MHRA to review evidence of cross-generational effects of sodium valproate


The Medicines and Healthcare Products Regulatory Agency (MHRA) is reviewing data suggesting that the genetic changes triggered by sodium valproate could be passed down from generation to generation.

As part of its safety review of the epilepsy drug, the MHRA has confirmed that it has asked the Commission for Medicinal Products for Human Use (CHM) – an independent group of experts – to review data showing its transgenerational effects in mice.

Data published by NHS Digital in March 2022 showed that 46 pregnant women were prescribed sodium valproate between October 2020 and September 2021, despite the guidelines stating that it should not be prescribed during pregnancy due to the risk of birth defects.

The MHRA announced its safety review of sodium valproate in May 2022, part of which involved seeking the opinions of patients and healthcare professionals.

The product information for sodium valproate already includes a warning about behavioral abnormalities in first-generation offspring of mice and rats after exposure to sodium valproate during pregnancy, the MHRA said.

However, he seeks advice on research as some of these behavioral changes have been observed in their second generation offspring and, although less pronounced, in the third generation.

An MHRA spokesperson said: ‘As part of our ongoing review of the safety of sodium valproate, we have carefully assessed all available data on its benefits and risks and have sought independent advice from the government expert scientific body, the CHM, on the effectiveness of current measures to support the safe use of valproate.

“Available data reviewed by the CHM include animal data that show changes in the testes in juvenile male animals and transgenerational effects in mice.

“The CHM review benefited from incorporating the views of a wide range of stakeholders, including patients and families. We will communicate in more detail on the outcome of these discussions as soon as the opinion is finalized. »

In a report published in Birth defects research in November 2021, data from 108 people from 90 families who had complications after exposure to valproate in the womb, who then had children of their own, also suggested that the drug could affect future generations. It is not yet clear whether the MHRA is considering this study.

The study authors called for more pharmacoepidemiological investigations into epigenetic inheritance caused by valproate and other drugs, and potential links to malformations or neurodevelopmental disorders.

A national valproate register, which details the number of women who have been prescribed valproate in England and any pregnancies among these women, was set up in June 2021. The register also shows whether or not valproate continued to be prescribed during pregnancy.

In response to NHS Digital figures released in April 2022, Jeremy Hunt, Chairman of the House of Commons Health and Social Affairs Committee, called for a ban on prescribing sodium valproate to pregnant women with epilepsy.

Daniel Jennings, senior policy and campaign manager at the charity Epilepsy Action, said that while it was concerning to read about the possible transgenerational risks of sodium valproate, it was important to point out that what we seen in animal studies does not necessarily mean the same is true for humans. .

“People severely affected by valproate use during pregnancy have reported that their children have birth defects and/or learning and developmental problems,” he said.

“But the evidence is very limited and more research is needed to show whether there is a link between the use of valproate during pregnancy and any problems in the children of those affected.”

Nicola Swanborough, External Affairs Manager at the Epilepsy Society, said: “For families whose lives have already been devastated by sodium valproate, it is heartbreaking to learn that the drug’s teratogenic effects can be passed down through generations. future.

“The MHRA still has a lot of work to do to effectively communicate the risks of valproate and now they must proactively ensure that children with fetal valproate spectrum disorder are identified, counseled and monitored through a proper longitudinal study.”

Read more: Everything you need to know about sodium valproate and other antiepileptic drugs during pregnancy


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