Propylthiouracil (PTU) Side Effects Increase Risk of Liver Injury: FDA Warns

The FDA is alerting health care professionals that side effects of propylthiouracil (PTU), a drug used to combat Graves’ disease, can lead to potentially fatal liver damage.

At least 32 cases of serious liver injury from propylthiouracil, also known as PTU, were identified by the FDA in a warning issued June 3, 2009. Of those adverse event reports, there were 12 deaths and five liver transplants. Ten of the cases involved children, of which six required liver transplants and one died.

PTU is a “second-line” treatment for Graves’ disease, used to treat overactive thyroid glands. It is an alternative treatment to methimazole, which the FDA notes has only been associated with five cases of liver damage.

Graves’ disease is an autoimmune disorder that leads to hyperthyroidism. It is estimated to affect 2% of the female population and appears in women at a 5:1 to 10:1 ratio when compared to men. It can cause goiter, disturbed sleep, hypertension, irritability, muscle weakness and increased heartbeat.

“Health care professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease,” said Amy Egan, M.D., from the FDA’s Center for Drug Evaluation and Research. “If PTU therapy is chosen, the patient should be closely monitored for symptoms and signs of liver injury, especially during the first six months after initiating therapy.”

Symptoms of liver injury from propylthiourail (PTU) could include yellowing of the skin or eyes associated with jaundice, abdominal pain, swelling or tenderness, blood in the stool or urine, brown urine, vomiting, faintness or rapid heart rate.

Patients who are allergic or intolerant of methimazole, or women who are pregnant, are often given PTU instead of methimazole, which has been linked to rare cases of birth defects which are not seen in PTU users. Despite the propylthiouracil liver injury risk, the FDA noted that PTU may still be a better option for pregnant women with Graves’ disease who are in the first trimester.

PTU was approved for marketing in 1947, and it is currently only available as a generic, with no brand names for the drug sold in the United States.

The FDA warning comes after an April 18 public workshop with the American Thyroid Association (ATA) that discussed the PTU liver damage side effects. The FDA said it will continue to monitor PTU side effects and may make changes in labeling. The ATA is planning to update treatment guidelines for Graves’ disease to account for the new findings in upcoming months.

In an editorial published in the April 9, 2009 issue of the New England Journal of Medicine, two doctors warned that the propylthiouracil liver side effects should cause doctors to seek alternative treatments for children with Graves’ disease. The authors estimated that liver failure from propylthiouracil requiring a transplant or resulting in death could occur in between 1 in 2000 and 1 in 400 children treated. However, the number of children who suffer reversible liver injury could be 10 times that number.