What is the recommended dosing for ursodiol (ursodeoxycholic acid) in a pregnant woman diagnosed with Intrahepatic Cholestasis of Pregnancy (ICP)?

Ursodiol Dosing for Intrahepatic Cholestasis of Pregnancy

Start ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day divided into 2-3 doses daily for treatment of intrahepatic cholestasis of pregnancy. 1

Initial Dosing Strategy

• Begin with 10-15 mg/kg/day as the standard starting dose, which translates to typical regimens of 300 mg twice or three times daily, or 500 mg twice daily 1
• Divide the total daily dose into 2-3 administrations to optimize tolerability and maintain therapeutic levels 1, 2
• For a 70 kg woman, this equates to approximately 700-1050 mg total daily dose 1

Dose Titration and Adjustment

• If pruritus does not improve within 1-2 weeks, titrate upward to a maximum of 21 mg/kg/day 1, 3
• Biochemical improvement (reduction in bile acids and liver enzymes) typically occurs within 3-4 weeks of treatment 1
• The European guidelines suggest slightly higher dosing at 15-20 mg/kg/day for cholestatic conditions, though this is based primarily on primary biliary cholangitis data 1, 4

Evidence Supporting This Dosing

The 2021 Society for Maternal-Fetal Medicine guidelines provide the strongest recommendation for 10-15 mg/kg/day based on multiple meta-analyses showing improvement in maternal pruritus 1. The 2024 American Gastroenterological Association guidelines reinforce this exact dosing range 1. While a large 2019 randomized controlled trial (PITCHES) with 605 women found that UDCA did not reduce the composite perinatal outcome of death, preterm delivery, or NICU admission 5, the guidelines continue to recommend UDCA primarily for maternal symptom relief rather than perinatal outcomes 1.

Important Clinical Considerations

Timing and Duration

• Continue UDCA from diagnosis until delivery 3
• Discontinue at delivery, as symptoms typically resolve postpartum 3
• If pruritus or abnormal liver tests persist 4-6 weeks postpartum, investigate for underlying chronic liver disease 1, 3

Tolerability

• UDCA is generally well-tolerated with mild nausea and dizziness reported in up to 25% of patients 1
• No known adverse fetal effects have been documented 1, 2
• UDCA is FDA pregnancy category B 2

Drug Interactions

• Separate UDCA from cholestyramine or other bile acid sequestrants by at least 4 hours to prevent binding and reduced UDCA absorption 1, 2, 3
• If using rifampicin (300-600 mg daily) as adjunctive therapy for refractory pruritus, monitor vitamin K status 1, 2, 3

Alternative Dosing Considerations

Some research suggests lower doses (4-6 mg/kg/day or 300-450 mg/day) may be effective in improving biochemical markers and symptoms in nearly 90% of patients 6. However, this contradicts guideline recommendations and should not be used as standard practice 1. The established 10-15 mg/kg/day dosing has the strongest evidence base and guideline support.

When UDCA Fails

• Approximately 10-25% of patients may not respond adequately to UDCA 1, 6
• For refractory pruritus despite maximum UDCA dosing, consider adding rifampicin (300-600 mg daily) or cholestyramine (4-8 g/day) 1, 2, 3
• In severe cases with unbearable pruritus, plasmapheresis may provide transient relief 1, 3

Monitoring Requirements

• Measure serum bile acids at least weekly starting at 32 weeks gestation 2, 3
• Bile acid levels >100 μmol/L warrant delivery planning at 36 weeks 1, 3
• Bile acid levels <40 μmol/L may allow expectant management to term 1