What is the appropriate initial dose of methimazole when switching a hyperthyroid patient from Propylthiouracil (PTU) 25 mg daily to methimazole during the second trimester?

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. The patient is being switched from PTU to methimazole, but the initial dosage of methimazole is not directly related to the PTU dosage.

• The initial daily dosage of methimazole for adults is 15 mg for mild hyperthyroidism, 30 mg to 40 mg for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism. Since the patient's hyperthyroidism severity is not specified, and considering the need for a conservative clinical decision, the dosage should be chosen based on the minimum effective dose.
• The FDA label does not provide a direct conversion from PTU to methimazole, so the decision should be based on the standard initial dosages provided. Given the information provided and the standard dosing, it would be reasonable to start with the lowest initial dose for mild hyperthyroidism, which is 15 mg daily, divided into 3 doses. However, this is not among the answer options provided. Considering the options provided (5 mg or 10 mg), neither is the standard initial dose according to the label. However, since 5 mg is within the range of the maintenance dosage and considering the principle of starting with a lower dose and titrating up as needed, especially when switching medications and given the lack of direct guidance on conversion, 5 mg could be considered a cautious approach, but it is essential to note that this is not the standard initial dosage as per the label. 1

From the Research

For a patient with hyperthyroidism transitioning from PTU 25 mg daily to methimazole in the second trimester, I recommend starting with methimazole 5 mg daily, as this dose is likely sufficient given the potency ratio of approximately 10-15 mg of PTU to 1 mg of methimazole. The decision to start with a lower dose is based on the patient's current thyroid function tests and symptom control, as well as the need to minimize the risk of hepatotoxicity associated with PTU, especially after the first trimester 2. When making this transition, it is advisable to discontinue PTU and start methimazole immediately without overlap, ensuring continuous management of hyperthyroidism while minimizing potential side effects. Key considerations include:

• Monitoring thyroid function tests 2-4 weeks after the medication change to ensure adequate control and adjust the dose as needed 3.
• Recognizing that methimazole is preferred over PTU after the first trimester due to its lower risk of hepatotoxicity, while maintaining good placental transfer characteristics 2.
• Understanding that the potency ratio between PTU and methimazole suggests that a 25 mg PTU dose would convert to a relatively low methimazole dose, supporting the choice of starting with 5 mg daily 4. Regular monitoring throughout pregnancy remains essential, as thyroid medication requirements may change, particularly in the third trimester when doses often can be reduced 5. Given the most recent and highest quality evidence, methimazole's efficacy in reducing thyroid hormone levels and its safety profile make it the preferred choice for managing hyperthyroidism in the second trimester and beyond 2.