PROPYLTHIOURACIL
TABLETS, USP

Revised 11/02

Rx Only

Propylthiouracil (6-propyl-2-thiouracil) is one of the thiocarbamide compounds. It is a white, crystalline substance that has a bitter taste and is very slightly soluble in water.

Propylthiouracil is an antithyroid drug administered orally. The structural formula is:

Each tablet contains propylthiouracil 50 mg and the following inactive ingredients: anhydrous lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate.

Propylthiouracil inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The drug does not inactivate existing thyroxine and triodothyronine that are stored in the thyroid or circulating in the blood, nor does it interfere with the effectiveness of thyroid hormones given by mouth or by injection.

Propylthiouracil is readily absorbed from the gastrointestinal tract. It is metabolized rapidly and requires frequent administration. Approximately 35% of the drug is excreted in the urine, in intact and in conjugated forms, within 24 hours.

In laboratory animals, various interventions, including propylthiouracil administration, that continuously suppress thyroid function and thereby increase TSH secretion result in thyroid tissue hypertrophy.

Propylthiouracil is indicated in the medical treatment of hyperthyroidism. Long-term therapy may lead to remission of the disease. Propylthiouracil may also be used to ameliorate hyperthyroidism in preparation for subtotal thyroidectomy of radioactive iodine therapy. Propylthiouracil is also used when thyroidectomy is contraindicated or not advisable.

Propylthiouracil is contraindicated in the presence of hypersensitivity to the drug or any of the other product components and in nursing mothers because the drug is excreted in milk.

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.

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 should report symptoms suggestive of hepatic dysfunction (anorexia, pruritis, right upper quadrant pain, etc).

Major adverse reactions (much less common than the minor adverse reactions) include inhibition of myelopoiesis (agranulocytosis, granulopenia, and thrombo-cytopenia), aplastic anemia, drug fever, a lupus-like syndrome including solenomegaly, hepatitis, periartentis, and hypoprothrombinemia and bleeding. Nephritis, glomerulonephritis, interstitial pneumonitis, exfoliative dermatitis, and erythema nodosum have been reported. Reports of a vasculitic syndrome associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA) have also been received. Manifestations of ANCA-positive vasculitis may include rapidly progressive glomerulonephritis (crescentic and pauci-immune necrotizing glomerulonephritis) sometimes leading to acute renal failure; fever; pulmonary infiltrates or alveolar hemorrhage; skin ulcers; and leucocytoclastic vasculitis.

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

It should be noted that about 10% of patients with untreated hyperthyroidism have leukopenia (white blood cell count of less than 4,000/mm³), often with relative granulopenia.

Propylthiouracil is administered orally. The total daily dosage is usually given in 3 equal doses at approximately 8-hour intervals.

Propylthiouracil Tablets, USP, 50 mg: White, scored tablet, imprinted “West-ward 480”.

•  Bottles of 100 tablets.
•   Bottles of 1000 tablets.
•   Unit Dose Boxes of 100 tablets.

Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Reference:

• International Agency for Research on Cancer, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. 1974; 7:67-76.

Manufactured By:
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised November 2002