Birth Defects Warning Over Hyperthyroidism Treatment

Peter Russell

February 19, 2019

A drug safety update warning of an increased risk of congenital malformations and a risk of acute pancreatitis associated with carbimazole was issued by the Medicines and Healthcare products Regulatory Agency (MHRA).

The MHRA advised women of childbearing age to use effective contraception while being treated with carbimazole as the risk of congenital malformations may be higher when administered in the first trimester of pregnancy and at higher doses of 15mg or more each day.

Congenital Malformations Reported

Reported malformations included 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.

Carbimazole is authorised for use in the management of hyperthyroidism, including preparation for thyroidectomy, and treatment before and after radioiodine treatment.

An estimated 45,000 to 50,000 prescriptions for carbimazole are dispensed each month by GP practices in England.

The drug safety warning stemmed from a meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency which reviewed evidence from epidemiological studies and case reports.

Because carbimazole crosses the placental barrier and can cause foetal harm, healthcare professionals were advised it should only be used during pregnancy when clinically indicated and after a strict individual assessment of the benefits versus the risks. Also, treatment with carbimazole should be at the lowest effective dose without additional administration of thyroid hormones, the MHRA said.

The Agency said the use of carbimazole during pregnancy should be restricted to 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.

In cases where carbimazole was used during pregnancy, close maternal, foetal and neonatal monitoring was recommended.

Acute Pancreatitis Concerns

The PRAC review also found reports of acute pancreatitis associated with the use of carbimazole and thiamazole, the latter of which is not authorised for use in the UK.

The MHRA said that although there had never been a report of acute pancreatitis linked to carbimazole in 55 years, there was sufficient evidence to suggest a possible association.

The updated advice was to immediately discontinue treatment with carbimazole in patients who develop acute pancreatitis during treatment and offer an alternative treatment based on an assessment of the individual benefits and risks.

The Agency said that restarting treatment with carbimazole must be avoided in patients who have previously experienced acute pancreatitis with carbimazole or thiamazole as re-exposure could result in recurrence of potentially life-threatening acute pancreatitis, with a decreased time to onset.

SGLT2 Inhibitors

In other drug alerts, the MHRA said the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors should be stopped in cases where Fournier's gangrene was suspected.

It said that although the condition was rare, consequences were potentially life-threatening and alternative treatments were urgently needed, including with antibiotics and surgical debridement.

The Agency said it had received six Yellow Card reports (four in men and two in women) of UK cases of Fournier’s gangrene in association with SGLT2 inhibitors up to January 2019.

SGLT2 inhibitors, used to treat type 2 diabetes, were those containing dapagliflozin, canagliflozin, empagliflozin, and ertugliflozin.

Health professionals should be aware of symptoms of severe pain, tenderness, erythema, or swelling in the genital or perineal area accompanied by fever or malaise in patients taking SGLT2 inhibitors.

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