What is the recommended dose of ursodeoxycholic acid (UDCA)?

Ursodeoxycholic Acid Dosing

The recommended dose of ursodeoxycholic acid is 13-15 mg/kg/day for primary biliary cholangitis (PBC), administered as a single bedtime dose, which represents the established first-line therapy with proven mortality benefit. 1, 2

Dosing by Indication

Primary Biliary Cholangitis (PBC)

• Standard dose: 13-15 mg/kg/day is the established treatment of choice based on multiple placebo-controlled trials 1, 2
• This dose significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 1
• Long-term treatment at this dose delays histological progression when started at early disease stages 2
• Treatment is associated with significant reduction in likelihood of liver transplantation or death in patients with moderate to severe PBC 2
• Administer as a single bedtime dose for optimal convenience and compliance 2
• Doses of 5-7 mg/kg/day are suboptimal and produce inferior biochemical responses 3
• Doses of 23-25 mg/kg/day provide no additional benefit over the standard 13-15 mg/kg/day dose 3, 4

Primary Sclerosing Cholangitis (PSC)

• UDCA is NOT recommended for routine use in PSC - this is a strong recommendation from multiple major societies 5, 2
• Low-dose (10-15 mg/kg/day) improves liver biochemistry but does not improve clinical outcomes including death, transplantation, or disease progression 2
• Moderate-dose (15-20 mg/kg/day) may be considered in select cases as it can improve serum liver tests and surrogate markers of prognosis, though evidence for hard clinical endpoints is lacking 5, 1
• High-dose (28-30 mg/kg/day) MUST BE AVOIDED due to association with increased serious adverse events, higher rates of death, liver transplantation, and development of varices 5, 2

Intrahepatic Cholestasis of Pregnancy

• Recommended dose: 10-15 mg/kg/day divided into 2-3 doses daily 1, 2
• Decrease in pruritus typically occurs within 1-2 weeks, and biochemical improvement is usually seen within 3-4 weeks 2
• If pruritus is not relieved, the dose can be titrated to a maximum of 21 mg/kg/day 2
• UDCA is considered safe during pregnancy and breastfeeding 2

Gallstone Dissolution

• Recommended dose: 8-10 mg/kg/day given in 2 or 3 divided doses 6
• This dose appears optimal based on clinical trial results in 868 patients treated for periods ranging from 6 to 78 months 6
• Complete stone dissolution can be anticipated in about 30% of unselected patients with uncalcified gallstones <20 mm in maximal diameter treated for up to 2 years 6
• The chance of dissolution increases to 50% in patients with floating or floatable stones (high cholesterol content) 6
• Complete dissolution was observed in 81% of patients with stones up to 5 mm in diameter 6

Gallstone Prevention During Rapid Weight Loss

• Recommended dose: 600 mg/day (300 mg twice daily) 6

Critical Safety Considerations

Dose-Related Toxicity

• There is a very narrow therapeutic window between the recommended dose (13 mg/kg/day) and toxic dose (28 mg/kg/day) 7
• High-dose UDCA (28-30 mg/kg/day) in PSC was associated with more than double the number of deaths and eligibility for liver transplantation compared to control groups, necessitating trial halt 7
• UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, and immune-suppression 7

Monitoring Requirements

• Regular monitoring of liver biochemistry is essential to assess treatment response 2
• Biochemical response should be evaluated after 1 year of therapy to identify patients at risk of progressive disease 2
• For gallstone dissolution, ultrasound images should be obtained at 6-month intervals for the first year to monitor response 6
• If partial stone dissolution is not seen by 12 months of therapy, the likelihood of success is greatly reduced 6

Common Pitfalls to Avoid

• Do not use UDCA routinely in PSC - multiple major societies recommend against this practice due to lack of efficacy and potential harm at higher doses 5, 2
• Do not exceed 20 mg/kg/day in PSC - doses of 28-30 mg/kg/day are associated with increased mortality and serious adverse events 5
• Do not use doses below 13 mg/kg/day for PBC - lower doses (5-7 mg/kg/day) produce inferior biochemical responses and are suboptimal 3
• Do not use doses above 15 mg/kg/day for PBC - higher doses (23-25 mg/kg/day) provide no additional benefit over standard dosing 3, 4
• Gallbladder nonvisualization developing during UDCA treatment predicts failure of complete stone dissolution and therapy should be discontinued 6