The FDA has issued a strong advisory concerning the use of thiopurines during pregnancy, highlighting a newly identified risk for intrahepatic cholestasis of pregnancy (ICP). Thiopurines, known for their established risk of hepatotoxicity, are already flagged for potential fetal harm when used during pregnancy. However, the FDA now urges pregnant patients to cease thiopurine use immediately upon developing symptoms of ICP.
To bolster patient safety, the FDA mandates that drug manufacturers update their product labeling with comprehensive warnings detailing the association between thiopurine use and ICP risk.
Dr. Uma Mahadevan, an expert in pregnancy and inflammatory bowel disease (IBD) from the University of California, San Francisco, emphasized that while ICP remains a rare complication of thiopurine therapy, careful monitoring is crucial. She recommends periodic monitoring of liver enzymes throughout pregnancy and suggests measuring thiopurine metabolites. If liver enzyme levels rise, discontinuation of thiopurines is advised. Dr. Mahadevan also noted that adjusting the dosing schedule of thiopurines can potentially mitigate risks.
Reported cases of ICP primarily involved pregnant patients using 6-mercaptopurine (6-MP) or azathioprine, medications typically prescribed for IBD or systemic lupus erythematosus (SLE). Despite not being FDA-approved for Crohn’s disease, ulcerative colitis, or SLE treatment, guidelines from medical associations suggest their use under specific circumstances.
In response to these safety concerns, the FDA mandates that updated labeling for 6-MP, 6-thioguanine, and azathioprine include clear information regarding:
Post-marketing reports linking thiopurine use during pregnancy to ICP.
Improvement of ICP symptoms and bile acid levels upon discontinuation of azathioprine.
Immediate cessation of thiopurine use if ICP symptoms develop during pregnancy.
Healthcare providers, caregivers, and patients are encouraged to report any adverse effects associated with thiopurine medications to the FDA’s MedWatch program to facilitate ongoing monitoring and safety assessments.
