FDA Warns of ICP Associated With Thiopurine Use

On April 29, the US Food and Drug Administration (FDA) issued an alert to health care professionals concerning the rare risk of intrahepatic cholestasis of pregnancy (ICP) associated with the use of thiopurines (azathioprine, 6-mercaptopurine, and 6-thioguanine).  

“Pregnant patients should stop using thiopurines if they develop ICP,” the agency stated in a release. “FDA is requiring manufacturers to update labeling to include additional warning information on the risk of ICP associated with thiopurines.”  

Cases of ICP reported to FDA were found among pregnant patients using azathioprine or 6-mercaptopurine, primarily to treat inflammatory bowel disease (IBD) or systemic lupus erythematosus (SLE). Although thiopurines are not FDA-approved to treat Crohn’s disease, ulcerative colitis, or SLE, treatment guidelines from the American Gastroenterological Association and the American College of Rheumatology state that azathioprine or 6-mercaptopurine may be appropriate to continue during pregnancy on an individual basis among patients with these conditions.

The agency is now requiring all new drug application and abbreviated new drug application holders for thiopurines to include the following information in updated labeling:  

• “Postmarketing cases of ICP have been reported in women treated with drugs in the thiopurine class during pregnancy. 
• ICP symptoms and elevated bile acid levels improved following azathioprine discontinuation. 
• Pregnant persons should discontinue use of thiopurines if they develop ICP.”

Reference:

FDA alerts health care professionals of pregnancy problems associated with thiopurines. News release. US Food and Drug Administration; April 29, 2024. Accessed May 6, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-pregnancy-problems-associated-thiopurines