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 disease, with a target maintenance dose of 5-15 mg daily once euthyroid. 1
Initial Dosing Strategy
The FDA-approved dosing regimen stratifies initial therapy by disease severity 1:
- Mild hyperthyroidism: 15 mg daily
- Moderately severe hyperthyroidism: 30-40 mg daily
- Severe hyperthyroidism: 60 mg daily
Important caveat: European guidelines recommend limiting the starting dose to 15-20 mg daily maximum to reduce the dose-dependent risk of agranulocytosis 2. This creates a tension between FDA labeling and safety data, but for severe disease requiring higher doses, the benefit typically outweighs this risk with appropriate monitoring.
Dosing Schedule
Single daily dosing is as effective as divided doses and should be preferred 3, 4, 5. The traditional FDA label recommends dividing doses every 8 hours 1, but multiple studies demonstrate that 15 mg once daily achieves euthyroidism in 93% of patients within 5-6 weeks, with fewer adverse effects than divided dosing 4, 5.
Maintenance Therapy
Once euthyroid (typically within 5-8 weeks), reduce to a maintenance dose of 5-15 mg daily, keeping free T4 in the high-normal range 3, 1. The American Academy of Family Physicians emphasizes using the lowest effective dose to minimize adverse effects 3.
Monitoring Protocol
- Initial phase: Check free T4 or free thyroxine index every 2-4 weeks and adjust dosing accordingly 3
- After stabilization: Extend monitoring intervals to every 6-12 months 3
- TSH normalization lags behind T4 by weeks to months, so don't over-adjust based on TSH alone during initial treatment 3
Dose Escalation for Inadequate Response
If hyperthyroidism persists on 15 mg daily after 4-6 weeks, escalate up to 30-40 mg daily in divided doses 3. If control is not achieved at this level, refer to endocrinology for consideration of radioactive iodine or thyroidectomy 3.
Special Population: Pregnancy
Use the lowest possible dose to maintain free T4 in the high-normal range during pregnancy 3. Both methimazole and propylthiouracil are effective with similar neonatal outcomes 3, though propylthiouracil is traditionally preferred in the first trimester due to concerns about methimazole-associated embryopathy (aplasia cutis, choanal/esophageal atresia) 6. After the first trimester, methimazole is preferred due to lower risk of hepatotoxicity 2.
Pediatric Dosing
Initial dose is 0.4 mg/kg daily divided into 3 doses at 8-hour intervals, with maintenance at approximately half the initial dose 1.
Critical Safety Monitoring
Agranulocytosis is the most serious adverse effect, presenting with sore throat and fever 3. If these symptoms develop, obtain an immediate complete blood count and discontinue methimazole if confirmed 3. Other serious adverse effects include hepatitis, vasculitis, and thrombocytopenia 3. The risk of agranulocytosis is dose-dependent, reinforcing the importance of using the lowest effective dose 2.