What is the recommended dosage of Ursodiol (ursodeoxycholic acid) for treating gallstones and liver diseases?

Ursodiol Dosage Recommendations

For gallstone dissolution, use 8-10 mg/kg/day divided into 2-3 doses; for primary biliary cholangitis (PBC), use 13-15 mg/kg/day as a single bedtime dose; and avoid routine use in primary sclerosing cholangitis (PSC) due to lack of efficacy and potential harm at higher doses. 1, 2, 3

Gallstone Dissolution

The FDA-approved dosage for dissolving radiolucent gallbladder stones is 8-10 mg/kg/day given in 2 or 3 divided doses. 1

• This dosing achieves approximately 30-50% complete dissolution rates for uncalcified stones smaller than 20 mm in diameter treated for up to 2 years 1, 4
• Patients with floating or floatable stones (high cholesterol content) have up to 50% dissolution success, with 81% complete dissolution observed in stones up to 5 mm in diameter 1
• Ultrasound monitoring should occur at 6-month intervals during the first year, and if partial dissolution is not seen by 12 months, the likelihood of success is greatly reduced 1
• Research suggests that doses as low as 4-5 mg/kg/day can produce significant improvements in serum enzyme levels, though higher doses (around 8-10 mg/kg/day) optimize dissolution rates 5, 6

Important Caveats for Gallstone Treatment

• Calcified gallstones, stones >20 mm in diameter, and gallbladder non-visualization during treatment predict failure and warrant discontinuation 1
• Stone recurrence occurs in 30-50% of patients within 2-5 years after complete dissolution 1
• Ursodiol is ineffective for gallstones in cystic fibrosis patients, as cholesterol is typically not the main stone component 7

Primary Biliary Cholangitis (PBC)

The established first-line therapy for PBC is 13-15 mg/kg/day, typically given as a single bedtime dose. 2, 8, 3

• This dosage significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 2
• Long-term treatment delays histological progression when started at early disease stages and reduces the likelihood of liver transplantation or death in moderate to severe PBC 2
• Research demonstrates that 900 mg/day (approximately 13.5 mg/kg/day for a 67 kg patient) produces optimal enrichment of ursodiol in serum bile acids and the greatest normalization of abnormal liver function tests 9
• Doses of 900-1200 mg/day show no significant difference in efficacy, supporting the 13-15 mg/kg/day recommendation 9

Primary Sclerosing Cholangitis (PSC)

Ursodiol should NOT be routinely used for PSC, as major guidelines do not support its use due to limited efficacy and potential harm. 2, 3

• The American Association for the Study of Liver Diseases and British Society of Gastroenterology recommend against routine ursodiol use in PSC 2
• If used at all, doses should be limited to 15-20 mg/kg/day, as this may improve serum liver tests and surrogate markers, though clinical outcome benefits remain uncertain 2, 3
• Critical safety warning: Doses of 28-30 mg/kg/day are contraindicated in PSC, as they significantly worsen outcomes despite improving liver function tests, with enhanced risk of liver transplantation and variceal development in advanced disease 10, 2
• Ursodiol doses should never exceed 20 mg/kg/day in PSC patients 10

Gallstone Prevention During Rapid Weight Loss

For preventing gallstone formation during rapid weight loss (such as bariatric surgery), use 600 mg/day (300 mg twice daily) or 500-600 mg/day. 1, 10

• Five randomized controlled trials including 616 patients demonstrated significant reduction in postoperative gallstone formation with this dosing regimen 10
• Treatment should be continued for 6 months after surgery 10
• This prophylaxis is recommended only for patients without gallstones at the time of surgery 10

Intrahepatic Cholestasis of Pregnancy (ICP)

The recommended dosage for ICP is 10-15 mg/kg/day divided into 2-3 doses. 2

• Pruritus typically decreases within 1-2 weeks, with biochemical improvement within 3-4 weeks 2
• If pruritus is not relieved, the dose can be titrated to a maximum of 21 mg/kg/day 2
• Ursodiol is considered safe during pregnancy and breastfeeding 2, 3
• Serum bile acids should be measured at least weekly starting at 32 weeks gestation 2

Special Considerations

Renal Insufficiency

• No dosage adjustment is necessary for renal insufficiency, as ursodiol is primarily metabolized in the liver and excreted through bile, not via renal excretion 8
• Creatinine clearance calculation is not required to adjust ursodiol dosing 8

Monitoring and Duration

• Regular monitoring of liver biochemistry is essential to assess treatment response 2
• Long-term therapy is generally required for chronic liver diseases 3
• In patients with hepatic decompensation or advanced disease, discontinuation may be necessary 2