Carbimazole: increased risk of congenital malformations; strengthened advice on contraception

Carbimazole is associated with an increased risk of congenital malformations, especially when administered in the first trimester of pregnancy and at high doses. Women of childbearing potential should use effective contraception during treatment with carbimazole.

Advice for healthcare professionals:

  • carbimazole is associated with an increased risk of congenital malformations when used during pregnancy, particularly in the first trimester of pregnancy and at high doses (15 mg or more of carbimazole daily)

  • women of childbearing potential should use effective contraception during treatment with carbimazole

  • carbimazole should only be considered in pregnancy after a thorough individual assessment of benefits and risks of treatment, and only at the lowest effective dose without additional administration of thyroid hormones; close maternal, foetal, and neonatal monitoring is recommended

  • please report to the Yellow Card Scheme any suspected adverse reactions associated with medicines taken during pregnancy experienced by women or the baby or child

Background

Carbimazole is authorised for use in the management of hyperthyroidism, including preparation for thyroidectomy and treatment before and after radioiodine treatment. Around 45,000–50,000 prescriptions for carbimazole a month are dispensed across GP practices in NHS England (data from openprescribing.net).

Carbimazole is a prodrug that undergoes rapid metabolism to the active metabolite, thiamazole. Thiamazole (synonym methimazole) is an antithyroid agent that acts by blocking the production of thyroid hormones. Thiamazole is not authorised for use in the UK.

Risk of congenital malformations

Adequate treatment of hyperthyroidism in pregnant women prevents serious maternal and foetal complications.

Carbimazole crosses the placental barrier and can cause foetal harm. An EU review of available evidence from epidemiological studies and case reports concluded there was evidence that carbimazole is associated with an increased risk of congenital malformations, especially when administered in the first trimester of pregnancy and at high doses (15 mg or more of carbimazole daily).

Reported malformations include aplasia cutis congenita (absence of a portion of skin, often localised on the head), craniofacial malformations (choanal atresia; facial dysmorphism), defects of the abdominal wall and gastrointestinal tract (exomphalos, oesophageal atresia, omphalo-mesenteric duct anomaly), and ventricular septal defect.

New advice on contraception and pregnancy

Women of childbearing potential should use effective contraception during treatment with carbimazole – see FSRH statement on contraception for women using known teratogenic drugs or drugs with potential teratogenic effects. The Patient Information Leaflet advises patients to tell their doctor straight away if they think they may be pregnant or are planning to have a baby.

Carbimazole must only be used during pregnancy when clinically indicated and after a strict individual benefit/risk assessment and only at the lowest effective dose without additional administration of thyroid hormones. The use of carbimazole during pregnancy should be preserved for the situations in which a definitive therapy of the underlying disease (thyroidectomy or radioiodine treatment) was not suitable prior to pregnancy and in case of new occurrence or reoccurrence during pregnancy.

If carbimazole is used during pregnancy, close maternal, foetal and neonatal monitoring is recommended.

Report suspected adverse drug reactions via the Yellow Card Scheme

Please continue to report any suspected adverse drug reactions via the Yellow Card Scheme. Remember only a suspicion is needed to report – if in doubt, please complete a Yellow Card.

For more about the importance of reporting suspected adverse drug reactions associated with medicines in pregnancy see Drug Safety Update July 2018.

Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card App. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

You can also use the app to access the latest safety information from the MHRA about medicines and medical devices on the Newsfeed. The App is also piloting additional questions on medicine use during pregnancy – download the app and try it out for yourself.

Further information

Direct Healthcare Professional Communication.

PRAC recommendations on signals adopted 26-29 November 2018 PRAC meeting.

Article citation: Drug Safety Update volume 12, issue 7: February 2019: 1.

Published 18 February 2019