What are the guidelines for using Udiliv (Ursodeoxycholic acid) during pregnancy?

Udiliv (Ursodeoxycholic Acid) in Pregnancy

Ursodeoxycholic acid (UDCA/Udiliv) should be continued during pregnancy as it is safe for both mother and fetus, and is effective for treating cholestatic liver conditions including intrahepatic cholestasis of pregnancy, primary biliary cholangitis, and primary sclerosing cholangitis. 1

Safety Profile

UDCA is classified as FDA pregnancy category B, meaning animal studies have shown no fetal risk, though adequate human studies are limited. 2 However, extensive clinical experience demonstrates safety:

• No adverse maternal or fetal effects have been documented in multiple clinical trials and case series 1, 3, 4
• Four women inadvertently exposed to therapeutic UDCA doses during the first trimester showed no evidence of fetal harm or effects on newborns 2
• UDCA is safe during breastfeeding, as significant amounts are not found in breast milk during lactation 1

Indications and Dosing During Pregnancy

Pre-existing Cholestatic Liver Disease

• Continue UDCA throughout pregnancy in women with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) who were on treatment pre-conception 1
• Standard dosing: 15-20 mg/kg/day (typically 1000 mg daily or divided doses) 1
• Do not discontinue UDCA when pregnancy is confirmed, unlike obeticholic acid which must be stopped immediately 1

Intrahepatic Cholestasis of Pregnancy (ICP)

• UDCA is first-line treatment for symptomatic cholestasis developing during pregnancy 1, 3, 4
• Initiate at 10 mg/kg/day and slowly increase to 20 mg/kg/day as tolerated 1
• Treatment duration: from diagnosis until delivery 3

Clinical Benefits Demonstrated

Maternal Outcomes

• Significant reduction in pruritus (66.6% of patients achieved >50% improvement vs 19% with cholestyramine) 4
• Marked improvement in liver biochemistry: 78.5% reduction in ALT, 73.8% reduction in AST 4
• Reduction in serum bile acids by approximately 60% 4
• Decreased serum bilirubin levels (0.36 mg/dL vs 0.95 mg/dL with placebo) 3

Fetal Outcomes

• Prolonged gestation: deliveries occurred at mean 38 weeks vs 36 weeks with placebo 3
• Reduced preterm birth rate: babies delivered significantly closer to term (38.7 weeks vs 37.4 weeks with cholestyramine) 4
• Prevention of stillbirth: no stillbirths occurred in UDCA-treated patients vs one stillbirth in placebo group 3
• Normal birth weights for gestational age in all UDCA-exposed infants 3

Important Drug Interactions and Timing

Critical timing considerations to maintain UDCA efficacy:

• Separate UDCA from bile acid sequestrants by at least 4 hours 1

  • Cholestyramine (4-8 g/day) and colestipol (5-10 g/day) can bind UDCA and reduce absorption 1, 2
  • Give anion exchange resins at least 4 hours after UDCA dose 1

• Aluminum-based antacids may interfere with UDCA absorption and should be avoided or separated by several hours 2

• Calcium-containing products (like Gaviscon with calcium carbonate) should be separated by appropriate intervals, though specific timing is less critical than with bile acid sequestrants 5

Monitoring Requirements

For women on UDCA during pregnancy:

• Monitor serum bile acids repeatedly in those with worsening or new-onset pruritus, as higher levels correlate with reduced gestation length 1
• Check liver enzymes (AST/ALT) at initiation and as clinically indicated 2
• Assess vitamin K status if patient is also taking anion exchange resins or rifampicin, as these can exacerbate vitamin K deficiency 1
• Monitor INR in women receiving concurrent medications that affect vitamin K 1
• Correct vitamin K deficiency when prothrombin time is prolonged 1

Additional Pruritus Management

If UDCA alone provides insufficient relief:

• Rifampicin 300-600 mg daily can be added as second-line therapy 1

  • Considered safe in pregnancy with limited data 1
  • Neonates of rifampicin-treated mothers should receive vitamin K at birth 1
  • Monitor for hepatotoxicity (occurs in 5% but resolves with cessation) 1

• Anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day) as alternative 1

  • Must be given at least 4 hours after UDCA 1

Common Pitfalls to Avoid

Do not confuse UDCA with obeticholic acid:

• Obeticholic acid is contraindicated in pregnancy and must be discontinued immediately when pregnancy is confirmed 1
• UDCA has 100% consensus for safety and continuation during pregnancy 1

Do not delay treatment:

• Early-onset cholestasis (before week 33) benefits most from prompt UDCA initiation 3
• Delaying treatment may result in preterm delivery or stillbirth 3

Do not use inadequate doses:

• Doses below 15 mg/kg/day may be subtherapeutic 1
• Gradual dose escalation from 10 to 20 mg/kg/day optimizes tolerability 1