What is the recommended dose and frequency of methimazole (MMI) for treating hyperthyroidism?

Methimazole Dosing and Frequency for Hyperthyroidism

For adults with hyperthyroidism, methimazole should be initiated at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, and 60 mg daily for severe hyperthyroidism, administered as a single daily dose rather than divided doses. 1

Initial Dosing Strategy

Adult Dosing by Disease Severity

• Mild hyperthyroidism: Start with 15 mg once daily 1
• Moderately severe hyperthyroidism: Start with 30-40 mg once daily 1
• Severe hyperthyroidism: Start with 60 mg once daily 1

The FDA-approved labeling traditionally recommends dividing the total daily dose into 3 doses at 8-hour intervals 1, but substantial evidence supports single daily dosing as equally effective with better compliance and potentially fewer adverse effects 2, 3.

Single Daily Dose vs. Divided Dosing

Single daily dosing is the preferred approach based on multiple lines of evidence:

• Methimazole concentrates in thyroid tissue and maintains intrathyroidal levels for at least 24-26 hours, making once-daily dosing pharmacologically rational 4
• Studies demonstrate 93% of patients achieve euthyroid status with 15 mg single daily dose within 12 weeks, comparable to divided dosing regimens 3
• A single daily dose of 15 mg causes fewer adverse effects compared to higher doses (2% vs 19% side effect rate with 30 mg) 3
• No significant difference exists between single daily dosing and divided dosing in time to achieve euthyroid state (approximately 5-6 weeks for both) 3

Maintenance Dosing

Once euthyroid status is achieved, reduce to maintenance dose of 5-15 mg daily 1. The goal is to maintain free T4 or free thyroxine index in the high-normal range using the lowest possible dose 5.

Monitoring During Treatment

• Check free T4 or FTI every 2-4 weeks during initial treatment phase 5
• Adjust dose based on thyroid function tests to maintain target levels 5
• Continue monitoring until stable, then extend intervals 5

Pediatric Dosing

For children with hyperthyroidism:

• Initial dose: 0.4 mg/kg/day divided into 3 doses at 8-hour intervals 1
• Maintenance dose: Approximately half of the initial dose 1

Special Considerations in Pregnancy

Both methimazole and propylthiouracil are effective for treating hyperthyroidism in pregnancy, with no significant differences in neonatal outcomes 5. However, important caveats exist:

• Methimazole has been associated with rare cases of aplasia cutis and choanal/esophageal atresia 6
• Use the lowest possible dose to maintain free T4 in the high-normal range 5
• Both drugs are safe for breastfeeding 5
• Monitor fetal growth and maternal heart rate regularly 5

Optimizing Initial Therapy

For moderate to severe hyperthyroidism (free T4 ≥5 ng/dL), combining methimazole 15 mg daily with inorganic iodine 38 mg daily achieves faster control than methimazole 30 mg alone 7:

• 45% achieve normal free T4 within 30 days with combination therapy vs 25% with methimazole 30 mg alone 7
• Adverse effects requiring drug discontinuation occur less frequently with the combination (7.5% vs 14.8%) 7
• Discontinue iodine once free T4 normalizes, continue methimazole 7

Critical Safety Monitoring

Agranulocytosis Warning

Agranulocytosis is the most serious adverse effect, typically presenting with sore throat and fever 5:

• If these symptoms develop, obtain immediate complete blood count 5
• Discontinue methimazole immediately if agranulocytosis confirmed 5
• Other serious adverse effects include hepatitis, vasculitis, and thrombocytopenia 5

Dose-Response Relationship

• Intrathyroidal methimazole concentrations increase with doses from 5-15 mg daily but plateau above 15 mg 4
• This saturable uptake mechanism explains why 15 mg daily is often sufficient and higher doses primarily increase adverse effect risk without proportional therapeutic benefit 4

Common Pitfalls to Avoid

• Avoid unnecessarily high initial doses: 15 mg single daily dose controls most cases of mild to moderate hyperthyroidism effectively 3, 4
• Don't use divided dosing unless single daily dosing fails: Only approximately 2% of patients require divided dosing for adequate control 2
• Never delay treatment for agranulocytosis if fever and sore throat develop: This is a medical emergency requiring immediate drug discontinuation and blood count 5
• Don't continue iodine indefinitely: When using combination therapy, discontinue iodine once free T4 normalizes 7