June 4, 2009 – Yesterday, The American Food and Drug Administration (FDA) has published the following safety alert (adapted) on propylthiouracil.
FDA is notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil (PTU) in adult and pediatric patients.
Reports to FDA’s Adverse Event Reporting System (AERS) suggest there is an increased risk of hepatotoxicity with PTU when compared to methimazole (MMI). Although both PTU and MMI 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 PTU therapy for symptoms and signs of liver injury, especially during the first six months after initiation of therapy.
FDA has identified 32 AERS cases (22 adult and 10 pediatric) of serious liver injury associated with PTU 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 MMI 5 AERS cases of serious liver injury were identified. All five cases were in adult patients and 3 resulted in death.
PTU and MMI were approved in 1947 and 1950, respectively. In general, PTU 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 MMI during pregnancy, while no such cases have been reported with PTU use. Thus, PTU may be more appropriate for patients with Graves’ disease who are in their first trimester of pregnancy.
On April 18, 2009, FDA held a public workshop with the American Thyroid Association (ATA) to discuss PTU-related hepatotoxicity. FDA is continuing to monitor these serious reported adverse events and working to make changes to the PTU prescribing information, particularly for use in pediatric patients. Also, the ATA plans to update its treatment guidelines for Graves’ disease in the upcoming months.
You are encouraged to report all serious adverse events and product quality problems to FDA MedWatch at www.fda.gov/medwatch/report.htm.
