Urdoxa^® (Capsules) Instructions for Use

Marketing Authorization Holder

Aliym, JSC (Russia)

Contact Information

BINNOPHARM GROUP LLC (Russia)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN registered by WHO)

Dosage Form

Urdoxa®

Capsules 250 mg: 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 0, with a white or almost white body and cap; the capsule contents are a mixture of powder and granules, white or almost white in color.

Excipients: corn starch, colloidal anhydrous silicon dioxide (aerosil), magnesium stearate; hard gelatin capsules No. 0 (capsule body and cap: titanium dioxide, gelatin).

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (7) – cardboard packs.
10 pcs. – blister packs (8) – cardboard packs.
10 pcs. – blister packs (9) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.
20 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Hepatoprotective agent with choleretic and cholelitholytic action

Pharmacotherapeutic Group

Hepatoprotective agent

Pharmacological Action

Hepatoprotective agent, has choleretic, cholelitholytic, hypocholesterolemic, hypolipidemic, and immunomodulatory effects.

It is incorporated into the hepatocyte membrane, stabilizes its structure, and protects the hepatocyte from the damaging effects of bile salts, thereby reducing their cytotoxic effect. In cholestasis, it activates Ca²⁺-dependent alpha-protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic, and others), the concentrations of which are elevated in patients with chronic liver diseases.

It competitively reduces the absorption of lipophilic bile acids in the intestine, increases their “fractional” turnover during enterohepatic circulation, induces choleresis, stimulates bile flow, and promotes the excretion of toxic bile acids through the intestine.

It shields nonpolar bile acids (chenodeoxycholic acid), resulting in the formation of mixed (nontoxic) micelles.

It reduces cholesterol saturation of bile by decreasing cholesterol synthesis and secretion in the liver and inhibiting its absorption in the intestine.

It increases the solubility of cholesterol in the biliary system, stimulates the formation and secretion of bile. It reduces the lithogenicity of bile, increases the concentration of bile acids in it, enhances gastric and pancreatic secretion, increases lipase activity, and has a hypoglycemic effect.

It causes partial or complete dissolution of cholesterol gallstones, reduces cholesterol saturation of bile, which promotes its mobilization from gallstones.

It has an immunomodulatory effect, influences immunological reactions in the liver: reduces the expression of some histocompatibility antigens – HLA-1 on hepatocyte membranes and HLA-2 on cholangiocytes, affects the number of T-lymphocytes, the formation of interleukin 2, reduces the number of eosinophils, and suppresses immunocompetent Ig (primarily IgM).

Pharmacokinetics

Absorption

Ursodeoxycholic acid is absorbed in the small intestine by passive diffusion (about 90%), and in the ileum by active transport. C_max after oral administration of a 50 mg dose at 30, 60, 90 min is 3.8 mmol/L, 5.5 mmol/L, and 3.7 mmol/L respectively and is achieved within 1-3 hours.

Distribution

Plasma protein binding is high – up to 96-99%. It crosses the placental barrier. With systematic administration of the drug, Ursodeoxycholic acid becomes the main bile acid in the blood serum and constitutes 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

It is metabolized in the liver (first-pass clearance through the liver) to taurine and glycine conjugates. The resulting conjugates are secreted into the bile.

About 50-70% of the total drug dose is excreted in the bile. A small amount of unabsorbed ursodeoxycholic acid enters the large intestine, where it is broken down by bacteria (7-dehydroxylation); the resulting lithocholic acid is partially absorbed from the large intestine but is sulfated in the liver and rapidly excreted as sulfolithocholylglycine or sulfolithocholyltaurine conjugate.

Indications

• Primary biliary cirrhosis without signs of decompensation (symptomatic treatment);
• Dissolution of cholesterol gallstones;
• Biliary reflux gastritis;
• Primary sclerosing cholangitis;
• Alcoholic liver disease;
• Non-alcoholic steatohepatitis;
• Cystic fibrosis (mucoviscidosis);
• Chronic hepatitis of various origins;
• Biliary dyskinesia.

ICD codes

Dosage Regimen

Urdoxa^® capsules are taken orally, without chewing, with a small amount of water.

Symptomatic treatment of primary biliary cirrhosis

The daily dose depends on body weight and ranges from 3 to 7 capsules (approximately 14±2 mg of ursodeoxycholic acid per 1 kg of body weight). During the first 3 months of treatment, the intake of Urdoxa^® should be divided into several doses throughout the day. After improvement of liver parameters, the daily dose of the drug can be taken once, in the evening.

The following application regimen is recommended

Urdoxa^® should be taken regularly. The duration of therapy is unlimited.

Dissolution of cholesterol gallstones

The recommended dose is 10 mg of ursodeoxycholic acid per 1 kg of body weight/day, which corresponds to

Urdoxa^® must be taken daily in the evening, before going to bed. The duration of therapy is 6-12 months. To prevent recurrent cholelithiasis, the drug is recommended to be taken for several months after the dissolution of stones.

Treatment of biliary reflux gastritis

1 capsule of Urdoxa^® daily, once/day before bedtime. The course of treatment ranges from 10-14 days to 6 months, if necessary up to 2 years.

Primary sclerosing cholangitis

The daily dose is 12-15 mg/kg; if necessary, the dose can be increased to 20-30 mg/kg in 2-3 divided doses. The duration of therapy is from 6 months to several years.

Alcoholic liver disease

The average daily dose is 10-15 mg/kg in 2-3 divided doses. The duration of therapy is from 6-12 months or more.

Non-alcoholic steatohepatitis

The average daily dose is 10-15 mg/kg in 2-3 divided doses. The duration of therapy is from 6-12 months or more.

Cystic fibrosis (mucoviscidosis)

The daily dose is 12-15 mg/kg; if necessary, the dose can be increased to 20-30 mg/kg in 2-3 divided doses. The duration of therapy is from 6 months to several years or for life.

Chronic hepatitis of various origins

The daily dose is 10-15 mg/kg in 2-3 divided doses. The duration of therapy is 6-12 months or more.

Biliary dyskinesia

The average daily dose is 10 mg/kg in 2 divided doses. The duration of therapy is from 2 weeks to 2 months. If necessary, the course of treatment is recommended to be repeated.

For children over 3 years old the drug is prescribed individually at a dose of 10-20 mg/kg/day.

Adverse Reactions

The frequency of adverse reactions is presented according to the following scale: very common (>10%); common (>1% and <10%); uncommon (>0.1% and <1%); rare (>0.01% and <0.1%); very rare (<0.01%).

From the gastrointestinal tract common – diarrhea; rare – nausea, vomiting, transient increase in liver enzyme activity; very rare – calcification of gallstones. When treating advanced stages of primary biliary cirrhosis, very rarely – decompensation of liver cirrhosis, which disappears after drug withdrawal.

From the skin very rare – urticaria.

Contraindications

• Radiopaque (high calcium content) gallstones;
• Non-functioning gallbladder;
• Acute inflammatory diseases of the gallbladder, bile ducts, and intestine;
• Decompensated liver cirrhosis;
• Severe impairment of renal, hepatic, pancreatic function;
• Hypersensitivity to the components of the drug.

Ursodeoxycholic acid has no age restrictions for use, however, it is not recommended for children under 3 years of age to use the drug in this dosage form.

Use with caution in children aged 3 to 4 years, because difficulty in swallowing capsules is possible.

Use in Pregnancy and Lactation

In experimental studies on animals, no mutagenic or carcinogenic effects of ursodeoxycholic acid were detected.

Use of the drug during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus (adequate strictly controlled studies of the use of ursodeoxycholic acid in pregnant women have not been conducted).

If it is necessary to use the drug during lactation, the issue of discontinuing breastfeeding should be considered. Data on the excretion of ursodeoxycholic acid into breast milk are currently unavailable.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment, decompensated liver cirrhosis.

Use in Renal Impairment

Contraindication: severe renal impairment.

Pediatric Use

Ursodeoxycholic acid has no age restrictions for use, however, it is not recommended for children under 3 years of age to use the drug in this dosage form.

Use with caution in children aged 3 to 4 years, because difficulty in swallowing capsules is possible.

For children over 3 years old ursodeoxycholic acid is prescribed individually at a dose of 10-20 mg/kg/day.

Geriatric Use

Ursodeoxycholic acid has no age restrictions for use.

Special Precautions

Urdoxa^® should be taken under medical supervision.

When taking the drug for the purpose of dissolving gallstones, the following conditions must be met: the stones must be cholesterol (radiopaque), their size should not exceed 15-20 mm, the gallbladder must remain functional and should be filled with stones by no more than half, the patency of the cystic and common bile duct must be preserved. With long-term (more than 1 month) use of the drug, a biochemical blood test to determine the activity of liver transaminases should be performed every 4 weeks during the first 3 months of treatment, and then every 3 months. Treatment effectiveness should be monitored every 6 months based on ultrasound data of the biliary tract. After complete dissolution of stones, it is recommended to continue the use of the drug for at least 3 months in order to promote the dissolution of stone remnants that are too small for detection and to prevent the recurrence of stone formation.

In patients with primary biliary cirrhosis, in rare cases, clinical symptoms may worsen at the beginning of treatment, for example, itching may become more frequent. In this case, treatment should be continued, taking 1 capsule daily, then the dose should be increased (increasing the daily dose weekly by 1 capsule) until the recommended dosing regimen is reached again.

In case of adverse or severe reactions, the patient must immediately inform the attending physician and in no case continue taking the drug without his recommendation.

Effect on ability to drive vehicles and operate machinery

No effect on the ability to drive vehicles and operate machinery was identified.

Overdose

Cases of overdose with ursodeoxycholic acid are unknown. In case of overdose, symptomatic treatment is recommended.

Drug Interactions

Cholestyramine, colestipol, and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce the absorption of ursodeoxycholic acid in the intestine and thus reduce its uptake and effectiveness. If the use of drugs containing at least one of these substances is necessary, they should be taken at least 2 hours before taking Urdoxa^®.

Ursodeoxycholic acid may increase the absorption of cyclosporine from the intestine. Therefore, in patients taking cyclosporine, the concentration of cyclosporine in the blood should be checked and the dose of cyclosporine adjusted if necessary.

In some cases, Urdoxa^® may reduce the absorption of ciprofloxacin.

Hypolipidemic drugs (especially clofibrate), estrogens, neomycin, or progestins increase cholesterol saturation of bile and may reduce the ability to dissolve cholesterol gallstones.

The patient should inform the doctor about all medications they are taking.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 4 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.