FDA Alert: Propylthiouracil-Induced Liver Failure

The U.S. Food and Drug Administration (FDA) is notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil in adult and pediatric patients.

Reports suggest there is an increased risk of hepatotoxicity with when compared to methimazole. Although both propylthiouracil and methimazole are indicated for the treatment of hyperthyroidism due to Graves’ disease, healthcare professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease. Physicians should closely monitor patients on propylthiouracil therapy for symptoms and signs of liver injury, especially during the first six months after initiation of therapy. Propylthiouracil and methimazole were approved in 1947 and 1950, respectively.

FDA has identified 32 AERS cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil use. Of the adult cases, 12 deaths and 5 liver transplants occurred. Among the pediatric patients, 1 case resulted in death and 6 in liver transplants.

In contrast, for methimazole 5 AERS cases of serious liver injury were identified. All five cases were in adult patients and 3 resulted in death.

In general, propylthiouracil is considered second-line drug therapy except in patients who are allergic to or intolerant of methimazole. Rare cases of embryopathy, including aplasia cutis, have been reported with use of methimazole during pregnancy, while no such cases have been reported with propylthiouracil use. Thus, propylthiouracil may be more appropriate for patients with Graves’ disease who are in their first trimester of pregnancy.

This information reflects FDA’s current analysis of data available to FDA concerning propylthiouracil. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing the product. FDA intends to update this document when additional information or analyses become available.

Adverse reactions or quality problems experienced with the use of this Product may be reported to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail or by fax, using the contact information at the bottom of this sheet. More details are available on the FDA Web site.