Starting Methimazole for Hyperthyroidism
For an adult with hyperthyroidism and no significant comorbidities, initiate methimazole at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, or 60 mg daily for severe hyperthyroidism, divided into three doses given every 8 hours. 1
Determining Disease Severity and Initial Dose
Assess disease severity based on free T4 levels to guide initial dosing:
- Mild hyperthyroidism: Start methimazole 15 mg daily (5 mg three times daily at 8-hour intervals) 1, 2
- Moderately severe hyperthyroidism: Start 30-40 mg daily (10-15 mg three times daily) 1
- Severe hyperthyroidism (free T4 ≥7 ng/dL): Start 60 mg daily (20 mg three times daily) 1, 2
Methimazole is the preferred antithyroid drug over propylthiouracil due to its longer half-life, once-daily dosing option, and significantly lower rate of severe adverse effects 3.
Alternative Single Daily Dosing
For mild to moderate disease, a single daily dose of 15-30 mg methimazole is equally effective and causes fewer adverse effects than divided dosing. 4
- Single daily dose of 15 mg achieves euthyroidism in 93% of patients within 12 weeks, with mean time to euthyroidism of 5.3 weeks 4
- Single daily dose of 30 mg achieves euthyroidism in 91% of patients with similar timeframe 4
- Adverse effects occur less frequently with single daily dosing (2% with 15 mg vs 12% with divided doses) 4
However, the FDA-approved dosing remains three times daily at 8-hour intervals 1.
Monitoring Protocol
Check thyroid function tests every 2-4 weeks during initial treatment to assess response and adjust dosing. 5
- Target free T4 or free T3 in the high-normal range using the lowest effective dose 5
- Continue monitoring every 2-4 weeks until thyroid function stabilizes 5
- Once stable, monitoring intervals can be extended 5
Maintenance Dosing
Once euthyroidism is achieved (typically within 4-8 weeks), reduce to maintenance dose of 5-15 mg daily. 1
The goal is to maintain thyroid function in the normal range with the lowest effective dose 5.
Critical Safety Warnings
Counsel patients to immediately discontinue methimazole and seek urgent medical attention if they develop sore throat, fever, or signs of infection. 5
- Agranulocytosis is a life-threatening complication that requires immediate CBC and drug discontinuation 5
- Most adverse reactions (75%) occur within the first 6 months of treatment 6
- Skin reactions are the most common adverse effect, comprising 68% of reactions 6
- After 24 months on low-dose therapy (5 mg daily), no further adverse reactions were recorded in one study 6
Monitor for hepatotoxicity, which occurs more frequently with propylthiouracil but can occur with methimazole, especially at higher doses. 2
Methimazole 30 mg daily causes significantly more hepatotoxicity than 15 mg daily 2.
Special Considerations for Severe Disease
For patients with severe hyperthyroidism (free T4 ≥7 ng/dL), methimazole 30 mg daily normalizes thyroid function more effectively than propylthiouracil 300 mg daily or methimazole 15 mg daily. 2
At 12 weeks, methimazole 30 mg normalized free T4 in 96.5% of patients versus 78.3% with propylthiouracil 300 mg (p=0.001) and 86.2% with methimazole 15 mg (p=0.023) 2.
Common Pitfalls to Avoid
- Never use propylthiouracil as first-line therapy unless methimazole is contraindicated, as it has higher rates of severe hepatotoxicity 3, 2
- Do not delay treatment while waiting for additional testing in symptomatic patients with confirmed hyperthyroidism 1
- Avoid underdosing in severe disease, as methimazole 15 mg is insufficient for patients with free T4 ≥7 ng/dL 2
- Do not continue high doses indefinitely without attempting dose reduction once euthyroidism is achieved 1
- Never ignore development of low TSH during therapy, as this suggests overtreatment requiring dose reduction or discontinuation 5