Starting Dose of Methimazole in Hyperthyroidism
The starting dose of methimazole is 15 mg daily for mild hyperthyroidism, 30-40 mg daily for moderately severe hyperthyroidism, and 60 mg daily for severe hyperthyroidism, typically divided into three doses at 8-hour intervals, though single daily dosing is equally effective. 1
Dosing Strategy Based on Disease Severity
The FDA-approved dosing regimen stratifies initial therapy by hyperthyroid severity 1:
- Mild hyperthyroidism: 15 mg daily
- Moderately severe hyperthyroidism: 30-40 mg daily
- Severe hyperthyroidism: 60 mg daily
These doses are traditionally divided into three administrations at 8-hour intervals 1. However, single daily dosing is equally effective and may reduce side effects 2, 3.
Single Daily Dose vs. Divided Dosing
Single daily dosing of 15 mg methimazole achieves euthyroidism in 93% of patients within 12 weeks, with a mean time of 5.3 weeks 2. This compares favorably to divided dosing (86% euthyroid, mean 5.6 weeks) 2.
The pharmacologic rationale for single daily dosing is compelling 3:
- Intrathyroidal methimazole concentrations plateau at doses above 15 mg daily
- The drug maintains therapeutic intrathyroidal levels for at least 26 hours
- A saturable uptake mechanism exists in thyroid tissue 3
Single daily dosing of 15 mg causes fewer adverse effects than 30 mg daily (2 patients vs. 6 patients in one study) 2, making it preferable for most patients with mild to moderate disease.
Maintenance Dosing
Maintenance dosing ranges from 5-15 mg daily 1. After achieving euthyroidism, the dose should be titrated downward to the lowest effective amount.
Special Populations
Pediatric Patients
Initial pediatric dosing is 0.4 mg/kg body weight divided into three doses at 8-hour intervals, with maintenance at approximately half the initial dose 1.
Pregnancy
Propylthiouracil is preferred in the first trimester due to methimazole's association with aplasia cutis and choanal/esophageal atresia; methimazole is preferred in the second and third trimesters due to propylthiouracil-associated hepatotoxicity 4, 5. The goal is to maintain free T4 in the high-normal range using the lowest possible thioamide dosage 4.
Important Caveats
Monitor for agranulocytosis, which typically presents with sore throat and fever 4. If these symptoms develop, obtain a complete blood count immediately and discontinue methimazole 4. Other serious adverse effects include hepatitis, vasculitis, and thrombocytopenia 4.
Beta-blockers (e.g., propranolol, atenolol 25-50 mg daily) should be used for symptomatic relief until thyroid hormone levels normalize 4.
Measure free T4 or free thyroxine index every 2-4 weeks during initial treatment to guide dose adjustments 4.