Prescription Drugs

CLINICAL PHARMACOLOGY Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) administration, that continuously suppress thyroid function and thereby increase TSH secretion result in thyroid tissue hypertrophy.

Find Lowest Prices on PROPYLTHIOURACIL (propylthiouracil) Tablet DESCRIPTION Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) (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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) is an antithyroid drug administered orally. The structural formula is: Molecular Weight : 170.23 C7H10N2OS Each tablet contains propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 50 mg and the following inactive ingredients: anhydrous lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate.

INDICATIONS Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) is indicated in the medical treatment of hyperthyroidism. Long-term therapy may lead to remission of the disease. Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) may also be used to ameliorate hyperthyroidism in preparation for subtotal thyroidectomy of radioactive iodine therapy. Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) is also used when thyroidectomy is contraindicated or not advisable. DOSAGE AND ADMINISTRATION Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) is administered orally. The total daily dosage is usually given in 3 equal doses at approximately 8-hour intervals. Adults The initial dose is 300 mg daily. In patients with severe hyper-thyroidism, very large goiters, or both, the beginning dosage usually should be 400 mg daily, an occasional patient will require 600 to 900 mg/day initially. The usual maintenance dosage is 100 to 150 mg daily. Pediatric Patients For children 6 to 10 years of age, the initial dosage is 50 to 150 mg daily. For pediatric patients 10 years and over, the initial dosage is 150 to 300 mg daily. The maintenance dosage is determined by the response of the patient. HOW SUPPLIED Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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. Manufactured By: West-ward Pharmaceutical Corp., Eatontown, NJ 07724. Revised November 2002

PATIENT INFORMATION 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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).

OVERDOSE Signs and Symptoms Nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritus, edema, and pancytopenia. Agranulocytosis is the most serious effect. Rarely, exfoliative dermatitis, hepatitis, neuropathies, or CNS stimulation or depression may occur. No information is available on the following LD50: concentration of propyl-thiouracil in biologic fluids associated with toxicity and/ or death; the amount of drug in a single dose usually associated with symptoms of overdosage; or the amount of propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) in a single dose likely to be life-threatening. Treatment To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physician's Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. The patient's bone marrow function should be monitored. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric empyting or charcoal. Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of propylthiouracil. CONTRAINDICATIONS Propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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.

SIDE EFFECTS 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. DRUG INTERACTIONS Anticoagulants (oral) The activity of anticoagulants may be potentiated by anti-vitamin-K activity attributed to propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) . 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.

WARNINGS Agranulocytosis is potentially the most serious side effect of propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) should not nurse their babies. Rare reports exist of severe hepatic reactions including encephalopathy, fulminant hepatic necrosis, and death in patients receiving propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) . Symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function. Treatment with propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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. Laboratory Tests Because propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) 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 (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) should be employed. Carcinogenesis, Mutagenesis, Impairment of Fertility Laboratory animals treated with propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) for > 1 year have demonstrated thyroid hyperplasia and carcinoma formation1. 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 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 and older, see DOSAGE & ADMINISTRATION. REFERENCE 1. International Agency for Research on Cancer, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. 1974; 7:67-76.