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 a dosage of 13-15 mg/kg/day and for dissolution of small, radiolucent, noncalcified gallstones (<20 mm) in patients with increased surgical risk at 8-10 mg/kg/day. 1, 2

Primary Biliary Cirrhosis (PBC)

• Standard dosage: 13-15 mg/kg/day divided into 2-3 doses
• Evidence strongly supports this as the optimal dosage:
  • Higher doses (23-25 mg/kg/day) show no additional benefit over standard dosing 3
  • Lower doses (5-7 mg/kg/day) are significantly less effective 3
• Clinical benefits:
  • Slows disease progression (relative risk reduction of 72%) 4
  • Reduces need for liver transplantation (79% risk reduction) 4
  • Improves liver biochemistry markers (bilirubin, alkaline phosphatase, aminotransferases) 5
  • Improves histologic features except fibrosis 5

Monitoring and Prognosis

• Liver function tests should be performed every 3-6 months to assess response 1
• Patients with high baseline bilirubin (>2 mg/dL) or established cirrhosis have poorer outcomes despite treatment 1, 4
• Treatment should be continued long-term as benefits increase with duration 4

Gallstone Dissolution

• Indicated for radiolucent, noncalcified gallstones <20 mm in patients with:
  • Increased surgical risk due to systemic disease
  • Advanced age
  • Idiosyncratic reaction to general anesthesia
  • Refusal of surgery 2
• Dosage: 8-10 mg/kg/day for up to 2 years 1
• Best results (up to 50% dissolution rate) seen with:
  • Floating or floatable stones
  • Stones <20 mm in diameter
  • Uncalcified stones 1
• Complete dissolution expected in approximately 30% of unselected patients 1

Monitoring for Gallstone Treatment

• Ultrasound monitoring every 6 months during the first year 1
• If partial dissolution is observed within 6 months, >70% chance of complete dissolution with continued therapy 1
• Stone recurrence occurs in 30-50% of patients within 2-5 years after dissolution 1

Prevention of Gallstones

• Indicated for prevention of gallstone formation in obese patients experiencing rapid weight loss 2

Other Cholestatic Liver Diseases

• Evidence suggests benefit in:
  • Primary sclerosing cholangitis
  • Intrahepatic cholestasis of pregnancy
  • Liver disease associated with cystic fibrosis
  • Chronic graft versus host disease
  • Total parenteral nutrition-associated cholestasis
  • Various pediatric cholestatic liver diseases 6

Safety Profile

• Generally well-tolerated with minimal side effects 1, 3
• No significant adverse effects on liver function tests 1
• No increase in biliary lithocholic acid concentration during therapy 1
• Treatment duration safety:
  • For PBC: Long-term treatment is safe and beneficial 4
  • For gallstones: Safety beyond 24 months is not established 2

Clinical Pitfalls to Avoid

• Using inadequate dosing for PBC (less than 13 mg/kg/day) significantly reduces effectiveness 3
• Attempting gallstone dissolution in patients with calcified stones or stones >20 mm is unlikely to succeed 1, 2
• Discontinuing therapy prematurely in PBC can lead to disease progression 4
• Failing to monitor for gallstone recurrence after successful dissolution 1