INDICATIONS AND USAGE Propylthiouracil is indicated: in patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option to ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy in patients who are intolerant of methimazole

WARNINGS Liver Toxicity Liver injury resulting in liver failure, liver transplantation, or death, has been reported with propylthiouracil therapy in adult and pediatric patients.

No cases of liver failure have been reported with the use of methimazole in pediatric patients.

For this reason, propylthiouracil is not recommended for pediatric patients except when methimazole is not well-tolerated and surgery or radioactive iodine therapy are not appropriate therapies.

Biochemical monitoring of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT, AST) is not expected to attenuate the risk of severe liver injury due to its rapid and unpredictable onset.

Patients should be informed of the risk of liver failure.

Patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.), particularly in the first six months of therapy.

When these symptoms occur, propylthiouracil should be discontinued immediately and liver function tests and ALT and AST levels obtained.

Use in Pregnancy There are cases of liver injury, including liver failure and death, in women treated with propylthiouracil during pregnancy.

Two reports of in utero exposure with liver failure and death of a newborn have been reported.

If propylthiouracil is used during pregnancy, or if the patient becomes pregnant while taking propylthiouracil, the patient should be warned of the rare potential hazard to the mother and fetus of liver damage.

Propylthiouracil crosses the placenta and can cause fetal goiter and cretinism when administered to a pregnant woman (see Precautions, Pregnancy ).

After the first trimester of pregnancy, the use of an alternative antithyroid medication may be advisable (see Precautions, Pregnancy ).

Agranulocytosis Agranulocytosis occurs in approximately 0.2% to 0.5% of patients and is a potentially life-threatening side effect of propylthiouracil therapy.

Agranulocytosis typically occurs within the first 3 months of therapy.

Patients should be instructed to immediately report any symptoms suggestive of agranulocytosis, such as fever or sore throat.

Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur.

Propylthiouracil should be discontinued if agranulocytosis, aplastic anemia (pancytopenia) is suspected, and the patient's bone marrow indices should be obtained.

Vasculitis Cases of vasculitis resulting in severe complications and death have been reported in patients receiving propylthiouracil therapy.

The cases of vasculitis include: glomerulonephritis, leukocytoclastic cutaneous vasculitis, alveolar/pulmonary hemorrhage, cerebral angiitis, and ischemic colitis.

Most cases were associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis.

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis.

If vasculitis is suspected, discontinue therapy and initiate appropriate intervention.

Hypothyroidism Propylthiouracil can cause hypothyroidism necessitating routine monitoring of TSH and free T4 levels with adjustments in dosing to maintain a euthyroid state.

Because the drug readily crosses placental membranes, propylthiouracil can cause fetal goiter and cretinism when administered to a pregnant woman (see Precautions, Pregnancy ).

ADVERSE REACTIONS The following adverse reactions have been reported with the use of propylthiouracil.

Because these events generally come from voluntary reporting from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Severe adverse reactions include liver injury presenting as hepatitis, liver failure necessitating liver transplantation or resulting in death (see WARNINGS ).

Inhibition of myelopoiesis (agranulocytosis, granulopenia, aplastic anemia, and thrombocytopenia), drug fever, a lupus-like syndrome (including splenomegaly and vasculitis), periarteritis, hypoprothrombinemia, and bleeding have been reported.

Nephritis, glomerulonephritis, interstitial pneumonitis, exfoliative dermatitis, and erythema nodosum have also been reported.

There are reports of a vasculitis associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA), resulting in severe complications and death (see WARNINGS ).

There have been rare reports of serious hypersensitivity reactions (e.g., Stevens Johnson syndrome and toxic epidermal necrolysis) in patients treated with propylthiouracil.

Other adverse reactions include skin rash, uticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesias, loss of taste, taste perversion, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy.