New prescribing practices for valproate

Additional new restrictions are to be introduced for the prescribing of valproate from 31 January 2024.

KEY MESSAGES

• Men and women under the age of 55 should not be started on valproate without two specialists signing off prescription 
• Women already taking valproate will need sign off from two specialists to continue
• Men already taking valproate will need sign off from two specialists to continue, later next year
• No-one should stop taking their medication without consulting their doctor
• Patients will be called in for a review of their prescription
• Valproate  is also known as sodium valproate, valproate semisodium, or valproic acid. Brand names Epilim, Depakote, Convulex, Episenta, Epival, Syonell, Belvo and Dyzantil

Current regulatory measures already mean that no woman or girl of childbearing age can be prescribed valproate, unless there is a pregnancy prevention programme in place. Or unless there is no other effective treatment available.

But the new measures mean that from the end of January, no-one under the age of 55 – both men and women - should be started on valproate unless two specialists independently agree and document that there is no other safe and effective medication, or that there are compelling reasons why the reproductive risks linked to valproate, do not apply.

Ten per cent of babies exposed to valproate during pregnancy are born with birth defects and 40 per cent are at risk of developmental disorders.

All women who could become pregnant and girls who are currently taking valproate will be reviewed at their next annual specialist review, using a revised valproate Annual Risk Acknowledgement Form. This will include the need for a second opinion’s signature if the person is to continue with valproate.  

A similar system will be introduced later in 2024 for men who are currently taking valproate. This follows advice from an independent expert group of the Commission on Human Medicines that the measures should be introduced in a phased manner to ensure ongoing patient care is not disrupted.

Concerns around continued use of valproate

The new restrictions follow concerns that women of childbearing age are still being prescribed valproate, even during pregnancy. 

There are also concerns about the link between valproate and the risk of impaired male fertility. While these have been recognised since 2011, additional emerging data from animal studies show adverse effects of valproate on the testes of juvenile animals as well as transgenerational effects. It is not yet known what this means for humans, but further studies are being undertaken.

The medicines regulator, MHRA, has issued instructions to healthcare organisations to ensure that systems are in place to implement the changes from 31 January 2024.

People taking valproate will be invited for an appointment with their to doctor to discuss their treatment plan.

No-one should stop taking valproate without  first consulting their doctor. 

Charities' reaction to changes

The epilepsy charities, including the Epilepsy Society, have questioned the changes, the lack of consultation and the timing of the new guidance. They have questioned the capacity of the NHS to implement these changes when it is already on its knees. Importantly, they underline that for some people valproate is the only medication that will control their seizures.

Nicola Swanborough, Head of External Affairs at the Epilepsy Society, said: “Sodium valproate is one of the most effective medications for controlling seizures but, sadly, it also carries the greatest risk of harm for an unborn child during pregnancy. It is important that women and girls of childbearing age are only prescribed the medication as part of the Prevent programme. However, it is equally important that there is an amplified care pathway for those who are switched to a safer, but potentially less effective medication. The same applies for men who may now not be prescribed valproate which could have been the best medication for their epilepsy.

“The challenges around treating epilepsy are not limited to valproate. Other commonly prescribed epilepsy medications also carry an elevated risk for an unborn child, while for many of the newer anti-seizure medications, there is not the data to say whether they are safe during pregnancy. This is why the Epilepsy Society is asking the government to invest £20m in genomic research which could identify at a genetic level which drugs are likely to cause problems for women and their unborn baby during pregnancy, and which might be safer.

“We cannot wait another five or ten years to see what the long-term outcomes are for babies exposed today to some of the alternative drugs to valproate. We need to allow our scientists to unpick the information which is written in our DNA and prescribe at an individual level rather than taking a blanket approach which has long-term consequences.

“The new restrictions introduced by the MHRA  could leave many men and women vulnerable to seizures with all that goes with them. We need to be innovative and creative in finding better solutions through science and personalised medicines.”

Find out more

New measures to reduce ongoing harms linked to valproate

How the risks around valproate compare with other epilepsy medications