What is the recommended dosage and frequency of Ursodeoxycholic acid (UDCA)?

UDCA Dosage and Frequency

The recommended dosage of UDCA varies by indication: 13-15 mg/kg/day divided into 2-3 doses for primary biliary cirrhosis (PBC), 10-15 mg/kg/day divided into 2-3 doses for intrahepatic cholestasis of pregnancy (ICP), and 15-20 mg/kg/day for primary sclerosing cholangitis (PSC), though routine use in PSC is not recommended due to limited efficacy and potential harm at higher doses. 1, 2

Primary Biliary Cirrhosis (PBC)

The established first-line dose for PBC is 13-15 mg/kg/day, which should be divided into 2-3 daily doses. 2, 3 This dosing is supported by multiple placebo-controlled trials demonstrating significant improvements in serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels. 2

• Long-term treatment at this dose delays histological progression when started at early disease stages and reduces the likelihood of liver transplantation or death in patients with moderate to severe PBC. 2
• Research demonstrates that 900 mg/day (approximately 13.5 mg/kg/day) produces optimal enrichment of UDCA in serum bile acids and the greatest normalization of abnormal liver function tests. 4
• Doses of 10 mg/kg/day are suboptimal and fail to achieve adequate biochemical improvement compared to higher doses. 5

Intrahepatic Cholestasis of Pregnancy (ICP)

The typical starting dose for ICP is 10-15 mg/kg/day, divided into 2 or 3 daily doses. 1 Common regimens include 300 mg twice or three times daily, or 500 mg twice daily. 1

• UDCA is recommended as the first-line agent for treating maternal symptoms of ICP, with proven efficacy in reducing pruritus and improving laboratory abnormalities without known adverse fetal effects. 1
• A decrease in pruritus typically occurs within 1-2 weeks, and biochemical improvement is usually seen within 3-4 weeks. 1
• If pruritus is not relieved, the dose can be titrated to a maximum of 21 mg/kg/day. 1
• The drug is generally well tolerated, though mild nausea and dizziness occur in up to 25% of patients. 1

Primary Sclerosing Cholangitis (PSC)

UDCA at doses of 15-20 mg/kg/day can be given for PSC since it may improve serum liver tests and surrogate markers of prognosis, though available data does not support a firm recommendation. 1, 2

Critical Safety Warning

UDCA at doses of 28-30 mg/kg/day should NOT be given in PSC. 1, 3 A large multicenter study using these high doses was aborted due to enhanced risk of reaching primary endpoints including liver transplantation and development of varices in more advanced disease. 1, 3

• The American Association for the Study of Liver Diseases does not support routine use of UDCA for PSC. 2, 3
• The British Society of Gastroenterology recommends against routine use of UDCA for newly diagnosed PSC due to limited efficacy and potential harm at high doses. 2
• Research shows that doses of 20-25 mg/kg/day demonstrated improvements in liver fibrosis histology and cholangiographic appearances, but clinical outcome benefits remain uncertain. 6, 7
• Biliary enrichment of UDCA reaches a plateau at 22-25 mg/kg/day, with no further benefit at higher doses. 7

ABCB4 Deficiency and SC-CIP

Low-to-medium-dose UDCA (10-15 mg/kg/day) can be given in patients with ABCB4 deficiency and SC-CIP, though evidence is limited. 1 This dosing range provides anticholestatic and anti-inflammatory effects while stimulating biliary bicarbonate secretion. 1

Gallstone Dissolution (Non-Cholestatic Indication)

For radiolucent gallbladder stones, the FDA-approved dose is 8-10 mg/kg/day given in 2-3 divided doses. 8 For gallstone prevention during rapid weight loss, the recommended dose is 600 mg/day (300 mg twice daily). 8

Administration Considerations

• UDCA should be taken with food to optimize absorption and minimize gastrointestinal side effects. 8
• When taking UDCA with other medications, maintain appropriate timing between doses (at least 4 hours separation) to prevent potential interaction with absorption of other medications, particularly calcium-containing products. 9
• Long-term therapy is generally required for chronic liver diseases. 3

Monitoring Requirements

• Regular monitoring of liver biochemistry is essential to assess treatment response. 2
• For ICP, serum bile acid levels should be measured at least weekly starting at 32 weeks of gestation. 2
• For PBC, biochemical response should be evaluated after 1 year of therapy to identify patients at risk of progressive disease. 2
• Ultrasound monitoring at 6-month intervals is recommended for gallstone dissolution therapy. 8

Common Pitfalls to Avoid

• Do not use doses of 28-30 mg/kg/day in PSC due to documented harm in late-stage disease. 1, 3
• Do not use suboptimal doses of 10 mg/kg/day for PBC as they fail to achieve adequate biochemical improvement. 5
• Do not expect UDCA to improve symptoms like fatigue or pruritus in PBC, as it primarily affects biochemical markers. 2
• Do not discontinue UDCA abruptly as withdrawal syndrome has been reported. 10