What is the use of Ursodiol (Ursodeoxycholic acid)?

From the Guidelines

Ursodiol should not be used for the routine treatment of newly diagnosed primary sclerosing cholangitis (PSC) due to lack of evidence showing improvement in outcomes and potential harm in high doses. The medication is primarily used to treat gallstones and certain liver conditions, working by decreasing cholesterol production and increasing bile flow to help dissolve gallstones. For gallstone dissolution, the typical dosage is 8-10 mg/kg/day, while for primary biliary cholangitis, the standard dose is 13-15 mg/kg/day 1. Treatment duration for gallstones typically ranges from 6 months to 2 years, with regular monitoring to assess effectiveness. Ursodiol is generally well-tolerated with minimal side effects, which may include diarrhea, nausea, or abdominal discomfort.

Key Points:

• Ursodiol is not recommended for routine treatment of PSC due to lack of evidence and potential harm in high doses 1.
• The medication is used to treat gallstones and certain liver conditions by decreasing cholesterol production and increasing bile flow.
• Typical dosage for gallstone dissolution is 8-10 mg/kg/day, and for primary biliary cholangitis, it is 13-15 mg/kg/day.
• Treatment duration for gallstones is 6 months to 2 years, with regular monitoring to assess effectiveness.
• Ursodiol is generally well-tolerated with minimal side effects, including diarrhea, nausea, or abdominal discomfort.

Evidence Summary:

Studies have shown that ursodiol improves liver biochemistry but does not improve outcomes in PSC patients, and high doses may be harmful 1. A large, multicenter study of high-dose ursodiol in 150 PSC patients was terminated early due to higher rates of serious adverse events and primary endpoints in the ursodiol-treated group 1. Meta-analyses of published data report no benefit from ursodiol in patients with PSC 1.

Recommendations:

Ursodiol should not be used for the routine treatment of newly diagnosed PSC. For patients already established on ursodiol therapy, there may be evidence of harm in patients taking high-dose ursodiol (28-30 mg/kg/day) 1. Regular liver function tests are typically recommended during treatment to monitor progress and adjust dosing if necessary. Patients should inform their healthcare provider about all medications they're taking, as certain drugs may interfere with ursodiol's effectiveness.

From the FDA Drug Label

Ursodiol capsules are indicated for patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Ursodiol capsules are indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss.

The main indications for ursodiol are:

• Treatment of patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter who are at increased surgical risk
• Prevention of gallstone formation in obese patients experiencing rapid weight loss The safety of use of ursodiol capsules beyond 24 months is not established 2

From the Research

Ursodiol Studies

• The efficacy of ursodiol in treating primary biliary cirrhosis has been studied in several trials 3, 4, 5, 6.
• A multicenter, controlled trial published in 1991 found that ursodiol improved the condition of patients with primary biliary cirrhosis, with significant improvements in serum levels of bilirubin, alkaline phosphatase, and other liver function tests 3.
• A follow-up study published in 1994 found that long-term ursodiol therapy slowed the progression of primary biliary cirrhosis and reduced the need for liver transplantation 4.
• A study published in 1999 found that the optimum dose of ursodiol was 900 mg/day, which produced the greatest enrichment of ursodiol in serum bile acids and improved liver function tests 5.
• A long-term follow-up study published in 2002 found that ursodiol treatment was associated with biochemical improvement, histological stability, and increased survival free of transplantation 6.
• However, some patients may not respond adequately to ursodiol, and alternative treatments such as obeticholic acid may be effective in these cases 7.

Ursodiol Dosage

• The optimum dose of ursodiol has been found to be 900 mg/day, which is equivalent to 13.5 mg/kg/day 5.
• However, the dose of ursodiol used in clinical trials has varied, ranging from 10-15 mg/kg/day 3, 4.
• The efficacy of ursodiol has been found to be dose-dependent, with higher doses producing greater improvements in liver function tests 5, 6.

Ursodiol Efficacy

• Ursodiol has been found to be effective in improving liver function tests, including alkaline phosphatase, bilirubin, and alanine aminotransferase 3, 4, 5, 6.
• Ursodiol has also been found to slow the progression of primary biliary cirrhosis and reduce the need for liver transplantation 4, 6.
• However, some patients may not respond adequately to ursodiol, and alternative treatments may be necessary 7.