Epilepsy Drug Birth Defects Impacted 2,150 to 4,100 Children in France: Report

A new report indicates that as many as 4,100 children from France may have suffered birth defects due to exposure to Depakote and similar valproate-based epilepsy drugs during pregnancy. 

In findings released last week by the ANSM, France’s drug regulatory agency looked at likely Depakote-based malformations that occurred in the womb between 1967 and 2016, suggesting that a minimum of 2,150 children to a maximum of 4,100 suffered neurological defects due to the Sanofi drug. The full report is expected to be released later this year.

Depakote was introduced in the late 1970s for treatment of certain forms of epilepsy, containing the active ingredient valproic acid. However, pregnancy side effects of Depakote have been linked to a number of severe birth defects, including spina bifida, cleft palate, abnormal skull development, malformed limbs, holes in the heart and urinary tract problems; especially when the drug is taken during the first 28 days, when neural tube closure and other critical formations are taking place.

In 2006, the FDA added a “black box” warning in the United States about the potential Depakote birth defects risks, after a study found that 20% of pregnant mothers who gave birth while on Depakote had a child with malformations or a birth defect.

Last summer, a study published by ANSM and the health insurance agency CNAMTS found that more than 10,000 pregnant French women were exposed to Depakote between 2007 and 2014. An earlier study, released in February, estimated that about 450 children were born with birth defects or were stillborn during that time.

The French parliament is expected to determine responsibility and possible compensation for those born with Depakote-related birth defects and a judicial review is underway as the result of complaints from French families. It is unclear how much Sanofi would be expected to pay at this time.

In May 2013, the FDA put new restrictions on Depakote pregnancy use, contraindicating the drug for pregnant women, but only when it was used for the treatment of migraines. The agency did not contraindicate it for pregnant women using it to treat epilepsy. The FDA changed all valproate-based drugs from a class “D” to a class “X” pregnancy drug, which indicates that the risks involve din use of the drug by pregnant women outweigh the benefits.

In 2014, the European Medicines Agency declared that the drug should only be used as a drug of last resort, and then only after expecting mothers were warned of the possible side effects.

Before the drug’s patent expired in 2007, Depakote was a blockbuster drug generating about $1.5 billion in annual sales for AbbVie’s predecessor. In France and some other countries the drug is known as Depakene.

In the U.S., the drug is distributed by AbbVie and Abbott Laboratories. In France, it is distributed by Sanofi.

Abbott Laboratories and AbbVie, a subsidiary it spun off, have faced hundreds of Depakote lawsuits in state and federal courts nationwide. Plaintiffs say the company should be held liable for failing to warn women and the medical community about the risks associated with using the medication during pregnancy.