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DRUG INFORMATION ROUNDS

Propylthiouracil Versus Methimazole in Treatment of Graves' Disease During Pregnancy

Managed Care Pharmacy Practice Resident, Department of Clinical Pharmacy, College of Pharmacy, Ferris State University, Big Rapids, MI

Teresa B Klepser, PharmD

Associate Professor, Department of Clinical Pharmacy, College of Pharmacy, Ferris State University

Reprints: Dr. Klepser, Ferris State University College of Pharmacy, 1000 Oliver St., Kalamazoo, MI 49008, fax 269/324-8618, klepsert{at}ferris.edu

OBJECTIVE: To evaluate the evidence supporting the use of propylthiouracil (PTU) versus methimazole for the treatment of Graves' disease during pregnancy.

DATA SOURCES: An English-language literature search was conducted using MEDLINE (1966-March 2007). Identified articles were then reviewed for additional sources. Search terms included hyperthyroidism, Graves' disease, pregnancy, propylthiouracil, and methimazole.

STUDY SELECTION AND DATA EXTRACTION: All clinical trials and case reports that were published in English and reported either subjective or objective outcomes were reviewed.

DATA SYNTHESIS: Rationale supporting the use of PTU over methimazole in treatment of Graves' disease during pregnancy is limited. Theories suggesting that PTU has less placental transfer to the fetus than methimazole are not supported by current literature. Studies demonstrating a causal relationship between methimazole use during pregnancy and congenital anomalies and/or fetal hypothyroidism do not exist.

CONCLUSIONS: The selection of PTU versus methimazole for the treatment of Graves' disease during pregnancy should not be based solely on the following assumptions: that PTU crosses the placenta less than methimazole, that PTU leads to less fetal hypothyroidism, or that exposure to methimazole during pregnancy leads to decreased intellectual function in children. However, due to a possible association between the use of methimazole during pregnancy and fetal anomalies such as aplasia cutis, esophageal atresia, and choanal atresia, methimazole may be a less desirable first-line treatment for Graves' disease in pregnancy than PTU. Therefore, in the absence of a compelling indication for the use of methimazole, PTU should still be considered as the first-line agent in the treatment of Graves' disease during pregnancy. Methimazole should be considered a viable second choice if the patient is intolerant to PTU, has an allergic reaction to PTU, or fails to become euthyroid while receiving PTU.

Key Words: Graves' disease, methimazole, pregnancy, propylthiouracil

Published Online, May 15, 2007. www.theannals.com, DOI 10.1345/aph.1H535