Ursosan: instructions for use for adults

Description of the dosage form

White, hard, opaque gelatin capsules. Capsule contents: white or almost white powder, or white or almost white powder with pieces of mass, or white or almost white powder, compressed in a column and disintegrating when pressed.

Pharmacokinetics

Ursodeoxycholic acid is absorbed in the small intestine by passive diffusion (about 90%), and in the ileum by active transport. Cmax is achieved after 1-3 hours and is 3.8 when taken orally 50 mg after 30, 60 and 90 minutes; 5.5 and 3.7 mmol/l, respectively. Plasma protein binding - up to 96-99%. Penetrates through the placental barrier.

With systematic use of the drug Ursosan, ursodeoxycholic acid becomes the main bile acid in the blood serum and accounts for about 48% of the total amount of bile acids in the blood. The therapeutic effect of the drug depends on the concentration of ursodeoxycholic acid in bile.

Metabolized in the liver into taurine and glycine conjugates, which are secreted into bile. About 50-70% of the total dose is excreted in bile. A small amount of unabsorbed ursodeoxycholic acid enters the large intestine, where it is broken down by bacteria (7-dehydroxylation); the resulting lithocholic acid is partially absorbed from the colon, sulfated in the liver and quickly excreted in the form of sulfolithocholylglycine or sulfolitocholyltaurine conjugate.

Pharmacodynamics

Possessing high polarity, ursodeoxycholic acid forms non-toxic mixed micelles with apolar (toxic) bile acids, which reduces the ability of gastric refluxate to damage cell membranes in biliary reflux gastritis and reflux esophagitis. In addition, ursodeoxycholic acid forms double molecules that can be included in cell membranes (hepatocytes, cholangiocytes, epithelial cells of the gastrointestinal tract), stabilize them and make them immune to the action of cytotoxic micelles - a cytoprotective, hepatoprotective effect.

By reducing the concentration of bile acids toxic to the liver cell and stimulating choleresis with a high content of bicarbonates, ursodeoxycholic acid helps resolve intrahepatic cholestasis - an anticholestatic effect. Reduces the saturation of bile with cholesterol by inhibiting its absorption in the intestine, suppressing synthesis in the liver and reducing secretion into bile - a hypocholesterolemic effect. Increases the solubility of cholesterol in bile, forming liquid crystals with it; reduces the lithogenic index of bile.

The result is the dissolution of cholesterol gallstones and the prevention of the formation of new stones - the litholytic effect. The immunomodulatory effect is due to inhibition of the expression of HLA-1 antigens on the membranes of hepatocytes and HLA-2 on cholangiocytes, normalization of the natural killer activity of lymphocytes, etc. Significantly delays the progression of fibrosis in patients with primary biliary cirrhosis, cystic fibrosis and alcoholic steatohepatitis - antifibrotic effect; reduces the risk of developing varicose veins of the esophagus. Ursodeoxycholic acid regulates the processes of apoptosis (aging and cell death) that are disrupted in the pathology of the liver and other organs - an anti-apoptotic effect.

Ursosan forte 500 mg 50 pcs. film-coated tablets

pharmachologic effect

Hepatoprotective agent.

Composition and release form Ursosan forte 500 mg 50 pcs. film-coated tablets

Tablets - 1 tablet:

Active substance: Ursodeoxycholic acid - 500.00 mg;
Excipients (core): Corn starch; Pregelatinized corn starch; Sodium carboxymethyl starch (type A); Colloidal silicon dioxide; Magnesium stearate;
Excipients (shell): Opadry white 03B28796; Containing hypromellose 6; Titanium dioxide; Macrogol 400.

Film-coated tablets, 500 mg. 10 tablets per blister pack (blister) made of PVC/PVDC/aluminum foil. 1, 5 or 10 blister packs (blisters) together with instructions for use are placed in a cardboard box.

Description of the 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.

Directions for use and doses

Orally, during or after meals, without chewing, with plenty of water.

To ensure the recommended dosage, 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 body weight, which corresponds to:

Body weight (kg)	Daily dose (tablets)
up to 60	1 table
61-80	1½ tab.
81-100	2 tables
more than 100	2½ tab.

During the first 3 months of treatment, the daily dose should be divided into several doses. It usually takes 6-24 months for gallstones to dissolve. If after 12 months of treatment the size of the stones does not decrease, then treatment should be stopped.

The effectiveness of treatment should be assessed every 6 months with ultrasound or radiography. During the interim examination, it is necessary to assess whether calcification of the stones has occurred during the intervening period. In case of calcification of stones, treatment should be discontinued.

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

For chronic hepatitis of various origins (toxic, medicinal, etc.), non-alcoholic fatty liver disease, including 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, including primary biliary cirrhosis (in the absence of signs of decompensation), the daily dose depends on body weight and ranges from 1 ½ to 3 ½ tablets (14 ± 2 mg UDCA per 1 kg of body weight). During the first three months of treatment, the intake of URSOSAN® FORTE tablets should be distributed throughout the day. If liver test values improve, the daily dose can be taken once a day in the evening.

Body weight (kg)	Daily dose (mg/kg body weight)	Single dose (tablets), 500 mg
		first 3 months			in the future
		morning	day	evening	evening (single dose)
47-62	12-16	½ tab.	½ tab.	½ tab.	1½ tab.
63-78	13-16	½ tab.	½ tab.	1 table	2 tables
79-93	13-16	½ tab.	1 table	1 table	2½ tab.
94-109	14-16	1 table	1 table	1 table	3 tables
>110	—	1 table	1 table	1½ tab.	3½ tab.

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.

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 the human body, 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 Ursosan forte 500 mg 50 pcs. film-coated tablets

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

X-ray positive (high calcium) gallstones;
Impaired contractility of the gallbladder;
Acute inflammatory diseases of the gallbladder and bile ducts;
Occlusion of the biliary tract (occlusion of the common bile or cystic duct);
Frequent episodes of biliary colic;
Liver cirrhosis in the stage of decompensation;
Severe liver and/or renal failure;
Hypersensitivity to the active and auxiliary components of the drug or other bile acids.

Pediatric population

Unsuccessfully performed portoenterostomy or cases of failure to restore normal bile flow in children with biliary atresia.

Ursodeoxycholic acid has no age restrictions for use, however, children under 3 years of age are not recommended to use the drug in this dosage form. It is also not recommended for those who have problems swallowing tablets.

Application of Ursosan forte 500 mg 50 pcs. film-coated tablets 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.

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 ducts, 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.

Impact on the ability to drive vehicles and moving 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.).

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.

Side effects Ursosan forte 500 mg 50 pcs. film-coated tablets

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

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.

Drug interactions

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.

Indications for use of Ursosan

Ursosan is prescribed if:

uncomplicated cholelithiasis: biliary sludge;
dissolution of cholesterol gallstones in the gallbladder if it is impossible to remove them surgically or endoscopically; prevention of recurrent stone formation after cholecystectomy;
chronic active hepatitis;
acute hepatitis;
toxic (including medicinal) liver damage;
alcoholic liver disease;
non-alcoholic steatohepatitis;
primary biliary cirrhosis of the liver;
primary sclerosing cholangitis;
cystic fibrosis of the liver (cystic fibrosis);
atresia of the intrahepatic biliary tract, congenital atresia of the bile duct;
biliary dyskinesia;
biliary reflux gastritis and reflux esophagitis;
biliary dyspeptic syndrome (with cholecystopathy and biliary dyskinesia);
prevention of liver damage when using hormonal contraceptives and cytostatics.

Contraindications for use

hypersensitivity;
X-ray positive (high calcium) gallstones;
non-functioning gallbladder;
bile-gastrointestinal fistula;
acute cholecystitis;
acute cholangitis;
liver cirrhosis in the stage of decompensation;
liver and/or kidney failure;
obstruction of the biliary tract;
acute infectious diseases of the gallbladder and bile ducts;
empyema of the gallbladder.

Although Ursosan has no age restrictions for use, the drug capsules are used with caution in children aged 2 to 4 years due to possible difficulty in swallowing them.

Ursosan dosage

Ursosan is taken orally with a sufficient amount of water.

Diffuse liver diseases, cholelithiasis (cholesterol gallstones and biliary sludge) - continuously for a long time (from several months to several years) in a daily dose of 10 to 12-15 mg/kg (2-5 caps.). For diffuse liver diseases, the daily dose of Ursosan is divided into 2-3 doses, the capsules are taken with food. For cholelithiasis, the entire daily dose of Ursosan is taken once at night. The duration of treatment for dissolving stones is until complete dissolution, plus another 3 months. for the prevention of recurrent stone formation.
For biliary reflux gastritis and reflux esophagitis, Ursosan is taken 250 mg/day (1 capsule) before bedtime. The course of treatment is from 10–14 days to 6 months, if necessary – up to 2 years.
After cholecystectomy, to prevent recurrent cholelithiasis, Ursosan is used at a dose of 250 mg 2 times a day for several months.
Toxic, drug-induced liver damage, alcoholic liver disease and biliary atresia - 10-15 mg/kg/day in 2-3 doses. Duration of therapy is 6–12 months. and more.
Primary biliary cirrhosis - 10-15 mg/kg/day (if necessary - up to 20 mg/kg) in 2-3 doses. The duration of therapy is from 6 months. up to several years.
Primary sclerosing cholangitis - 12–15 mg/kg/day (up to 20 mg/kg) in 2–3 doses. The duration of therapy is from 6 months. up to several years.
Non-alcoholic steatohepatitis - 13-15 mg/kg/day in 2-3 doses. The duration of therapy is from 6 months. up to several years.
Cystic fibrosis - 20-30 mg/kg in 2-3 doses. The duration of therapy is from 6 months. up to several years or for life.

For children over 2 years of age, Ursosan is prescribed individually at a dose of 10–20 mg/kg/day.

Ursosan capsules 250 mg No. 100

Compound

Active substance: ursodeoxycholic acid 250 mg.
Excipients: corn starch, pregelatinized corn starch, colloidal silicon dioxide, magnesium stearate.

Capsule shell composition: gelatin, titanium dioxide.

Pharmacokinetics

Suction and distribution

UDCA is absorbed in the jejunum and upper ileum by passive diffusion (about 90%), and in the terminal ileum by active transport. The resorption rate is usually 60-80%.

When 50 mg of UDCA is taken orally, Cmax after 30, 60, 90 minutes is 3.8 mmol/L, 5.5 mmol/L and 3.7 mmol/L, respectively. The time to reach Cmax is 1-3 hours. Plasma protein binding is high - up to 96-99%. Penetrates through the placental barrier.

When taking the drug systematically, UDCA becomes the main bile acid in the blood serum.

Metabolism and excretion

Metabolized in the liver (first-pass clearance 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); the resulting lithocholic acid is partially absorbed from the colon, sulfated in the liver and quickly excreted in the bile in the form of sulfolitocholylglycine or sulfolitocholyltaurine conjugate.

Indications for use

Uncomplicated cholelithiasis: biliary sludge; dissolution of cholesterol gallstones with a functioning gallbladder; prevention of recurrent stone formation after cholecystectomy;
chronic hepatitis of various origins (including toxic, medicinal);
cholestatic liver diseases of various origins, incl. primary biliary cirrhosis (in the absence of signs of decompensation), primary sclerosing cholangitis, cystic fibrosis (cystic fibrosis);
non-alcoholic fatty liver disease, incl. non-alcoholic steatohepatitis;
alcoholic liver disease;
chronic viral hepatitis;
biliary dyskinesia;
biliary reflux gastritis and reflux esophagitis.

Contraindications

Hypersensitivity to ursodeoxycholic acid;
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 dissolve cholesterol gallstones, the average daily dose is 10 mg/kg (up to 12-15 mg/kg). The daily dose 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, ursodeoxycholic acid should be discontinued.

To prevent re-formation of stones, it is recommended to use it 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 should be divided into 2-3 doses. If biochemical blood parameters improve, the daily dose 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.

Storage conditions

In a place protected from light at a temperature not exceeding 25 °C. Keep out of the reach of children.

Best before date

4 years. Do not use after the expiration date.

special instructions

Ursosan® should be taken under the supervision of a physician.

When taking the drug to dissolve gallstones, the following conditions must be met: the stones must be cholesterol (X-ray negative), their size should not exceed 15-20 mm. The gallbladder must remain functional and must be no more than half filled with gallstones, and the patency of the cystic and common bile ducts must be preserved.

With long-term (more than 1 month) use of the drug to dissolve gallstones, every 4 weeks in the first 3 months of treatment, and then every 3 months, a biochemical blood test should be performed to determine the activity of microsomal liver enzymes (transaminases, alkaline phosphatase and gamma-phosphatase). glutamyl transpeptidase).

The effectiveness of treatment is monitored every 6 months according to ultrasound examination of the gallbladder and biliary tract. 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, poor contractility of the gallbladder or frequent attacks of colic, Ursosan® should not be used.

Patients taking Ursosan® to dissolve gallstones must use effective non-hormonal methods of contraception, since hormonal contraceptives can increase stone formation in the gall bladder (see sections “Interaction with other drugs” and “Use during pregnancy and breastfeeding”) .

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, a partial reversal of decompensation was observed.

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 and then gradually increased again, as described in the “Method of administration and dosage” section.

When used 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.

Description

Hepatoprotector with choleretic and cholelitholytic effects.

Use in children

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.

Pharmacodynamics

Hepatoprotector. It 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 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 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.

Side effects

Determination of the frequency of side effects (number of cases/number of observations): very often (≥1/10); often (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000), frequency cannot be calculated from available data.

From the digestive system: in clinical studies, diarrhea or pasty stools were often observed during treatment with ursodeoxycholic acid. In the treatment of primary biliary cirrhosis, severe pain in the upper abdomen has been very rarely reported.

From the liver and biliary tract: during treatment with ursodeoxycholic acid, in very rare cases, calcification of gallstones was observed. When treating primary biliary cirrhosis in the later stages, in very rare cases decompensation of liver cirrhosis was observed, which regressed after cessation of treatment.

From the skin and subcutaneous tissues: in very rare cases, urticaria may occur.

Use during pregnancy and breastfeeding

The use of ursodeoxycholic acid during pregnancy is possible only when the expected benefit to the mother outweighs the potential risk to the fetus or newborn (there have been no adequate, strictly controlled studies of the use of ursodeoxycholic acid in pregnant women).

Women of reproductive age should take ursodeoxycholic acid while using reliable contraception. Before starting treatment, pregnancy should be excluded.

There are no data on the excretion of ursodeoxycholic acid in breast milk. If it is necessary to use ursodeoxycholic acid during lactation, breastfeeding should be stopped.

Interaction

The drug should not be used simultaneously with antacids containing aluminum hydroxide or smectite (aluminum oxide) and ion exchange resins (colestyramine, colestipol), since these drugs may reduce the absorption of ursodeoxycholic acid in the intestine. thus reducing 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®.

In some cases, ursodeoxycholic acid may reduce the absorption of ciprofloxacin.

In healthy volunteers, ursodeoxycholic acid has been shown to reduce the maximum concentration and area under the pharmacokinetic concentration-time curve (AUC) of the slow calcium channel blocker nitrendipine. In case of concomitant use of nitrendipine and ursodeoxycholic acid, careful monitoring is recommended. The dose of nitrendipine may need to be increased. There are also reports of a decrease in the therapeutic effect of dapsone. This information, as well as data obtained in vitro, gives reason to believe that ursodeoxycholic acid is capable of inducing enzymes of the cytochrome P450 3A system. However, the results of controlled clinical studies of interaction with budesonide. which is a known substrate of cytochrome P450 3A, indicate that ursodeoxycholic acid does not have a pronounced inducing effect on enzymes of the cytochrome P450 3A system.

Some drugs, such as estrogens, progestogens (oral contraceptives), neomycin, lipid-lowering drugs (clofibrate), increase the secretion of cholesterol in the liver and the saturation of bile with cholesterol, and can stimulate the formation of gallstones, which neutralizes the effect of ursodeoxycholic acid, which is used to dissolve gallstones.

Overdose

Other symptoms of overdose are unlikely. since 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® 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.).