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USE OF CARBIMAZOLE/METHIMAZOLE IN PREGNANCY

Date of issue: March 2024, Version: 3

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A corresponding patient information leaflet on USE OF CARBIMAZOLE/METHIMAZOLE IN PREGNANCY is available.

Carbimazole and methimazole are thionamide antithyroid agents used in the management of hyperthyroidism and licensed for the treatment of Graves’ disease, in the preparation of hyperthyroid patients for thyroidectomy, and as an adjunct to radioiodine therapy. Following absorption, carbimazole is rapidly and completely metabolised to methimazole, which inhibits the synthesis of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

 It is critical that maternal hyperthyroidism during pregnancy receives appropriate treatment, as it has been associated with serious maternal complications, including hypertension, thyroid storm, heart failure, preterm labour, pre-eclampsia, and placental abruption. Noted fetal and neonatal complications include stillbirth, intrauterine growth restriction, low birth weight, heart failure, and goitre. High levels of maternal thyroid hormones may also lead to abnormal fetal thyroid development and some studies have linked maternal hyperthyroidism during pregnancy to congenital malformations in the infant.

 Exposure to carbimazole/methimazole (CMZ/MMI) during early pregnancy has been linked with an embryopathy that incorporates a number of birth defects, including aplasia cutis, choanal atresia, gastrointestinal anomalies, and abdominal wall defects. These defects have been seen to occur either in isolation or in combination, and in some cases with facial dysmorphism and developmental delay. Although the relative risk of these specific and often rare malformations appears to be greatly increased following exposure to CMZ/MMI, studies have estimated that <2% of infants exposed to CMZ/MMI in utero will be affected.

 There is no firm evidence to link CMZ/MMI exposure during pregnancy to miscarriage, perinatal death, low birth weight, or premature delivery, although for most of these outcomes, data are inadequate to permit a full and accurate risk assessment. Finally, a number of case reports have linked in utero CMZ/MMI exposure to developmental delay in children, most of whom had structural birth defects. While controlled epidemiological studies have not confirmed this association, these data are also limited. 

 Due to the possible risk of CMZ/MMI embryopathy, pregnant women with hyperthyroidism are often treated with propylthiouracil (PTU). However, hepatotoxicity is a rare side effect of PTU, and its use has also been associated with infant congenital malformations (albeit at a lower rate than with CMZ/MMI). The potential risks and benefits of PTU over CMZ should be made on an individual patient basis. Maternal hyperthyroidism should be treated with titrated doses of antithyroid drugs, as block-and-replace regimes result in fetal hypothyroidism since thyroxine cannot easily cross the placenta.

 Pregnant women being treated for hyperthyroidism should be managed by an obstetric unit. Where exposure to CMZ/MMI has occurred in the first trimester, a routine 20-week anomaly scan should be strongly advised, although it should be noted that some CMZ/MMI-associated defects would be unlikely to be detected. Women with hyperthyroidism should be offered serial growth scans to screen for fetal growth restriction. Features of fetal hyper- and hypothyroidism (goitre, tachycardia, hydrops, bone maturity) can also be detected on serial scanning.

 Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from UKTIS.org to ensure you are using the most up-to-date version.