Cardiovascular: Edema, cutaneous vasculitis, leukocytoclastic vasculitis, ANCA-positive vasculitis

Central nervous system: Fever, drowsiness, vertigo, headache, drug fever, dizziness, neuritis

Dermatologic: Skin rash, urticaria, pruritus, exfoliative dermatitis, alopecia, erythema nodosum

Endocrine & metabolic: Goiter, weight gain, swollen salivary glands

Gastrointestinal: Nausea, vomiting, loss of taste perception, stomach pain, constipation

Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, bleeding, aplastic anemia

Hepatic: Cholestatic jaundice, hepatitis

Neuromuscular & skeletal: Arthralgia, paresthesia

Renal: Nephritis, glomerulonephritis, acute renal failure

Respiratory: Interstitial pneumonitis, alveolar hemorrhage

Miscellaneous: SLE-like syndrome

Anticoagulants: Anticoagulants may be potentiated by anti-vitamin-K effect of propylthiouracil. Oral anticoagulant activity is increased only until metabolic effect stabilizes.

Correction of hyperthyroidism may alter disposition of beta-blockers, digoxin, and theophylline, necessitating a dose reduction of these agents.

Onset of action: Therapeutic: 24-36 hours

Peak effect: Remission: 4 months of continued therapy

Duration: 2-3 hours

Distribution: Concentrated in the thyroid gland

Protein binding: 75% to 80%

Metabolism: Hepatic

Bioavailability: 80% to 95%

Half-life elimination: 1.5-5 hours; End-stage renal disease: 8.5 hours

Time to peak, serum: ~1 hour

Excretion: Urine (35%)

Children: Initial: 5-7 mg/kg/day or 150-200 mg/m²/day in divided doses every 8 hours

or

6-10 years: 50-150 mg/day

>10 years: 150-300 mg/day

Maintenance: Determined by patient response or¹/3 to ²/3 of the initial dose in divided doses every 8-12 hours. This usually begins after 2 months on an effective initial dose.

Adults: Initial: 300 mg/day in divided doses every 8 hours. In patients with severe hyperthyroidism, very large goiters, or both, the initial dosage is usually 450 mg/day; an occasional patient will require 600-900 mg/day; maintenance: 100-150 mg/day in divided doses every 8-12 hours

Elderly: Use lower dose recommendations; Initial: 150-300 mg/day

Withdrawal of therapy: Therapy should be withdrawn gradually with evaluation of the patient every 4-6 weeks for the first 3 months then every 3 months for the first year after discontinuation of therapy to detect any reoccurrence of a hyperthyroid state.

Dosing adjustment in renal impairment: Adjustment is not necessary

Total T4: 5-12 mcg/dL

Serum T3: 90-185 ng/dL

Free thyroxine index (FT4 I): 6-10.5

TSH: 0.5-4.0 microunits/mL

The use of antithyroid thioamides is as effective in elderly as in younger adults; however, the expense, potential adverse effects, and inconvenience (compliance, monitoring) make them undesirable. The use of radioiodine, due to ease of administration and less concern for long-term side effects and reproduction problems, makes it a more appropriate therapy.

Triturate six 50 mg tablets in a mortar, reduce to a fine powder, add 30 mL of carboxymethylcellulose 1.5%, transfer to a graduate and qs to 60 mL

Shake well before using and keep in refrigerator; protect from light

Nahata MC and Hipple TF, Pediatric Drug Formulations, 3rd ed, Cincinnati, OH: Harvey Whitney Books Co, 1997.

Jackson GL, Flickinger FW, and Wells LW, "Massive Overdosage of Propylthiouracil,"Ann Intern Med, 1979, 91(3):418-9.

Johnson DG and Campbell S, "Hormonal and Metabolic Agents,"Geriatric Pharmacology, Bressler R and Katz MD, eds, New York, NY: McGraw-Hill, 1993, 427-50.

Limaye A and Ruffolo R, "Propylthiouracil-Induced Fatal Hepatic Necrosis,"Am J Gastroenterol, 1987, 82(2):152-4.

Raby C, Lagorce JF, Jambut-Absil AC, et al, "The Mechanism of Action of Synthetic Antithyroid Drugs: Iodine Complexation During Oxidation of Iodide,"Endocrinology, 1990, 126(3):1683-91.

Romas E, Henderson DR, and Kirkham BW, "Propylthiouracil Therapy: An Unusual Cause of Antineutrophil Cytoplasmic Antibody Associated Alveolar Hemorrhage,"J Rheumatol, 1995, 22(4):803.