propylthiouracil (PTU)
Propyl-Thyracil ◆

Available forms
Available by prescription only
Tablets: 50 mg

Indications and dosages
 Hyperthyroidism. Adults: 300 to 450 mg P.O. daily in divided doses. Continue until patient is euthyroid; then start maintenance dose of 100 mg daily to t.i.d.
Neonates and children: 5 to 7 mg/kg P.O. daily in divided doses q 8 hours. Or give according to age below.
Children age 10 and older: Initially, 100 mg P.O. t.i.d. Continue until patient is euthyroid; then start maintenance dose determined by patient’s response.
Children ages 6 to 10: 50 to 150 mg P.O. daily in divided doses q 8 hours. Continue until patient is euthyroid; then start maintenance dose determined by patient’s response.

Pharmacodynamics
Antithyroid action: When used to treat hyperthyroidism, PTU inhibits synthesis of thyroid hormone by interfering with the incorporation of iodine into thyroglobulin; it also inhibits the formation of iodothyronine. Besides blocking hormone synthesis, it also inhibits the peripheral deiodination of thyroxine to triiodothyronine (liothyronine). Clinical effects become evident only when the preformed hormone is depleted and circulating hormone levels decline.
 As preparation for thyroidectomy, PTU inhibits synthesis of the thyroid hormone and causes a euthyroid state, reducing surgical problems during thyroidectomy; as a result, the mortality for a single-stage thyroidectomy is low. Iodide reduces the vascularity of the gland and makes it less friable.
 When used in treating thyrotoxic crisis, PTU inhibits peripheral deiodination of thyroxine to triiodothyronine. Theoretically, it’s preferred over methimazole in thyroid storm because of its peripheral action.

Pharmacokinetics
Absorption: About 80% absorbed rapidly and readily from GI tract.
Distribution: Appears to be concentrated in thyroid gland. Readily crosses the placental barrier; distributed into breast milk. 75% to 80% protein-bound.
Metabolism: Metabolized rapidly in liver.
Excretion: About 35% of dose excreted in urine. Half-life is 1 to 2 hours in patients with normal renal function; 8 1/2 hours in anuric patients.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in breast-feeding patients. Use cautiously in pregnant women.

Interactions
Drug-drug. Adrenocorticoids, corticotropin: Alters effects. May require dosage adjustment of the steroid when thyroid status changes.
Bone marrow depressants: Increases risk of agranulocytosis. Monitor hematologic studies.
Hepatotoxic drugs: Increases risk of hepatotoxicity. Monitor patient for toxicity.
Iodinated glycerol, lithium, potassium iodide: Potentiates hypothyroid effects. Monitor patient closely.
Oral anticoagulants: Potentiates by anti-vitamin K activity attributed to PTU. Monitor PT and INR.

Adverse reactions
CNS: fever.
GU: nephritis.
Hematologic: agranulocytosis, thrombocytopenia, aplastic anemia, leukopenia.
Hepatic: jaundice, hepatotoxicity, hepatitis.
Metabolic: altered selenomethionine levels and liothyronine uptake, dose-related hypothyroidism (mental depression; hypoprothrombinemia and bleeding; cold intolerance; hard, nonpitting edema).
Skin: rash, urticaria, skin discoloration, pruritus, erythema nodosum, exfoliative dermatitis, lupuslike syndrome.
Other: lymphadenopathy.

Effects on lab test results
• May increase BUN and serum creatinine levels. May increase or decrease AST, ALT, and LDH levels.
• May decrease hemoglobin, hematocrit, and granulocyte, WBC, and platelet counts. May increase or decrease INR.

Overdose and treatment
Toxicity may cause nausea, vomiting, epigastric distress, fever, headache, arthralgia, pruritus, edema, and pancytopenia.
 Treatment of toxicity includes withdrawal of drug in the presence of agranulocytosis, pancytopenia, hepatitis, fever, or exfoliative dermatitis. For depression of bone marrow, treatment may require antibiotics and transfusions of fresh whole blood. For hepatitis, treatment includes rest, adequate diet, and symptomatic support, including analgesics, gastric lavage, I.V. fluids, and mild sedation.

Special considerations
• Best response occurs when drug is administered around the clock and given at the same time each day in respect to meals.
• Maintenance dose can be approximated by givng 1/3 to 2/3 of initial daily dose.
• A beta blocker, usually propranolol, commonly is given to manage peripheral signs of hyperthyroidism, which are primarily cardiac-related (tachycardia).
• Stop drug if patient develops severe rash or enlarged cervical lymph nodes.
• Watch for signs and symptoms of hypothyroidism (mental depression; cold intolerance; hard, nonpitting edema; hair loss).
Breast-feeding patients
• Drug appears in breast milk. Women shouldn’t breast-feed during treatment. However, if breast-feeding is needed, PTU is the preferred antithyroid drug.

Patient education
• Warn patient to avoid using self-prescribed cough medicines; many contain iodine.
• Suggest taking drug with meals to reduce GI adverse effects.
• Instruct patient to store drug in a light-resistant container and not to store in the bathroom; heat and humidity may cause drug to deteriorate.
• Tell patient to promptly report fever, sore throat, malaise, unusual bleeding, yellowing of eyes, nausea, or vomiting.
• Advise patient to have medical review of thyroid status before undergoing surgery (including dental surgery).
• Teach patient how to recognize signs of hyperthyroidism and hypothyroidism and what to do if they occur.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use