Ursodex (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN registered by WHO)

Dosage Forms

	Ursodex	Film-coated tablets, 150 mg: 10, 50 or 100 pcs.
		Film-coated tablets, 300 mg: 10, 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets brownish-red in color, round, biconvex, with a score on one side; the core is white on the break.

Excipients: lactose – 43.5 mg, starch – 9 mg, microcrystalline cellulose – 22 mg, sodium carboxymethyl starch – 13 mg, sodium lauryl sulfate – 3 mg, magnesium stearate – 3 mg, colloidal silicon dioxide – 1.5 mg, purified talc – 6.4 mg, povidone K-30 – 10 mg.

Film coating composition: hypromellose E5 – 4.8 mg, macrogol-6000 – 0.95 mg, titanium dioxide – 0.48 mg, yellow iron oxide – 0.08 mg, red iron oxide – 0.09 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Film-coated tablets brownish-red in color, round, biconvex, with a score on one side; the core is white on the break.

Excipients: lactose – 87 mg, starch – 18 mg, microcrystalline cellulose – 44 mg, sodium carboxymethyl starch – 26 mg, sodium lauryl sulfate – 6 mg, magnesium stearate – 6 mg, colloidal silicon dioxide – 3 mg, purified talc – 20 mg, povidone K-30 – 10 mg.

Film coating composition: hypromellose E5 – 9.6 mg, macrogol-6000 – 1.9 mg, titanium dioxide – 0.96 mg, yellow iron oxide – 0.16 mg, red iron oxide – 0.18 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Hepatoprotective agent with choleretic and cholelitholytic action

Pharmacotherapeutic Group

Hepatoprotective agent

Pharmacological Action

Hepatoprotector. Also has choleretic, cholelitholytic, hypolipidemic, hypocholesterolemic, and immunomodulatory effects. Stabilizes the membranes of hepatocytes and cholangiocytes, has a direct cytoprotective effect. As a result of the drug’s action on the gastrointestinal circulation of bile acids, the content of hydrophobic (potentially toxic) acids decreases. By reducing cholesterol absorption in the intestine and through other biochemical effects, it exerts a hypocholesterolemic effect. Suppresses cell death induced by toxic bile acids.

Possessing high polar properties, Ursodeoxycholic acid 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, Ursodeoxycholic acid forms double molecules capable of incorporating into cell membranes, stabilizing them and making them resistant to the action of cytotoxic micelles. Reduces cholesterol saturation of bile by inhibiting its absorption in the intestine, suppressing its synthesis in the liver, and decreasing its secretion into bile; increases the solubility of cholesterol in bile, forming liquid crystals with it; reduces the lithogenic index of bile. The result is the dissolution of cholesterol gallstones (a consequence of changing the cholesterol/bile acids ratio in bile) and the prevention of new stone formation (a result of decreased cholesterol content in bile). Induces choleresis rich in bicarbonates, which leads to increased bile flow and stimulates the excretion of toxic bile acids through the intestine.

The immunomodulatory effect is due to the inhibition of HLA antigen expression (HLA – human leucocyte antigens – histocompatibility antigens) on the membranes of hepatocytes and cholangiocytes, normalization of the natural killer activity of lymphocytes. Significantly delays the progression of fibrosis in patients with primary biliary cirrhosis, cystic fibrosis, and alcoholic steatohepatitis, reduces the risk of developing esophageal varices.

Pharmacokinetics

Absorption and Distribution

Ursodeoxycholic acid is absorbed from the jejunum by passive diffusion and from the ileum by active transport. Plasma concentration after oral administration of 500 mg is reached in 30, 60, 90 minutes – 3.8 mmol/L, 5.5 mmol/L, 3.7 mmol/L respectively.

The distribution of ursodeoxycholic acid is characterized by a high degree of binding to plasma proteins, which can be 96-99%. Penetrates the placental barrier.

Metabolism and Excretion

As a result of presystemic elimination of ursodeoxycholic acid, taurine and glycine conjugates are formed, which are secreted into the bile. About 50-70% of the total administered dose of ursodeoxycholic acid is excreted in the bile.

The remaining portion of the unabsorbed fraction of ursodeoxycholic acid enters the large intestine, where it undergoes bacterial cleavage (7-dehydroxylation) to form lithocholic acid. Lithocholic acid is partially absorbed from the intestine, biotransformed in the liver into sulfolithocholylglycine and sulfolithocholyltaurine conjugates and excreted.

Indications

• primary biliary cirrhosis in the absence of signs of decompensation (symptomatic therapy);
• Dissolution of small and medium-sized cholesterol gallstones in a functioning gallbladder;
• biliary reflux gastritis.

ICD codes

Dosage Regimen

The tablets are taken orally, in the evening, without chewing, with a small amount of water.

For dissolving cholesterol gallstones the average daily dose of Ursodex is 10 mg/kg. The course of treatment is 6-12 months.

For preventing the recurrence of stones, it is recommended to take the drug for several more months after the stones have dissolved.

For biliary reflux gastritis the dose is 250 mg once daily. The course of treatment is from 10-14 days to 6 months, if necessary – up to 2 years.

For symptomatic therapy of primary biliary cirrhosis the average daily dose is 10-15 mg/kg.

For patients with a body weight less than 34 kg, administration of the drug as a suspension is recommended.

Adverse Reactions

From the digestive system: calcification of gallstones, increased activity of hepatic transaminases, diarrhea, nausea, abdominal pain; when treating primary biliary cirrhosis, transient decompensation of liver cirrhosis may occur, which resolves after discontinuation of the drug.

Other allergic reactions (including urticaria).

Contraindications

• Radiopaque (high calcium content) gallstones;
• Non-functioning gallbladder;
• Acute inflammatory diseases of the gallbladder, biliary tract, and intestine;
• Decompensated liver cirrhosis;
• Severe hepatic and/or renal impairment;
• Pancreatitis;
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• Pregnancy;
• Lactation period;
• Adults and children with a body weight under 34 kg (for this dosage form);
• Increased individual sensitivity to the components of the drug.

Use in Pregnancy and Lactation

The use of Ursodex during pregnancy is contraindicated. If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment, liver cirrhosis.

Use in Renal Impairment

Contraindication: severe renal impairment

Pediatric Use

Contraindication: children with a body weight under 34 kg (for this dosage form);

Special Precautions

For successful dissolution, the stones must be purely cholesterol, no larger than 15-20 mm, the gallbladder must be filled with stones by no more than half, and the biliary tract must be fully functional.

When prescribed for dissolving gallstones, monitoring of hepatic transaminases, ALP, GGT activity, and bilirubin concentration is necessary. If elevated levels persist, the drug should be discontinued.

Cholecystography should be performed every 4 weeks during the first 3 months of treatment, and thereafter every 3 months. Treatment efficacy should be monitored every 6 months via ultrasound examination during the first year of therapy. After complete dissolution of the stones, it is recommended to continue use for at least 3 months to facilitate the dissolution of residual stone fragments that are too small to be detected.

If partial dissolution of stones does not occur within 6-12 months after the start of therapy, it is unlikely that the treatment will be effective.

Detection of a non-visualized gallbladder during treatment indicates that complete dissolution of stones has not occurred, and treatment should be discontinued.

If calcification of gallstones occurs, impaired gallbladder contractility, or frequent episodes of biliary colic, treatment should be discontinued.

Effect on ability to drive vehicles and operate machinery

There are no data on the effect of ursodeoxycholic acid on the ability to drive vehicles and operate machinery.

Overdose

Cases of overdose with ursodeoxycholic acid are not known.

Drug Interactions

The drug should not be used simultaneously with antacids containing aluminum and ion-exchange resins, as these drugs may impair the absorption of ursodeoxycholic acid.

When used concomitantly, hypolipidemic drugs, estrogens, neomycin, or progestins (oral contraceptives) increase the cholesterol saturation of bile and may reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.

Ursodex may increase the absorption of cyclosporine from the intestine, which requires monitoring of cyclosporine blood concentration and, if necessary, adjustment of its dosing regimen.

Storage Conditions

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

Shelf Life

Shelf life – 2 years.

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.