FDA Warning
Thyroid Drug Linked to Liver Disease
Agency Issues Recommendations for Propylthiouracil Use
By News Staff
6/5/2009
The FDA is warning physicians about the risks of liver injury, including liver failure and death, associated with the use of propylthiouracil. On June 4, the agency advised clinicians to "carefully consider" whether to prescribe the drug, which is used to treat hyperthyroidism due to Graves' disease in certain patients.
Propylthiouracil generally is considered second-line drug therapy for this indication and typically is used in patients who cannot tolerate methimazole. Because methimazole has been associated with rare cases of embryopathy, including aplasia cutis, propylthiouracil may also be preferred for patients with Graves disease who are in their first trimester of pregnancy. No such anomalies have been reported with propylthiouracil use.
The FDA said in a June 3 news release that 32 cases of serious liver injury associated with the use of propylthiouracil had been reported to MedWatch, the agency's Safety Information and Adverse Event Reporting Program, through October 2008. Of 22 adult cases linked to the drug, the FDA has identified 12 deaths and five liver transplants. Of the remaining 10 pediatric cases, one death and six liver transplants have been reported.
Methimazole has been linked to five cases of serious liver injury in adults, including three deaths.
FDA officials said propylthiouracil should not be used in pediatric patients unless the patient cannot tolerate methimazole and no other treatment options are available.
Amy Egan, M.D., deputy director for safety, Division of Metabolism and Endocrinology Products, in the FDA's Center for Drug Evaluation and Research, said in the June 3 news release that physicians should carefully consider which drug to initiate in a patient recently diagnosed with Graves' disease.
"If propylthiouracil 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," she said.
The FDA said physicians should counsel patients to advise them if they experience any of the following symptoms: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin. If liver injury is suspected, propylthiouracil therapy should be discontinued and the patient evaluated for evidence of liver injury.
FDA officials said they will continue to monitor adverse events linked to propylthiouracil, and the agency plans to require changes to the drug's prescribing information. The agency also said that the American Thyroid Association, which had a workshop in conjunction with FDA in April, is expected to update its treatment guidelines for Graves' disease later this year.
Adverse events associated with propylthiouracil use can be reported to MedWatch online or by fax at (800) FDA-0178.
The FDA said in a June 3 news release that 32 cases of serious liver injury associated with the use of propylthiouracil had been reported to MedWatch, the agency's Safety Information and Adverse Event Reporting Program, through October 2008. Of 22 adult cases linked to the drug, the FDA has identified 12 deaths and five liver transplants. Of the remaining 10 pediatric cases, one death and six liver transplants have been reported.
Methimazole has been linked to five cases of serious liver injury in adults, including three deaths.
FDA officials said propylthiouracil should not be used in pediatric patients unless the patient cannot tolerate methimazole and no other treatment options are available.
Amy Egan, M.D., deputy director for safety, Division of Metabolism and Endocrinology Products, in the FDA's Center for Drug Evaluation and Research, said in the June 3 news release that physicians should carefully consider which drug to initiate in a patient recently diagnosed with Graves' disease.
"If propylthiouracil 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," she said.
The FDA said physicians should counsel patients to advise them if they experience any of the following symptoms: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin. If liver injury is suspected, propylthiouracil therapy should be discontinued and the patient evaluated for evidence of liver injury.
FDA officials said they will continue to monitor adverse events linked to propylthiouracil, and the agency plans to require changes to the drug's prescribing information. The agency also said that the American Thyroid Association, which had a workshop in conjunction with FDA in April, is expected to update its treatment guidelines for Graves' disease later this year.
Adverse events associated with propylthiouracil use can be reported to MedWatch online or by fax at (800) FDA-0178.
