WARNINGS
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 In some instances, propylthiouracil can be withdrawn 2 or 3 weeks before delivery.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard to the fetus.
Postpartum patients receiving propylthiouracil should not nurse their babies.
Rare reports exist of severe hepatic reactions including encephalopathy, fulminant hepatic necrosis and death in patients receiving propylthiouracil. Symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function. Treatment with propylthiouracil should be discontinued promptly in the event of clinically significant evidence of liver abnormality, including hepatic transaminases in excess of 3 times the upper limit of normal.
PRECAUTIONS
General
Patients who receive propylthiouracil should be under close surveillance and should be impressed with the necessity of reporting immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. In such cases, white-blood-cell and differential counts should be made to determine whether agranulocytosis has developed. Particular care should be exercised with patients who are receiving additional drugs known to cause agranulocytosis.
Information for Patients
Patients should be advised that if they become pregnant during therapy or intend to become pregnant, they should contact their physician immediately about the desirability of discontinuing the drug. They also should not use propylthiouracil while nursing.
Patients should report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. They also should report symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc).
Laboratory Tests
Because propylthiouracil may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy with the drug, especially before surgical procedures. Thyroid function tests should be monitored periodically during therapy. Once clinical evidence of hyperthyroidism has resolved, the finding of an elevated serum TSH indicates that a lower maintenance dose of propylthiouracil should be employed.
Drug Interactions
Anticoagulants (Oral): The activity of anticoagulants may be potentiated by anti-vitamin-K activity attributed to propylthiouracil.
β-Adrenergic Blocking Agents: Hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. A dose reduction of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid.
Digitalis Glycosides: Serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dosage of digitalis glycosides may be required.
Theophylline: Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Laboratory animals treated with propylthiouracil for > 1 year have demonstrated thyroid hyperplasia and carcinoma formation.1 Such animal findings are seen with continuous suppression of thyroid function by sufficient doses of a variety of antithyroid agents, as well as in dietary iodine deficiency, subtotal thyroidectomy, and implantation of autonomous thyrotropic hormone-secreting pituitary tumors. Pituitary adenomas have also been described.
Pregnancy
Pregnancy- Pregnancy Category D-See Warnings:
Nursing Mothers
The drug appears in human milk and is contraindicated in nursing mothers. (See CONTRAINDICATIONS and WARNINGS.)
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 6 have not been established. For pediatric patients 6 years of age and older, see DOSAGE AND ADMINISTRATION.
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