in patients with decompensated liver cirrhosis, immediate-release torasemide has been most studied. A number of studies have demonstrated that the pharmacokinetics of torasemide IV, in particular bioavailability, are comparable to those of immediate-release torasemide [20]. In liver cirrhosis, an increase in bioavailability (2.5 times) and half-life of torsemide (up to 4.8 hours) was noted [21].

However, an increase in accumulation with long-term use of the drug is not expected, because in such patients, about 80% of the drug dose was excreted in the urine per day (unchanged and in the form of metabolites), i.e. no dose adjustment is required for liver cirrhosis [22].

In the treatment of edematous-ascitic syndrome in patients with liver cirrhosis, it is possible to use torasemide both as monotherapy and in combination with spironolactone [23]. Torsemide therapy is indicated both for decompensation of ascites and for its prevention. Torsemide does not cause hypokalemia even with long-term use [24].

To evaluate the effectiveness of diuretic therapy in patients with liver cirrhosis and ascites, a number of comparative studies of torasemide and furosemide were conducted. A randomized study of 28 patients with ascites treated with spironolactone (200 mg/day) compared the results of 6 weeks of therapy with torasemide (20 mg/day) and furosemide (40 mg/day). Both drugs had comparable effects on body weight, diuresis, and excretion of uric acid, sodium, and chloride, but excretion of potassium, calcium, inorganic phosphate, and magnesium was lower in the torsemide group [25].

In a double-blind crossover study, the results of oral administration of furosemide (80 mg) and torasemide (20 mg) were compared in 14 patients. Torsemide was superior to furosemide in diuretic and natriuretic activity.

Five patients had a weak response to furosemide, while torasemide caused a significant increase in natriuresis and diuresis [26].

The positive effect of torasemide on diuresis and saluresis was shown in a study involving 124 patients with liver cirrhosis: 61 people received torasemide and 63 received furosemide. Doses were selected individually, taking into account the gradation of ascites and response to diuretic therapy. In the torsemide group, daily urinary sodium excretion significantly increased compared with that in the furosemide group (p < 0.05) [10].

An increase in natriuresis (p=0.012) and diuresis (p=0.018) was also observed in our study when using torasemide ZV. A group of 46 patients with liver cirrhosis complicated by ascites (randomized trial) were treated with torasemide 20 mg/day or furosemide 40 mg/day in combination with spironolactone 200 mg/day. If it was not possible to achieve a weight loss of 300 g/day, the doses of diuretics were increased every 3 days to 40, 120 and 400 mg/day, respectively. Torasemide ZV caused a more pronounced increase in diuresis than furosemide, although in general the treatment results in the 2 groups were comparable. Increases in diuretic doses were required in 2 patients in the torasemide 3V group and in 9 patients in the furosemide group (p<0.05) [15].

In our study, when comparing torasemide ZV with furosemide, no statistically significant differences in the dynamics of body weight were detected (p = 0.06). The lack of significant differences between the average body weight of the experimental group and the comparison group may be due to the targeted dosed weight reduction in both groups according to the recommended regimens. It is worth noting that an increase in diuretic doses was required only in the furosemide group.

Torsemide did not affect plasma blood pressure, creatinine and electrolyte levels when using the drug at a dose of 20 mg/day compared with furosemide at a dose of 50 mg/day [22, 27]. The duration of diuretic therapy was 7 days. In our study, patients took torasemide ZV for an average of 3 weeks. In the study group, there was a trend towards lower blood pressure levels before inclusion in the study. However, Britomar had no effect on blood pressure levels. There were no changes in the levels of potassium, sodium and creatinine in the blood.

One study showed that during therapy with torasemide, compared with furosemide, treatment-resistant ascites develops significantly less often (16.4 and 38.1%; p<0.05). The duration of therapy was 15 days [9]. However, only patients with grade III ascites were included. More than 50% of patients had recurrent ascites that could not be corrected with diuretic therapy on an outpatient basis. A decrease in the synthetic function of the liver (hypoalbuminemia) was corrected by transfusion of fresh frozen plasma only. In our study, loss of sensitivity to diuretics was not detected in any of the groups. This may be due to concomitant therapy. Thus, the main method of correcting hypoproteinemia was the transfusion of albumin, rather than fresh frozen plasma. In addition, the severity of ascites was less pronounced. The study involved patients with stage II ascites, 42% had not previously received diuretic therapy, and in 14.2% liver cirrhosis debuted with edematous-ascitic syndrome.

When planning the study, we assumed that the use of torasemide ZV would reduce the length of hospital stay due to a more rapid regression of the edematous-ascitic syndrome. There were no significant differences in the length of stay of patients in the hospital. The dose ratio of torasemide and furosemide is 10–20 and 40 mg/day [21, 28]. In most studies, the starting dose of immediate-release torasemide was 20 mg/day [9, 23–27]. In our study, approximately 50% of patients had not previously received diuretic therapy, had relatively preserved natriuresis and a trend towards lower blood pressure. In this regard, the initial dose of torasemide pollutant was 10 mg/day. During the therapy, positive dynamics were observed in the form of increased diuresis and natriuresis without the development of hypotension, electrolyte disturbances, and a stable creatinine level.

Given the calm safety profile of torasemide ZV, it is likely that a more rapid clinical effect will be observed with increasing doses.

Thus, torasemide ZV (Britomar) can serve as an alternative to furosemide in the treatment of edematous-ascitic syndrome in patients with decompensated liver cirrhosis.

AUDITOR (Torasemide) tab 5mg N30