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

Methimazole Dosing for Hyperthyroidism

Initial Dosing Based on Disease Severity

For adults with hyperthyroidism, methimazole should be initiated at 15 mg daily for mild disease, 30-40 mg daily for moderately severe disease, and 60 mg daily for severe hyperthyroidism, with the total daily dose traditionally divided into three doses at 8-hour intervals. 1

However, a single daily dose of 15 mg methimazole is equally effective as divided dosing for most patients with Graves' hyperthyroidism and causes fewer adverse effects. 2, 3

Disease Severity Classification

• Mild hyperthyroidism: Start 15 mg daily 1
• Moderately severe hyperthyroidism: Start 30-40 mg daily 1
• Severe hyperthyroidism: Start 60 mg daily 1

Single Daily Dose vs. Divided Dosing

The single daily dose regimen (15 mg once daily) achieves euthyroidism in 93% of patients within 12 weeks, with a mean time to euthyroid state of 5.3 weeks, which is equivalent to divided dosing (10 mg three times daily). 2

• Single daily dosing of 15 mg causes adverse effects in only 13% of patients compared to 24% with divided dosing 3
• A single daily dose of 30 mg causes side effects in 19% of patients, which is higher than the 15 mg dose 2
• For most patients with Graves' disease, 15 mg once daily is preferable to higher doses or divided regimens due to superior safety profile without compromising efficacy 2, 3

Time to Achieve Euthyroid State

Approximately 80% of patients become euthyroid within 8 weeks of initiating methimazole therapy, with a mean time of 5.3-5.8 weeks regardless of whether single daily or divided dosing is used. 2, 3

• Within 12 weeks, 91-93% of patients achieve euthyroid status 2
• The duration of action of methimazole extends beyond 24 hours, supporting once-daily dosing 2

Maintenance Dosing

Once euthyroidism is achieved, the maintenance dose should be reduced to 5-15 mg daily, with the goal of maintaining free T4 or free thyroxine index in the high-normal range using the lowest possible dose. 4, 1

• Monitor free T4 or FTI every 2-4 weeks during the titration phase 4
• A rising TSH indicates the need for a lower maintenance dose 1

Pediatric Dosing

For children, the initial dose is 0.4 mg/kg body weight divided into three doses at 8-hour intervals, with a maintenance dose of approximately half the initial dose. 1

• Methimazole is the preferred antithyroid drug for pediatric patients due to severe liver injury risk with propylthiouracil 1

Critical Safety Monitoring

Patients must be instructed to immediately report sore throat, fever, skin eruptions, headache, or general malaise, as these may indicate agranulocytosis, which typically presents with sore throat and fever. 4, 1

• Obtain complete blood count with differential if these symptoms develop and discontinue methimazole immediately 4
• Monitor prothrombin time before surgical procedures due to potential hypoprothrombinemia 1
• Monitor thyroid function tests periodically during therapy 1

Adjunctive Therapy

Until methimazole reduces thyroid hormone levels, a beta blocker such as propranolol should be used to control symptoms of thyrotoxicosis. 4

Pregnancy Considerations

Methimazole is Pregnancy Category D and crosses the placenta, potentially causing fetal goiter and cretinism, particularly when used during the first trimester when it is associated with rare congenital malformations. 1

• It may be appropriate to use propylthiouracil in the first trimester, then switch to methimazole for the second and third trimesters 1
• Adjust dosing to provide sufficient but not excessive treatment during pregnancy 1
• Many pregnant women experience diminishing thyroid dysfunction as pregnancy progresses, allowing dose reduction or discontinuation weeks to months before delivery 1

Comparative Efficacy: Methimazole vs. Propylthiouracil

A single daily dose of 15 mg methimazole is significantly more effective than 150 mg propylthiouracil once daily, achieving lower serum T3, T4, and free T4 levels after 4 weeks and superior reduction in thyrotropin receptor antibodies. 5

Common Pitfalls to Avoid

• Do not use divided dosing routinely when single daily dosing of 15 mg is equally effective and causes fewer side effects 2, 3
• Do not start with 30 mg single daily dose when 15 mg is sufficient for most patients and has a better safety profile 2
• Do not delay beta blocker therapy while waiting for methimazole to take effect 4
• Do not ignore symptoms of agranulocytosis (sore throat, fever) as this requires immediate drug discontinuation and blood count evaluation 4, 1