What is the dosage and treatment duration of ursodiol (ursodeoxycholic acid) for primary biliary cirrhosis and gallstone dissolution?

Ursodiol Dosing and Treatment Duration

For primary biliary cirrhosis, ursodiol should be dosed at 13-15 mg/kg/day divided into 2-3 doses and continued long-term indefinitely, while for gallstone dissolution, use 8-10 mg/kg/day divided into 2-3 doses for up to 2 years with ultrasound monitoring every 6 months. 1, 2, 3

Primary Biliary Cirrhosis (PBC)

Standard Dosing

• The established first-line dose is 13-15 mg/kg/day, divided into 2-3 daily doses 1, 2
• This dosing regimen significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 2
• Multiple dose-comparison studies confirm that 13-15 mg/kg/day is superior to lower doses (5-7 mg/kg/day) but equivalent to higher doses (23-25 mg/kg/day) in improving liver biochemistries and Mayo risk scores 4, 5

Treatment Duration and Monitoring

• Treatment should be continued long-term indefinitely - long-term therapy delays histological progression when started at early disease stages 1, 2
• Ursodiol reduces the likelihood of liver transplantation or death by 68-79% in patients with moderate to severe PBC 6, 7
• Regular monitoring of liver biochemistry is essential to assess treatment response 1
• Biochemical response should be evaluated after 1 year of therapy to identify patients at risk for progressive disease 1

Important Caveats

• Ursodiol does not significantly improve symptoms like fatigue or pruritus, so additional symptomatic treatments may be needed 1, 2
• The medication is generally well tolerated, though nausea and mild dizziness occur in up to 25% of patients 2
• Ursodiol is safe during pregnancy and breastfeeding for women requiring continued treatment 1, 8

Gallstone Dissolution

Dosing Protocol

• Use 8-10 mg/kg/day divided into 2-3 doses for radiolucent gallstones 3
• This lower dose compared to PBC is based on extensive clinical trial data showing optimal efficacy at this range 3

Treatment Duration and Monitoring Strategy

• Obtain ultrasound images at 6-month intervals during the first year 3
• If partial stone dissolution is not evident by 12 months, the likelihood of success is greatly reduced and therapy should be discontinued 3
• Continue treatment if stones appear dissolved, then confirm dissolution on repeat ultrasound within 1-3 months 3
• Complete stone dissolution can be anticipated in approximately 30% of unselected patients with uncalcified stones <20 mm treated for up to 2 years 3

Predictors of Success and Failure

• Success rates increase to 50% in patients with floating/floatable stones (high cholesterol content) 3
• Complete dissolution occurs in 81% of patients with stones ≤5 mm in diameter 3
• Calcified gallstones, stones >20 mm, or gallbladder non-visualization developing during treatment predict failure - discontinue therapy in these cases 3

Stone Recurrence

• Stone recurrence occurs in 30-50% of patients within 2-5 years after complete dissolution 3
• Serial ultrasonographic examinations should monitor for recurrence 3
• Radiolucency must be re-established before instituting another course of ursodiol 3

Gallstone Prevention During Rapid Weight Loss

• Use 600 mg/day (300 mg twice daily) for patients undergoing rapid weight loss 3
• This indication applies specifically to obese patients at risk for gallstone formation during very low calorie diets 3

Primary Sclerosing Cholangitis (PSC) - Critical Warning

• Do NOT use ursodiol routinely for PSC - both the American Association for the Study of Liver Diseases and British Society of Gastroenterology recommend against routine use due to limited efficacy 1, 2
• If used at all, doses of 15-20 mg/kg/day may improve serum liver tests, though clinical benefit remains uncertain 1
• High-dose ursodiol (>20 mg/kg/day or 28-30 mg/kg/day) should NEVER be given in PSC - it increases risk of liver transplantation and variceal development in advanced disease 1, 2

Intrahepatic Cholestasis of Pregnancy

• Use 10-15 mg/kg/day divided into 2-3 doses 1
• Pruritus typically decreases within 1-2 weeks, with biochemical improvement in 3-4 weeks 1
• If pruritus persists, titrate to a maximum of 21 mg/kg/day 1
• Measure serum bile acids at least weekly starting at 32 weeks gestation 1