FDA Requires Warning Label Change for Thiopurines

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

Reported cases of ICP have occurred among pregnant patients using azathioprine or 6-mercaptopurine, primarily to treat inflammatory bowel disease (IBD) or systemic lupus erythematosus (SLE).

“While thiopurines have been shown to be low risk for use throughout pregnancy, monitoring is needed given the rare risk of ICP,” commented Uma Mahadevan, MD, professor of gastroenterology, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco, and the principal investigator for the PIANO (Pregnancy Inflammatory bowel disease And Neonatal Outcomes) national study of women with IBD and their children to assess the safety of IBD medications on the pregnancy and short- and long-term outcomes of the children.

“In the upcoming Helmsley PIANO Global Consensus on the management of the pregnant patient with IBD, it is recommended that women who continue thiopurines during pregnancy should have measurement of liver enzymes, metabolite levels, and consideration of split dosing,” she added.

Although thiopurines are not FDA-approved to treat IBD or SLE, the FDA notice stated that “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 following key pieces of 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 August 13, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-pregnancy-problems-associated-thiopurines