Ursosan forte, 500 mg, film-coated tablets, 10 pcs.

Ursosan forte, 500 mg, film-coated tablets, 10 pcs.

Hepatoprotective drug. It also has choleretic, cholelitholytic, hypolipidemic, hypocholesterolemic and immunomodulatory effects. Possessing high polar properties, ursodeoxycholic acid (UDCA) is embedded in the membrane of hepatocytes, cholangiocytes and epithelial cells of the gastrointestinal tract, stabilizes its structure and protects the cell from the damaging effects of toxic bile acid salts, thus reducing their cytotoxic effect. Forms non-toxic mixed micelles with lipophilic (toxic) bile acids, which reduces the ability of gastric reflux to damage cell membranes in cholestatic liver diseases, biliary reflux gastritis and reflux esophagitis.

In cholestasis, UDCA activates Ca 2 -dependent alpha protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic, etc.), the concentrations of which are increased in patients with chronic liver diseases. By reducing their concentration and stimulating bicarbonate-rich choleresis, UDCA effectively promotes the resolution of intrahepatic cholestasis. Competitively reduces the absorption of lipophilic bile acids in the intestine, increases their “fractional” turnover during enterohepatic circulation, induces choleresis, stimulates the passage of bile and the excretion of toxic bile acids through the intestine.

Reduces the saturation of bile with cholesterol by inhibiting its absorption in the intestine, suppressing synthesis in the liver and reducing secretion into bile; promotes the gradual disintegration of cholesterol gallstones, which is achieved mainly due to the dispersion of cholesterol and the formation of liquid crystals; reduces the lithogenic index of bile, increases the concentration of bile acids in it. The result is the dissolution of cholesterol gallstones and the prevention of the formation of new stones.

Causes increased gastric and pancreatic secretion, enhances lipase activity, and has a hypoglycemic effect.

The immunomodulatory effect of UDCA is due to inhibition of the expression of histocompatibility antigens - HLA-1 - on the membranes of hepatocytes and HLA-2 - on cholangiocytes, normalization of the natural killer activity of lymphocytes, the formation of interleukin-2, a decrease in the number of eosinophils, suppression of immunocompetent immunoglobulins (Ig), primarily - IgM; regulation of apoptosis of hepatocytes and epithelial cells of the gastrointestinal tract. Delays the progression of fibrosis.

Ursosan forte tab ppo 500mg No. 100

Compound

Active substance: ursodeoxycholic acid 500 mg.

Pharmacokinetics

Following oral administration, UDCA is rapidly absorbed from the jejunum and proximal ileum by passive diffusion and from the distal ileum by active transport. Approximately 60-80% is absorbed.

With systematic use of the drug, ursodeoxycholic acid becomes the main bile acid in the blood serum. Depending on the daily dose, type of disease or liver condition, more or less UDCA accumulates in the bile. At the same time, there is a relative decrease in the content of other more lipophilic bile acids.

Metabolized in the liver (clearance during the “primary passage” through the liver is up to 60%) into taurine and glycine conjugates. The resulting conjugates are secreted into bile. About 50-70% of the total dose of the drug is excreted in the bile.

A small amount of UDCA that is not absorbed in the small intestine enters the large intestine, where it is broken down by bacteria (7-dehydroxylation) to form 7-keto-lithocholic and lithocholic acids. Lithocholic acid is hepatotoxic and causes damage to the liver parenchyma in some animal species. In humans, it is absorbed only in small quantities, sulfated in the liver into sulfolitocholylglycine or sulfolitocholyltaurine conjugate and thus detoxified before excretion into bile and excretion in feces.

The half-life of ursodeoxycholic acid is 3.5-5.8 days.

Indications for use

• uncomplicated cholelithiasis (GSD): biliary sludge; dissolution of cholesterol gallstones with a functioning gallbladder;
• chronic hepatitis of various origins (toxic, medicinal, etc.);
• cholestatic liver diseases of various origins, including primary biliary cirrhosis (in the absence of signs of decompensation), primary sclerosing cholangitis, cystic fibrosis (cystic fibrosis);
• non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis;
• alcoholic liver disease;
• biliary dyskinesia;
• biliary reflux gastritis.

Contraindications

• hypersensitivity to the active and auxiliary components of the drug;
• X-ray positive (high calcium) gallstones;
• non-functioning gallbladder;
• acute inflammatory diseases of the gallbladder, bile ducts and intestines;
• liver cirrhosis in the stage of decompensation;
• severe renal dysfunction;
• severe liver dysfunction;
• severe dysfunction of the pancreas.

Ursodeoxycholic acid has no age restrictions for use, however, it is not recommended to use the drug in this dosage form in children under 3 years of age.

Directions for use and doses

Take orally, during or after meals, without chewing, with a sufficient amount of water.

To ensure the recommended dose, the tablet should be divided in half, breaking at the score. Segments broken incorrectly should not be used. When holding the segment in the mouth, a bitter taste is felt.

To dissolve cholesterol gallstones, the average daily dose of the drug is 10 mg/kg (up to 12-15 mg/kg). The daily dose of the drug is taken once at night. The course of treatment is 6-12 months or more until the stones are completely dissolved. If gallstones do not decrease in size after 12 months of treatment, the drug should be discontinued.

To prevent re-formation of stones, it is recommended to use the drug for several months after the stones have dissolved.

To prevent recurrent cholelithiasis after cholecystectomy, prescribe 250 mg (1 capsule or 1/2 tablet) 2 times a day for several months.

For chronic hepatitis of various origins (including toxic, medicinal), chronic viral hepatitis, non-alcoholic fatty liver disease, incl. non-alcoholic steatohepatitis, alcoholic liver disease, the average daily dose is 10-15 mg/kg in 2-3 doses. The duration of therapy is 6-12 months or more.

For cholestatic liver diseases of various origins, incl. primary biliary cirrhosis (in the absence of signs of decompensation), primary sclerosing cholangitis, cystic fibrosis (cystic fibrosis), the average daily dose is 12-15 mg/kg, if necessary - 20-30 mg/kg. During the first 3 months of treatment, the daily dose of the drug should be divided into 2-3 doses. If biochemical blood parameters improve, the daily dose of the drug is taken once at night. The duration of therapy ranges from 6 months to several years.

For biliary dyskinesia, the average daily dose is 10 mg/kg in 2 divided doses for 2 weeks to 2 months. If necessary, it is recommended to repeat the course of treatment.

For biliary reflux gastritis and reflux esophagitis, the average daily dose is 250 mg (1 capsule or 1/2 tablet) 1 time at night. The course of treatment is from 2 weeks to 6 months, if necessary - up to 2 years.

Calculation of the daily amount of capsules and tablets depending on the patient’s body weight and the recommended dose of the drug per 1 kg of body weight, mg/kg/day:

Storage conditions

In a place protected from light, at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Best before date

5 years. Do not use after the expiration date.

special instructions

Taking the drug URSOSAN®FORTE should be carried out under the supervision of a doctor.

The use of the drug for the purpose of dissolving gallstones is possible subject to the following conditions: the stones must be cholesterol (X-ray negative), their size is no more than 15-20 mm, a functioning gallbladder with preserved patency of the cystic and common bile duct, no more than half filled with gallstones .

With long-term use of the drug to dissolve gallstones, a biochemical blood test should be performed every 4 weeks in the first 3 months of treatment, and every 3 months thereafter, to determine the activity of microsomal liver enzymes (transaminases, alkaline phosphatase and gamma-glutamyl transpeptidase).

Monitoring these parameters makes it possible to identify liver dysfunction in the early stages. This also applies to patients in the later stages of primary biliary cirrhosis.

In addition, it can quickly determine whether a patient with primary biliary cirrhosis is responding to treatment.

When used in patients to dissolve cholesterol gallstones.

In order to assess progress in treatment and for the timely detection of signs of calcification of stones depending on the size of the stones, the gallbladder should be visualized (oral cholecystography) with examination of opacities in the standing and supine position (ultrasound examination) after 6- 10 months after the start of treatment.

If the gallbladder cannot be visualized on x-rays or in cases of calcification of stones, weak contractility of the gallbladder or frequent attacks of colic, URSOSAN®FORTE should not be used.

When treating patients in the later stages of primary biliary cirrhosis

Cases of decompensation of liver cirrhosis have been reported extremely rarely. After cessation of therapy, regression of decompensation manifestations was noted.

In patients with primary biliary cirrhosis, in rare cases, at the beginning of treatment, clinical symptoms may increase, for example, itching may increase. In this case, the dose of the drug must be reduced to 250 mg (1/2 tablet), and then gradually increased again, as described in the “Method of administration and dosage” section.

Use in patients with primary sclerosing cholangitis

Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients with this pathology can cause serious side effects.

In patients with diarrhea, the dosage of the drug should be reduced. If diarrhea persists, treatment should be discontinued.

Women of reproductive age should take URSOSAN®FORTE while using reliable contraception. It is recommended to use non-hormonal contraceptives or oral contraceptives with low estrogen content, since hormonal oral contraceptives may increase gallstone formation. Before starting treatment, possible pregnancy should be excluded.

Description

Hepatoprotector with choleretic and cholelitholytic effects.

Dosage form

Film-coated tablets, white or almost white, biconvex, oblong in shape, scored on one side and a deep dividing line on the other side. On the break it is white or almost white.

Use in children

Children under 3 years of age are not recommended to use the drug in this dosage form.

Pharmacodynamics

A hepatoprotective agent, it also has choleretic, cholelitholytic, hypocholesterolemic and immunomodulatory effects.

Possessing high polar properties, ursodeoxycholic acid (UDCA) is embedded in the membrane of hepatocytes, cholangiocytes and epithelial cells of the gastrointestinal tract, stabilizes its structure and protects the cell from the damaging effects of toxic bile acid salts, thus reducing their cytotoxic effect.

Forms non-toxic mixed micelles with lipophilic (toxic) bile acids, which reduces the ability of gastric reflux to damage cell membranes in cholestatic liver diseases and biliary reflux gastritis.

In cholestasis, UDCA activates Ca2+-dependent alpha protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic, etc.), the concentrations of which are increased in patients with chronic liver diseases. By reducing their concentration and stimulating bicarbonate-rich choleresis, UDCA effectively promotes the resolution of intrahepatic cholestasis. Competitively reduces the absorption of lipophilic bile acids in the intestine, increases their “fractional” turnover during enterohepatic circulation, induces choleresis, stimulates the passage of bile and the excretion of toxic bile acids through the intestine.

Reduces the saturation of bile with cholesterol by inhibiting its absorption in the intestine, suppressing synthesis in the liver and reducing secretion into bile; promotes the gradual disintegration of cholesterol gallstones, which is achieved mainly through the mobilization of cholesterol from gallstones; reduces the lithogenic index of bile, increases the concentration of bile acids in it. The result is partial or complete dissolution of cholesterol gallstones.

Causes increased gastric and pancreatic secretion, enhances lipase activity, and has a hypoglycemic effect.

The immunomodulatory effect of UDCA is due to inhibition of the expression of histocompatibility antigens - HLA-1 - on the membranes of hepatocytes and HLA-2 - on cholangiocytes, normalization of the natural killer activity of T-lymphocytes, the formation of interleukin-2, a decrease in the number of eosinophils, suppression of immunocompetent immunoglobulins (Ig), firstly turn - IgM; regulation of apoptosis of hepatocytes and epithelial cells of the gastrointestinal tract. Delays the progression of fibrosis. Regulates the processes of apoptosis of hepatocytes, cholangiocytes and epithelial cells of the gastrointestinal tract.

Pediatric population

Cystic fibrosis (cystic fibrosis)

According to clinical reports, there is many years of experience (up to 10 years or more) in treating pediatric patients with cystic fibrosis-associated hepatobiliary disease (CFAHD) with ursodeoxycholic acid. There is evidence that ursodeoxycholic acid therapy can reduce bile duct proliferation, slow the development of lesions detected by histological examination, and even promote the reversal of changes in the hepatobiliary system if therapy is started in the early stages of CFAHD. To optimize treatment efficacy, ursodeoxycholic acid therapy should be initiated as soon as possible after the diagnosis of CFAHD.

Side effects

The frequency of occurrence of side effects (number of cases/number of observations) in accordance with the classification of the World Health Organization is presented in the following gradation: very often (≥ 1/10); often (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to <1/1000); very rare (< 1/10,000), frequency not established (frequency cannot be calculated from available data).

Gastrointestinal disorders:

In clinical studies, diarrhea or loose stools were frequently observed during treatment with ursodeoxycholic acid.

During the treatment of primary biliary cirrhosis, acute pain in the right upper abdomen was very rarely observed.

Disorders of the liver and biliary tract:

During treatment with ursodeoxycholic acid, calcification of gallstones has been observed in very rare cases.

In the treatment of primary biliary cirrhosis in the later stages, in very rare cases, decompensation of liver cirrhosis was observed, which regressed after discontinuation of the drug.

Disorders of the skin and subcutaneous tissues:

In very rare cases, allergic reactions, including urticaria, may occur.

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

Use during pregnancy and breastfeeding

Fertility

According to animal studies, ursodeoxycholic acid has no effect on fertility. There are no data on the effects of ursodeoxycholic acid treatment on fertility in humans.

The use of the drug by women of childbearing potential is only possible if they use reliable methods of contraception.

It is recommended to use non-hormonal contraceptives or oral contraceptives with low estrogen content, since hormonal oral contraceptives may increase gallstone formation. Before starting treatment, possible pregnancy should be excluded.

Pregnancy

There have been no adequate and strictly controlled studies of the use of ursodeoxycholic acid in pregnant women. Animal studies have shown reproductive toxicity in early pregnancy.

During pregnancy, URSOSAN®FORTE should not be used. The use of URSOSAN®FORTE during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk of side effects in the fetus or newborn.

Breast-feeding

Based on several documented case reports, the level of ursodeoxycholic acid in breast milk in women is very low and therefore adverse reactions are not expected in breastfed infants.

Interaction

• The drug should not be used simultaneously with antacids containing aluminum hydroxide or smectite (aluminum oxide), ion exchange resins (cholestyramine, colestipol), since these drugs can reduce the absorption of ursodeoxycholic acid in the intestine and, thus, reduce its absorption and effectiveness. If the use of drugs containing at least one of these substances is still necessary, they should be taken 2 hours before or 2 hours after taking URSOSAN®FORTE.
• Ursodeoxycholic acid may increase the absorption of cyclosporine from the intestine, which requires monitoring the concentration of cyclosporine in the blood plasma and, if necessary, adjusting its dosage regimen.
• In some cases, ursodeoxycholic acid may reduce the absorption of ciprofloxacin.
• In a clinical study involving healthy volunteers, simultaneous use of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) led to a slight increase in rosuvastatin plasma levels. The clinical significance of this interaction, including with other statins, is unknown.
• Ursodeoxycholic acid has been shown to reduce the maximum concentration and area under the pharmacokinetic concentration-time curve of the calcium antagonist nitrendipine. In case of concomitant use of nitrendipine and ursodeoxycholic acid, careful monitoring is recommended. The dose of nitrendipine may need to be increased. In addition, a decrease in the therapeutic effect of dapsone has been reported.
• These data, as well as in vitro data, suggest that ursodeoxycholic acid may induce CYP3A isoenzymes. However, the results of controlled clinical studies indicate that ursodeoxycholic acid does not have a significant inducing effect on the CYP3A isoenzyme.
• Some medications, such as estrogens, progestogens (oral contraceptives), neomycin, clofibrate, can increase cholelithiasis, thereby having the opposite effect of the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.

Overdose

In case of overdose, diarrhea may occur. In case of established, prolonged diarrhea, drug therapy should be discontinued. Treatment of diarrhea is symptomatic (restoration of water and electrolyte balance).

Other symptoms of overdose are unlikely because the resorption of ursodeoxycholic acid worsens as the dose increases, leading to increased excretion in the feces.

Impact on the ability to drive vehicles and operate machinery

The use of the drug URSOSAN®FORTE does not affect the performance of potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (the ability to drive vehicles, work with moving mechanisms, etc.).

Ursosan®

A hepatoprotective agent, it also has choleretic, cholelitholytic, hypocholesterolemic and immunomodulatory effects.

Possessing high polar properties, ursodeoxycholic acid (UDCA) is embedded in the membrane of hepatocytes, cholangiocytes and epithelial cells of the gastrointestinal tract, stabilizes its structure and protects the cell from the damaging effects of toxic bile acid salts, thus reducing their cytotoxic effect. Forms non-toxic mixed micelles with lipophilic (toxic) bile acids, which reduces the ability of gastric reflux to damage cell membranes in cholestatic liver diseases and biliary reflux gastritis.

In cholestasis, UDCA activates Ca2-dependent alpha protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic, etc.), the concentrations of which are increased in patients with chronic liver diseases. By reducing their concentration and stimulating bicarbonate-rich choleresis, UDCA effectively promotes the resolution of intrahepatic cholestasis. Competitively reduces the absorption of lipophilic bile acids in the intestine, increases their “fractional” turnover during enterohepatic circulation, induces choleresis, stimulates the passage of bile and the excretion of toxic bile acids through the intestine.

Reduces the saturation of bile with cholesterol by inhibiting its absorption in the intestine, suppressing synthesis in the liver and reducing secretion into bile; increases the solubility of cholesterol in bile; reduces the lithogenic index of bile, increases the concentration of bile acids in it, causes increased gastric and pancreatic secretion, enhances lipase activity, and has a hypoglycemic effect. Causes partial or complete dissolution of cholesterol gallstones, reduces the saturation of bile with cholesterol, which promotes its mobilization from gallstones. The result is the dissolution of cholesterol gallstones. The immunomodulatory effect of UDCA is due to inhibition of the expression of histocompatibility antigens - HLA-1 - on the membranes of hepatocytes and HLA-2 - on cholangiocytes, normalization of the natural killer activity of T-lymphocytes, the formation of interleukin-2, a decrease in the number of eosinophils, and suppression of immunocompetent immunoglobulins (Ig). primarily IgM.

Regulates the processes of apoptosis of hepatocytes, cholangiocytes and epithelial cells of the gastrointestinal tract. Delays the progression of fibrosis.

Pediatric population

Cystic fibrosis (cystic fibrosis)

According to clinical reports, there is many years of experience (up to 10 years or more) in treating pediatric patients with cystic fibrosis-associated hepatobiliary disease (CFAHD) with ursodeoxycholic acid. There is evidence of that. that ursodeoxycholic acid therapy can reduce bile duct proliferation, slow the progression of lesions detected by histological examination, and even promote the reversal of changes in the hepatobiliary system if therapy is started in the early stages of CFAHD. To optimize treatment efficacy, ursodeoxycholic acid therapy should be initiated as soon as possible after the diagnosis of CFAHD.