[4/29/2024] FDA is alerting health care professionals of the rare risk of intrahepatic cholestasis of pregnancy (ICP) associated with the use of thiopurines (azathioprine, 6-mercaptopurine, and 6-thioguanine).
Thiopurines are immunosuppressants with a known risk of hepatotoxicity and are currently labeled for risk of fetal harm with use during pregnancy. Pregnant patients should stop using thiopurines if they develop ICP. FDA is requiring manufacturers to update labeling to include additional warning information on the risk of ICP associated with thiopurines.
Reported cases of ICP occurred among pregnant patients using azathioprine or 6-mercaptopurine primarily to treat inflammatory bowel disease (IBD)—including Crohn's disease (CD) and ulcerative colitis (UC)—or systemic lupus erythematosus (SLE). Thiopurines are not FDA-approved to treat CD, UC, or SLE; however, the American Gastroenterological Association and the American College of Rheumatology have published treatment guidelines indicating that azathioprine or 6-mercaptopurine may be appropriate to continue on an individualized basis for management of some immunologic conditions during pregnancy.
FDA is requiring all new drug application and abbreviated new drug application holders for azathioprine, 6-mercaptopurine, and 6-thioguanine drug products to include the below key pieces of information in updated labeling:
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Postmarketing cases of ICP have been reported in women treated with drugs in the thiopurine class during pregnancy.
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ICP symptoms and elevated bile acid levels improved following azathioprine discontinuation.
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Pregnant persons should discontinue use of thiopurines if they develop ICP.
Health care professionals, caregivers, and patients should report adverse events or side effects related to the use of any medicines to FDA's MedWatch Safety Information and Adverse Event Reporting Program:
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Complete and submit the report online at MedWatch Online Voluntary Reporting Form, or;
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Download and complete the form, then submit it via fax at 1-800-FDA-0178.
