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Carbimazole and increased risk of congenital malformations

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Carbimazole: increased risk of congenital malformations

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

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)

  • congenital malformations reported associated with use of carbimazole 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

  • 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.

Reference:

  • MRHA (February 2019). Drug Safety Update 12(7):1-8.

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