Methimazole Dosing for Hyperthyroidism
Adults with Graves Disease
For adults with Graves disease, initiate methimazole at 15 mg daily for mild hyperthyroidism, 30-40 mg daily for moderate disease, and 60 mg daily for severe hyperthyroidism, divided into three doses at 8-hour intervals, then reduce to a maintenance dose of 5-15 mg daily once euthyroid. 1
Initial Dosing Strategy
- Mild hyperthyroidism: Start 15 mg daily divided into 3 doses 1
- Moderate hyperthyroidism: Start 30-40 mg daily divided into 3 doses 1
- Severe hyperthyroidism: Start 60 mg daily divided into 3 doses 1
- All doses should be administered at approximately 8-hour intervals 1
Alternative Lower-Dose Regimen
- A single daily dose of 15 mg methimazole achieves euthyroidism in 93% of patients within 12 weeks, with mean time to euthyroidism of 5.3 weeks 2
- Single daily dosing of 15 mg causes fewer adverse effects compared to 30 mg daily (2 patients vs 6 patients experienced side effects) 2
- For moderate to severe hyperthyroidism (free T4 ≥5 ng/dL), combining methimazole 15 mg daily with inorganic iodine 38 mg daily achieves faster normalization than methimazole 30 mg alone (45.3% vs 24.8% normalized within 30 days), with significantly fewer adverse effects requiring discontinuation (7.5% vs 14.8%) 3
Maintenance Dosing
- Once clinical hyperthyroidism resolves, reduce to maintenance dose of 5-15 mg daily 1
- A rising serum TSH indicates the need for a lower maintenance dose 1
- Monitor thyroid function tests periodically during therapy 1
Children and Adolescents
For pediatric patients with Graves disease, initiate methimazole at 0.4 mg/kg/day divided into three doses at 8-hour intervals, then reduce to approximately half the initial dose for maintenance—doses ≥0.7 mg/kg/day cause significantly more adverse effects without improving efficacy. 1, 4
Initial Dosing
- Start at 0.4 mg/kg/day divided into 3 doses given at 8-hour intervals 1
- Do not exceed 0.7 mg/kg/day: Higher doses (0.9 mg/kg/day) cause adverse effects in 62% of patients compared to only 9.1% at 0.4 mg/kg/day, without faster normalization of thyroid function 4
Maintenance Dosing
- Reduce to approximately 1/2 of the initial dose for maintenance 1
- Time to normalization of free T4 does not differ between low-dose (0.4 mg/kg/day) and high-dose (0.9 mg/kg/day) regimens (1.9 months vs 1.9 months) 4
Safety Considerations
- Methimazole is the preferred antithyroid drug for pediatric patients due to severe liver injury risk with propylthiouracil 1
- Higher doses (≥0.7 mg/kg/day) cause significantly more adverse events (50% vs 20% with <0.7 mg/kg/day) without improving remission rates 5
- Neutropenia and rash can occur at any dose, requiring vigilance regardless of dosing regimen 5
Pregnant Patients
In pregnant women with Graves disease, use the lowest effective methimazole dose to maintain free T4 in the high-normal range, switching from propylthiouracil to methimazole after the first trimester when organogenesis is complete, and monitor thyroid function at frequent (weekly or biweekly) intervals. 6, 1
First Trimester Considerations
- Methimazole is associated with rare congenital malformations (aplasia cutis, choanal/esophageal atresia), making propylthiouracil preferable during the first trimester 1, 7
- Consider switching from propylthiouracil to methimazole for the second and third trimesters to avoid maternal hepatotoxicity 1
Dosing During Pregnancy
- Use the lowest dose necessary to maintain free T4 in the high-normal range 6
- Thyroid dysfunction often diminishes as pregnancy progresses, allowing dose reduction 1
- In some cases, antithyroid therapy can be discontinued several weeks or months before delivery 1
Monitoring Requirements
- Monitor thyroid function at frequent (weekly or biweekly) intervals 1
- Check free T4 or free thyroxine index every 2-4 weeks to adjust dosage appropriately 6
- Adjust dose to control symptoms while minimizing fetal exposure 6
Special Situations
- For patients with elevated TRAb levels (e.g., 200 IU/L), continue methimazole throughout pregnancy to prevent fetal and neonatal thyrotoxicosis, regardless of maternal euthyroid status 6
- Maternal TRAb antibodies cross the placenta and can stimulate the fetal thyroid, necessitating continued treatment 6
- Inform the newborn's physician about maternal Graves disease due to risk of neonatal thyroid dysfunction 6
Temporary Symptom Control
- Beta-blockers (e.g., propranolol) can be used temporarily to control symptoms like palpitations until methimazole reduces thyroid hormone levels 6
Monitoring and Dose Adjustment
Laboratory Monitoring
- Monitor prothrombin time during therapy, especially before surgical procedures, as methimazole may cause hypoprothrombinemia 1
- Monitor thyroid function tests periodically 1
- A rising serum TSH indicates need for lower maintenance dose 1
Drug Interactions Requiring Dose Adjustments
- Oral anticoagulants: Methimazole may increase warfarin activity; monitor PT/INR closely, especially before surgery 1
- Beta-blockers: Reduce dose when hyperthyroid patient becomes euthyroid due to decreased clearance 1
- Digitalis: Reduce dose when patient becomes euthyroid as serum levels may increase 1
- Theophylline: Reduce dose when patient becomes euthyroid as clearance decreases 1
Critical Safety Warnings
Vasculitis Risk
- Promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, as vasculitis with severe complications has occurred 1
Agranulocytosis Risk
- Exercise particular care with patients receiving other drugs known to cause agranulocytosis 1
Pregnancy Notification
- Patients who become pregnant or intend to become pregnant should immediately contact their physician 1