According to the FDA Propylthiouracil (PTU) can cause serious liver injury, including liver failure and death.

PTU is used to manage hyperthyroidism associated with Grave’s disease. It is also used to decrease symptoms of hyperthyroidism in preparation for surgically removing the thyroid gland or before inactivating the thyroid gland with radioactive iodine therapy

Reports to FDA’s Adverse Event Reporting System (AERS) suggest there is an increased risk of hepatotoxicity with PTU when compared with methimazole (MMI).

The FDA has identified 32 AERS cases (22 adult and 10 paediatric) of serious liver injury associated with PTU use. Of the adult cases, 12 deaths and 5 liver transplants occurred. Among the paediatric patients, 1 case resulted in death and 6 in liver transplants.

In contrast, for MMI only 5 AERS cases of serious liver injury were identified. All five cases were in adult patients and 3 resulted in death.

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. PTU may also be used when it is not advisable to remove the thyroid gland.

Physicians should closely monitor patients on PTU therapy for symptoms and signs of liver injury, especially during the first 6 months after initiation of therapy (fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising or yellowing of the eyes or skin).

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.

Agranulocytosis is potentially the most serious side effect of Propylthiouracil therapy. Patients should be instructed to report any symptoms of agranulocytosis, such as fever or sore throat. Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. The drug should be discontinued in the presence of agranulocytosis, aplastic anemia (pancytopenia), ANCA-positive vasculitis, hepatitis, interstitial pneumonitis, fever, or exfoliative dermatitis. The patient’s bone marrow function should be monitored. Propylthiouracil can cause fetal harm when administered to a pregnant woman.

Because the drug readily crosses placental membranes and can induce goiter and even cretinism in the developing fetus, it is important that a sufficient, but not excessive, dose be given. In many pregnant women, the thyroid dysfunction diminishes as the pregnancy proceeds; consequently a reduction of dosage may be possible. In some instances, Propylthiouracil can be withdrawn 2 or 3 weeks before delivery.

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

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. PTU and MMI were approved in 1947 and 1950, respectively.