What are the indications for Ursodiol (ursodeoxycholic acid)?

Indications for Ursodiol (Ursodeoxycholic Acid)

Ursodiol is primarily indicated for the treatment of primary biliary cirrhosis (PBC) at doses of 13-15 mg/kg/day, and for the dissolution of small, radiolucent gallstones in patients with functioning gallbladders who are at increased surgical risk or refuse surgery. 1, 2

FDA-Approved Indications

• Dissolution of radiolucent, noncalcified gallstones less than 20 mm in greatest diameter in patients with functioning gallbladders who would otherwise undergo cholecystectomy but have increased surgical risk due to systemic disease, advanced age, or idiosyncratic reactions to anesthesia 1
• Prevention of gallstone formation in obese patients experiencing rapid weight loss 1

Evidence-Based Clinical Indications

Primary Biliary Cirrhosis (PBC)

• Standard recommended dosage: 13-15 mg/kg/day 2, 3
• Significantly improves liver biochemistry (decreases serum bilirubin, alkaline phosphatase, cholesterol, and IgM levels) 4
• Delays histological progression when started at early disease stages 2, 5
• Reduces likelihood of liver transplantation or death in patients with moderate to severe PBC 5
• Slows disease progression with long-term therapy 5, 4

Other Cholestatic Liver Conditions

• May be used in cholestatic liver diseases through mechanisms that include:
  • Modulation of mitochondrial membrane perturbation 6
  • Inhibition of apoptosis in hepatocytes 6
  • Protection against bile acid-induced damage 6

Dosing Considerations

• For PBC: Optimal dose is 13-15 mg/kg/day (approximately 900 mg/day for average adult) 7, 3
• For gallstone dissolution: 13-15 mg/kg/day 1, 8
• Higher doses (>20 mg/kg/day) have not shown additional benefit in PBC and may be harmful in primary sclerosing cholangitis 9, 2

Important Patient Selection Criteria

For Gallstone Dissolution

• Small, primarily cholesterol stones (radiolucent on plain film) 1, 8
• Functioning gallbladder (visualized on oral cholecystogram) 8
• Absence of severe acute or chronic intrahepatic cholestasis 8
• Not recommended during pregnancy or in women likely to become pregnant 8

For PBC

• Diagnosis confirmed by liver biopsy and/or presence of antimitochondrial antibodies 2
• Regular monitoring of liver biochemistry to assess treatment response 2
• Safety established for long-term use with minimal adverse effects 9, 4

Common Adverse Effects

• Generally well-tolerated with minimal side effects 9, 3
• Possible mild nausea and dizziness in up to 25% of patients 2
• No significant treatment discontinuations due to adverse effects in clinical trials 4, 3

Monitoring Recommendations

• Regular assessment of liver biochemistry to evaluate treatment response 2
• Annual reassessment of biochemical markers of cholestasis in AMA-positive individuals with normal liver tests 2
• Liver biopsy may be needed for diagnosis in the absence of PBC-specific antibodies 2