What is the appropriate dose of Methimazole (MMI) for treatment?

From the Guidelines

Methimazole should be started at a dose of 10-30 mg daily for adults with hyperthyroidism, with the goal of maintaining FT4 or FTI in the high-normal range using the lowest possible thioamide dosage. This approach is supported by the American College of Obstetricians and Gynecologists (ACOG) practice bulletin on thyroid disease in pregnancy, which suggests that thioamides, including methimazole, should be used at the lowest possible dose to minimize the risk of side effects 1. The dose may need to be adjusted based on regular monitoring of thyroid function tests, which should be performed every 2-4 weeks.

• Key considerations for methimazole dosing include:
  • Starting dose: 10-30 mg daily for adults
  • Dose adjustment: based on thyroid function tests every 2-4 weeks
  • Goal: maintain FT4 or FTI in the high-normal range using the lowest possible thioamide dosage
  • Potential side effects: agranulocytosis, hepatitis, vasculitis, and thrombocytopenia, which require immediate medical attention if symptoms develop 1.
• It is essential to monitor patients for signs of side effects, such as sore throat and fever, which may indicate agranulocytosis, and to discontinue the medication if these symptoms occur 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Methimazole tablets, USP are administered orally. The total daily dosage is usually given in 3 divided doses at approximately 8-hour intervals. Adult The initial daily dosage is 15 mg for mild hyperthyroidism, 30 mg to 40 mg for moderately severe hyperthyroidism and 60 mg for severe hyperthyroidism, divided into 3 doses at 8-hour intervals. The maintenance dosage is 5 mg to 15 mg daily. Pediatric Initially, the daily dosage is 0.4 mg/kg of body weight divided into 3 doses and given at 8-hour intervals. The maintenance dosage is approximately 1/2 of the initial dose. The recommended methimazole dose is:

• Adult:
  • Initial dose:
    • Mild hyperthyroidism: 15 mg daily
    • Moderately severe hyperthyroidism: 30 mg to 40 mg daily
    • Severe hyperthyroidism: 60 mg daily
  • Maintenance dose: 5 mg to 15 mg daily
• Pediatric:
  • Initial dose: 0.4 mg/kg of body weight daily
  • Maintenance dose: approximately 1/2 of the initial dose 2

From the Research

Methimazole Dose

• The usual initial dose of methimazole for severe Graves' disease hyperthyroidism is 30 mg/day, but adverse effects are more frequent at this dose than at 15 mg/day 3.
• A study compared the efficacy and adverse effects of methimazole 15 mg + inorganic iodine 38 mg/day and methimazole 30 mg/day as initial therapy for Graves' disease patients with moderate to severe hyperthyroidism, and found that the proportions of patients achieving a serum free thyroxine level within the reference range in ≤30 or ≤60 days were significantly larger in the 15 mg + inorganic iodine group 3.
• Another study found that a single daily dose of 15 mg methimazole is effective in most patients with Graves' hyperthyroidism and causes fewer adverse effects than 30 mg/day 4.
• A prospective randomized trial found that a small single daily dose of 15 mg methimazole controls Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily) 5.
• A long-term follow-up study found that there is no difference in the clinical and immunological course or in the long-term remission rate of Graves' hyperthyroidism when the treatment is initiated with either a small single daily dose (15 mg) or the conventional regimen (10 mg 3 times daily) 6.
• A study on single daily dose methimazole treatment of hyperthyroidism found that all patients became euthyroid using this method, with a mean time required to achieve a euthyroid state of 16.7 weeks in patients with their initial episode of hyperthyroidism, and 14.9 weeks in patients with a relapse of hyperthyroidism 7.

Adverse Effects

• Adverse effects that required discontinuation of methimazole were more frequent in the 30 mg/day group than in the 15 mg + inorganic iodine group (14.8% vs. 7.5%) 3.
• Side-effects occurred in 2 patients treated with 15 mg single daily dose and in 6 treated with 30 mg single daily dose 4.
• Adverse effects occurred more frequently in patients treated with conventional divided doses (24%) than in patients treated with a small single daily dose (13%) 6.