MHRA Revises Valproate Guidance for Male Patients

The Medicines and Healthcare products Regulatory Agency (MHRA) has revised its guidance on sodium valproate use in men, removing a requirement for dual specialist reviews for those already on the medication.

In September 2src24, the MHRA advised prescribers that men taking valproate, and their female partners, should use effective contraception while on the drug, and for 3 months after stopping treatment. The precautionary advice followed research suggesting a possible increased risk for neurodevelopmental disorders in children born to men who had been treated with valproate in the 3 months prior to conception.

Following a review by the Commission on Human Medicines, the MHRA said it would no longer require that men under 55 currently taking valproate be reviewed by two specialists. However, the dual review process remains in place for new male patients under 55 and for women under 55, unless reproductive risks do not apply. 

The agency stipulated that men already on valproate should be asked at their next review whether they planned to start a family in the next year. If so, they should be referred to a specialist to discuss alternative treatment options. Existing rules already required that valproate could only be prescribed to women of childbearing potential if a specialist judged other treatments to be ineffective or not tolerated and if a pregnancy prevention programme was in place.

Risks in Men Outweighed by Risks of Nontreatment

The initial restrictions faced strong criticism. An evidence review found “no clear evidence for an adverse impact of paternal antiseizure medication use on offspring outcomes”. Experts concluded that the risks of prescribing less effective medication — including increased morbidity, mortality, and breakthrough seizures — outweighed the “unlikely” risk for adverse outcomes for offspring. 

Concerns also arose from data on women, for whom restrictions on valproate had led to an increased risk for sudden death in epilepsy. The drug is known to have teratogenic potential, with up to a 1src% risk for birth defects and a 4src% risk for developmental problems.

In response to the updated guidance, the Association of British Neurologists (ABN) this week issued an update to their previous statement and acknowledged that the ruling would be “difficult” for patients, neurologists, and neurology services. The ABN urged neurologists to “recognise and adopt the new regulatory framework, balancing the risk from seizures with the reproductive risk from medication.” 

Valproate Still an Option for Some Patients

The agency noted that a recent update to guidance from the National Institute for Health and Care Excellence (NICE) reflect the new regulatory stance. Although valproate may be the most effective treatment for some idiopathic (genetic) generalised epilepsies, lamotrigine, levetiracetam, or valproate are now all recommended as first-line monotherapy for many of the epilepsies for which valproate was previously the only first-line medication. However, NICE continues to recommend valproate as the single first-line choice for specific syndromes such as Dravet and Lennox-Gastaut.
“Valproate can, with appropriate counselling and documentation, still be used,” the ABN said. “Working within these new recommendations should ensure that valproate remains available for those who need it.”

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.