Ursodeoxycholic acid - instructions for use, dose, side effects, contraindications

Composition:Active substance:
Ursodeoxycholic acid 250.00 mg
Excipients:
Corn starch 72.80 mg
Silicon dioxide colloidal anhydrous 1.60 mg
Magnesium stearate 0.60 mg
Capsule shell:
Titanium dioxide (E171) 1.92 mg
Gelatin 94.08 mg

Description:Hard gelatin capsules No. 0, body and cap of white color. The contents of the capsules are white powder.

Pharmacotherapeutic group:Hepatoprotective agent

ATX: & nbsp

A.05.A.A Preparations of bile acids

Pharmacodynamics:Hepatoprotective agent also has choleretic, cholelitholytic, hypolipidemic 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 with biliary reflux gastritis and reflux esophagitis. Besides, ursodeoxycholic acid forms double molecules,able to be included in the composition of cell membranes (hepatocytes cholangiocytes, epithelial cells of the GI tract), stabilize them and make impervious to the action of cytotoxic micelles. Reducing the concentration of toxic for the hepatic cell bile acids and stimulating choleresis, rich in bicarbonates, ursodeoxycholic acid effectively promotes 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 in bile; increases the solubility of cholesterol in bile, forming with it liquid crystals; reduces the lithogenic bile index. The result is the dissolution of cholesterol gallstones and the prevention of the formation of new concrements.
The immunostimulating effect is due to inhibition of HLA-1 antigens expressed on the membranes of hepatocytes and HLA-2 cholangiocytes, normalizing activity of natural killer lymphocytes and others. Reliably delaying the progression of fibrosis in patients with primary biliary cirrhosis, cystic fibrosis, and alcoholic steatohepatitis. reduces the risk of developing varicose veins of the esophagus .. Ursodeoxycholic acid slows down the processes of premature aging and cell death (hepatocytes, cholangiocytes, etc.).

Pharmacokinetics:Ursodeoxycholic acid absorbed in the small intestine due to passive diffusion (about 90%), and in the ileum through active transport. The maximum concentration in the blood plasma (C_max) with oral administration of 50 mg after 30, 60, 90 min -3.8 mmol / l, 5.5 mmol / l and 3.7 mmol / l, respectively. C_max is achieved in 1-3 hours. The connection with plasma proteins is high - up to 96-99%. Penetrates through the placental barrier. With systematic admission ursodeoxycholic acid becomes the main bile acid in the 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 the bile.
Metabolised in the liver (clearance during primary passage through the liver) into taurine and glycine conjugates. The resulting conjugates are secreted in bile. About 50-70% of the total dose of the drug is excreted by bile. A small amount of non-absorbed ursodeoxycholic acid enters the large intestine, where it undergoes cleavage by bacteria (7-dehydroxylation); the resulting lithocholic acid is partially absorbed from the colon,but sulfated in the liver and rapidly excreted as a sulfolithocholylglycine and sulfolitocholyltaurine conjugate.

Indications:- uncomplicated cholelithiasis (biliary sludge, dissolution of cholesterol gallstones in the gallbladder with a functioning gallbladder, prevention of recurrence of stone formation after cholecystectomy);
- chronic hepatitis of various genesis;
- toxic (including medicinal) liver damage;
- alcoholic liver disease;
- non-alcoholic steatohepatitis;
- primary biliary cirrhosis of the liver;
- primary sclerosing cholangitis;
- cystic fibrosis;
- biliary dyskinesia;
- Biliary reflux-gastritis and reflux-esophagitis.

Contraindications:hypersensitivity;
- X-ray positive (high in calcium) gallstones;
- non-functioning gallbladder;
- a bile-gastric fistula;
- Acute cholecystitis;
- Acute cholangitis;
- cirrhosis of the liver in the stage of decompensation;
- acute infectious diseases of the gallbladder, bile ducts and intestines;
- marked hepatic and / or renal insufficiency;
- Obstruction of the biliary tract;
- Empyema of the gallbladder;
- Children's age up to 3 years.

Carefully:Although ursodeoxycholic acid has no age restrictions in the use, with caution apply the drug in children aged 3 to 4 years, t. possible difficulty in swallowing capsules.

Pregnancy and lactation:Women of childbearing age are advised to use non-hormonal contraceptives during the period of drug use. The use of ursodeoxycholic acid in pregnancy is possible only if the expected benefit for the mother exceeds the potential risk to the fetus. Data on the isolation of ursodeoxycholic acid with breast milk are currently not available. If it is necessary to use ursodeoxycholic acid during lactation, the question of stopping breastfeeding should be solved.

Dosing and Administration:Inside, not liquid, squeezed enough water.
With diffuse liver diseases, cholelithiasis (cholesterol gallstones and biliary sludge): in a daily dose of 10 mg / kg body weight to 12-15 mg / kg body weight (2-5 capsules) continuously for a long time (from several months to several years).With diffuse liver disease, the daily dose of the drug is divided into 2-3 doses, the capsules are taken with food. With cholelithiasis, the whole daily intake is taken once for the night. Duration of taking the drug to dissolve the stones - until complete dissolution, plus another 3 months. for the prevention of recurrence of stone formation.
To dissolve cholesterol gallstones, the recommended dose of ursodeoxycholic acid is 10 mg per 1 kg of body weight per day, which corresponds to:

Body mass	Daily dose
Up to 60 kg	500 mg (2 capsules)
61-80 kg	750 mg (3 capsules)
81-100 kg	1000 mg (4 capsules)
Over 100 kg	1250 mg (5 capsules)

With biliary reflux gastritis and reflux esophagitis: 250 mg (1 capsule) per day, before bedtime. The course of treatment is from 10-14 days to 6 months, if necessary up to 2 years.
With cholecystectomy, for the prevention of recurrent cholelithiasis, the recommended dose is -250 mg 2 times a day for several months.
With toxic, medicinal liver damage, alcoholic liver disease and atresia of the biliary tract: daily dose of 10-15 mg / kg of body weight in 2-3 divided doses. The course of treatment is 6-12 months. and more.
In primary biliary cirrhosis: at 10-15 mg / kg / day (if necessary up to 20 mg / kg) in 2-3 hours. The course of treatment - from 6 months. up to several years.
The following dosing regimen is recommended:

Body mass	Daily dose	In the morning	In the afternoon	In the evening
47-62 kg	750 mg (3 capsules)	1 capsule	1 capsule	1 capsule
63-78 kg	1000 mg (4 capsules)	1 capsule	1 capsule	2 capsules
79-93 kg	1250 mg (5 capsules)	1 capsule	2 capsules	2 capsules
94-109 kg	1500 mg (6 capsules)	2 capsules	2 capsules	2 capsules
Over 100 kg	1750 mg (7 capsules)	2 capsules	2 capsules	3 capsules

With the primary sclerosing cholangitis: at 12-15 mg / kg / day (up to 20 mg / kg) in 2-3 divided doses. The course of treatment - from 6 months. up to several years.
With non-alcoholic steatohepatitis: at 13-15 mg / kg / day in 2-3 divided doses. The course of treatment - from 6 months. up to several years.
In cystic fibrosis: on 20-30 mg / kg / day in 2-3 reception. The course of treatment - from 6 months. up to several years.
For children over the age of 3, the drug is prescribed individually at a rate of 10-20 mg / kg / day.

Side effects:Pain in the back, epigastric region and right hypochondrium, nausea, vomiting, diarrhea (can be dose-dependent), constipation, transient (transient) increase in the activity of "liver" transaminases, allergic reactions, rarely (> 0.01% and <0.1% ) -caling of gallstones, exacerbation of previously existing psoriasis, alopecia.

Overdose:Cases of an overdose have not been revealed. In case of an overdose, symptomatic treatment is performed.

Interaction:Kolestimarin, colestipol and antacids, containing aluminum hydroxide or aluminum oxide, reduce the absorption of ursodeoxycholic acid in the intestine and, thus, reduce its absorption and efficacy. If the use of drugs containing at least one of these substances is nevertheless necessary, they should be taken at least 2 hours prior to taking ursodeoxycholic acid.
Ursodeoxycholic acid can increase the absorption of cyclosporine from the intestine. Therefore, in patients receiving ciclosporin, the doctor should check the concentration of cyclosporine in the blood and adjust the dose of cyclosporine, if necessary.
In some cases ursodeoxycholic acid can reduce the absorption of ciprofloxacin.
Lipid-lowering drugs (especially clofibrate), estrogens, neomycin and progestins increase bile saturation with cholesterol and may reduce the ability to dissolve cholesterol bile stones.

Special instructions:To successfully dissolve it is necessary that the stones are pure cholesterol, with a size not exceeding 15-20 mm, the gallbladder is filled with stones no more than half and the bile ducts fully retained their function.
At the appointment with the purpose of dissolution of gallstones, it is necessary to control the activity of "liver" transaminases and alkaline phosphatase, y-glutamine transferase, bilirubin concentration. Cholecystography should be performed every 4 weeks in the first 3 months. treatment, in the future - every 3 months. Monitor the effectiveness of treatment every 6 months. during ultrasound during the first year of therapy.
If the increased indices remain, the drug should be discontinued. After complete dissolution of the calculus, it is recommended to continue use for at least 3 months, in order to facilitate the dissolution of stone residues, the size of which is too small to detect and to prevent the recurrence of stone formation. If within 6-12 months. After the beginning of therapy of partial dissolution of concrements did not occur, it is unlikely that the treatment will be effective. Detection during treatment of a non-visualizable gallbladder is evidence that no complete dissolution of the calculi has occurred, and treatment should be discontinued.

Effect on the ability to drive transp. cf. and fur:There is no evidence of the influence of ursodeoxycholic acid on the ability to drive vehicles and work withmechanisms.

Form release / dosage:Capsules 250 mg.

Packaging:10 capsules in a planar cell package. By 1, 2, 3, 5 or 10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:5 years. Do not use the drug after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003465

Date of registration:17.02.2016

Expiration Date:17.06.2021

The owner of the registration certificate:OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC Russia

Manufacturer: & nbsp

OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC Russia

Information update date: & nbsp04.12.2016

Illustrated instructions

Instructions

Ursodeoxycholic acid (Ursodesoxycholic acid)