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Active ingredients
Ursodeoxycholic acid
Composition
1 caps Ursodeoxycholic acid * 250 mg. Excipients: corn starch, magnesium stearate, colloidal silicon dioxide, titanium dioxide, gelatin.
Pharmacological effect
Hepatoprotector. It also has choleretic, cholelitholytic, hypolipidemic, cholesterol-lowering and some immunomodulatory effects. Possessing high polar properties, ursodeoxycholic acid forms non-toxic mixed micelles with apolar (toxic) bile acids, which reduces the ability of gastric reflux to damage cell membranes during biliary reflux gastritis and reflux esophagitis. In addition, ursodeoxycholic acid forms double molecules that can be included in the cell membranes of hepatocytes, cholangiocytes, gastrointestinal epithelial cells, stabilize them and make them immune to the action of cytotoxic micelles. By reducing the concentration of bile acids that are toxic to hepatocytes and stimulating choleresses rich in bicarbonates, ursodeoxycholic acid effectively contributes to the resolution of intrahepatic cholestasis. 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 to bile; increases the solubility of cholesterol in bile, forming with it liquid crystals; reduces lithogenic bile index. The result is the dissolution of cholesterol gallstones and the prevention of the formation of new stones. The immunomodulatory effect is due to the inhibition of the expression of HLA-1 antigens on hepatocyte and HLA-2 membranes on cholangiocytes, normalization of lymphocyte natural killer activity, etc. reduces the risk of varicose veins of the esophagus. Ursodeoxycholic acid slows down the processes of premature aging and cell death (hepatocytes, cholangiocytes).
Pharmacokinetics
Absorption and distribution: Ursodeoxycholic acid is absorbed from the small intestine due to passive diffusion (about 90%), and in the ileum via active transport.At the same time, the concentration of ursodeoxycholic acid when taking the drug orally at a dose of 50 mg at 30, 60, 90 min is 3.8 mmol / l, 5.5 mmol / l and 3.7 mmol / l, respectively. Cmax is achieved in 1-3 hours. Plasma protein binding is high - up to 96-99%. It penetrates the placental barrier. When systematically taking Ursosan, ursodeoxycholic acid becomes the main bile acid in the blood serum and makes up 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 the bile. Metabolism and excretion: Metabolized in the liver (clearance during the initial passage through the liver) to the taurine and glycine conjugates. The resulting conjugates are secreted into the bile. About 50-70% of the total dose of the drug is excreted in the bile. An insignificant amount of non-absorbed ursodeoxycholic acid enters the colon, where it is broken down by bacteria (7-dehydroxylation); The formed lithocholic acid is partially absorbed from the colon, but is sulfated in the liver and rapidly excreted in the form of a sulfolithocholyl glycine or sulfolithocholyl taurin conjugate.
Indications
- uncomplicated cholelithiasis: biliary sludge dissolution of cholesterol gallstones in the gallbladder, if it is impossible to remove them by surgical or endoscopic methods, prevention of stone recurrence after cholecystectomy - chronic active hepatitis - acute hepatitis - toxic (including medicinal) liver damage - alcoholic liver - nonalcoholic steatohepatitis - primary biliary cirrhosis - primary sclerosing cholangitis - cystic fibrosis (cystic fibrosis) of the liver - atr intrahepatic biliary tract esia (including congenital atresia of the bile duct) - biliary tract dyskinesia - biliary reflux-gastritis and reflux esophagitis - biliary dyspeptic syndrome (with cholecystopathy and biliary duct dyskinesia) - prevention of liver lesions; .
Contraindications
- X-ray positive (high calcium) gallstones - not functioning gallbladder - cholel-gastrointestinal fistula - acute cholecystitis - acute cholangitis - liver cirrhosis in the decompensation stage - liver failure -renal failure - obturation of the biliary tract - acute infectious diseases of the gallbladder and bile ducts - empyema of the gallbladder - hypersensitivity to the drug. Ursosan is used with caution in children aged 2 to 4 years, because It may be difficult to swallow capsules, although ursodeoxycholic acid has no age limit to use.
Use during pregnancy and lactation
The use of ursodeoxycholic acid during pregnancy is possible only when the expected benefit to the mother outweighs the potential risk to the fetus (there are no adequate, strictly controlled studies of the use of ursodeoxycholic acid in pregnant women). Data on the allocation of ursodeoxycholic acid in breast milk are currently not available. If necessary, the use of ursodeoxycholic acid during lactation should decide on the termination of breastfeeding.
Dosage and administration
Ursosan capsules are taken orally, drinking plenty of water. For diffuse diseases of the liver, cholelithiasis (cholesterol gallstones and biliary sludge), the drug is prescribed continuously for a long time (from several months to several years) in a daily dose of 10 mg / kg body weight to 12-15 mg / kg (2 5 caps.). In diffuse liver diseases, the daily dose of Ursosan is divided into 2-3 doses, capsules are taken with food. In gallstone disease, the entire daily dose is taken once a night. The duration of the drug to dissolve the stones - until complete dissolution, and then another 3 months for the prevention of recurrence of stone formation. When biliary reflux gastritis and reflux esophagitis, the drug is prescribed in 250 mg (1 capsule) per day, before bedtime. The course of treatment - from 10-14 days to 6 months, if necessary - up to 2 years. After cholecystectomy, for the prevention of repeated cholelithiasis, the recommended dose is 250 mg 2 times / day for several months. With toxic, medicinal lesions of the liver, alcoholic liver disease and biliary tract atresia, the daily dose is established at the rate of 10-15 mg / kg / in 2-3 doses. The duration of therapy is 6-12 months or more. In case of primary biliary cirrhosis, the drug is prescribed at the rate of 10-15 mg / kg / day (up to 20 mg / kg if necessary) in 2-3 doses.The duration of therapy ranges from 6 months to several years. With primary sclerosing cholangitis - 12-15 mg / kg / day (up to 20 mg / kg) in 2-3 doses. The duration of therapy ranges from 6 months to several years. With non-alcoholic steatohepatitis - 13-15 mg / kg / day in 2-3 doses. The duration of therapy ranges from 6 months to several years. In cystic fibrosis, the dose is established at the rate of 20-30 mg / kg / day in 2-3 doses. The duration of therapy ranges from 6 months to several years. Children over the age of 2 years set the dose of the drug individually at the rate of 10-20 mg / kg / day.
Side effects
On the part of the digestive system: nausea, vomiting, diarrhea (can be dose-dependent), constipation, transient (transient) increased activity of hepatic transaminases; rarely, calcification of gallstones. Others: back pain, allergic reactions, exacerbation of previously existing psoriasis, alopecia; rarely - calcification of gallstones ..
Overdose
Cases of overdose with ursodeoxycholic acid are not known.
Interaction with other drugs
When used together, antacids containing aluminum and ion exchange resins (Kolestiramine) reduce the absorption of UDCA. With simultaneous use, lipid-lowering drugs (especially clofibrate), estrogens, neomycin, or progestins increase the saturation of bile with cholesterol and may decrease the ability of UDCA to dissolve cholesterol biliary stones.
special instructions
When using the drug to dissolve gallstones, the following conditions must be met: the stones must be cholesterol (X-ray negative), their size must not exceed 15-20 mm, the gallbladder must remain functional and must be filled with no more than half of the stones; common bile duct should be maintained. With prolonged (more than 1 month) administration of the drug every 4 weeks in the first 3 months of treatment, then every 3 months a biochemical blood test should be performed to determine the activity of hepatic transaminases. Monitoring the effectiveness of treatment should be carried out every 6 months according to ultrasound of the biliary tract. After complete dissolution of the stones, it is recommended to continue the use of Ursosan for at least 3 months in order to facilitate the dissolution of the remains of stones, the dimensions of which are too small to detect them and to prevent the recurrence of stone formation. In experimental animal studies, no mutagenic and carcinogenic effect of ursodeoxycholic acid was detected.