What is the dose equivalent of Methimazole (MMI) for patients switching from Propylthiouracil (PTU)?

Dose Equivalence of Methimazole and Propylthiouracil for Hyperthyroidism

When switching from propylthiouracil (PTU) to methimazole (MMI), the appropriate dose conversion is approximately 10 mg of PTU to 1 mg of MMI. 1 This means that a patient taking 300 mg of PTU daily would be switched to approximately 30 mg of MMI daily.

Pharmacological Differences Between PTU and MMI

Potency and Half-Life

• MMI is 10 times more potent than PTU on a milligram-to-milligram basis 1, 2
• MMI has a longer half-life (3-5 hours) compared to PTU (1-2 hours) 2
• MMI's longer half-life allows for once-daily dosing, while PTU typically requires multiple daily doses 1, 2

Mechanism of Action

• Both drugs inhibit thyroid hormone synthesis
• PTU has the additional effect of blocking peripheral conversion of T4 to T3 1, 2
• MMI is virtually non-protein-bound, while PTU is approximately 80% protein-bound 2

Dosing Considerations When Switching

Initial Dosing Guidelines

1. For mild to moderate hyperthyroidism:

   • If patient is on 150 mg PTU daily → switch to 15 mg MMI daily 3, 4
   • If patient is on 300 mg PTU daily → switch to 30 mg MMI daily 5

2. For severe hyperthyroidism:

   • Higher doses of MMI (30 mg daily) are more effective than equivalent PTU doses (300 mg daily) 5

Monitoring After Switching

• Check thyroid function tests (free T4 or Free T4 Index) 2-4 weeks after switching medications 1
• Adjust dose based on thyroid function tests
• Goal: Maintain free T4 or Free T4 Index in high-normal range using lowest possible dose 1

Clinical Efficacy Comparison

Research shows that MMI is more effective than equivalent doses of PTU:

• 15 mg MMI daily is more effective than 150 mg PTU daily in normalizing thyroid hormone levels 3, 4
• MMI normalizes T3 levels more rapidly than equivalent doses of PTU 3
• At 12 weeks of treatment, 77.1% of patients on MMI achieved normal T3 and T4 levels compared to only 19.4% of patients on equivalent PTU doses 3

Special Considerations

Pregnancy

• PTU is preferred in the first trimester due to lower risk of congenital malformations 1
• MMI is preferred in the second and third trimesters due to lower risk of hepatotoxicity 1
• When switching from PTU to MMI after the first trimester, use the 10:1 conversion ratio 1

Side Effect Profile

• MMI at lower doses (15 mg daily) has fewer adverse effects than higher doses (30 mg daily) 5
• PTU has higher rates of mild hepatotoxicity compared to equivalent doses of MMI 5
• Both drugs can cause agranulocytosis, hepatitis, vasculitis, and thrombocytopenia 1

Practical Application

When switching a patient from PTU to MMI:

1. Calculate the equivalent dose (divide PTU dose by 10)
2. Consider the severity of hyperthyroidism (may need higher MMI dose for severe cases)
3. Monitor thyroid function 2-4 weeks after switching
4. Adjust dose based on thyroid function tests
5. Aim for the lowest effective dose to maintain euthyroidism

Remember that MMI can be taken once daily, which may improve medication adherence compared to the multiple daily doses required with PTU 1, 2.