Clinical

Propylthiouracil implicated in severe liver toxicity in younger patients

Last Updated: 2010-05-11 17:32:09 -0400 (Reuters Health)

By Scott Baltic

NEW YORK (Reuters Health) - The antithyroid drug propylthiouracil is associated with severe liver injury and vasculitis in patients under 17 years of age, while methimazole is not. Both drugs are widely used to treat Graves' disease.

As reported online on April 28 in the Journal of Clinical Endocrinology and Metabolism, "far fewer and less serious adverse events" were reported for methimazole than for propylthiouracil.

The U.S. researchers' findings support "recommendations that propylthiouracil...be avoided, especially in the pediatric population," they write, noting that severe propylthiouracil hepatotoxicity is also a concern for adults.

The risk of severe liver injury in children from propylthiouracil use is estimated at about 1 in 2,000, co-author Dr. Scott A. Rivkees of Yale University School of Medicine told Reuters Health by e-mail,

He believes this study is the first to systematically compare the adverse events associated with propylthiouracil and methimazole.

Dr. Rivkees also noted that on April 21, the U.S. Food and Drug Administration added a Boxed Warning: <www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm> to the label for propylthiouracil.

The warning, which adds "information about reports of severe liver injury and acute liver failure, some of which have been fatal, in adult and pediatric patients using this medication," supplements an original FDA notice dated June 4, 2009.

In 40 years of data from the FDA's Adverse Event Reporting System (from 1968 through 2008), Dr. Rivkees and his colleague Dr. Ana Szarfman found 651 reports for propylthiouracil and 822 for methimazole, across all age groups.

Twenty-three cases of severe liver injury from propylthiouracil were found in patients younger than 17 years, versus no cases with methimazole. Similarly, four cases of mild liver injury were seen in children and adolescents treated with propylthiouracil, versus one in a child treated with methimazole.

These findings are consistent with earlier case reports and liver transplantation data, which had found "serious liver injury associated with propylthiouracil use in children and adolescents, but not with methimazole."

More than 30 cases of propylthiouracil-induced liver failure have been reported in patients between the ages of 6 and 62, most of them in the past 20 years.

In addition to liver injury, vasculitis was also identified as a major safety concern of propylthiouracil use in children and adolescents, to a greater extent than was methimazole.

Methimazole-associated hepatotoxicity, most commonly in the form of cholestasis, was seen primarily in adults 61 and older.

J Clin Endocrinol Metab 2010.