Udiliv (Ursodeoxycholic Acid + Silymarin) Dosing for Adult Liver Disease
For adult patients with chronic liver disease, ursodeoxycholic acid should be dosed at 13-15 mg/kg/day for primary biliary cholangitis, but is NOT recommended for primary sclerosing cholangitis due to lack of efficacy and potential harm at higher doses. 1, 2
Primary Biliary Cholangitis (PBC) - First-Line Therapy
Ursodeoxycholic acid at 13-15 mg/kg/day is the established first-line treatment for PBC, administered as a single bedtime dose. 3, 4, 2
- This dosing significantly reduces serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 3, 2
- Long-term treatment delays histological progression when initiated at early disease stages 3, 4
- Treatment reduces the likelihood of liver transplantation or death in patients with moderate to severe PBC 3, 2
- Biochemical response should be evaluated after 1 year of therapy to identify patients at risk of progressive disease 4, 2
Post-Liver Transplant PBC Management
- UDCA should be continued lifelong at 10-15 mg/kg/day in two divided doses after liver transplantation to prevent PBC recurrence 3, 4
- This approach reduces long-term risk of graft loss, liver-related death, and all-cause death 4
Primary Sclerosing Cholangitis (PSC) - Critical Warnings
UDCA is NOT recommended for routine treatment of PSC, and high-dose UDCA (28-30 mg/kg/day) MUST BE AVOIDED due to increased mortality and serious adverse events. 1, 2
- Low-dose UDCA (10-15 mg/kg/day) improves liver biochemistry but does not improve clinical outcomes including death, transplantation, or disease progression 2
- Moderate-dose UDCA (15-20 mg/kg/day) may improve serum liver tests and surrogate markers of prognosis, but available data does not support a firm recommendation 1, 2
- High-dose UDCA (28-30 mg/kg/day) is associated with significantly worse outcomes including higher rates of death, liver transplantation, and development of varices 1, 4, 2
- Doses should never exceed 20 mg/kg/day in any patient 1, 4
Silymarin Component
- One small study showed that adding silymarin (400 mg/daily) to UDCA (450 mg/daily) in 30 patients with chronic alcoholic liver disease induced further improvement of hepatic function beyond UDCA alone 5
- However, silymarin has limited evidence for suboptimal response to UDCA in PBC 1
Drug-Induced Cholestatic Liver Injury
UDCA is NOT established therapy for drug-induced cholestatic liver injury (DILI). 4, 6
- For cholestatic DILI with elevated ALP/GGT/TBil, ursodeoxycholic acid or S-adenosylmethionine may be selected, but this is based on weak evidence 6
- Primary management involves discontinuation of the offending agent, ruling out alternative causes, and supportive care 4
Gallstone-Related Indications (FDA-Approved)
For gallstone dissolution, the FDA-approved dosing is 8-10 mg/kg/day given in 2 or 3 divided doses 7
- Complete stone dissolution can be anticipated in about 30% of unselected patients with uncalcified gallstones <20 mm treated for up to 2 years 7
- For gallstone prevention during rapid weight loss, the dose is 600 mg/day (300 mg twice daily) 7
Critical Pitfalls to Avoid
- Never exceed 20 mg/kg/day in any cholestatic liver disease, as high-dose UDCA has been associated with worse outcomes, particularly in PSC 1, 4
- Do not use UDCA as first-line therapy for pruritus management, as cholestyramine and rifampin have stronger evidence for pruritus control 4
- UDCA may paradoxically worsen itching in some patients 4
- In patients with alcoholic liver disease, exercise special caution as excessive alcohol intake may potentiate hepatotoxicity of other medications like acetaminophen 8
Monitoring Requirements
- Regular monitoring of liver biochemistry is essential to assess treatment response 3, 2
- Ultrasound images should be obtained at 6-month intervals for the first year when treating gallstones 7
- For PBC, evaluate biochemical response after 1 year to identify non-responders who may need second-line therapies 4, 2