Methimazole Dosing for Hyperthyroidism
For adults with hyperthyroidism, initiate methimazole at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, and 60 mg daily for severe hyperthyroidism, with maintenance doses of 5-15 mg daily once euthyroid. 1
Initial Dosing Strategy
The FDA-approved dosing regimen stratifies initial therapy based on disease severity 1:
- Mild hyperthyroidism: 15 mg daily
- Moderately severe hyperthyroidism: 30-40 mg daily
- Severe hyperthyroidism: 60 mg daily
All doses should be divided into 3 doses given at 8-hour intervals initially 1. However, single daily dosing is equally effective and may reduce adverse effects 2. Studies demonstrate that 15 mg as a single daily dose achieves euthyroidism in 93% of patients within 12 weeks, with fewer side effects than higher doses 2.
Dosing Considerations Based on Evidence
The thyroid gland demonstrates saturable uptake of methimazole above 15 mg daily 3. Intrathyroidal concentrations increase with doses from 5-15 mg but show no significant increase beyond 15 mg 3. This pharmacokinetic property suggests that:
- For moderate hyperthyroidism, combining methimazole 15 mg with inorganic iodine (38 mg daily) may be superior to methimazole 30 mg alone, achieving faster normalization of free T4 (45.3% vs 24.8% within 30 days) with significantly fewer adverse effects requiring discontinuation (7.5% vs 14.8%) 4
- Single daily dosing maintains intrathyroidal concentrations for at least 24-26 hours 3
Maintenance and Monitoring
Reduce to maintenance dosing of 5-15 mg daily once euthyroid 1. The goal is maintaining free T4 in the high-normal range using the lowest effective dose 5. Monitor free T4 or Free T4 Index every 2-4 weeks during initial treatment 5.
If TSH becomes low during therapy, this indicates overtreatment or recovery of thyroid function—reduce or discontinue the dose with close follow-up 6.
Adjunctive Therapy
Add a beta-blocker (propranolol or atenolol) for symptomatic relief until thyroid hormone levels normalize 6, 5. This addresses tachycardia, tremor, and other adrenergic symptoms while awaiting methimazole's therapeutic effect.
Critical Safety Considerations
Agranulocytosis is a serious adverse effect that typically presents with sore throat and fever 5. If these symptoms develop:
- Obtain immediate complete blood count
- Discontinue methimazole immediately 5
Higher doses (30 mg vs 15 mg) are associated with significantly more adverse effects requiring drug discontinuation 4, 2. This supports using the lowest effective dose strategy.
Special Populations
In pregnancy, propylthiouracil is preferred over methimazole during the first trimester due to lower risk of birth defects (methimazole is associated with aplasia cutis and choanal/esophageal atresia) 5, 7. Methimazole can be used in second and third trimesters.
Pediatric Dosing
Initial dose: 0.4 mg/kg/day divided into 3 doses at 8-hour intervals 1
Maintenance dose: approximately half the initial dose 1
Common Pitfall to Avoid
Do not automatically use divided dosing—single daily dosing of 15 mg is as effective as divided doses and causes fewer side effects 2, 8. The traditional three-times-daily regimen is unnecessary given methimazole's prolonged intrathyroidal residence time 3.