FDA Health Alert Regarding Rare Pregnancy Complication

Risk of intrahepatic cholestasis of pregnancy (ICP)

FDA Safety Communication

In a recent health safety alert, the U.S. Food and Drug Administration (FDA) has cautioned healthcare professionals about the rare risk of intrahepatic cholestasis of pregnancy (ICP) associated with the use of thiopurines, including azathioprine, 6-mercaptopurine, and 6-thioguanine. Thiopurines are immunosuppressants commonly used to treat inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and other conditions.

Key Findings

The FDA’s alert highlights several key findings and recommendations:

Thiopurines are known to carry a risk of hepatotoxicity and fetal harm, as indicated in their current labeling.
Pregnant patients should discontinue thiopurine use if they develop ICP, a rare pregnancy complication characterized by impaired bile flow in the liver.
Reported cases of ICP have primarily occurred among pregnant patients using azathioprine or 6-mercaptopurine to manage conditions such as Crohn’s disease, ulcerative colitis, or systemic lupus erythematosus.
While thiopurines are not FDA-approved for these specific indications during pregnancy, treatment guidelines from medical associations may consider their continued use on an individualized basis for managing certain immunologic conditions.

Labeling Update

In response to these findings, the FDA is requiring manufacturers to update the labeling of azathioprine, 6-mercaptopurine, and 6-thioguanine drug products. The updated labeling will include:

Postmarketing reports of ICP associated with thiopurine use during pregnancy.
Improvement in ICP symptoms and bile acid levels upon discontinuation of azathioprine.
Guidance for pregnant individuals to discontinue thiopurines if they develop ICP.

Reporting Adverse Events

Healthcare professionals, caregivers, and patients are encouraged to report any adverse events or side effects related to the use of thiopurines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program. Reports can be submitted online through the MedWatch Online Voluntary Reporting Form or via fax.

Conclusion

The FDA’s health safety alert underscores the importance of vigilance in monitoring and managing the risks associated with thiopurine use during pregnancy. Healthcare professionals should be aware of the potential for ICP and take appropriate measures to ensure patient safety. By updating labeling and promoting adverse event reporting, the FDA aims to enhance awareness and facilitate informed decision-making regarding the use of thiopurines in pregnant individuals.