Riyadh, June 4, 2009 – The U.S. Food and Drug Administration (FDA), the American counterpart to the Saudi Food and Drug Authority (SFDA), notified 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 to FDA’s Adverse Event Reporting System (AERS) 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.

On April 18, 2009, FDA held a public workshop with the American Thyroid Association (ATA) to discuss propylthiouracil-related hepatotoxicity. FDA is continuing to monitor these serious reported adverse events and working to make changes to the propylthiouracil prescribing information, particularly for use in pediatric patients. Also, the ATA plans to update its treatment guidelines for Graves’ disease in the upcoming months.

Propylthiouracil is Marketed in Saudi Arabia

Recommendations and Information for Healthcare Professionals:

Reserve propylthiouracil use for patients who are in their first trimester of pregnancy, or who are allergic to or intolerant of methimazole.

Closely monitor patients on propylthiouracil therapy for signs and symptoms of liver injury, especially during the first six months after initiation of therapy.

If liver injury is suspected, promptly discontinue propylthiouracil therapy and evaluate the patient for evidence of liver injury and provide supportive care.

Propylthiouracil should not be used in pediatric patients unless the patient is allergic to or intolerant of methimazole, and there are no other treatment options available.

Rare cases of embryopathy, including aplasia cutis, have been reported with use of methimazole during pregnancy. No such cases have been reported with propylthiouracil use during pregnancy. Therefore, propylthiouracil may be more appropriate for patients with Graves’ disease who are in their first trimester of pregnancy.

Counsel patients to promptly advise you if they note any of the following signs or symptoms: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising or yellowing of the eyes or skin.

Report Adverse Dug Reaction to the SFDA:

The public and health care professionals are strongly encouraged to report adverse drug reaction to the National Pharmacovigilance Center (NPC) by filling the appropriate form on the following link:

http://www.sfda.gov.sa/En/Drug/Topics/National+Pharmacovigilance+Center.htm

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