When is Propylthiouracil (PTU) preferred over Methimazole?

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Last updated: May 8, 2025View editorial policy

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From the Guidelines

Propylthiouracil (PTU) should be given over methimazole during the first trimester of pregnancy due to the increased risk of rare embryopathies associated with methimazole use during early pregnancy. This is based on the American College of Obstetricians and Gynecologists (ACOG) practice bulletin on thyroid disease in pregnancy 1. The goal is to maintain FT4 or FTI in the high-normal range using the lowest possible thioamide dosage.

Some key points to consider when prescribing PTU over methimazole include:

  • The risk of aplasia cutis and other congenital malformations is higher with methimazole use during early pregnancy
  • PTU carries a higher risk of severe hepatotoxicity, making regular monitoring of liver function essential during PTU therapy
  • The typical starting dose of PTU is 100-150 mg three times daily, which provides more rapid control of thyrotoxicosis than methimazole
  • Women treated with PTU or methimazole can breastfeed safely, as stated in the ACOG practice bulletin 1

It's also important to note that after the first trimester, it is generally recommended to switch back to methimazole for the remainder of pregnancy due to the higher risk of severe hepatotoxicity associated with PTU. However, PTU is preferred over methimazole during the first trimester of pregnancy due to the increased risk of rare embryopathies associated with methimazole use during early pregnancy 1.

From the Research

Indications for PTU over Methimazole

  • PTU is preferred over methimazole in the first trimester of pregnancy due to the lower risk of teratogenic effects 2
  • Patients who experience side effects such as rash or itching with methimazole may be switched to PTU as an alternative treatment option 3
  • In cases of methimazole-induced agranulocytosis, PTU is contraindicated, and alternative treatments such as saturated solution of potassium iodide (SSKI) may be used 4

Contraindications for Methimazole

  • Methimazole is contraindicated in patients with a history of agranulocytosis or hepatotoxicity 5, 4
  • Patients who develop agranulocytosis or hepatotoxicity while taking methimazole should be switched to an alternative treatment 5, 4

Special Considerations

  • The initial dose of methimazole may affect the risk of agranulocytosis, with higher doses (30 mg daily) associated with a higher risk than lower doses (15 mg daily) 6
  • Patients taking methimazole should be closely monitored for signs of agranulocytosis and hepatotoxicity, and alternative treatments should be considered in cases of adverse effects 3, 5, 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The safety of methimazole and propylthiouracil in pregnancy: a systematic review.

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2012

Research

Desensitization to Methimazole.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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