Ursosan - instructions for use, dose, side effects, contraindications

The tablets covered with a film membrane, white or almost white, biconvex, oblong, with a notch on one side and a deep dividing risk on the other. On the fracture is white or almost white.

Pharmacotherapeutic group:Hepatoprotective agent

ATX: & nbsp

A.05.A.A Preparations of bile acids

Pharmacodynamics:

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

With cholestasis, UDCA activates Ca²⁺atfa -dependent protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic et al.) whose concentrations in patients with chronic liver disease increased. Reducing their concentration and stimulating cholepoiesis rich bicarbonates, UDCA effectively facilitates resolving intrahepatic cholestasis. Competitive reduces the absorption of lipophilic bile acids in the intestine, increases their "Fractional" turnover under enterohepatic circulation cholepoiesis induces, promotes the passage of bile and excretion of toxic bile acids across the gut.

Reduces the saturation of bile with cholesterol due to inhibition of its absorption in the intestine, suppression of synthesis in the liver and a decrease in secretion in 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 concrements.

It causes an increase in gastric and pancreatic secretion, increases lipase activity, and has a hypoglycemic effect.

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

Pharmacokinetics:

UDCA is absorbed in the jejunum and upper parts of the ileum due to passive diffusion (about 90%), and in the terminal sections of the ileum - through active transport. The resorption index is usually 60-80%.

When ingestion 50 mg UDCA the maximum concentration in the blood plasma (C_m_Oh) after 30, 60, 90 minutes is 3.8 mmol / L, 5.5 mmol / L and 3.7 mmol / L, respectively. Time to reach the maximum concentration in the plasma (T_Cm_Oh) comes in 1-3 hours. The connection with plasma proteins is high - up to 96-99%. Penetrates through the placental barrier.

With the systematic administration of the drug UDCA becomes the main bile acid in the blood serum. Metabolized in the liver (clearance for "primary passage" through the liver is up to 60%) into taurine and glycine conjugates. The resulting conjugates are secreted in bile. About 50-70% of the total dose of the drug is excreted with bile. A small amount of UDCA that is not absorbed in the small intestine enters the large intestine, where it undergoes cleavage by bacteria (7-dehydroxylation); the resulting lithocholic acid is partially absorbed from the colon, sulphated in the liver and rapidly excreted with bile in the form of a sulfolithocholylglycine or sulfolithocholyltaurine conjugate.

Indications:

- Uncomplicated cholelithiasis (SCI): biliary sludge; dissolution of cholesterol gallstones with a functioning gallbladder; prevention of recurrence of stone formation after cholecystectomy;

- chronic hepatitis of various genesis (toxic, medicinal, etc.);

- Cholestatic diseases of the liver of various genesis, 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;

- chronic viral hepatitis;

- biliary dyskinesia;

- biliary reflux gastritis and reflux esophagitis.

Contraindications:

- Hypersensitivity to the active and auxiliary components of the drug;

- X-ray positive (high in calcium) gallstones;

- non-functioning gallbladder;

- acute inflammatory diseases of the gallbladder, bile ducts and intestines;

- cirrhosis of the liver in the stage of decompensation;

- marked violations of the kidneys, liver, pancreas.

Ursodeoxycholic acid has no age limitation in use, but children under 3 years of age are not recommended to use the drug in this dosage form.

Pregnancy and lactation:

The use of UDCA during pregnancy is possible only if the expected benefit for the mother exceeds the potential risk of side effects in the fetus or newborn (adequate and strictly controlled studies of the use of ursodeoxycholic acid in pregnant women have not been conducted).

Data on the isolation of ursodeoxycholic acid with breast milk are absent. If UDCA is necessary during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, during or after a meal, without chewing, squeezed with enough water. To ensure the recommended dosage, the tablet should be divided in half, breaking up the risk. Segments broken incorrectly should not be used. When the segment is held in the oral cavity, a bitter taste is felt.

To dissolve cholesteric 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 for the night.The course of treatment is 6-12 months and more until the stones are completely dissolved. If the stones in the gall bladder do not decrease in size after 12 months of treatment, the drug should be discontinued.

To prevent the re-formation of stones, the use of the drug is recommended for several months after the dissolution of the stones.

For prevention of recurrent cholelithiasis after cholecystectomy, 250 mg (1/2 tablets) 2 times a day for several months.

With chronic hepatitis of various genesis (toxic, medicinal, etc.), chronic viral hepatitis, non-alcoholic fatty liver disease, including nonalcoholic 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.

With cholestatic liver diseases of various origins, including 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.In case of improvement of biochemical parameters of blood, the daily dose of the drug is taken once for the night. The duration of therapy is from 6 months to several years.

With dyskinesia biliary tract the average daily dose is 10 mg / kg in 2 divided doses for 2 weeks to 2 months. If necessary, the course of treatment is recommended to be repeated.

With biliary reflux gastritis and reflux esophagitis the average daily dose is 250 mg (14 tablets) once a night. The course of treatment is from 2 weeks to 6 months, if necessary - up to 2 years.

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

Body weight, kg	10 mg / kg / day	12 mg / kg / day	15 mg / kg / day	20 mg / kg / day	30 mg / kg / day
1	2	3	4	5	6
19-25	1/2 Table.	1/2 Table.	1 tab.	1 tab.	1 1/2 Table.
26-30	1/2 Table.	1/2 Table.	1 tab.	1 tab.	1 1/2 Table.
31-35	1/2 Table.	1 tab.	1 tab.	1 1/2 Table.	2 tab.
36-40	1 tab.	1 tab.	1 tab.	1 1/2 Table.	2 1/2 Table.
41-45	1 tab.	1 tab.	1 1/2 Table.	2 tab.	2 14 tab.
45-50	1 tab.	1 tab.	1 1/2 Table.	2 tab.	3 tab.
51-55	1 tab.	1 1/2 Table.	1 1/2 Table.	2 tab.	3 1/2 Table.
56-60	1 tab.	1 1/2 Table.	2 tab.	2 1/2 Table.	3 1/2 Table.
61-65	1 1/2 Table.	1 1/2 Table.	2 tab.	2 1/2 Table.	4 tab.
66-70	1 1/2 Table.	1 1/2 Table.	2 tab.	3 tab.	4 tab.
71-75	1 1/2 Table.	2 tab.	2 14 tab.	3 tab.	4 1/2 Table.
76-80	1 1/2 Table.	2 tab.	2 14 tab.	3 tab.	5 tab.
81-85	1 1/2 Table.	2 tab.	2 1/2 Table.	3 1/2 Table.	5 tab.
86-90	2 tab.	2 tab.	2 1/2 Table.	3 1/2 Table.	5 1/2 Table.
91-95	2 tab.	2 1/2 Table.	3 tab.	4 tab.	5 1/2 Table.
96-100	2 tab.	2 1/2 Table.	3 tab.	4 tab.	6 tab.
101-105	2 tab.	2 1/2 Table.	3 tab.	4 tab.	6 1/2 Table.
105-110	2 tab.	2 1/2 Table.	3 1/2 Table.	4 1/2 Table.	6 1/2 Table.

Side effects:

Frequency of occurrence of side effects (number of cases / number of observations) is presented in the following gradation: very often (≥ 1/10); often (≥ 1/100 to <1/10); infrequently (≥ 1/1000 to <1/100); rarely (≥ 1/10000 to <1/1000); very rarely (<1/10 000), the frequency can not be calculated from the available data.

From the gastrointestinal tract

In clinical studies, against the backdrop of treatment with ursodeoxycholic acid, diarrhea or pasty stools were often observed.

In the treatment of primary biliary cirrhosis, very rarely there was severe pain in the upper abdomen.

From the liver and biliary tract

On a background of treatment with ursodeoxycholic acid in very rare cases, calcification of gallstones was observed.

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

From the skin and subcutaneous tissues

In very rare cases, hives can be observed.

Overdose:

In case of an overdose, diarrhea may occur.With established long-term diarrhea, the drug should be discontinued. Treatment is symptomatic.

Other symptoms of an overdose are unlikely, since resorption of ursodeoxycholic acid worsens as the dose increases, which leads to increased excretion with feces.

Interaction:

Do not use the drug simultaneously with antacids containing aluminum, ion exchange resins (cholestyramine, colestipol), since these drugs can reduce the absorption of ursodeoxycholic acid. If necessary, these drugs should be taken 2 hours before or 2 hours after taking UDCA.

Some medications, such as estrogens, progestogens (oral contraceptives), neomycin, clofibrate, can increase cholelithiasis, thus having the opposite effect of the ability of ursodeoxycholic acid to dissolve cholesterol bile calculi.

Ursodeoxycholic acid can increase the absorption of cyclosporine from the intestine, which requires monitoring the concentration of cyclosporine in the blood plasma, and, if necessary, correcting its dosage regimen.

In some cases ursodeoxycholic acid can reduce the absorption of ciprofloxacin.

Special instructions:

The use of the drug for the purpose of dissolution of gallstones is possible if the following conditions are met: the stones should be cholesterol (X-ray negative), their size - no more than 15-20 mm, the functioning gallbladder with the preserved permeability of the vesicle and common bile duct, is filled with gallstones no more than half .

With prolonged use of the drug to dissolve gallstones every 4 weeks in the first 3 months of treatment, further - every 3 months, a biochemical blood test should be performed to determine the activity of microsomal liver enzymes, especially transaminases. Control of the effectiveness of treatment is carried out every 6 months according to ultrasound examination of the gallbladder, bile ducts.

After completely dissolving the stones, it is recommended to continue the use of the drug for 3 months in order to facilitate the dissolution of stone remains that are too small to detect and to prevent the recurrence of stone formation.

Women of reproductive age should take the drug Ursosan while using reliable contraceptives.Before starting treatment, pregnancy should be excluded.

Effect on the ability to drive transp. cf. and fur:

The use of Ursosan does not affect the performance of potentially hazardous activities requiring increased concentration and speed of psychomotor reactions (ability to drive vehicles, work with moving mechanisms, etc.).

Form release / dosage:Tablets, film-coated, 500 mg.

Packaging:

For 10 tablets in a contour mesh package (blister) made of PVC / PVDC / aluminum foil. For 1, 5 or 10 contour squares (blisters) together with the instruction for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years. Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LP-003388

Date of registration:28.12.2015

Expiration Date:28.12.2020

The owner of the registration certificate:PRO.MED.CS Prague as.PRO.MED.CS Prague as. Czech Republic

Manufacturer: & nbsp

PRO.MED.CS Praha, a.s. Czech Republic

Representation: & nbspPRO.MED.CS Prague as. PRO.MED.CS Prague as. Czech Republic

Information update date: & nbsp13.07.2016

Illustrated instructions

Instructions

Ursosan® (Ursosan®)