What are the typical initiation and maintenance doses of propylthiouracil (antithyroid medication) for a typical adult patient with hyperthyroidism?

Propylthiouracil Dosing for Hyperthyroidism

Initial Dose

For adults with hyperthyroidism, start propylthiouracil at 300 mg daily divided into three equal doses given every 8 hours (100 mg three times daily). 1

• For patients with severe hyperthyroidism or very large goiters, the initial dose may be increased to 400 mg daily divided into three doses 1
• Occasional patients with severe disease may require 600-900 mg daily initially, though higher doses carry increased hepatotoxicity risk 1, 2
• The FDA-approved dosing regimen specifies administration at approximately 8-hour intervals to maintain therapeutic drug levels, given the drug's short half-life of 1.65 hours 1, 3

Maintenance Dose

The usual maintenance dose is 100-150 mg daily, typically continued as divided doses every 8 hours. 1

• After achieving biochemical control (typically 4-8 weeks), reduce to maintenance dosing of 100-150 mg daily 1
• Continue the three-times-daily dosing schedule even at maintenance doses, as propylthiouracil's short serum half-life necessitates frequent administration 1, 3
• Monitor liver biochemical tests at 2 months and 5 months after starting therapy, as 28% of patients develop transient ALT elevations that typically resolve despite continued therapy 2

Critical Dosing Considerations

Propylthiouracil requires divided dosing every 8 hours due to its rapid clearance, unlike methimazole which can be given once daily. 1, 3, 4

• Single daily dosing of propylthiouracil 150 mg is significantly less effective than the standard three-times-daily regimen, achieving euthyroidism in only 19.4% of patients compared to 77.1% with once-daily methimazole 4
• The serum half-life remains constant at 1.65 hours in both hyperthyroid and euthyroid states, requiring consistent dosing intervals 3
• More frequent dosing (every 2 hours during waking hours) achieves faster normalization but is impractical for outpatient management 5

Hepatotoxicity Monitoring

Monitor liver function tests before starting therapy and at 2-month intervals, as propylthiouracil causes subclinical hepatic injury in 28% of patients. 2

• Most cases of severe liver injury occur with doses of 300 mg/day or higher, though injury has been reported with doses as low as 50 mg/day 1
• ALT elevations are usually transient and asymptomatic, with 87% resolving despite continued therapy at reduced doses 2
• Continue propylthiouracil with caution if ALT elevation occurs without symptoms or hyperbilirubinemia, but reduce the dose 2
• Discontinue immediately if symptoms develop or bilirubin rises 2

Pediatric Dosing

Propylthiouracil is generally not recommended for pediatric patients except when alternative therapies are inappropriate. 1

• For children 6 years or older when propylthiouracil must be used, initiate at 50 mg daily with careful upward titration based on TSH and free T4 levels 1
• Pediatric patients face the same hepatotoxicity risks as adults, making methimazole the preferred agent in this population 1

Geriatric Considerations

Use cautious dose selection in elderly patients, starting at the lower end of the dosing range due to decreased hepatic and renal function. 1

• Begin with 300 mg daily divided into three doses, but monitor closely for adverse effects 1
• Consider more frequent monitoring of liver function and thyroid parameters in elderly patients 1

Common Pitfalls to Avoid

• Never use once-daily dosing with propylthiouracil—the short half-life makes this regimen ineffective compared to methimazole 3, 4
• Do not discontinue therapy for asymptomatic ALT elevations alone—most resolve with dose reduction while continuing treatment 2
• Avoid assuming equal efficacy with methimazole—propylthiouracil requires 10-fold higher doses and more frequent administration 4, 6
• Do not overlook compliance issues—the three-times-daily regimen results in only 53% compliance compared to 83% with once-daily methimazole 6