Initial Methimazole Dosing for Hyperthyroidism
The initial dose of methimazole should be 15 mg daily for mild hyperthyroidism, 30-40 mg daily (divided into 3 doses at 8-hour intervals) for moderately severe hyperthyroidism, and 60 mg daily for severe hyperthyroidism. 1
Dosing Algorithm Based on Disease Severity
The FDA-approved dosing strategy is stratified by hyperthyroid severity 1:
- Mild hyperthyroidism: 15 mg daily
- Moderately severe hyperthyroidism: 30-40 mg daily in 3 divided doses
- Severe hyperthyroidism: 60 mg daily in 3 divided doses
All initial doses should be divided into 3 administrations at approximately 8-hour intervals 1.
Evidence Supporting Severity-Based Dosing
For patients with severe hyperthyroidism (free T4 ≥7 ng/dL), methimazole 30 mg/day achieves normalization of thyroid function more effectively than lower doses. 2 In a prospective randomized trial, 96.5% of patients on methimazole 30 mg/day achieved normal free T4 at 12 weeks compared to 86.2% on 15 mg/day 2.
For mild to moderate hyperthyroidism (free T4 <7 ng/dL), methimazole 15 mg/day is equally effective as higher doses and causes significantly fewer adverse effects 2. The lower dose is particularly advantageous because adverse effects requiring discontinuation occur in only 7.5% of patients on 15 mg versus 14.8% on 30 mg 3.
Alternative Initial Regimen for Moderate-Severe Disease
An alternative approach combines methimazole 15 mg daily with inorganic iodine 38 mg daily for patients with moderate to severe hyperthyroidism (free T4 ≥5 ng/dL) 3. This combination achieves faster normalization than methimazole 30 mg alone—45.3% of patients reached normal free T4 within 30 days versus 24.8% with methimazole 30 mg alone 3. Discontinue the iodine component once free T4 normalizes, continuing methimazole alone for maintenance. 3
Maintenance Dosing
Once thyroid function normalizes, reduce to a maintenance dose of 5-15 mg daily 1. The American Academy of Family Physicians recommends using the lowest possible dose to maintain free T4 in the high-normal range 4.
Monitoring Schedule
- Initial phase: Check free T4 every 2-4 weeks and adjust dosing accordingly 4
- After stabilization: Extend monitoring intervals to every 6-12 months 4
- Important caveat: TSH normalization lags behind T4 normalization by several weeks to months, so do not rely solely on TSH during initial dose adjustments 4
Critical Safety Considerations
Agranulocytosis is the most serious adverse effect, typically presenting with sore throat and fever. 4 If these symptoms develop, obtain an immediate complete blood count and discontinue methimazole if agranulocytosis is confirmed 4. Other serious adverse effects include hepatitis (more common with higher doses), vasculitis, and thrombocytopenia 4.
The risk of adverse effects requiring drug discontinuation is dose-dependent, occurring in approximately 15% of patients on 30 mg daily versus 7.5% on 15 mg daily 3. This reinforces the importance of using the lowest effective dose based on disease severity.
When to Escalate or Refer
If the patient fails to achieve biochemical control on 15 mg daily after 4-6 weeks, escalate the dose up to 30-40 mg daily in divided doses 4. If control is still not achieved after another 4-6 weeks on this higher dose, refer to endocrinology for consideration of radioactive iodine ablation or thyroidectomy 4.