Propylthiouracil

Pronunciation

(proe pil thye oh YOOR a sil)

Synonyms

PTU

Generic Available

Yes

Canadian Brand Names

Propyl-Thyracil®

Use

Palliative treatment of hyperthyroidism as an adjunct to ameliorate hyperthyroidism in preparation for surgical treatment or radioactive iodine therapy; management of thyrotoxic crisis

Pregnancy Risk Factor

Pregnancy Implications

Crosses the placenta and may induce goiter and hypothyroidism in the developing fetus (cretinism). May need to monitor infant's thyroid function periodically.

Lactation

Enters breast milk/use caution (AAP rates "compatible")

Contraindications

Hypersensitivity to propylthiouracil or any component of the formulation; pregnancy

Warnings/Precautions

Use with caution in patients >40 years of age because PTU may cause hypoprothrombinemia and bleeding; use with extreme caution in patients receiving other drugs known to cause agranulocytosis; may cause agranulocytosis, thyroid hyperplasia, thyroid carcinoma (usage >1 year). Discontinue in the presence of agranulocytosis, aplastic anemia, ANCA-positive vasculitis, hepatitis, unexplained fever, or exfoliative dermatitis. Safety and efficacy have not been established in children <6 years of age.

Adverse Reactions

Frequency not defined.

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

Overdosage/Toxicology

Symptoms of overdose include nausea, vomiting, epigastric pain, headache, fever, arthralgia, pruritus, edema, pancytopenia, epigastric distress, headache, fever, CNS stimulation, or depression. Treatment is supportive. Monitor bone marrow response. Forced diuresis, dialysis, and charcoal hemoperfusion have been used to enhance elimination.

Drug Interactions

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.

Ethanol/Nutrition/Herb Interactions

Food: Propylthiouracil serum levels may be altered if taken with food.

Mechanism of Action

Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland; blocks synthesis of thyroxine and triiodothyronine

Pharmacodynamics/Kinetics

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%)

Dosage

Oral: Administer in 3 equally divided doses at approximately 8-hour intervals. Adjust dosage to maintain T3, T4, and TSH levels in normal range; elevated T3 may be sole indicator of inadequate treatment. Elevated TSH indicates excessive antithyroid treatment.

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

6-10 years: 50-150 mg/day

>10 years: 150-300 mg/day

Maintenance: Determined by patient response or ¹ /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

Monitoring Parameters

CBC with differential, prothrombin time, liver function tests, thyroid function tests (TSH, T3, T4); periodic blood counts are recommended chronic therapy

Reference Range

Normal laboratory values:

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

Dietary Considerations

Administer at the same time in relation to meals each day, either always with meals or always between meals.

Patient Education

Take as directed, at the same time each day at around-the-clock intervals; at the same time in relation to meals, either always with meals or always between meals. Do not miss doses or make up missed doses. This drug may need to be taken for an extended period of time to achieve appropriate results and you may need periodic blood tests to assess effectiveness of therapy. May cause nausea or vomiting (small, frequent meals may help); constipation (increased exercise, fluids, fruit, or fiber may help); or dizziness or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report rash, skin eruptions, or loss of hair; fever; unusual bleeding or bruising; unusual weight gain (>5 lb/week); unresolved headache or fever; yellowing of eyes or skin; changes in color of urine or feces; or joint or muscle pain or weakness. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant while taking this medication. Consult prescriber for appropriate contraceptive measures. Consult prescriber if breast-feeding.

Additional Information

Preferred over methimazole in thyroid storm due to inhibition of peripheral conversion as well as synthesis of thyroid hormone.

Anesthesia and Critical Care Concerns/Other Considerations

Agranulocytosis, when it occurs, is usually seen during the first several months of therapy.

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.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness or drowsiness

Mental Health: Effects on Psychiatric Treatment

Leukopenia is common; avoid clozapine and carbamazepine

Dosage Forms

Tablet: 50 mg

Extemporaneously Prepared

A 5 mg/mL oral suspension was stable for 10 days when refrigerated when compounded as follows:

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.

References

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.

International Brand Names

Biolab Propiltiouracil® (BR); Propiltiouracil® (BR, HR, SI, YU); Propiltiouracilo L.CH.® (CL); Propycil® (BG, CZ, DE, HU, PL, PT, TR); Propyl® (TH); Propyl-Thiocil® (IL); Propylthiouracil® (AU, GB, LU, NO); Propylthiouracil DHA® (SG); Propylthiouracile AP-HP® (FR); Propylthiouracile® (BE); Propylthiouracil Evans® (SG); Propylthiouracil Lederle® (TH); Propyl-Thyracil® (CA); Propyltiouracil Medic® (DK); Prothiucil® (AT); Thyreostat II® (DE); Thyrosan® (PL); Tiotil® (SE); Tirostat® (CO); Uracil® (TH)

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