What is Ursodeoxycholic acid (UDCA) most commonly prescribed for?

Primary Indications for Ursodeoxycholic Acid (UDCA)

UDCA is most commonly prescribed for primary biliary cirrhosis (PBC) as the established first-line treatment at doses of 13-15 mg/kg/day. 1, 2

Primary Indications with Strong Evidence

• UDCA at 13-15 mg/kg/day is the recommended first-line therapy for primary biliary cirrhosis (PBC), with substantial evidence supporting its efficacy 1, 2
• UDCA treatment in PBC significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 1
• Long-term UDCA treatment delays histological progression of PBC when started at an early stage of the disease 1, 2
• UDCA treatment is associated with a significant reduction in the likelihood of liver transplantation or death in patients with moderate to severe PBC 1, 2

Secondary Indications

• UDCA is indicated for patients with radiolucent, noncalcified gallbladder stones <20 mm in greatest diameter at doses of 8-10 mg/kg/day given in 2 or 3 divided doses 3
• UDCA is indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss at a dose of 600 mg/day (300 mg twice daily) 3
• UDCA may be considered for treatment of maternal pruritus in intrahepatic cholestasis of pregnancy (ICP) at doses of 10-15 mg/kg/day 2

Controversial Indications

• For primary sclerosing cholangitis (PSC), the evidence is mixed and current guidelines do not support routine use 4
• The American Association for the Study of Liver Diseases recommends against the use of UDCA as medical therapy for adult patients with PSC 4
• Higher doses of UDCA (20-25 mg/kg/day) have shown some improvements in liver fibrosis histology and cholangiographic appearances in PSC patients, but clinical outcomes remain uncertain 4, 5
• Very high doses (28-30 mg/kg/day) have shown potential harm in late-stage PSC, with increased risk of reaching endpoints such as liver transplantation 5

Mechanism of Action

• UDCA exerts anticholestatic effects through stimulation of impaired hepatocellular secretion and stimulation of ductular alkaline choleresis 2
• UDCA changes bile acid composition from hydrophobic to more hydrophilic, reducing the amount of toxic bile acids 2
• UDCA has both anti-inflammatory and anti-apoptotic properties that contribute to its therapeutic effects 6

Monitoring and Safety

• Regular monitoring of liver biochemistry is essential to assess treatment response in patients on UDCA therapy 1, 2
• UDCA is generally well tolerated, with mild side effects such as nausea and dizziness occurring in up to 25% of patients 1
• UDCA is considered safe during pregnancy and breastfeeding, particularly for women with PBC and PSC who require continued treatment 4
• The therapeutic window of UDCA is relatively narrow, with recommended doses (13-15 mg/kg/day) being well-tolerated while higher doses (28 mg/kg/day) may be harmful in certain conditions like PSC 7

In summary, while UDCA has several approved and off-label uses, its primary and most established indication remains the treatment of primary biliary cirrhosis, where it has demonstrated significant improvements in biochemical parameters and long-term outcomes.