Trade name of the drug: Ursokodar.
Active ingredient (INN): ursodeoxycholic acid.
Pharmaceutical dosage form: Capsules.
Composition: One capsule contains: active ingredient: Ursodeoxycholic acid – 250 mg.
Excipients: pregelatinized starch, sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate.
Composition of capsule shell: gelatin, titanium dioxide, water.
Description: “0” size solid gelatin capsules. The body and cap are white. The content of capsules is white or almost white powder.
Pharmacotherapeutic group: hepatoprotectors.
Pharmacological properties: Active ingredient, provides the pharmacological effect of the drug – ursodeoxycholic acid.
It has hepatoprotective, choleretic, cholelitolitic, cholesterol-lowering, lipid-lowering, antiholestatistic, antifibrotic, antiapoptotic and some immunomodulatory effects.
It enters the hepatocyte membrane, stabilizes its structure and protects the hepatocyte from the damaging effect of bile salts, thereby reducing the cytotoxic effect. In case of cholestasis activates Ca2 + – dependent alpha-protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic etc.), the concentration of which in patients with chronic liver disease is higher.
With its 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 cases of biliary reflux gastritis and reflux esophagitis. In addition, ursodeoxycholic acid has cytoprotective and hepatoprotective effects, forms double molecules that can be included in the composition of cell membranes (hepatocytes cholangiocytes, epithelial cells of the GI tract), stabilize them and make immune to the effects of cytotoxic micelles.
It reduces the saturation of bile with cholesterol by inhibiting its absorption in the intestine, suppression of the synthesis in the liver and decrease secretion in the bile; increases the solubility of cholesterol in bile, forming with it the liquid crystals; it reduces the lithogenic index of bile. As a result, the dissolution of cholesterol gallstones (a consequence of changes in the ratio of cholesterol / bile acids in bile) takes place and the formation of new stones (the result of reducing the content of cholesterol in bile) is prevented – litholytic effect.
It induces cholepoiesis rich in bicarbonate, which leads to an increase in the passage of bile and stimulates the excretion of toxic bile acids through the intestine, thereby resolving intrahepatic cholestasis – antiholestatichesky effect.
Immunomodulatory effect is caused by inhibition of expression of HLA-antigen on the membranes of hepatocytes and cholangiocytes, decreased activity of immune immunoglobulin (first Ig M), normalization of natural killer lymphocyte activity, the influence on the formation of interleukin-2, a decrease in number of eosinophils.
Significantly delays the progression of fibrosis in patients with primary biliary cirrhosis, cystic fibrosis and alcoholic steatohepatitis – antifibrolitic effect. It reduces the risk of developing esophageal varices.
Ursodeoxycholic acid slows down the process of premature aging and death of cells (hepatocytes, cholangiocytes et al.) – anti-apoptotic effect.
Inhibits the growth of colorectal cancer cells (anti-tumor activity against colon cancer).
Pharmacokinetics: When administered orally, it is absorbed into the small intestine through passive diffusion, and in the ileum through active transport. The maximum concentration (Cmax) is achieved after 1-3 h. There is a high rate of bonding with protein (in healthy volunteers, at least 70% of non-conjugated ursodeoxycholic acid bonds with proteins).
When taking a single dose of 500 mg its concentration in blood serum in 30, 60 and 90 minutes reaches 3.8; 5.5 and 3.7 mmol / l respectively. During the systematic intake, ursodeoxycholic acid becomes primary biliary blood serum acid (48% of total bile acids).
The therapeutic effect is dependent on the concentration of ursodeoxycholic acid in bile; during therapy, there is a dose-dependent increase of its composition in the pool of bile acids to 50-75% (at daily doses of 10-20 mg / kg).
It forms part of the gastrointestinal circulatory system.
In the liver, ursodeoxycholic acid binds with taurine and glycine; the resulting conjugates are secreted into bile.
It passes through the placental barrier.
The substence is excreted predominantly (50-70%) through the intestine, a very small amount (less than 1%) – with urine. A small amount of non-absorbable ursodeoxycholic acid in the colon undergoes transfromation by bacteria (7-dehydroxylation) into lithocholic acid, which is partially absorbed from the colon, sulfated in the liver and rapidly excreted in faeces in the form of sulfo-tilholil-taurine-absorbing or sulfo-tilholil-taurine-releasing conjugates. Part of lithocholic acid in the enterohepatic circulation enters the liver and is retransformed again into heno- and ursodeoxycholic acid.
Indications for usage:
— Dissolution of biliary cholesterol stones in patients with high operative risk and patients after lithotripsy;
— Primary biliary cirrhosis stage I and II;
— Primary sclerotic cholangitis;
— Hepatitis (chronic, active including atypical forms of chronic autoimmune, chronic and acute viral hepatitis);
— Non-alcoholic steatohepatitis;
— Toxic (including alcohol, drugs) liver disease;
— Cystic fibrosis (cystic fibrosis of the liver);
— Biliary reflux gastritis;
— Biliary reflux esophagitis;
— Biliary dyspepsia;
— Biliary dyskinesia;
— Cholestatic liver disease in children (including biliary atresia);
— Cholestasis after liver transplantation;
— Chronic opisthorchiasis;
— Prevention of colon cancer in patients with high-risk for its development (eg. ulcerative colitis);
— Prevention of the formation of gallstones in overweight patients during rapid weight loss.
Dosage and method of administration: The capsules are taken orally, regardless of food intake, with sufficient amount of liquid. Method of dosage and duration of treatment are defined individually, depending on the indications and the severity of the patient’s condition.
An average dosage consists of 8-10 mg / kg / day for 6-12 months.
The following data can be used for the convenience of dosing:
Up to 60 kg 500 mg
Up to 80 kg 750 mg
Up to 100 kg 1000 mg
More than 100 kg 1,250 mg
Gallstone disease, reflux gastritis: 1 capsule once a day at bedtime.
Chronic liver disease, cholesterol gallstones: continuously for a long time (from several months to several years) at a daily dose of 10 mg / kg up to 12-15 mg / kg (2-5 caps.). Duration of the treatment aimed at dissolution of stones – until complete dissolution + 3 months for the prevention of recurrence of stone formation.
Biliary reflux gastritis and biliary reflux esophagitis: 250 mg / day (1 capsule); treatment from 10-14 days to 2 years.
Primary biliary cirrhosis: 8-15 mg / kg / day (if necessary – up to 20 mg / kg / day) for 6-24 months (up to several years).
Primary sclerosing cholangitis: 12-15 mg / kg / day (20 mg / kg / day) for 6-24 months (up to several years).
Cystic fibrosis: 20-30 mg / kg / day for 6-24 months and more.
Toxic and alcoholic liver disease: 10-15 mg / kg / day for 6-12 months and more.
Side effects: The drug is well tolerated by patients. Rarely, there may be diarrhea or constipation, nausea, vomiting, epigastric pain and pain in the upper right quadrant, the calcination of gallstones, increased activity of hepatic transaminases, exacerbation of previously-existing psoriasis, allergic reactions (rash, pruritus), dizziness, allergic reactions.
During the treatment of primary biliary cirrhosis, there may be a transient decompensation of cirrhosis, which disappears after discontinuation of the drug.
In the event of any unusual reactions, drug usage should be stopped and a doctor consulted.
— high in calcium gallstones;
— Acute inflammatory diseases of the gallbladder, bile duct and intestine, Crohn’s disease;
— Non-functioning gall bladder;
— Complete obstruction of the biliary tract;
— Cirrhosis of the liver at the decompensation stage;
— Impaired function of kidneys, liver and pancreas.
— Bile-gastrointestinal fistula;
— Acute cholecystitis;
— Acute cholangitis;
— Children under 6 (body weight up to 35 kg);
— Frequent biliary colic.
Drug interactions: Cholestyramine, colestipol and antacids containing aluminum hydroxide bind ursodeoxycholic acid in the gut, reducing its absorption and weakening its effectiveness. If there is need for the simultaneous treatment using the above drugs, it is recommended to use them two hours before or after the drug intake.
Lipid-lowering agents (especially clofibrate, estrogen, neomycin, progestin) may increase the saturation of bile with cholesterol, and reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.
The drug can increase the absorption of cyclosporin in the intestine. Therefore, for people taking the drugit is necessary to be simultaneously control the levels of cyclosporine and adjust its dose.
Special instructions: During the cholelithic treatment, efficiency control of the treatment is carried out every 6 months, through X-ray and ultrasound analysis of the biliary tract in order to prevent recurrence of cholelithiasis.
Positive results can be achieved only if there is pure cholesterol (roentgen) gallstones of size no more than 15-20 mm, with the gall bladder retaining its function, and the permeability of the cystic and common bile ducts.
During long-term (more than 1 month) treatments, a monthly biochemical analysis of blood must be carried out to determine the activity of hepatic transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase and bilirubin (especially during the first 3 months of the therapy). In case high levels are maintained, drug usage should be stopped.
After the concretions are completely dissolved, its usage should be maintained for at least 3 months, in order to facilitate the dissolution of calculi residues that are too small to be detected.
If during a period of 6-12 months after initiating the therapy, there is no partial dissolution of stones, it is very unlikely that the treatment will be effective.
Detection during treatment of the non-detectable gallbladder certainly indicates that the stones are not completely dissolved, and treatment should be discontinued.
During treatment of women of childbearing age, non-hormonal methods of contraception or contraceptives with low estrogen level should be used.
The drug has no effect on the ability to drive a car, or work with technology.
The drug should be stored out of the reach of children, and should not be used after the expiration date.
Overdose: Symptoms: In cases of overdose, diarrhea may occur. Treatment: cessation of the drug usage. Treatment is symptomatic, maintaining liquid and electrolyte balance.
Dosage forms: Gelatin capsules, 10 capsules per blister, with 1, 2, 3, 5, 6, 10-contour of blisters in the pack.
Storage conditions: Keep dry, avoid exposure to direct sunlight, at a temperature not exceeding 25 ° C.
Shelf life: 3 years.
Dispensing requirements: On prescription.
Manufacturer: Codepharm LLC (IE), 30-Gulistan Str, 4th quarter, Gulistan, Sirdaryo Region, The Republic of Uzbekistan.