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A two-clinician sign-off for men aged under 55 years currently taking valproate will not be required, but will remain in place for other patients aged under 55 years who are starting valproate, the Medicines and Healthcare products Regulatory Agency (MHRA) has said.
In an announcement published on 13 February 2025, the MHRA said: “The review by two specialists remains in place for patients starting valproate under 55 years of age, but the Commission on Human Medicines (CHM) has advised that it will not be required for men (or males) currently taking valproate.”
The advice forms part of a report, also published on 13 February 2025, on managing reproductive risks from valproate in males aged under 55 years.
The requirement for a two-clinician sign-off for valproate initiation came into effect on 31 January 2024. Under the measures, two specialists must independently agree that there is no other effective or tolerated treatment, or there are “compelling reasons” that the reproductive risks do not apply.
The requirement was first announced by the MHRA in December 2022 following advice from the CHM. The measure was initially applied to all new patients aged under 55 years and women already under specialist review, with implementation for men planned to begin in a subsequent phase.
In March 2023, a coalition of 11 epilepsy organisations published a joint statement calling on the government to pause the decision “immediately”, warning that the measure was “totally out of proportion to the risks to patient safety”.
Sodium valproate is an antiseizure medicine used to treat epilepsy; however, babies exposed to it in the womb are at significant risk of developing foetal valproate spectrum disorder, which is the collective name for a variety of disorders and development issues, including spina bifida, autism and malformations of the brain, heart and kidneys.
Valproate is also associated with a risk of impaired fertility in males, which may be reversible upon its discontinuation.
MHRA advice issued on 5 September 2024 recommends that male patients and their female partner use effective contraception during valproate use and for at least three months after stopping treatment.
The guidance was published after study results revealed a possible connection between the use of valproate in men and a small increased risk of neurodevelopment disorders in their children.
Wing Tang, head of professional standards at the Royal Pharmaceutical Society, welcomed the guidance update: “Although male patients currently taking valproate are not required to be reviewed by two specialists, healthcare professionals should be aware of the risk minimisation measures and safety precautions and if a male patient is planning to father a child, they should be referred to a specialist.
“Patients should not stop taking valproate without advice from a specialist. RPS members with any questions or concerns can contact our support team for further guidance,” he added.
Alison Fuller, director of health improvement and influencing at Epilepsy Action, told The Pharmaceutical Journal that this latest guidance raises further questions and has asked the MHRA for more background on the decision-making process behind the guidance.
“This update also seems to suggest that a personalised clinical care plan will substitute a risk acknowledgement form for people currently on the medication. Again, we need to understand more about how this will work in practice and what measures will be in place to ensure that patients are receiving information about the risks,” she said.
“It’s also unclear whether all men taking sodium valproate will have access to this, even those who are newly prescribed and have to sign a risk acknowledgment form, or if this only applies to people currently on the medication.
“It could also leave many people wondering why women are required to sign the form every year, when men will only have to do this once, if newly-prescribed, or not at all, if they’re already on sodium valproate. We have heard of many women who find the process distressing and even belittling,” she added.
“While we understand risks for men are lower, we have written to [the] MHRA to give us more information about the process and who this applies to.”
- This article was updated on 14 February 2025 to include comment from the Royal Pharmaceutical Society
