How to Start Methimazole
Begin methimazole at 15 mg daily for mild hyperthyroidism, 30-40 mg daily for moderate hyperthyroidism, or 60 mg daily for severe hyperthyroidism, administered as a single daily dose, with monitoring of thyroid function tests every 2-4 weeks initially. 1
Initial Dosing Strategy
The FDA-approved dosing provides clear guidance based on disease severity 1:
- Mild hyperthyroidism: 15 mg daily
- Moderately severe hyperthyroidism: 30-40 mg daily
- Severe hyperthyroidism: 60 mg daily
Single daily dosing is as effective as divided dosing and improves adherence. Multiple studies demonstrate that once-daily administration achieves euthyroidism at the same rate as traditional three-times-daily regimens, with mean time to euthyroid state of approximately 5-6 weeks 2. The historical practice of dividing doses into three administrations at 8-hour intervals offers no therapeutic advantage 1, 3, 2.
Disease Severity Assessment
Pretreatment serum T3 levels, goiter size, and thyroid hormone levels are the primary determinants of therapeutic response. 4 Patients with the following characteristics require higher initial doses and longer time to achieve euthyroidism:
- Large goiters
- Pretreatment free T4 ≥5 ng/dL
- Elevated T3 levels
- Urinary iodide excretion ≥100 mcg/g creatinine 4
With 40 mg daily, 64.6% of patients achieve euthyroidism within 3 weeks and 92.6% within 6 weeks, compared to 40.2% and 77.5% respectively with 10 mg daily. 4
Monitoring Protocol
Check thyroid function tests (TSH, free T4) every 2-4 weeks during initial therapy until stable, then every 2-3 months during maintenance. 5, 1
Obtain baseline complete blood count (CBC) before starting therapy. 1 While routine CBC monitoring is not required, patients must be instructed to report immediately any signs of agranulocytosis including sore throat, fever, or general malaise, at which point CBC with differential must be obtained urgently 1.
Monitor for signs of vasculitis including new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, as severe complications have occurred with methimazole 1.
Dose Adjustment and Maintenance
Once euthyroid, reduce to maintenance dose of 5-15 mg daily. 1 A rising TSH indicates the need for dose reduction 1. The average time to maximum therapeutic effect is 10 weeks, with minimal additional benefit after 12-16 weeks of dose escalation 6.
Treatment duration is typically 12-18 months based on therapeutic efficacy for Graves' disease. 7 Long-term remission rates are approximately 40-45% at one year and 56-63% at 4-6 years, regardless of whether initial dosing was 10 mg or 40 mg daily 8, 2.
Special Populations
In pregnancy, methimazole should be avoided during the first trimester due to risk of congenital malformations; propylthiouracil is preferred during organogenesis. 1 If methimazole is used after the first trimester, use the lowest effective dose to maintain free T4 in the high-normal range, with monitoring every 2-4 weeks 5.
In elderly patients or those with renal impairment, start with 2.5 mg daily and titrate cautiously. 6
Critical Precautions
Warn patients to report immediately any illness, particularly sore throat, skin eruptions, fever, headache, or general malaise, as agranulocytosis can occur. 1 This life-threatening complication requires immediate discontinuation and CBC evaluation.
Check prothrombin time before surgical procedures, as methimazole may cause hypoprothrombinemia 1.
Adjust doses of concomitant medications including warfarin (may need 50% reduction), beta-blockers, digoxin, and theophylline as patients transition from hyperthyroid to euthyroid state 1.
Common Pitfall to Avoid
Do not use divided dosing unnecessarily. The traditional three-times-daily regimen increases pill burden without improving efficacy and may increase adverse effects compared to single daily dosing 2. Single daily administration is equally effective and better tolerated.