What is the recommended dose of Ursofalk (Ursodeoxycholic acid) for an adult patient with gallstones or primary biliary cirrhosis?

Ursofalk (Ursodeoxycholic Acid) Dosing

For primary biliary cholangitis (PBC), give Ursofalk 13-15 mg/kg/day as a single bedtime dose; for gallstone dissolution, use 8-10 mg/kg/day in divided doses; and critically, avoid routine use in primary sclerosing cholangitis (PSC) as it provides no clinical benefit and high doses (>20 mg/kg/day) cause harm. 1, 2

Primary Biliary Cholangitis (PBC) - First-Line Therapy

Standard dosing is 13-15 mg/kg/day administered as a single bedtime dose. 1, 3

• This represents the established first-line treatment for PBC, supported by multiple placebo-controlled trials demonstrating significant reductions in serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels. 4, 1
• Long-term treatment delays histological progression when initiated at early disease stages and significantly reduces the likelihood of liver transplantation or death in patients with moderate to severe PBC. 4, 3
• Biochemical response should be evaluated after 1 year of therapy to identify patients at risk of progressive disease who may require second-line therapies. 1, 3
• Research suggests that 900 mg/day (approximately 13.5 mg/kg/day for a 67 kg patient) produces optimal enrichment of UDCA in serum bile acids with maximal improvement in liver function tests. 5

Post-liver transplant PBC patients require lifelong therapy at 10-15 mg/kg/day in two divided doses to prevent disease recurrence, which has been associated with lower risk of graft loss, liver-related death, and all-cause death. 6, 4, 3

Gallstone Dissolution

Use 8-10 mg/kg/day divided into 2-3 doses for radiolucent gallbladder stones. 2

• This FDA-approved dosing achieves complete stone dissolution in approximately 30% of unselected patients with uncalcified stones <20 mm treated for up to 2 years. 2
• Dissolution rates increase to 50% in patients with floating/floatable stones (high cholesterol content) and 81% in patients with stones ≤5 mm in diameter. 2
• Ultrasound monitoring should occur at 6-month intervals during the first year; if partial dissolution is not evident by 12 months, success is unlikely and therapy should be discontinued. 2

For gallstone prevention during rapid weight loss, use 600 mg/day (300 mg twice daily). 2

Primary Sclerosing Cholangitis (PSC) - Critical Warnings

Do NOT use UDCA routinely for newly diagnosed PSC. 6, 1

• The British Society of Gastroenterology provides a STRONG recommendation against routine use, and the American Association for the Study of Liver Diseases gives a Grade 1A recommendation against UDCA as medical therapy for adult PSC patients. 6, 1
• Low-dose UDCA (10-15 mg/kg/day) improves liver biochemistry but does not improve clinical outcomes including death, transplantation, or disease progression. 6, 1
• A large trial of 105 PSC patients treated with 13-15 mg/kg/day for 2.2 years showed no difference in time to treatment failure compared to placebo, despite biochemical improvements. 7

HIGH-DOSE UDCA (28-30 mg/kg/day) MUST BE AVOIDED in PSC as it causes serious harm. 6, 1, 3

• A multicenter study was terminated early due to enhanced risk of liver transplantation, death, and development of varices in the high-dose UDCA group. 6
• Moderate-dose UDCA (15-20 mg/kg/day) may be considered in highly selected cases as it can improve surrogate markers, but available data does not support a firm recommendation. 4, 1

Intrahepatic Cholestasis of Pregnancy

Use 10-15 mg/kg/day divided into 2-3 doses daily. 4, 1, 3

• Pruritus typically decreases within 1-2 weeks, and biochemical improvement occurs within 3-4 weeks. 4, 1
• If pruritus persists, titrate to a maximum of 21 mg/kg/day. 1
• UDCA is considered safe during pregnancy and breastfeeding. 4

Critical Pitfalls to Avoid

• Never exceed 20 mg/kg/day in any cholestatic liver disease except under specific protocols, as high-dose UDCA has been associated with worse outcomes, particularly in PSC. 3
• Monitor late-stage PBC patients (stages III-IV) closely during the first 2 months of therapy with biweekly bilirubin checks, as some patients may experience worsening bilirubin and pruritus requiring dose reduction or discontinuation. 8
• Do not use UDCA as first-line therapy for pruritus management in cholestatic diseases, as cholestyramine and rifampicin have stronger evidence for symptom control. 3
• Recognize that calcified gallstones, stones >20 mm, or gallbladder nonvisualization developing during treatment predict failure of dissolution and warrant discontinuation. 2