What is the treatment protocol for Urisodol (Ursodeoxycholic acid)?

Ursodeoxycholic Acid (UDCA) Treatment Protocol

For primary biliary cirrhosis (PBC), ursodeoxycholic acid should be administered at 13-15 mg/kg/day divided into 2-3 doses, which is the established first-line therapy that reduces disease progression and need for liver transplantation. 1, 2, 3

Primary Indications and Dosing

Primary Biliary Cirrhosis (PBC)

• Dose: 13-15 mg/kg/day divided into 2-3 doses 1, 2, 3
• This dosing is supported by multiple randomized controlled trials showing significant improvements in liver biochemistry and clinical outcomes 4
• Long-term treatment delays histological progression when started at early disease stages 1, 2
• Treatment significantly reduces likelihood of liver transplantation or death in moderate to severe PBC 1, 2, 5

Gallstone Dissolution

• Dose: 8-10 mg/kg/day given in 2-3 divided doses 6
• Monitor with ultrasound at 6-month intervals during first year 6
• If partial dissolution not seen by 12 months, likelihood of success is greatly reduced 6
• Continue therapy and confirm dissolution on repeat ultrasound within 1-3 months after apparent dissolution 6

Gallstone Prevention (Rapid Weight Loss)

• Dose: 600 mg/day (300 mg twice daily) 6

Intrahepatic Cholestasis of Pregnancy (ICP)

• Dose: 10-15 mg/kg/day divided into 2-3 doses 1, 2, 3
• Can titrate to maximum of 21 mg/kg/day if pruritus not relieved 2
• Pruritus typically decreases within 1-2 weeks; biochemical improvement within 3-4 weeks 2
• May reduce risk of spontaneous preterm birth when serum bile acids >40 μmol/L 1

Dosing Comparison Study

A randomized trial comparing three doses (5-7,13-15, and 23-25 mg/kg/day) in 155 PBC patients demonstrated that 13-15 mg/kg/day is the optimal dose 7:

• Standard (13-15 mg/kg/day) and high doses (23-25 mg/kg/day) showed significantly greater improvements in alkaline phosphatase, AST, and Mayo risk score compared to low dose (5-7 mg/kg/day) 7
• No significant difference between standard and high doses 7
• All doses were safe and well-tolerated with no discontinuations due to side effects 7

Contraindicated or Not Recommended Uses

Primary Sclerosing Cholangitis (PSC)

• Do NOT use routinely - both AASLD and British Society of Gastroenterology recommend against routine use 2, 3
• NEVER use high-dose UDCA (>20 mg/kg/day or 28-30 mg/kg/day) - associated with worse outcomes including increased risk of liver transplantation and variceal development 2, 3
• If used at all, limit to 15-20 mg/kg/day, though evidence of benefit is limited 2

Monitoring Protocol

Initial Assessment

• Baseline liver biochemistry: bilirubin, alkaline phosphatase, AST, ALT, GGT, cholesterol, immunoglobulin M 1, 3
• Alkaline phosphatase and GGT are the earliest cholestasis markers 3

Ongoing Monitoring

• Regular liver biochemistry monitoring to assess treatment response 1, 2, 3
• Evaluate biochemical response after 1 year to identify patients at risk for progressive disease 2
• For AMA-positive individuals with normal liver tests: annual reassessment of biochemical markers 2, 3
• For ICP: weekly serum bile acid measurements as levels may continue rising with advancing gestation 1

Expected Biochemical Improvements in PBC

• Significant decreases in serum bilirubin, alkaline phosphatase, GGT, cholesterol, and IgM levels 1, 2, 3
• High bilirubin levels and cirrhosis at baseline predict disease progression 5

Mechanisms of Action

UDCA works through multiple pathways 4, 8:

• Stimulates impaired hepatocellular secretion via posttranscriptional mechanisms 1
• Changes bile acid composition from hydrophobic to hydrophilic, reducing toxic bile acid exposure 1, 8
• Protects cholangiocytes against toxic bile acid effects 8
• Inhibits hepatocyte apoptosis through modulation of mitochondrial membrane perturbation 4
• Provides cytoprotective, anti-apoptotic, membrane-stabilizing, anti-oxidative, and immunomodulatory effects 9

Safety Profile

Tolerability

• Generally well tolerated 2, 3, 7
• Nausea and mild dizziness may occur in up to 25% of patients 2, 3
• No significant toxicity reported in doses ranging from 5-25 mg/kg/day 7
• Not significantly associated with adverse events in systematic reviews 4

Pregnancy and Breastfeeding

• Considered safe during pregnancy and breastfeeding 2, 3
• Should be continued in pregnant patients with PBC and PSC who require treatment 2

Important Clinical Caveats

Symptom Management

• UDCA does NOT significantly improve fatigue or pruritus in PBC 2, 3
• Additional treatments (such as rifaximin) may be needed for symptom management, particularly pruritus 3

When to Discontinue

• Consider discontinuation in patients with hepatic decompensation or advanced disease 2

Histological Effects

• Slows liver fibrosis progression in PBC when started early 4
• Effect on histological progression is most pronounced in early-stage disease 1, 2