Choludexan (Capsules) Instructions for Use

Marketing Authorization Holder

World Medicine İlaç San. ve Tic. A.Ş. (Turkey)

Manufactured By

World Medicine İlaç San. ve Tic. A.Ş. (Turkey)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN registered by WHO)

Dosage Form

Choludexan

Capsules 300 mg: 20 or 60 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 0, pink body, red cap; capsule contents – granulated powder white or almost white in color.

Excipients: corn starch (granulated) – 10.364 mg, corn starch – 66.016 mg (including an additional 4 mg for moisture compensation), colloidal silicon dioxide (Aerosil 200) – 5.5 mg, magnesium stearate – 2 mg, potassium sorbate – 0.34245 mg.

Capsule body composition gelatin – 96.254 mg, titanium dioxide – 1.585 mg, azorubine dye – 0.116 mg.
Capsule cap composition gelatin – 96.254 mg, titanium dioxide – 1.585 mg, azorubine dye – 0.116 mg, crimson dye (Ponceau R) – 0.044 mg.

10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.

Clinical-Pharmacological Group

Hepatoprotective agent with choleretic and cholelitholytic action

Pharmacotherapeutic Group

Hepatoprotective agent

Pharmacological Action

Choludexan is a hepatoprotective agent that also has choleretic, cholelitholytic, hypolipidemic, hypocholesterolemic, and some immunomodulatory effects.

Possessing high polar properties, Ursodeoxycholic acid (UDCA) forms non-toxic mixed micelles with apolar (toxic) bile acids, which reduces the ability of gastric refluxate to damage cell membranes in biliary reflux gastritis and reflux esophagitis. Furthermore, UDCA forms double molecules capable of incorporating into the composition of cell membranes (hepatocytes, cholangiocytes, gastrointestinal epithelial cells), stabilizing them and making them resistant to the action of cytotoxic micelles. By reducing the concentration of bile acids toxic to the liver cell and stimulating bicarbonate-rich choleresis, UDCA effectively promotes the resolution of intrahepatic cholestasis. It reduces the cholesterol saturation of bile by inhibiting its absorption in the intestine, suppressing its synthesis in the liver, and reducing its secretion into bile; it increases the solubility of cholesterol in bile, forming liquid crystals with it; it reduces the lithogenic index of bile. The result is the dissolution of cholesterol gallstones and the prevention of new stone formation. The immunostimulatory effect is due to the inhibition of HLA-1 antigen expression on hepatocyte membranes and HLA-2 on cholangiocytes, normalization of the natural killer activity of lymphocytes, etc. It significantly delays the progression of fibrosis in patients with primary biliary cirrhosis, cystic fibrosis, and alcoholic steatohepatitis; it reduces the risk of developing esophageal varices. UDCA slows down the processes of premature aging and cell death (hepatocytes, cholangiocytes, etc.).

Pharmacokinetics

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

Protein binding is high – up to 96-99%. It penetrates the placental barrier. With systematic administration, Choludexan-UDCA 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 UDCA in bile.

It is metabolized in the liver (first-pass clearance) to taurine and glycine conjugates. The resulting conjugates are secreted into bile. About 50-70% of the total dose of the drug is excreted in the bile. A small amount of unabsorbed UDCA enters the large intestine, where it is broken down by bacteria (dehydroxylation); the resulting lithocholic acid is partially absorbed from the large intestine but is sulfated in the liver and rapidly excreted as a sulfolithocholylglycine or sulfolithocholyltaurine conjugate.

Indications

• Uncomplicated cholelithiasis (biliary sludge; dissolution of cholesterol gallstones in the gallbladder when their removal by surgical or endoscopic methods is impossible; prevention of recurrent stone formation after cholecystectomy);
• Chronic active hepatitis;
• Toxic (including drug-induced) liver damage;
• Alcoholic liver disease (ALD);
• Non-alcoholic steatohepatitis;
• Primary biliary cirrhosis of the liver;
• Primary sclerosing cholangitis;
• Cystic fibrosis;
• Atresia of the intrahepatic bile ducts, congenital atresia of the bile duct;
• Biliary dyskinesia;
• Biliary reflux gastritis and reflux esophagitis.

ICD codes

Dosage Regimen

Choludexan is taken orally with a sufficient amount of water. For biliary reflux gastritis and reflux esophagitis – once a day, before bedtime. For diffuse liver diseases – 2-3 times a day with meals.

Chronic liver diseases, cholelithiasis (cholesterol gallstones and biliary sludge) – continuously for a long time (from several months to several years) at a daily dose of 10 mg/kg to 12-15 mg/kg (2-5 capsules). The duration of administration for stone dissolution is until complete dissolution plus another 3 months to prevent recurrent stone formation.

For biliary reflux gastritis and reflux esophagitis – 300 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.

After cholecystectomy, for the prevention of recurrent cholelithiasis – 300 mg twice a day for several months.

Toxic, drug-induced liver damage, ALD and biliary atresia – 10-15 mg/kg/day for 6-12 months or more.

Primary biliary cirrhosis – 10-15 mg/kg/day (if necessary – up to 20 mg/kg) from 6 months to several years.

Primary sclerosing cholangitis – 12-15 mg/kg/day (up to 20 mg/kg) from 6 months to several years.

Non-alcoholic steatohepatitis – 13-15 mg/kg/day from 6 months to several years.

Cystic fibrosis – 20-30 mg/kg/day (up to 20 mg/kg) from 6 months to several years.

For children over 3 years old UDCA is prescribed individually, at a rate of 10-20 mg/kg/day.

Adverse Reactions

Back pain, nausea, vomiting, diarrhea (may be dose-dependent), constipation, transient increase in liver transaminase activity, allergic reactions; rarely – calcification of gallstones, exacerbation of pre-existing psoriasis, alopecia.

Contraindications

• Radiopaque (high calcium content) gallstones;
• Non-functioning gallbladder;
• Biliary-gastric fistula;
• Acute cholecystitis;
• Acute cholangitis;
• Liver cirrhosis in the stage of decompensation;
• Acute infectious diseases of the gallbladder, bile ducts and intestines;
• Severe hepatic and/or renal failure;
• Obstruction of the biliary tract;
• Empyema of the gallbladder;
• Children under 3 years of age;
• Hypersensitivity to the drug.

With caution although UDCA has no age restrictions for use, Choludexan capsules should be used with caution in children aged 3 to 4 years, as difficulty in swallowing the capsules is possible.

Use in Pregnancy and Lactation

Women of childbearing age are recommended to use non-hormonal contraceptives during the use of the drug. The use of UDCA 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 UDCA in pregnant women have not been conducted). Data on the excretion of UDCA in breast milk are currently unavailable. If it is necessary to use UDCA during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure.

Use in Renal Impairment

Contraindicated in severe renal failure.

Pediatric Use

Since difficulty in swallowing the capsules is possible, the drug should not be used in this dosage form in children under 3 years of age; in children aged 3 to 4 years, it is used with caution.

Special Precautions

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 should be performed every 4 weeks during the first 3 months of treatment, and then every 3 months to determine the activity of liver transaminases. Control of treatment effectiveness should be carried out every 6 months according to ultrasound and X-ray examination of the biliary tract. After complete dissolution of the stones, it is recommended to continue the use of Choludexan for at least 3 months in order to promote the dissolution of stone remnants, the size of which is too small for their detection, and to prevent recurrent stone formation.

If partial dissolution of stones has not occurred within 6 months after the start of therapy, it is unlikely that the treatment will be effective.

Use in pediatrics

Since difficulty in swallowing the capsules is possible, the drug should not be used in this dosage form in children under 3 years of age; in children aged 3 to 4 years, it is used with caution.

Effect on ability to drive vehicles and mechanisms

The drug does not have a negative effect on the ability to drive vehicles and/or other mechanisms.

Overdose

Cases of UDCA overdose are not known.

Drug Interactions

Antacids containing aluminum and ion-exchange resins (cholestyramine) reduce the absorption of the drug. Hypolipidemic drugs (especially clofibrate, estrogens, neomycin or progestins) increase the cholesterol saturation of bile and may reduce the ability to dissolve cholesterol gallstones. It enhances the effect of oral hypoglycemic drugs.

Storage Conditions

Store at a temperature from 15 to 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.