Is ursodeoxycholic acid (UDCA) safe to use during pregnancy?

Ursodeoxycholic Acid Safety in Pregnancy

Ursodeoxycholic acid (UDCA) is safe to use during pregnancy and is strongly recommended to be continued in pregnant women with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). 1

Safety Profile

• UDCA at medium doses (15-20 mg/kg/day) is considered safe during pregnancy and breastfeeding, with strong guideline support from the European Association for the Study of Liver (EASL) 1
• FDA labeling notes that reproduction studies in rats and rabbits at doses up to 200-fold the therapeutic dose revealed no evidence of fetal harm at doses of 20-100 fold the human dose in rats and 5-fold in rabbits 2
• Inadvertent exposure of 4 women to therapeutic doses of UDCA in the first trimester during clinical trials showed no evidence of effects on the fetus or newborn baby 2
• Clinical studies have confirmed good safety profiles with no complications attributable to UDCA treatment during fetal life, delivery, or early neonatal period 3

Efficacy in Pregnancy-Related Liver Conditions

• UDCA is specifically recommended for intrahepatic cholestasis of pregnancy (ICP), particularly when serum bile acid concentrations exceed 40 μmol/L 1
• UDCA treatment in ICP has been shown to:
  • Reduce the risk of spontaneous preterm birth 1
  • Potentially provide protection against stillbirth 1
  • Improve maternal pruritus symptoms 4, 3
  • Significantly decrease serum total bile acids, bilirubin concentration, and aminotransferase activity 4

Dosing Considerations

• For PBC and PSC, the recommended dose is 15-20 mg/kg/day 1
• For ICP, treatment can start with a lower dose (10 mg/kg/day) and gradually increase to 20 mg/kg/day 1
• Even low doses (300-450 mg/day; 4-6 mg/kg/day) have been shown to improve biochemical markers and clinical symptoms in almost 90% of ICP patients 4

Special Considerations

• UDCA is not detected in breast milk in significant amounts, making it safe during breastfeeding 5
• When administering UDCA with other medications:
  • UDCA and cholestyramine administration should be separated by at least 4 hours 1
  • Bile acid sequestering agents (cholestyramine, colestipol) may interfere with UDCA by reducing its absorption 2
  • Aluminum-based antacids may interfere with UDCA absorption 2

Monitoring During Treatment

• In women with cholestasis treated with UDCA, it's reasonable to monitor:
  • Liver function tests (ALT/AST, bilirubin) 1
  • Coagulation tests (INR), especially when combined with anion exchange resins or in women with steatorrhea 1
  • Vitamin K status, as cholestasis and use of anion exchange resins may exacerbate vitamin K deficiency 1

Important Caveats

• While UDCA is recommended for PBC and ICP, a 2019 randomized controlled trial (PITCHES) questioned its efficacy in reducing adverse perinatal outcomes in ICP, suggesting its routine use should be reconsidered 6
• However, the most recent EASL guidelines (2023) still strongly recommend UDCA for ICP with elevated bile acids 1
• Obeticholic acid (another bile acid treatment) should be discontinued as soon as pregnancy is confirmed due to lack of safety data 1

UDCA remains the first-line treatment for cholestatic liver conditions during pregnancy, with a well-established safety profile and documented efficacy in improving maternal biochemical parameters and symptoms.