What is the recommended initial dose of methimazole (antithyroid medication) for a patient with hyperthyroidism?

Methimazole Dosing for Hyperthyroidism

Initial Dosing Recommendations

For mild hyperthyroidism, start methimazole at 15 mg daily; for moderately severe hyperthyroidism, start 30-40 mg daily; and for severe hyperthyroidism, start 60 mg daily. 1

The FDA-approved dosing regimen traditionally divides the total daily dose into three administrations at 8-hour intervals 1. However, a single daily dose of 15 mg methimazole is equally effective for most patients with Graves' hyperthyroidism and causes fewer adverse effects than higher doses or divided regimens 2, 3.

Evidence Supporting Single Daily Dosing

• For mild to moderate hyperthyroidism, a single daily dose of 15 mg methimazole achieves euthyroidism in 93% of patients within 12 weeks, with a mean time of 5.3 weeks 2
• For severe hyperthyroidism (free T4 ≥7 ng/dL), 30 mg daily as a single dose normalizes thyroid function more effectively than 15 mg or propylthiouracil 300 mg 4
• Single daily dosing (15 mg) produces fewer adverse effects (13%) compared to divided dosing regimens (24%) 3

Dosing Algorithm by Disease Severity

Mild hyperthyroidism (free T4 <7 ng/dL):

• Start methimazole 15 mg once daily 1, 2
• Expected time to euthyroid state: 5-6 weeks 2, 3

Moderately severe hyperthyroidism:

• Start methimazole 30 mg once daily 1, 4
• Can be given as single dose rather than divided 2

Severe hyperthyroidism (free T4 ≥7 ng/dL):

• Start methimazole 30-60 mg daily 1, 4
• 30 mg once daily is more effective than lower doses for severe cases 4

Maintenance Dosing and Monitoring

After achieving euthyroid state, reduce to maintenance dose of 5-15 mg daily, using the lowest possible dose to maintain free T4 in the high-normal range 5.

• Monitor free T4 or free thyroxine index every 2-4 weeks during the titration phase 5
• Goal is to maintain free T4 in the high-normal range using the lowest effective dose 5
• Maintenance dose is typically approximately half the initial dose 1

Adjunctive Therapy

Use a beta blocker such as propranolol to control symptoms of thyrotoxicosis until methimazole reduces thyroid hormone levels 5. This provides symptomatic relief during the initial weeks before thyroid hormone normalization occurs 5.

Critical Safety Monitoring

Patients must immediately report sore throat, fever, skin eruptions, headache, or general malaise, as these may indicate agranulocytosis 5.

• Agranulocytosis typically presents with sore throat and fever 5
• If symptoms of agranulocytosis develop, obtain complete blood count with differential immediately and discontinue methimazole 5
• Adverse effects occur less frequently with 15 mg single daily dosing (2-13%) compared to higher doses (24%) 2, 3

Common Pitfalls to Avoid

• Avoid starting with divided doses when single daily dosing is equally effective and better tolerated 2, 3
• Do not use propylthiouracil as initial therapy, as it causes more hepatotoxicity and is less effective than methimazole 4
• For severe hyperthyroidism, do not underdose—use 30 mg daily minimum, as 15 mg is insufficient 4
• Never delay obtaining CBC if agranulocytosis symptoms develop, as this is a medical emergency requiring immediate drug discontinuation 5