Composition, form of production and packaging
Capsules hard gelatinous, в„–00, with a white case and a pink lid; the contents of the capsules are a granular powder of white or almost white color.
1 caps.
ursodeoxycholic acid 250 mg
Excipients: lactulose - 300 mg, povidone low molecular weight K17 - 7.5 mg, magnesium stearate - 4.5 mg, talc - 6 mg, cellulose microcrystalline - until the contents of the capsule weighing 600 mg.
The composition of the capsule body: titanium dioxide - 2%, gelatin - up to 100%.
Composition of capsule cap: dye azorubin (E122) - 0.05%, titanium dioxide - 1%, gelatin - up to 100%.
10 pieces. - packings of cellular contour (1) - packs cardboard.
10 pieces. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (5) - packs cardboard.
10 pieces. - packings cellular planimetric (10) - packs cardboard.
10 pieces. - plastic bottles (1) - packs of cardboard.
20 pcs. - plastic bottles (1) - packs of cardboard.
30 pcs. - plastic bottles (1) - packs of cardboard.
50 pcs. - plastic bottles (1) - packs of cardboard.
100 pieces. - plastic bottles (1) - packs of cardboard.
10 pieces. - polymer cans (1) - packs of cardboard.
20 pcs. - polymer cans (1) - packs of cardboard.
30 pcs. - polymer cans (1) - packs of cardboard.
50 pcs. - polymer cans (1) - packs of cardboard.
100 pieces. - polymer cans (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
The drug has hepatoprotective, choleretic, cholelitholytic, hypolipidemic, hypocholesterolemic and some immunomodulating action.
In vitro studies have shown that ursodeoxycholic acid (UDCA) has a direct protective effect on liver cells and reduces the hepatotoxicity of hydrophobic bile salts.
The main effects of UDCA on cholesterol metabolism include: lowering cholesterol secretion, reducing its intestinal absorption and stimulating the release of cholesterol from cholesterol stones to bile. UDCA, inhibiting the GMK-CoA reductase, also has a moderate inhibitory effect on the synthesis of cholesterol in the liver, increases the solubility of cholesterol in the bile-excreting system. Causes partial or complete dissolution of cholesteric gallstones with enteral application, reduces the saturation of bile with cholesterol. Stimulates the formation and secretion of bile, accelerates the excretion of toxic bile acids through the intestine.
When administered orally, the proportion of UDCA in the common pool of bile acids increases significantly. UDCA competes with other bile acids in the course of absorption in the small intestine, as well as through penetration of the hepatocyte membrane, which leads to a decrease in the absorption of toxic bile acids in the intestine and their entry into the liver, preventing their cytopathogenic action. It reduces the lithogenicity of bile, increases the concentration of bile acids in it, causes an increase in gastric and pancreatic secretion, increases lipase activity, and has a hypoglycemic effect.
It influences immunological reactions, reducing the pathological expression of antigens of the main histocompatibility complex of HLA I on hepatocytes and HLA II on cholangiocytes, suppresses the production of interleukin-2, and reduces the number of eosinophils.
PHARMACOKINETICS
Suction
UDCA is absorbed in the small intestine (about 90%), while Cmax in blood plasma when taking the drug inside at a dose of 250 mg is about 3.3 Ојg / ml, T max - about 2 hours.
Distribution
Binding to plasma proteins of unconjugated UDCA in healthy people is at least 70%. Penetrates through the placental barrier. With systematic administration in doses of 13-15 mg / kg / day, UDCA becomes the main bile acid in the serum and accounts for 30 to 50% of the total bile acid content in the blood. The therapeutic effect of the drug depends on the concentration of UDCA in the bile.
Metabolism and excretion
Metabolised in the liver with conversion into taurine and glycine conjugates, which are secreted into bile. About 50-70% of the dose taken internally is excreted with bile. Excretion in urine does not exceed 1%. A small amount of non-sucked after oral administration of UDCA 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 as a sulfolithocholylglycine or sulfolitocholyltaurine conjugate.
INDICATIONS
- primary biliary cirrhosis in the absence of signs of decompensation (symptomatic therapy);
- Dissolution of small and medium cholesterol stones with a functioning gallbladder;
- Biliary reflux-gastritis;
- chronic hepatitis of various genesis;
- primary sclerosing cholangitis;
- Cystic fibrosis (cystic fibrosis);
- non-alcoholic steatohepatitis;
- alcoholic liver disease;
- biliary dyskinesia.
DOSING MODE
The drug is prescribed inside. If swallowing is difficult, the capsule can be opened and taken up with its contents, squeezed with enough liquid.
When dissolving cholesterol gallstones, capsules should be taken in the evening, before going to bed, with a sufficient amount of liquid.
The dose is approximately 10 mg / kg of body weight daily, which corresponds to:
2 capsules of Ursoliv В® in patients with body weight up to 60 kg ;
3 capsules - in patients with a body weight of up to 80 kg ;
4 capsules - in patients with a body weight of up to 100 kg ;
5 capsules - in patients with a body weight of more than 100 kg .
Duration of treatment - 6-12 months.
For the prevention of repeated formation of stones, it is recommended to take the drug for several months after the dissolution of the stones.
With symptomatic treatment of primary biliary cirrhosis, the daily dose depends on the body weight and ranges from 2 to 6 capsules (10 to 15 mg ursodeoxycholic acid per 1 kg of body weight).
The drug is taken with food, squeezed with enough liquid.
The following application mode is recommended:
Body weight Daily dose Morning Afternoon Evening
34-50 kg 2 capsules 1 - 1
51-65 kg 3 capsules 1 1 1
66-85 kg 4 capsules 1 1 2
86-110 kg 5 capsules 1 2 2
More than 110 kg 6 capsules 2 2 2
For the treatment of biliary reflux gastritis , one capsule is prescribed 1 time / day before bedtime. The course of treatment - from 10-14 days to 6 months, if necessary - up to 2 years.
With chronic hepatitis of various genesis (toxic, medicinal and other), non-alcoholic fatty liver disease, incl. nonalcoholic steatohepatitis, alcoholic liver disease, theaverage daily dose is 10-15 mg / kg in 2-3 doses. The duration of therapy is 6-12 months or more.
With the primary sclerosing cholangitis, cystic fibrosis (cystic fibrosis), the average daily dose is 12-15 mg / kg; if necessary, the average daily dose can be increased to 20-30 mg / kg in 2-3 doses. The duration of therapy is from 6 months to several years.
When dyskinesia of the bile ducts is hypokinetic, 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.
SIDE EFFECT
From the digestive system: nausea, vomiting, pain in the epigastric region and right hypochondrium, constipation, transient increase in the activity of hepatic transaminases; rarely - diarrhea (can be dose-dependent), calcification of gallstones. In the treatment of primary biliary cirrhosis, transient decompensation of liver cirrhosis can occur, which disappears after drug withdrawal.
Other: headache, malaise, myalgia, dizziness, allergic reactions (itching, urticaria, angioedema), exacerbation of previously existing psoriasis, alopecia.
CONTRAINDICATIONS
- the size of cholesterol stones in the gall bladder is more than 20 mm;
- presence of radiopaque (with a high content of calcium) gallbladder stones and common bile duct;
- Atrophy of the gallbladder with cholelithiasis, a dysfunctional gallbladder;
- Obstruction of the biliary tract;
- acute inflammatory diseases of the gallbladder, bile ducts and intestines;
- cirrhosis of the liver in the stage of decompensation;
- severe hepatic impairment;
- severe renal failure;
- pancreatitis (active phase);
- Pregnancy;
- lactation period;
- adults and children with a body weight of up to 34 kg (for this dosage form);
- Hypersensitivity to the components of the drug.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindication: marked renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindication: marked hepatic insufficiency, cirrhosis of the liver in the stage of decompensation.
APPLICATION FOR CHILDREN
Contraindications: children with a body weight of up to 34 kg (for this dosage form).
SPECIAL INSTRUCTIONS
To dissolve gallstones UDCA stones must be cholesterol (not radiopaque), a size of not more than 15-20 mm. In this case, the gallbladder should remain functional, and the permeability of the cystic and common bile ducts should be preserved.
In appointing with the purpose of dissolution of gallstones, a biochemical blood test must be performed monthly, and then every 3 months to determine the activity of hepatic transaminases, alkaline phosphatase, GGT, and bilirubin concentrations. If the increased indices remain, the drug should be discontinued.
To monitor the effectiveness of treatment, it is recommended to perform x-ray and ultrasound examination of the bile ducts every 6 months.
When calcification of gallstones, violation of the contractility of the gallbladder or frequent attacks of biliary colic, treatment should be discontinued. 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 nonvisualizable gallbladder is evidence that no complete dissolution of the calculi has occurred, and treatment should be discontinued.
After complete dissolution of the stones, in order to avoid relapses, it is recommended that UDCA be continued for 3 months.
Impact on the ability to drive vehicles and manage mechanisms
The drug does not adversely affect the ability to drive vehicles and / or other mechanisms.
OVERDOSE
Cases of overdose UDCA have not been described to date.
DRUG INTERACTION
When combined, antacids containing aluminum and ion exchange resins (colestyramine) reduce the absorption of UDCA.
With simultaneous use, lipid-lowering drugs (especially clofibrate), estrogens, neomycin or progestogens (oral contraceptives) increase bile saturation with cholesterol and may reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.
With the simultaneous use of UDCA can increase the absorption of cyclosporine.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 4 years. Do not use after the expiration date.
