MHRA increases scrutiny of valproate prescribing to protect patients from its side effects

The epileptic drug may cause serious harm to unborn babies, if taken during pregnancy, and impair fertility in males

The Medicines and Healthcare products Regulatory Agency (MHRA) has instructed healthcare organisations to start planning for implementing new regulatory measures to reduce the known harms of sodium valproate, the drug used to treat epilepsy and bipolar disorder.

Valproate use during pregnancy can cause serious harm to the unborn child, as well as impair fertility in males, it said.

The UK's medicines regulator has asked healthcare professionals to stop prescribing the antiepileptic drug to new patients (male or female) younger than 55 years from January 2024, unless “there is no other effective or tolerated treatment” or there are compelling reasons that “the reproductive risks do not apply.”

Girls and women of child-bearing potential who are currently taking valproate will be reviewed at their next annual specialist review, using a revised Annual Risk Acknowledgement Form, and a second opinion’s signature would be required if the patient is to continue with the drug.

A similar system will be introduced later in 2024 for male patients currently taking valproate.

The regulatory changes have been recommended by the Commission on Human Medicines, comprising of representatives from across the healthcare system, to increase scrutiny of valproate prescribing and ensure that drug is only used when the benefits outweigh the risk.

As advised by the independent expert group, these measures would be introduced in a phased manner to ensure ongoing patient care is not disrupted.

Health Minister Maria Caulfield expressed her sympathies for all those affected by the side effects of sodium valproate.

“These regulatory measures will help to further improve patient safety and ensure valproate is only used when the benefits outweigh the risk,” she said.

MHRA Chief Safety Officer, Dr Alison Cave cautioned that valproate should only be used in girls and women of child-bearing potential if a pregnancy prevention programme is in place.

“To better protect patients from these harms, we are taking robust regulatory action to ensure greater scrutiny of valproate prescribing. Valproate should only be used when no other treatment is effective,” she said.

Dr Alison also urged patients who are on valproate to attend any appointments offered over the next year to discuss their treatment plan and talk to a healthcare professional if they are concerned.

But no one should stop taking valproate without advice from a specialist, she added.

Side effects of Valproate 

“Valproate is a highly teratogenic medicine that also carries known risks to male fertility – it is therefore vital valproate is only used when there is no other effective or tolerated treatment option,” said Professor Munir Pirmohamed, Chair of The Commission on Human Medicines.

“We have consulted with patients and healthcare professionals with experience of valproate to inform our recommendations and to ensure that they are introduced in a way that does not disrupt ongoing patient care,” he added.

According to Patient Safety Commissioner Dr Henrietta Hughes, exposure to teratogens can cause physical and learning disabilities in children.

To dramatically reduce the number of babies exposed to these harmful substances, all organisations must bring in new measures from January 2024, the expert stated.

It is estimated that one in nine babies exposed to valproate during pregnancy have major birth defects, while it causes neurological disorder in as many as 4 in 10 babies.