Carbimazole Safety Issues

Carbimazole is an anti-thyroid medication indicated for the treatment of hyperthyroidism. Two safety issues have recently been highlighted following a review by the European Medicines Agency (EMA):

1. Risk of pancreatitis; and
2. The importance of contraceptive measures.

Post-marketing surveillance reveals an association between acute pancreatitis and carbimazole therapy. Although the mechanism for this effect is poorly understood, it is thought to have an immunological basis. If acute pancreatitis occurs, carbimazole should be discontinued immediately and not restarted. Re-exposure may result in life-threatening acute pancreatitis with a reduced time to onset.

Pancreatitis may present with fever, nausea, vomiting, and abdominal pain that is usually central and epigastric; plasma lipase levels are often at least three times greater than the reference range. While a number of case reports have been published on this issue, only one report of pancreatitis with carbimazole can be found in the almost 50 years of data available on the Australian Database of Adverse Event Notifications. It is also worth noting that carbimazole was not the only medication suspected of causing the adverse event in this case.

Available data now also strengthens the evidence that carbimazole can cause congenital malformations when administered during pregnancy. Reported malformations include aplasia cutis congenita, craniofacial malformations, exomphalos, oesophageal atresia, omphalo-mesenteric duct anomaly, and ventricular septal defect. The risk appears to be greatest during the first trimester and when high doses are used. It is, therefore, recommended that women of childbearing potential use effective contraceptive measures while undertaking therapy with carbimazole.

Studies also demonstrate that the risk of congenital malformations is greater when maternal hyperthyroidism remains untreated. Carbimazole should only be used during pregnancy after a careful individual risk/benefit assessment. If carbimazole is deemed appropriate, the lowest effective dose should be prescribed without additional administration of thyroid hormones. Close maternal, foetal, and neonatal monitoring is recommended.

The manufacturer has advised that the product information for carbimazole will be updated to reflect these safety issues.