Thiopurines and the Risk of Intrahepatic Cholestasis of Pregnancy

Introduction

Thiopurines, including azathioprine, mercaptopurine, and tioguanine, are commonly used immunosuppressants for conditions such as inflammatory bowel disease and to prevent organ transplant rejection. Recent reports have identified a rare occurrence of intrahepatic cholestasis of pregnancy (ICP) in patients treated with these medications.

Clinical Observations

ICP linked to thiopurine use tends to manifest earlier in pregnancy compared to non-drug-induced cases. Notably, elevated bile acid levels in these instances may not respond to standard treatment with ursodeoxycholic acid. However, discontinuation or dose reduction of the thiopurine has been associated with improvements in liver function tests.

Guidance for Healthcare Professionals

• Maintain awareness of ICP symptoms in pregnant patients on thiopurines.
• Collaborate with specialists managing the patient’s immunosuppressive therapy and consider hepatology consultation.
• If ICP is diagnosed, evaluate the risks and benefits of continuing thiopurine therapy on a case-by-case basis.
• Measure serum bile acids to assess the risk of adverse pregnancy outcomes, particularly if levels are ≥40 µmol/L for preterm birth risk or ≥100 µmol/L for stillbirth risk.

Advice for Patients

• Immediately inform your doctor or midwife if you experience intense itching without a rash, nausea, or loss of appetite during pregnancy.
• Do not discontinue any prescribed medication without professional medical advice.

Conclusion

While the association between thiopurines and ICP is rare, it necessitates careful monitoring and management. Healthcare professionals should balance the therapeutic benefits of thiopurines against potential risks during pregnancy, ensuring informed decision-making and patient safety.

Citation:
Medicines and Healthcare products Regulatory Agency. (2025, May 15). Thiopurines and intrahepatic cholestasis of pregnancy. GOV.UK.