What are the recommended initial and maintenance doses of methimazole for treating hyperthyroidism (Graves disease) in adults, and how should the dose be adjusted for severe disease, elderly patients, hepatic impairment, renal impairment, children, and during the first trimester of pregnancy?

Methimazole Dosing for Hyperthyroidism (Graves Disease)

Initial Dosing for Adults

For adults with Graves disease, start methimazole at 15-30 mg daily as a single dose, with 30 mg reserved for severe hyperthyroidism (free T4 ≥7 ng/dL). 1

• Mild to moderate hyperthyroidism (free T4 <7 ng/dL): Initiate methimazole 15 mg once daily 1
• Severe hyperthyroidism (free T4 ≥7 ng/dL): Initiate methimazole 30 mg once daily 1
• Methimazole 30 mg/day normalizes free T4 more effectively than 15 mg/day in severe cases at 8 and 12 weeks 1
• The 15 mg dose produces fewer adverse effects, particularly hepatotoxicity, compared to 30 mg 1

Maintenance Dosing

Once euthyroid, reduce methimazole to 5-10 mg daily and continue for 12-18 months before considering discontinuation. 2

• The typical starting dose of 10-30 mg can be given as a single daily dose 2
• After achieving normal thyroid function, gradually taper to maintenance doses of 2.5-5 mg daily 3
• Long-term low-dose therapy (2.5-5 mg daily) may prevent relapse, particularly in patients >35 years old 3

Dose Adjustments for Special Populations

Severe Disease

• Use methimazole 30 mg daily for patients with free T4 ≥7 ng/dL 1
• This higher dose achieves normalization of free T4 in 96.5% of severe cases by 12 weeks, compared to 86.2% with 15 mg 1

Elderly Patients

• No specific dose reduction is required based solely on age 1
• However, patients >35 years benefit more from long-term low-dose maintenance therapy to prevent relapse 3
• In patients >35 years, continuing methimazole 2.5-5 mg daily long-term significantly reduces relapse risk compared to discontinuation 3

Hepatic Impairment

• Use methimazole 15 mg daily rather than 30 mg to minimize hepatotoxicity risk 1
• Mild hepatotoxicity occurs more frequently with higher doses 1
• Monitor liver function tests, though specific dosing adjustments for hepatic impairment are not well-established in the evidence provided

Renal Impairment

• No specific dose adjustments for renal impairment are provided in the available evidence
• Methimazole is primarily metabolized hepatically, not renally

Children and Adolescents

For pediatric Graves disease, initiate methimazole at 0.4-0.7 mg/kg/day; avoid doses ≥0.9 mg/kg/day due to high adverse effect rates. 4

• Recommended initial dose: 0.4-0.7 mg/kg/day 4
• Avoid high doses: Doses ≥0.9 mg/kg/day cause adverse effects in 62% of patients versus only 9-14% with lower doses 4
• Time to normalize free T4 is similar across all dose ranges (1.6-1.9 months), so higher doses provide no efficacy benefit 4
• Long-term therapy (96-120 months) with gradual dose reduction to 3.5 mg daily is safe and achieves 88-92% cure rates 5
• Only 3 cases of cutaneous reactions occurred during 120 months of therapy in pediatric patients 5

First Trimester of Pregnancy

Propylthiouracil (PTU) is preferred over methimazole in the first trimester due to teratogenicity concerns with methimazole. 2

• Methimazole is associated with aplasia cutis and choanal/esophageal atresia 2
• PTU 100-300 mg every 6 hours is the drug of choice in first trimester 2
• Both drugs have similar placental transfer kinetics and therapeutic efficacy 2
• After the first trimester, switching to methimazole may be considered due to PTU's hepatotoxicity risk, though this is not explicitly stated in the provided evidence

Critical Monitoring and Safety Considerations

• Check free T4 and free T3 at 4,8, and 12 weeks to assess response 1
• Methimazole is preferred over PTU for initial therapy due to once-daily dosing, lower cost, better availability, and fewer major side effects 2
• PTU is not recommended for initial use in non-pregnant adults 1
• Both drugs are safe during lactation despite presence in breast milk 2

Common Pitfalls to Avoid

• Do not use doses >0.7 mg/kg/day in children—this dramatically increases adverse effects without improving efficacy 4
• Do not use PTU as first-line therapy except in first trimester pregnancy—it has higher hepatotoxicity and requires multiple daily doses 1, 2
• Do not discontinue therapy too early—consider long-term low-dose maintenance (2.5-5 mg daily) especially in patients >35 years to prevent relapse 3
• In pediatric patients, long-term therapy (96-120 months) achieves nearly 3 times higher cure rates than short-term therapy (12-24 months) 5